TUTORIAL REPORT

HEMATOIMUNOLOGI BLOCK
Modul 5 : "HIV-positive man and HIV-negative wife"

By :
Abdul Rois Romdhon

(1218011001)

Alexander Dicky K.N

(1218011008)

Christoper A.M

(1218011029)

Eko Doni Irawan

(1218011043)

Gabriella Berta Risma

(1218011055)

Hera Julia Garamina

(1218011070)

Indhraswari Dyah W

(1218011081)

Ivani Ridwan

(1218011085)

Janis Rivandi

(1218011086)

Martin Paskal Giovani

(1218011103)

Singgih Suhan Nanto

(1218011145)

Talytha Aletha

(1218011152)

Aleya Yostha Kaban

(1018011107)

Medical Faculty
University of Lampung
2014

The PREFACE

Assalammualaikum wr. wb. Wb.

Praise the Lord, praised and thank heavens we said upper the Lord of the
Lord who gave the blessing and his gift so as we could compile the report on this
5st case that was entitled " HIV-positive man and HIV-negative wife ".
Further, this report was compiled in order to fill the task of the
Hematoimunologi to Bloc lecturers who were involved in this Bloc, we said
thankyou for all of his briefings so as this report could be compiled by us by being
good enough.
We realised that still often was gotten by the lack in the writing of this
report, good from the aspect of the contents, the language, the analysis, et cetera.
Therefore, we wanted to apologise for all these lacks, this was caused because still
the shortage of knowledge, the concept, and our skills. Moreover, criticism and
the suggestion from the reader really were hoped for by us, for for this report
perfection and the improvement for all of us.
It is hoped this report could be useful and give the concept took the form
of science for all of us.

Wassalammualaikum wr. wb. Wb.

Bandar Lampung, on April 4 ,2014

The team of the Writer

The CONTENT

The Preface..........
The Content..
Scenario ......
Step 1.......
Step 2.......
Step 3.......
Step 4.........................................................................................
Step 5.......
Step 6.......
Step 7.......
The Bibliography ....

SCENARIO 5

"HIV-positive man and HIV-negative wife"

A 50 years old man was admitted to a hospital with multiple nonspecific

symptoms for investigation. His HIV test turned out to be positive. Without
informing the man of the test or its outcome, the doctor discussed the situation
with the patient's wife and encouraged her to undergo an HIV test. She turned out
to be negative. Though the wife was quite upset about the situation, she showed
that she was a bold woman. She asked the doctor several questions on the disease
transmission, treatment, and curability.
Later, she came to the doctor and made just one request. The husband and wife
were living with the wife's brother. "Please don't tell my brother that my husband
is HIV-positive. We are labourers without any land and need my brother's help for
shelter and survival. If he finds out about this, he may ask us to leave the house.

STEP 1

Difficult words in the scenario

STEP 2

1.
2.
3.
4.
5.

HIV, etiology, epidemiology, pathogenesis, pathophysiology?

Criteria for diagnosis?
Why is HIV positive husband and wife HIV negative?
How to deal with HIV patients?
Whats antiretroviral (Art)?

STEP 3

1.

HIV, etiology, epidemiology, pathogenesis, pathophysiology?

HUMAN IMMUNODEFICIENCY VIRUS (HIV)

a type of virus that attacks the human immune system and can cause
AIDS. The virus is composed of two groups, namely HIV-1 and HIV-2.
ETIOLOGY
Including the HIV retrovirus subfamily members lentivirinae. Characteristic
of the unique morphology of HIV is the cylindrical shaped nucleoid in the mature
virion.

Gambar 2.1. Struktur anatomi HIV (TeenAIDS, 2008).

Gambar 2.2. Peta genome dari Lentivirus

EPIDEMIOLOGY

The first case of AIDS was reported from Bali in Indonesia in April 1987.
Sufferers are a Dutch tourist who died in the General Hospital Sanglah due to
secondary infection in his lungs. Until the end of 1990, an increase in HIV / AIDS
cases doubled.
Since mid-1999 began to look sharp increase due to the use of injectable
drugs. Worrying is the fact that the majority of drug users are teenagers and young
adults who are productive age group. At the end of March 2005 recorded 6789
cases of HIV / AIDS were reported.
Until the end of December 2008, the number of cases had reached 16,110
AIDS cases and 6,554 HIV cases. While the number of AIDS deaths were
recorded at 3,362 people. From all the AIDS patients, 12,061 patients were male
with the highest spread through sex (MOH, 2008).
PATHOGENESIS
virus enters the body, the main target is the CD4 lymphocytes because the
virus has an affinity for the CD4 surface molecule. This virus has the ability to
transfer their genetic information from DNA to RNA by using an enzyme called
reverse transcriptase. CD4 lymphocyte functions to coordinate a number of
important immunological functions. Loss of function causes a progressive
disorder of immune response.
After primary infection , there is a 4-11 day period between the beginning
of mucosal infection and viremia can be detected for 8-12 weeks . During this
period , the virus is widespread throughout the body and reach the lymphoid
organs . At this stage there has been a decrease in the number of CD4 T-cells .
Immune response to HIV occur 1 week to 3 months after infection , plasma
viremia decreased , and CD4 cell levels increased again but was unable to get rid
of the infection completely. This clinical latency period can last for 10 years .
During this period there will be an increased viral replication . It is estimated that
approximately 10 billion HIV particles produced and destroyed each day . The
half-life of virus in plasma is approximately 6 hours , and the viral life cycle an

average of 2.6 days . CD4 T - lymphocytes infected has a half-life of 1.6 days .
Due to the rapid proliferation of this virus and the error rate of HIV reverse
transcriptase binding , it is estimated that each nucleotide of the HIV genome may
mutate on a daily basis .
Eventually the patient will suffer constitutional symptoms and clinically
overt disease such as opportunistic infections or neoplasms. Higher levels of virus
can be detected in plasma during further stages of infection. HIV can be detected
in plasma during this stage of the infection further and more virulin than those
found in early infection.
Opportunistic infections can occur because of a decline in HIV infected
persons immune system to a level that is extremely low, so some types of
microorganisms can attack certain body parts. Even during these commensal
microorganisms which may be malignant and cause disease.
PATHOPHYSIOLOGY
Because of the important role of T cells in the "turn on" all the powers of
lymphocytes and macrophages, helper T cells can be considered as the "main
button" immune system. AIDS virus invaded selective T helper cells, destroy or
immobilize the cells that normally megatur largely immune response. This virus
also attacks macrophages, which further paralyzes the immune system, and is
sometimes also enter brain cells, causing dementia (impaired intellectual capacity
severe) were observed in the majority of AIDS patients.
In the body of people living with HIV, the virus particles join the DNA
cells of patients, so that one person is infected with HIV, he would remain a
lifelong infection. Of all people infected with HIV, the majority of AIDS in the
developing entry stage 3 The first year, 50% progressed to AIDS after 10 years,
and after 13 years of almost all people infected with HIV show symptoms of
AIDS, and then died. Resulting symptoms are fever, painful swallowing, swollen
lymph nodes, rash, diarrhea, or cough. After acute infection, asymptomatic HIV
infection began (without symptoms). This asymptomatic period usually lasts for
8-10 years.

2.

Criteria for diagnosis?

Revised criteria according to the Centers for Disease Control ( CDC ) United

States 1993 to a state associated with HIV :

1 . Candidiasis bronchus , and lung trakesa
2 . esophageal candidiasis
3 . Invasive cervical cancer
4 . Koksidioidomikosis disseminated or extra pulmonary
5 . Kriptokokokis extrapulmonary
6 . Cryptosporidiosis chronic intestinal ( > 1 month )

7 . Sitomegalivirus infection ( except in the liver , spleen , or lymph nodes )

8 . Rhinitis sitomegalivirus with impaired vision
9 . Associated with HIV encephalopathy
10 . Herpes simplex , chronic ulcers ( > 1 month ) or bronchitis , pneumonia ,
and esophagitis
11 . Disseminated or extrapulmonary histoplasmosis
12 . Isosporiasis chronic intestinal ( > 1 month )
13 . Kaposi sarcoma
14 . Burkitt's lymphoma
15 . immunoblastic lymphoma
16 . Primary lymphoma of the brain
17 . Mycobanterium avium complex or M. kansasii , disseminated or
extrapulmonary
18 . Mycobanterium tuberculosis , pulmonil or extrapulmonary
19 . Pneumocystis carinii pnemocystis
20 . recurrent pneumonia
21 . Progressive multifocal leukoencephalopathy
22 . Recurrent salmonella septicemia
23 . Toxoplasma encephalitis
24 . HIV -related wasting syndrome

Major symptoms:
a. Body weight decreased by more than 10% in 1 month
b. Chronic diarrhea that lasts more than 1 month
c. Prolonged fever of more than 1 month
d. Loss of consciousness and neurological disorders
e. Dementia / HIV encephalopathy
Minor symptoms:
a. Cough lasts more than 1 month
b. generalized dermatitis
c. The presence of herpes zoster and herpes zoster recurrent multisegmental

d. Kandidias oropharyngeal
e. Herpes simplex chronic progressive
f. generalized lymphadenopathy
g. Cytomegalovirus retinitis
3.

Why is HIV positive husband and wife HIV negative?

it is likely the husband had sexual intercourse with different partners, then do

a blood transfusion containing HIV. because of the way could cause HIV to her
husband. whereas wives never do that. therefore HIV positive husband.
4.

How to deal with HIV patients?

patients were given special protection, doctors working on is a doctor

who has been given a special education procedures for how a patient with
HIV/AIDS. by keeping the patient to foster self-confidence if you later have been
released or go home and face the wider community.
Efforts to do is to provide counseling and assistance (not only psychotherapy but
also psikoreligi), proper education about HIV / AIDS both in people, families and
communities. So that patients, families and communities to accept his condition
with the right attitude and provide support to patients. The support of various
parties can eliminate a variety of stress and can help patients improve their quality
of life so as to avoid stress, depression, anxiety and feeling ostracized.
5.

Whats antiretroviral (Art)?

Highly active antiretroviral therapy (HAART) means treating HIV infection

with multiple drugs. Because HIV is a retrovirus, the drug is commonly referred
to as an antiretroviral drug (ARV). ARVs do not kill the virus. However, HAART
can slow down the growth of the virus. Time slowed the growth of the virus, as
well as HIV disease.
There are several steps in the HIV life cycle:
1. Free virus circulating in the bloodstream
2. HIV binds to the cell

3. HIV penetrates the cell and emptied its contents in the cell
4. HIV genetic code of the modified forms of RNA into shape with the help of
DNA by the enzyme reverse transcriptase
5. HIV DNA mixed with the DNA of cells with the assistance by the integrase
enzyme. With this integration, the cells become infected with HIV.
6. When the infected cell reproduces, the HIV DNA is activated, and the raw
materials to make new virus
7. All the materials needed to make new viruses collected
8. Immature virus pushes beyond the infected cells by a process called 'budding
(bulge)'
9. Millions of immature virus released from infected cells
10. The new virus matures: raw materials cut by the enzyme protease and
assembled into a functioning virus
Class of anti-HIV drugs are nucleoside reverse transcriptase inhibitors or
NRTIs, also called nucleoside analogues. These drugs block the four steps above,
the changes HIV's genetic material RNA into the shape of the shape of DNA is
needed in the following steps. The drug in this class approved in the U.S. and still
made are:
3TC (lamivudine)
Abacavir (ABC)
Zidovudine (ZDV, zidovudine)
d4T (stavudine)
didanosine (ddI)
Emtricitabine (FTC)
Tenofovir (TDF: nucleotide analogue)
The second class of drugs inhibits the same step in the HIV life cycle, but
by other means. These drugs called non-nucleoside reverse transcriptase inhibitors
or NNRTIs. Five NNRTIs approved:

Delavirdine (DLV)

 Efavirenz (EFV)
Etravirine (ETV)
Nevirapine (NVP)
Rilpivirine (RPV)

STEP 4
1.

AIDS (Acquired Immunodeficiency Syndrome / immunodeficiency syndrome

obtained), is the final stage in a series of immunological abnormalities and
known as the clinical spectrum of HIV infection. HIV used to be called as
HTLV-III (Human T-cell

lymphotropic

virus

III) or

LAV

(Lymphadenophaty Virus) is a virus of the family cytopathic retroviruses

(Price,1992).
Structure of HIV

HIV virions are spherical and have a cone-shaped core, surrounded by a lipid
envelope derived from the host cell membrane. Virus core contains the largest
capsid protein is p24, the nucleocapsid protein p7/p9, two Coffee RNA genome,
and three viral enzymes are protease, reverse transcriptase and integrase. Protein
p24

is

rapid

viral

antigen

was

detected

and

antibody

targets

the HIV screening test. Viral core surrounded by a protein matrix called p17,
which is the layer beneath the lipid envelope. Whereas lipid envelope containing
two virus glycoprotein is critical in process of HIV infection in cells that gp120
and gp41. Viral genome that contains genes gag, pol, and env which will encode
viral proteins. The results of a translational large precursor protein and should be
cut by proteases into proteins matur.
Classification
Human Immunodeficiency Virus (HIV) is a group of RNA viruses:
Family : Retroviridae
Sub-family

: Lentivirinae

Genus

: Lentivirus

Species

: Human immunodeficiency virus 1 (HIV-1)

Human Immunodeficiency Virus 2 (HIV-2)

HIV shows many typical physicochemical picture of his family. There are two
different types of human AIDS viruses, namely HIV-1 and HIV-2. Both types are
distinguished by the arrangement of the genome and phylogenetic relationships
(Evolutionary) with other primate lentiviruses. Based on a row of env genes, HIV1 includes three groups of viruses Different namely M (main), N (New or non-M,
non-O) and O (outlier). The dominant group M subtypes consisting of 11 or clades
(AK). Already identified six subtypes of HIV-2 is a sub-type AF
Cycle of HIV

The virus enters the body primarily infects cells that have CD4 protein
molecules. The largest group of cells that have CD4 molecules The target cells are
T lymphocytes others are monocytes, macrophages, Dendritic cells, cells
Langerhans cells and microglia (Price, 1992). When HIV enters the body, the
glycoprotein (Gp 120) at the outer viruses attach themselves to receptors
CD4 (cluster of

differentiation

4), a

protein

on

the T-helper lymphocytes,

monocytes, macrophages, dendritic cells and brain microglia. Glycoprotein

composed of two subunits gp120 and gp41. Sub unit 120 has a high affinity for
the CD4 receptor and responsible for binding the virus to the cell early. This
attachment induces conformational changes that trigger attachment of both the
coreceptor. Two The main chemokine receptor used by HIV are CCR5 and
CXCR4. Ties with these chemoreceptors induces a conformational change in the
sub-units glycoprotein 41 (gp41), which encourages the entry of gp41 peptide
sequences to the target membrane facilitates fusion virus. After the fusion, the
virus is not sheathed prepare for conduct replication. Viral genetic material
is single stand-sense RNA positive (ssRNA), viral RNA must be transcribed in
DNA is optimally on the replication of human cells (normal transcription of DNA
into RNA, HIV working backwards so named retroviruses). To do HIV equipped
with a unique enzyme RNA-dependent DNA polymerase (reverse transcriptase).
reverse transcriptase first form a DNA chain complementary, using viral RNA as
a template. Results of a complete synthesis molecules of double-strand DNA
(dsDNA) was transferred into the core and integrate into the host cell
chromosome by integrase enzyme. The integration poses several problems, the
first HIV can cause chronic infection and persistent, usually in the cells are longlived immune system such as T-memory lymphocytes. Secondly, the random
integration of the target causing trouble. Furthermore, the random integration of
the HIV causes cellular abnormalities and affect apoptosis. Combined viral DNA
and host cell DNA is replicated, transcription and translation. DNA polymerase
record and integrate proviral. DNA into mRNA and translate the mRNA resulting
in the formation of viral proteins. First, transcription and translation is done in
low-level produces a variety of viral proteins such as Tat, Rev and Nef. Tat protein
is very contribute to HIV gene expression, binds to specific DNA section

extension of the transcription start and stabilize. There are no clear function of the
Nef protein . Arrange Rev protein post-transcriptional activity and very needed
for HIV reflikasi. New virion particle assembly begins with the union of HIV
proteins in the host cell. Nucleocapsid that has been formed by ssRNA viruses
prepared in one complex. Nucleoprotein complex is then wrapped with 1
wrapping membrane and released from the host cell through a process
of "budding" from the plasma membrane. Virus production speed can be very
high and causing the death of the host cell.
Pathogenesis
Typical trip untreated HIV infection, timed around a decade. The stages include
primary infection, the virus spread to organs lymphoid, clinical latency, increased
expression of HIV, clinical disease and death. Duration between primary infection
and progression to clinical disease average about 10 years. In untreated cases,
death usually occurs within 2 years after the onset of symptoms. After primary
infection, during the 4-11 day period between infection and the mucosal onset of
viremia, viremia can be detected for about 8-12 weeks. Virus spread widely
throughout the body during this period, and infected lymphoid organs. At this
stage the decline in the number of CD4 T-cells circulating in significant. Immune
response to HIV occurs during 1 week to 3 months after infection, decreased
plasma viremia and CD4 cell levels increased again. However, the immune
response is not able to completely get rid of the infection, and cell- HIV-infected
cells in lymphoid settled. This clinical latency period can last up to 10 years,
during this period many viral replication occurs. The life cycle of the virus to the
time when the infection of cells production of new breeds that infect the next cell
average of 2.6 days. CD4 T-lymphocytes, are the main target responsible for
producing virus. Patients will suffer constitutional symptoms and clinical
symptoms tangible, such as opportunistic infections or neoplasms. Higher levels
of virus can be detected in plasma during further stages of infection. HIV found in
patients with advanced disease, usually far more virulent and cytopathic strain of
the virus found early in infection.

Transmission
HIV is transmitted during sexual contact (including oral-genital sex), through
parenteral exposure (on a contaminated blood transfusion and sharing
needles / injecting drugs use (IDU)) and from mother to baby during the perinatal
period. Someone asymptomatic HIV-positive can transmit the virus, the presence
of other sexually transmitted diseases such as syphilis and gonorrhea increases the
risk sexual transmission of HIV as much as a hundred times greater, due to
inflammation assist the transfer of HIV to penetrate the mucosal barrier. Since the
first HIV found, homosexual activity has been recognized as a major risk factor
transmission of this disease. The risk increases with increasing number of
pertemual sex with a different partner. Blood transfusions or infected blood
products is a way transmission is most effective. Users of illegal drugs with often
infected through use of contaminated needles. Paramedics can HIV infection by
blood-contaminated needle scratches, but the number of relatively fewer
infections. Mother-to-child transmission rate varies from 13% to 48% in untreated
women. Babies can be infected in utero, during the process childbirth or more
often through breast milk (breast milk). Without transmission through breast milk,
about 30% of infections occur in utero and 70% when birth. The data show that
one-third to half of HIV infection perinatal in Africa is caused by the
ASI. Transmission during breastfeeding is usually occurs in the first 6 months
after birth.
Clinical Symptoms
The symptoms of acute HIV infection are not specific, include fatigue, skin rash,
headache, nausea and night sweats. AIDS is characterized with significant
suppression in the development of infection and immune sistem serious
opportunistic very varied or unusual neoplasms (Especially Kaposi's sarcoma).
More serious symptoms in adults are often preceded by prodormal symptoms
(diarrhea and weight loss) include fatigue, malaise, fever, shortness of breath,
chronic diarrhea, white patches on the tongue (oral candidiasis) and

lymphadenopathy . The symptoms of the disease of the gastrointestinal tract,

from the esophagus until the colon is a major cause of weakness. Without
treatment interval between primary infection by HIV and the onset of clinical
disease in the first adults usually long, an average of about 10 years.

WHO establishes four clinical stage in patients infected HIV / AIDS, as follows:
Table 2.1. Clinical stage of HIV
Asymptomatic Stage 1
No weight loss
There are no symptoms or only Persistent Generalized Lymphadenopathy
Stage 2 mild pain

Weight loss of 5-10%

Recurrent respiratory infection, such as sinusitis or otitis
Herpes zoster within the last 5 years
Sores around the mouth (angular cheilitis)
Recurrent mouth ulcers
Itchy skin rash (seborrheic or prurigo-PPE (Pruritic papular
Eruption))
seborrheic dermatitis
Fungal nail infection

Stage 3'm Sick

Weight loss> 10%

Diarrhea, fever of unknown cause, more than 1 month
Oral or vaginal candidiasis
Oral hairy leukoplakia
Pulmonary TB in the last 1 year
Severe bacterial infections (pneumonia, piomiositis, etc.)
TB lymphadenopathy
Gingivitis / Periodontitis acute necrotizing ulcerative
Anemia (HB <8 g%), neutropenia (<5000/ml), chronic thrombocytopenia

(<50.000/ml)

Pain severe stage 4 (AIDS)

HIV wasting syndrome
Pnemosistis pneumonia, recurrent severe bacterial pnemoni
Herpes simplex ulcerative more than one month
Esophageal candidiasis
TB Extraparu
Kaposi Sarcoma
CMV retinitis (cytomegalovirus)
Toxoplasmosis of brain abscess
HIV Encefalopati
Cryptococcus Meningitis
Non-tuberculous mycobacteria infection extends
Lekoensefalopati progressive multifocal (PML)
Peniciliosis, kriptosporidosis chronic, chronic isosporiasis, mycosis
expanded, extra-pulmonary histoplasmosis, cocidiodomikosis)
Cerebral lymphoma or B-cell, non-Hodgkin's lymphoma (impaired function
neurological and other causes not often improve with therapy
ARV)
Invasive cervical cancer
Atypical leishmaniasis widespread
Symptoms of neuropathy or HIV-associated cardiomyopathy
Diagnosis

The diagnosis of HIV infection is done by two methods, namely methods

Clinical examination and laboratory tests. Laboratory tests test include
immunology and virology test.
A). Clinical diagnosis
Since 1980 WHO has managed to define the clinical cases and clinical staging
system for HIV infection. WHO has issued a limit case HIV infection for the
purpose of monitoring and clinical stage classification change associated with
HIV infection in adults and children. These guidelines include criteria for clinical
diagnosis should be suspected in severe HIV disease to consider starting
antiretroviral therapy sooner.
Table 2.2 . Symptoms and clinical signs of HIV infection is suspected

General Situation
Weight loss > 10 % of body weight basis
Fever ( continuous or intermittent , oral temperature > 37.5 oC ) more than one
month.
Diarrhea ( continuous or intermittent ) of more than one month
Limfadenofati extends
skin
PPE * and extensive dry skin is a strong suspicion of HIV infection .
Some disorders such as genital warts ( genital warts ) , folliculitis and psoriasis
common in people living with HIV but not always associated with HIV.
Infection

Fungal infections

Oral candidiasis
seborrheic dermatitis
Recurrent vaginal candidiasis

viral infections

Herpes zoster ( recurrent / involving more than one

dermatome ) *
Genital herpes ( recurrent )
molluscum contagiosum

respiratory disorders

condyloma
Cough for more than one month
blown
TB
Pnemoni relapse
Chronic or recurrent sinusitis

neurological

Increasingly severe headache ( continuous and it is not

symptoms

clear cause )
febrile seizures
The decline in cognitive function

* The situation is a strong presumption against HIV infection

[Source : Dep Kes 2007 ]
b). Laboratory Diagnosis
Methods of basic laboratory tests for the diagnosis of HIV infection is divided in
two groups:
1). Test Immunology
Immunological test to find the antibody response to HIV-1 and used as a screening
test, including enzyme immunoassays or enzyme - linked immunosorbent
assays (ELISAs) as well as rapid serological test (rapid test). Testing Western
blot or indirect immunofluorescence assay (IFA) was used to strengthen the results
of the test krining reactive The test determines the approximate number of
abnormalities of the immune system include and the percentage of CD4+ and

CD8 + T-lymphocyte absolute. This test is now not used for the diagnosis of HIV
but are used for evaluation.
HIV antibody detection
This check is performed in patients suspected to have HIV infection. ELISA with
the results of a reactive (positive) should be repeated with blood samples same,
and the results confirmed by Western Blot or IFA (Indirect Immunofluorescence
Assays). While a negative result does not require the test further confirmation,
although in patients infected during the window (Window period), but must be
followed up with virological test The next date. False negative results can occur in
people who HIV-1-infected but not yet issued antibodies against HIV-1 (ie, within
6 (six) the first week of infection, including all clinical signs and symptoms of
acute retroviral syndrome. False positives can occur in individuals who have been
immunized or autoimmune disorders, pregnant women, and transfer of maternal
immunoglobulin G (IgG) antibodies newborn children of mothers who infected
with HIV 1 . Therefore, a positive ELISA result in a child aged less than 18
months must be confirmed by virological testing (test virus), before children
considered HIV-1.

Rapid test
Is a rapid serological tests for the detection of IgG antibodies against HIV-1. The
principle of the test is based on particle agglutination, imunodot (Dipstick),
imunofiltrasi or imunokromatografi. ELISA can not be used to confirm the results
of rapid tests and all the results of a reactive rapid test must confirmed by Western
blot or IFA.

Western blot
Used to confirm the results of a reactive ELISA or rapid serological results
tests as a result really positive. Western blot assay find the presence of antibodies
against HIV-1-specific proteins (structural and enzymatic). Western blot carried
out only as a confirmation of the results of screening recurrent (ELISA or rapid
tests). Western blot showed negative results that the positive results of ELISA
or rapid tests declared as false positive results and the patient does not have HIV-1
antibodies. Positive Western blot results indicate the presence of HIV-1 antibodies
in individuals over age 18 months.
Indirect Immunofluorescence Assays (IFA)
This test is simple to do and takes less time and slightly more expensive
than Western blot assay. Ig antibody labeled with fluorokrom additions and will
bind to the HIV antibodies if it is in samples. If the slide show fluorescent
cytoplasm is considered a positive result (Reactive), which indicates the presence
of HIV-1 antibodies.
The decrease in immune system
Progression of HIV infection is characterized by a decrease in CD4+
T lymphocytes, some major HIV target cells in humans. Speed of CD4 cell loss
has been shown to used as an indication of disease progression of AIDS. CD4 cell
count decreased gradually over the course of the disease. Degradation speed of
time time to an average of 100 cells / year.

2). Test Virology

Virological test for the diagnosis of HIV-1 infection include viral culture, the test
amplification of nucleic acid / nucleic acid amplification tests (NAATs), test for
find HIV-1 nucleic acids such as DNA Arau HIV-1 RNA and the test for viral
components (such as a test for the virus capsid protein (p24 antigen)).

HIV culture
HIV can be cultured from peripheral blood lymphocytes, higher viral titers in
plasma and peripheral blood cells of AIDS patients. Growth of virus was detected
by culture supernatant fluid test after 7-14 days to reverse the activity
transcriptase to viral or virus-specific antigens.
HIV-1 NAAT (Nucleic Acid Amplification Test)
Finding the viral RNA or proviral DNA is mostly done for diagnosis in children
aged less than 18 months. Because the virus may nuklet acid are in abundance in
the sample. RNA testing and Viral DNA by PCR amplification, using enzymatic
methods for amplifying HIV-1 RNA. HIV RNA level is a predictive marker
importance of disease progression and become a valuable tool for monitoring the
effectiveness of antiviral therapy.
P24 antigen test
P24 viral protein was in the form of antibodies bound to the p24 or in a free state
in the blood stream indivudu infected with HIV-1. On p24 antigen test is generally
less used than RNA amplification technique or because it is less sensitive HIV
DNA. The sensitivity of the test increases with improvement of techniques used to
separate the p24 antigen of antibody anti-p24

Opportunistic Infections
The main causes of morbidity and mortality in patients with advanced HIV is an
opportunistic infection, ie severe infections induced by agents rarely causes
serious illness in individuals with immune capability better. Therefore, treatment
is aimed at overcoming some of the agents allowing opportunistic pathogens in

AIDS patients survive more old. Opportunistic infections are most common in
AIDS patients include infection from:
(1). Species of protozoa Toxoplasma gondii, Isospora belli
(2). Fungus - Candida albicans, Cyyptococcus neoforman, Coccidioides immitis,
Histoplasma capsulatum, carinii pneumonitis
(3). Bacteria - Mycobacterium avium-intracellular Mycobacterium tuberculosis,
Lysteria monocytogen, Nocardia asteroids, salmonella species, species
streptococcal
(4). Virus-Cytomegalovirus, herves simplex virus, varicella-zoster virus,
adenovirus, the virus hepatitias
Immune Response
The immune response is the result of cooperation between cells that play a role in
the immune response itself. The cells are found in lymphoid organs such as lymph
nodes, bone marrow, thymus, and spleen. This immune response will moleku
detect the presence of foreign molecules where the molecule has different forms
with normal molecules. The immune response consists of: a specific immune
response and non-specific. Response specific immune components or also called
adaptive or acquired immunity is defense mechanisms that are specific to one type
of antigen, because it can not act against other types of antigens. Non-specific
immune response component also called non-adaptive or innate, or natural
immunity, meaning defense mechanisms which are not intended for only one type
of antigen, but for a wide variety of antigens. Natural immunity has existed since
the individual born and consists of a wide variety of non-specific elements. The
difference with the non-specific body defense is defense specific body should first
contact or induced by specific antigen, He recently formed. While the non-specific
defenses already exist before he had contact with the antigen. Imun when the nonspecific response can not cope with the invasion microorganisms that specific
immunity stimulated. Defense mechanisms (Immune response) is a specific
defense mechanisms played by cell lymphocytes, with or without the help of other
immune system components such as cell macrophages. Judging from the way he

obtained the specific defense mechanisms also called acquired immune

response (adaptive immunity). One to three weeks after infection, found a specific
immune response In the form of antibodies to HIV proteins gp120 and p24, were
also found T cells HIV-specific cytotoxic. Given the adaptive immune response,
decreased viremia and not accompanied by clinical symptoms. It lasted 2-12
years, with decreasing CD4 cell counts + will show clinical symptoms. In 3-6
weeks post-infective found HIV p24 antigen levels in plasma high. HIV-specific
antibodies and cytotoxic T cells decreased, whereas p24 increased. HIV infection
is characterized by multiple phases ending with immune deficiency. CD4 cell
count + in the blood begin to decline below normal 1500 cells/mm3 and the patient
becomes susceptible to infection and are called suffering from AIDS. AIDS
patients develop antibodies and showed a response Cytotoxic T Lymphocyte (CTL)
against viral antigens. But the response is not prevent the progress of the
disease. CTL also does not effectively kill the virus because the virus prevents the
infected cells to express Major Histompatibility Complex (MHC-1). Antibodies to
envelope glycoprotein gp120 may like ineffective, because the virus rapidly
mutated region of gp120 that is antibody targets. The immune response can
actually increase the spread of HIV disease. The virus is able to bind to the
antibody coated (Fragment crystalizable Receptor ) Fc-R on macrophages and
dendritic cells in lymphoid glands, this increasing viral entry into cells and create
The new reservoir. When CTL successfully destroy infected cells, the virus will be
removed and infect more cells.

Antiretroviral Drugs
Antiretroviral (ARV) is a drug that inhibits the replication of Human
Immunodeficiency Virus. Treatment of HIV infection with Antiretroviral used to
maintain immune function approaching normal circumstances, prevent disease
progression, prolonglife and maintain quality of life by means of inhibiting viral
replication HIV. Because of active HIV replication causes progressive damage to
the immune system, led to the development of opportunistic infections,
malignancies (malignasi), neurological disease, weight loss eventually leading to

death. There are more than 20 antiretroviral drugs are classified in 6 groups based
on their mechanism of action, consisting of:
Nucleoside / nucleotide reverse transcriptase inhibitors (NRTIs)
NRTIs work by competitively inhibiting the reverse transcriptase HIV-1 and can
be joined with the viral DNA chain is active and cause termination. These drugs
require activation intracytoplasmic, phosphorylated by the enzyme into the
triphosphate form. Group This consists of: Analog deoxythymidine (Zidovudine),
thymidine analogue (Stavudin), deoxyadenosine analog (Didanosin), analog
adenosisn (Tenovir disoproxil fumarate / TDF), cytosine analogue (lamivudine
and Zalcitabin) and analog guanosine (Abacavir)
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
NNRTIs work by forming a direct bond to the active site reverse
transcriptase enzyme that causes DNA polymerase activity inhibited. This group
does not compete with nucleoside triphosphate and not require phosphorylation to
be active. This group consists of: Nevirapin, Efavirenz, Delavirdine.
Protease inhibitors (PIs)
During the final stages of the growth cycle of HIV, the gene products Gag-Pol and
Gag

translated

into

polyprotein

and

subsequently

into

particles

immature. Protease responsible for the cleavage of the molecule prior to

generating the final form of the protein core mature virions and protease essential
for the production of mature infectious virions during replication. These drugs
block the action of the enzyme protease, preventing formation of new infectious
virions. This group consists of: Saquinavir, Ritonavir, Nelfinavir, amprenavir.
Fusion inhibitors (FIs)
FIs inhibit virus entry into cells by binding with gp 41 envelope glycoprotein
subunit virus so that the virus fusion to target cells is inhibited. These drugs
consist of: Enfuvirtide (T-20 or pentafuside).

 CCR5 antagonists
Works by binding to CCR5 (chemokine receptor 5) on the surface CD4 cells and
prevent the HIV virus attachment to host cells. Group This consists of: Maraviroc,
Aplaviroc, Vicrivirox.
integrase strand transfer inhibitors (INSTI)
Works by inhibiting the incorporation of circular DNA (cDNA) the virus with the
host cell DNA (host). This group consists of: Raltegravir and elvitegravir. Single
antiretroviral therapy led to rapid emergence of HIV mutants resistant to the
drug. Combination antiretroviral drugs is a strategy that clinically promising,
designated as highly active antiretroviral therapy (HAART). This combination has
a target multiple steps in the virus reflikasi thus slowing down the selection of
HIV mutants. However, HAART can not be cure HIV infection, because the virus
settled on the old reservoir length in infected cells, including CD4 memory T
cells, thus when HAART is stopped or there is a failure of therapy, viral
production back increased
Antiretroviral treatment purpose
Based on national guidelines in 2004, the goal of treatment with Antiretrovirals
are :
1. Reduce the rate of HIV transmission in the community
2. Reduce morbidity and mortality associated with HIV
3. Improving the quality of life of PLHIV
4. Restore and / or maintain immune function
5. Maximally suppress viral replication and continuous
Combination Antiretroviral
The selection principle of ARV drugs
a) The first option lamivudine (3TC), plus
b) Choice of one of the drugs of the nucleoside reverse

transcriptase inhibitors (NRTIs), Zidovudine (AZT) or Stavudin (d4T)

Table 2.3. Alloy choice for first-line ARV
Suggestion
First Choice

Alloys ARV
AZT +3 TC + NVP

Informations
AZT
can

cause

anemia,

hemoglobin is recommended for

monitoring, but preferably from
AZT to d4T due to toxic effects of
d4T (lipodystrophy,
lactic

acidosis,

peripheral

neuropathy) At the beginning of

the use of NVP especially in
female patients with CD4> 250 at
risk for liver disorders arise
symptomatic, which is usually a
skin rash that often occurs in 6
alternative

AZT +3 TC + EFV

options

weeks. The first of the therapy.

Efavirenz (EFV) as a substitution
of NVP when there is intolerance
and when
patients

received

therapy

ripamfisin. EFV should not be

given when there is an increase
aminotransferasi enzyme alanine
(ALT) at a rate of 4 or more.
Pregnant women should not be
treated with EFV. Women of
childbearing age should
undergo pregnancy tests before
starting therapy with EFV
d4T+3TC+ NVP or EFV

d4T can be used and does not

require laboratory monitoring

Profile of drug 3TC (lamivudine), AZT (Zidovudine), Stavudin (d4T),

Nevirapin (NVP) and Efavirenz (EFP) in Appendix 1

Indications initiate antiretroviral therapy

The procedure started ARVs in accordance with the National Guidelines 2007,
where HIV testing is offered to patients who want it after
pre-test

counseling

at

counseling

and

testing

services

unit

Voluntary (Voluntary Counseling and Testing / VCT) to find cases

require treatment and follow-up counseling services to provide
psychosocial support. Another indication for HIV testing is offered absence
sexually transmitted infections, pregnancy, tuberculosis (TB) is active, symptoms
and other signs lead to HIV infection as well as patients at high risk of contracting
HIV. The decision to initiate antiretroviral therapy in adults and adolescents
OHDA based on clinical and immunological examination. But in the
circumstances the specific clinical assessment alone can guide therapeutic
decisions start ARVs, all patients with stage 3 and 4 should start antiretroviral
therapy. Infection opportunistic and other HIV-related illnesses that need
treatment alleviated before antiretroviral therapy The most appropriate time to
initiate antiretroviral therapy before the patient is illness or the emergence of the
first IO. Disease progression will be quickly when starting ARV therapy when
CD4 <200 cells / mm 3 than whenvtherapy initiated at CD4 above that amount. If
CD4 testing facilities available the antiretroviral therapy should be started before
the CD4 less than 200 cells / mm3. Therapy ART is recommended in patients with
pulmonary tuberculosis or severe bacterial infection and CD4 <350 cells /
mm3 . Also in pregnant women with clinical stage any CD4 <350
cells / mm3
Table 2.4. When initiating therapy in adult ODHA

Clinical

When available CD4

If not available CD4

stage
1

Antiretroviral therapy initiated when ARV therapy is not given

CD4 <200 cells/mm3

2
3

If the total number of

lymphocytes <1200
CD4 cell count of 200-350 cells/mm , Starting
antiretroviral
3

consider therapy before CD4 <200 therapy regardless of the

cells/mm3. In pregnancy or tuberculosis:

total lymphocyte count

- Starting antiretroviral therapy to all

pregnant

women

with

CD4

<350

cells/mm3
- Starting antiretroviral therapy in all
people living with HIV with CD4 <350
cells/mm3 with pulmonary tuberculosis or
4

severe bacterial infection

starting antiretroviral therapy regardless
of the number \ CD4

Description:
CD4 is recommended to use to help determine the onset of therapy. Example,
pulmonary TB can appear at any time at any CD4 count and other conditions that
resemble disease is not caused by HIV (eg, chronic diarrhea, prolonged fever).
The exact value of above 200 CD4 cells / mm 3 where antiretroviral therapy
should not be initiated determined.
Total lymphocyte count 1200 cells / mm 3 can be used as a substitute when
CD4 can not be implemented and there are symptoms related to HIV (stage II or
III). It can not be used in people living with HIV are asymptomatic. So, if there is
no CD4, asymptomatic PLHA (Stage I) should not be treated as the current there
is no other reliable marker in areas with limited resources.

WHO in 2009 recommended to start antiretroviral therapy:

1. Starting ARV treatment in all patients with HIV who have CD4 cell count 350
cells / mm3 regardless of clinical symptoms
2. CD4 tests are required to determine if patients with clinical stage
1 and 2 need to initiate antiretroviral therapy.
3. Starting ARV treatment to all HIV patients with clinical stage 3
and 4 regardless of CD4 count.
In patients with active opotrunistik infection, do not start antiretroviral therapy
when IO are still active. Basically IO should be treated or mitigated first, except
for Mycobacterium avium Complex (MAC), where antiretroviral therapy is better
choice, especially if no specific therapy for MAC available. Other circumstances
which may be improved when starting ARV therapy is candidiasis and
riptosporidosis.
Other requirements before starting ARV therapy
Before the patient received antiretroviral therapy should be carefully
with adherence counseling that have been standard, so that the patient understands
right to benefits, how to use, side effects of drugs, the signs
and other hazards associated with antiretroviral therapy.
Patients will receive ARV therapy should have supervisory drink
drugs (PMO), which is close to the patients who will oversee compliance
taking medication.
Patients who were receiving antiretroviral therapy should undergo screening for
Clinical monitoring with regular
Antiretroviral therapy adherence

The

main

reason

is

the

failure

of

antiretroviral

therapy

adherence

oradherence (compliance) is bad. Compliance is monitored and evaluated

regularly and encouraged at every patient visit. Obedience on antiretroviral
treatment are strongly linked to viral suppression HIV, reduce resistance, increase
life expectancy and improve quality of life. Because HIV treatment is a lifelong
treatment, and because a lot of patients who initiate therapy in a state of good
health and not meunjukkan signs of HIV disease, the adherence to the challenge
specific and requires a commitment from the patient and the care
team.Compliance related to patient characteristics, rules and strong support from
the patient's family. Information should be given and the patient understand about
HIV disease and specific rules for the use of drugs is very important.

Several factors related to the lack of compliance, including:

Low education levels
Age (such as: lack of vision, forgot)
psychological conditions (such as depression, lack of social support, dementia,
psychosis)
active drug dependence
Difficulty receiving treatment (such as difficulty in swallowing drugs, drinking
schedule daily medication)
Rules are complicated (such as: frequency of drug administration, the
requirements food)
The effect of unwanted drugs
Treatment of exhausting
Evaluation of Antiretroviral therapy

After starting treatment with antiretroviral drugs, clinical monitoring is required

and laboratory, include:
Assessment of signs / symptoms of potential drug toxicity
Counseling and therapy response assessment of compliance assessment and
signs treatment failure
Measurement of body weight
CD4 testing at least every 6 months
Monitoring of Hb for patients taking zidovudine
Monitoring is done 2,4,8,12 and 24 weeks after treatment begins and
then every six months for patients who have been stabilized on therapy.
Antiretroviral therapy failure indication
Treatment failure can be defined clinically by assessing progression of the disease,
immunologically with a CD4 count and / or virological basis by measuring viral
load .
Clinical Failure:
The emergence of opportunistic infection in stage 4 after at least 6 months of
antiretroviral therapy, except tuberculosis, esophageal candidiasis, and severe
bacterial infection that is not always due to the failure of therapy. Assessing the
response of prior therapy, if the response is good then it should not be changed
first.
virological failure:
Viral load > 10,000 / mL after 6 months of antiretroviral therapy. Failure terapy
ARVs can not be diagnosed based on clinical criteria alone in First 6 months of
treatment. Viral load is an indicator that most sensitive in determining the
presence of therapeutic failure. Clinical symptoms are appear within 6 months of
therapy often indicate the presence of IRIS (Immune reconstitution inflammatory
syndrome) and not the failure of therapy ARVs.
Failure of immunologic

After one year of therapy CD4 back or lower than at the beginning ARV
therapy. CD4 cell decline of 50% of the highest value ever achieved during
antiretroviral therapy (if known).
Antiretroviral Replacement Indication
Drug side effects and treatment failure are two reasons. The main possible
combinations of ARVs changed.
Side effects
Sometimes the side effects of the drug can be so strong, can not be tolerated or
even life-threatening where the treatment should be changed. In the case of as is
usually safe to change drugs that cause only
efeksamping.
Failure of treatment
Changes required when ARV treatment fails to slow replication of virus in the
body. This can occur as a result of resistance drugs, lack of compliance, lack of
drug absorption, drug combination is weak, increase in viral load of HIV or the
onset of disease related signs ART failure. CD4 can also be used to determine
whether to change therapy or not. For example, the emergence of new diseases
included in the stage 3, where the consideration for changing therapy, but when
CD4> 200 cells / mm3
not recommended for therapeutic change. Optimal levels of viral load
as a limitation to change the alloy ARVs could not be determined with
sure. However, viral load> 5000-10000 derivative / ml known to be associated
with clinically significant changes or decline in CD4 cell count

2. Revised criteria according to the Centers for Disease Control ( CDC )

United States 1993 to a state associated with HIV :
1 . Candidiasis bronchus , and lung trakesa
2 . esophageal candidiasis
3 . Invasive cervical cancer
4 . Koksidioidomikosis disseminated or extra pulmonary
5 . Kriptokokokis extrapulmonary
6 . Cryptosporidiosis chronic intestinal ( > 1 month )
7 . Sitomegalivirus infection ( except in the liver , spleen , or lymph
nodes )
8 . Rhinitis sitomegalivirus with impaired vision
9 . Associated with HIV encephalopathy
10 . Herpes simplex , chronic ulcers ( > 1 month ) or bronchitis ,

pneumonia , and esophagitis

11 . Disseminated or extrapulmonary histoplasmosis
12 . Isosporiasis chronic intestinal ( > 1 month )
13 . Kaposi sarcoma
14 . Burkitt's lymphoma
15 . immunoblastic lymphoma
16 . Primary lymphoma of the brain
17 . Mycobanterium avium complex or M. kansasii , disseminated or
extrapulmonary
18 . Mycobanterium tuberculosis , pulmonil or extrapulmonary
19 . Pneumocystis carinii pnemocystis
20 . recurrent pneumonia
21 . Progressive multifocal leukoencephalopathy
22 . Recurrent salmonella septicemia
23 . Toxoplasma encephalitis
24 . HIV -related wasting syndrome

Major symptoms:
a. Body weight decreased by more than 10% in 1 month
b. Chronic diarrhea that lasts more than 1 month
c. Prolonged fever of more than 1 month
d. Loss of consciousness and neurological disorders
e. Dementia / HIV encephalopathy
Minor symptoms:
a. Cough lasts more than 1 month
b. generalized dermatitis
c. The presence of herpes zoster and herpes zoster recurrent
multisegmental
d. Kandidias oropharyngeal
e. Herpes simplex chronic progressive

f. generalized lymphadenopathy
g. Cytomegalovirus retinitis

3.

Case Management of HIV and AIDS is one of the service methods that can

be used to help people with HIV and AIDS ( PLWHA ) . Case Management
services using a holistic approach and integrated individual , who relate and
coordinate clients with excellent service source of medical , psychosocial and
spiritual . Positive Prevention one strategy that aims to improve self-esteem and
the ability of people living with HIV to protect their own health and prevent /
avoid transmission of infection to others . With a positive intervention in people
living with HIV prevention can keep their health conditions and improve quality
of life . Positive prevention interventions in the care of HIV and AIDS case
management includes education and health support , support commodities related
to care and treatment , development of referral network system services ,
involvement of people living with HIV in the HIV and AIDS by providing
training and skills . In many cases of people living with HIV , while knowing he
was infected with HIV early , it's hard for him to believe and accept . Fears and

worries they will be the stigma , discrimination from both sides of the family and
community environment . This happens because the information and
understanding of HIV and AIDS itself is still lacking . People think that HIV is a
contagious disease and can be transmitted to other people even if only social
contact . There are even thinking that HIV means sickly , can not perform the
activity , and even shunned other people think will soon die . With a given
intervention case management services dlaam HIV and AIDS , many people living
with HIV who find it helpful. The understanding of HIV and AIDS are better,
more aware and motivated to keep her health condition , knowing what to do to
prevent transmission to others and guard against contracting other infections , and
even some of them have become friends motivator for youth in the community
who use injection drugs to follow VCT ( Voluntary Counseling and Testing ) .
This was done after he gave information about HIV and AIDS , prevention and
transmission , do the benefits of VCT and VCT service venues , presence
information services case management of HIV and AIDS for those who test HIV
positive . All this is done on what is already felt , where knowing the results of
earlier tests would be better to be handling it early anyway so kesehatanpun
conditions can be better , do not quickly fall to the stage of AIDS .The above
experience shows that , positive intervention in the prevention of HIV and AIDS
case management can improve the quality of life of PLHIV encourage and be a
motivator for their peers and the surrounding communities .
4 . Although there are other factors that can help to keep a person with HIV
infection well for many years, eventually it becomes necessary to take
antiretroviral drugs in order to lengthen a persons life.
Antiretroviral drugs work directly on HIV and slow down its multiplication. This
in turn slows down the loss of CD4 T-cells that the virus destroys, and thus slows
down further damage to the immune system or even allows the immune system to
recover to some extent.
Controlling HIV infection and limiting damage to the immune system results in
weight gain and improvement in general health, fewer opportunistic infections,
less need for other medications and less time in hospital.

The purpose of antiretroviral therapy

Although antiretroviral therapy (or ART) is not a cure for Aids, the purpose of
anti-retroviral therapy is to:

reduce the HIV viral load as much as possible - preferably to undetectable

levels - for as long as possible (Virological goal).
assure that less damage will be inflicted on the immune system, so that the
patient will experience an improvement in his/her immune functioning and to
delay the onset of Aids (Immunological goal).

enhance quality of life and reduce opportunistic infections (Therapeutic goal).

reduce the impact of HIV transmission in the community (Epidemiological

goal).

The down sides and limitations of taking antiretroviral treatment:

It usually requires a fairly complex medication regimen: several different

tablets must be taken at different times every day, some with food and others
when the stomach is empty. Some tablets must be taken at exactly the correct
times of day or they will fail.
Often the drugs have unpleasant side-effects such as nausea and headache.

The drugs are very expensive and need to be taken for the rest of a persons
life to control HIV infection, although they will never cure it. Several
treatment changes will usually be required in the course of a persons life with
HIV. Therefore, you must be motivated and dedicated to take the treatment
successfully.

The virus can never be completely eradicated from the body. A reservoir of
infected cells persists even in the absence of viruses in the blood, and its
replenishment continues even during treatment.

HI viruses use Memory T cells where they build up a latent reservoir. These
latent cells can live for 44 months or longer and eradication of viruses from
these cells are simply not possible.

Active infected CD4 cells die and the viral pool in the latent T cells allows for
a rebound of HIV.

Three Groups of Antiretrovirals

At the moment, there are three main types of drugs available to treat HIV. These
three groups of drugs work against the virus in different ways, at different points
in the growth cycle of the virus.
Counting up the different drugs from the three groups, there are about 16 different
drugs available to treat HIV infection right now.
The function of ART is to protect activated CD4 cells - that is CD4 cells that are
infected by the HI virus, and are now being used to make new viruses. HIV uses
enzymes to replicate itself inside CD4 cells. Antiretroviral drugs act by blocking
the action of these enzymes.
1. Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
These drugs are usually the first choice for HIV treatment and the backbone of
HIV treatment.
The Reverse Transcriptase Inhibitors disturb the life cycle of the HI virus by
interfering with the reverse transcriptase enzyme in the replication of the virus.
The virus is no longer able to change its RNA into viral DNA.
NRTIs are: (with the proper name of each drug listed first, followed by the
manufacturers trade name in brackets).

AZT or zidovudine (Retrovir)

3TC or lamivudine (Epivir)

DDI or didanosine (Videx) etc.

2. Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Nevirapine (Viramune)
Efavirenz (Stocrin)

3. Protease Inhibitors
The Protease Inhibitors interfere with the formation of new viruses in the life
cycle of the virus by blocking the protease enzyme from allowing the assembly
and release of viable particles of HIV from the infected cells. PIs are:

Indinavir (Crixivan)

Ritonavir (Norvir)

Saquinivir (Invirase) etc

When to start treatment

The correct time to start antiretroviral treatment is a difficult decision, even
among medical specialists. In general, it is agreed that it is preferable to start
treatment before there is too much damage to the immune system, that is while the
CD4 cell count is still at a moderate level such as 350 cells/ul.
It is also agreed that a person with the signs of Aids should start treatment. On the
other hand, it may also be valuable to treat a person with very early (primary)
HIV infection, at least for some time. There is evidence that controlling the virus
early on means that it will not multiply to such high levels later on.
The choice of treatment may often be limited by what a person can afford, or what
a particular treatment programme can offer. There are some rules that have to be
followed for successful use of the drugs.
Why triple therapy?
One should never take one drug alone (monotherapy). This is because HIV will
very quickly become resistant to one drug on its own, and so that drug will
become ineffective and cannot be used for ongoing treatment.
However, if two or more drugs are used together the virus can only multiply very
slowly and will take much longer to become resistant to any one of the drugs.
Therefore, at least two drugs should be taken together (dual therapy), and
preferably three (triple therapy).
For optimum viral suppression, triple therapy (or HAART - highly active
antiretroviral therapy) is recommended, such as two NRTIs and one PI.
Some drugs work against each other, or cause the same bad side-effects and so
should not be taken at the same time. Other drugs help each other and so they are
good to combine.
From this it is apparent that antiretroviral treatment is complicated and so should
be prescribed by a healthcare provider who is experienced in managing HIV.
There are also guidelines on antiretroviral treatment available, such as World

Health Organisation (WHO) guidelines and the guidelines of the South African
HIV clinicians society.
Can HIV be eliminated completely from the body?
HIV can unfortunately not be eliminated completely from the body. Because the
virus remains latent or dormant in Memory T cells, it can easily become reactivated and infect CD4 cells.
When a person is on antiretroviral treatment, virus tests often show that the viral
load is undetectable in the blood. It means that the viral load is so low that it
cannot be detected with the kind of blood tests available to us. It does not mean
that there are no more viruses in the body. Once antiretroviral therapy is
discontinued, viral replication usually resumes and viral loads begin to rise again.
Practical guidelines
To take ART is not an easy option!
Therapy should be individualised: ART is not suitable for every person. Patients
should be educated about the risks, benefits and demands, they should be
committed to adhere to the medication for life, they should be able to take care of
their health, and go for laboratory tests (CD4 counts and viral loads) regularly.
Side-effects should be monitored, harmful drug interactions should be monitored
(e.g. St Johns Wort prevents absorption of some antiretroviral medications),
absorption and tissue distribution should be monitored by taking the meds
correctly - some with food, others on an empty stomach, some with lots of water,
others with fatty foods.
Drug adherence is extremely important, for two reasons:
1.

ART will fail completely if not taken correctly and consistently: If ART is
taken with more than 95% adherence, it is 81% effective; If adherence is less
than 70%, it has an effectivity of 6%.
2.
Drug resistance is one of the major problems if patients do not adhere to
the medication. Drug resistance occurs when the drugs cannot protect the
CD4 cell any more. The virus then breaks through and infects the cell.
Note definition of resistance: it is not the person who develops resistance, but the
virus that develops ways to resist the drugs, so that drug will not work in future.

Possible side-effects:
A person using ART must be carefully monitored. Some of the more serious sideeffects include:

Lipodistrophy (change in fat distribution - shoulders and neck)

Osteoporosis

High cholesterol

Metabolic disturbances (insulin resistance)

Stephens-Johnson syndrome (Nevirapine) - ulceration in oesophagus,

looks like chickenpox, causes burns, oedema. First signs: fever, rash, sore
throat.

STEP 5
1. Pharmacokinetics and Pharmacodynamics of ARV?
2. interpretation of test results hiv?
3. HIV case management? (Ethics and Education)
4. High Risk Individuals prophylactic HIV?
5. Differential diagnosis of HIV?

STEP 6

independent learning

STEP 7

1. Farmakokinetik dinamik ARV

The concept of drug absorption pharmacokinetics of orally feed all
incomplete or obstructed and the drug will experience first-pass
metabolism so bioavaibilitas ( F ) of the drug will be lower than the drug
given intravenously . The distribution of the drug will be influenced by
lipid solubility and binding to plasma proteins . The volume of distribution
( Vd ) illustrates the distribution of drugs dalamkompartemen body . Drugs

are mainly distributed in the plasma will have a relatively small Vd and
high concentration in the plasma . Drugs are widely distributed to various
body compartments will have a large Vd and a relatively low
concentration in plasma . Vd is necessary to calculate the loading dose .
Loading dosedapat used to achieve therapeutic concentrations immediately
. General drug metabolism occurs in the liver that causes chemical changes
easy for the drug so that the drug is eliminated from the body . Drugs are
metabolized by the system P450akan compete with drugs also metabolized
by this system . Drugs or substances that induce or inhibit the influence
P450apakah will cause the rate of metabolism of drugs metabolized by the
P450 system is interrupted . Drug elimination through the kidneys in
general , although some are through biliary excretion . Clearance /
Clearence ( Cl ) describe drug quantity of blood per unit time is cleared of
the drug . Without distinguishing the elimination , rate of drug elimination
from

the

body

expressed

as

the

half-life

of

the

drug.

The half-life of drugs can be used to determine the steady state

stateyaitu a condition where a constant drug concentration for continuous
drug delivery yangterus / repetitive . This condition is achieved after
approximately 5 half-life of the drug . After reaching steady state
conditions the administration of the next dose will not change unless the
concentration of the drug or the drug dose pharmacokinetic parameters
changed.
2. The CDC has recommended that screening for HIV infection be performed
as a matter of routine health care. The diagnosis of HIV infection depends
upon the demonstration of antibodies to HIV and/or the direct detection of
HIV or one of its components. As noted above, antibodies to HIV
generally appear in the circulation 212 weeks following infection. The
standard blood screening test for HIV infection is the ELISA, also referred
to as an enzyme immunoassay (EIA). This solid-phase assay is an
extremely good screening test with a sensitivity of >99.5%. Most
diagnostic laboratories use a commercial EIA kit that contains antigens
from both HIV-1 and HIV-2 and thus are able to detect either. These kits

use both natural and recombinant antigens and are continuously updated to
increase their sensitivity to newly discovered species, such as group O
viruses (Fig. 182-6). The fourth generation EIA tests combine detection of
antibodies to HIV with detection of the p24 antigen of HIV. EIA tests are
generally scored as positive (highly reactive), negative (nonreactive), or
indeterminate (partially reactive). While the EIA is an extremely sensitive
test, it is not optimal with regard to specificity.

This is particularly true in studies of low-risk individuals, such as volunteer

blood donors. In this latter population, only 10% of EIA-positive individuals
are

ubsequently confirmed to have HIV infection. Among the factors

associated with false-positive EIA tests are antibodies to class II antigens,

autoantibodies, hepatic disease, recent influenza vaccination, and acute viral
infections. For these reasons, anyone suspected of having HIV infection based
upon a positive or inconclusive EIA result must have the result confirmed with
a more specific assay such as the Western blot. One can estimate whether or
not an individual has a recent infection with HIV-1 by comparing the results
on a standard assay that will score positive for all infected individuals to the

results on an assay modified to be less sensitive (detuned assay) that will

score positive only for individuals with established HIV infection. In rare
instances, an HIV-infected individual treated early in the course of infection
may revert to a negative EIA. This does not indicate clearing of infection;
rather, it signifies levels of ongoing exposure to virus insufficient to maintain
a measurable antibody response. When these individuals have discontinued
therapy, viruses and antibodies have reappeared. The most commonly used
confirmatory test is the Western blot (Fig.182-26). This assay takes advantage
of the fact that multiple HIV antigens of different, well-characterized
molecular weights elicit the production of specific antibodies. These antigens
can be separated on the basis of molecular weight, and antibodies to each
component can be detected as discrete bands on the Western blot. A negative
Western blot is one in which no bands are present at molecular weights
corresponding to HIV gene products. In a patient with a positive or
indeterminate EIA and a negative Western blot, one can conclude with
certainty that the EIA reactivity was a false positive.
On the other hand, a Western blot demonstrating antibodies to products of all
three of the major genes of HIV (gag, pol, and env) is conclusive evidence of
infection with HIV. Criteria established by the U.S. Food & Drug
Administration (FDA) in 1993 for a positive Western blot state that a result is
considered positive if antibodies exist to two of the three HIV proteins: p24,
gp41, and gp120/160. Using these criteria, ~10% of all blood donors deemed
positive for HIV-1 infection lacked an antibody band to the pol gene product
p31. Some 50% of these blood donors were subsequently found to be false
positives. Thus, the absence of the p31 band should increase the suspicion that
one may be dealing with a false-positive test result. In this setting it is prudent
to obtain additional onfirmation with an RNA-based test and/or a follow-up
Western blot. By definition, Western blot patterns of reactivity that do not fall
into the positive or negative categories are considered indeterminate. There
are two possible explanations for an indeterminate Western blot result.

The most likely explanation in a lowrisk individual is that the patient being
tested has antibodies that crossreact with one of the proteins of HIV. The most
common patterns of cross-reactivity are antibodies that react with p24 and/or
p55. The least likely explanation in this setting is that the individual is infected
with HIV and is in the process of mounting a classic antibody response. In
either instance, the Western blot should be repeated in 1 month to determine
whether or not the indeterminate pattern is a pattern in evolution. In addition,
one may attempt to confirm a diagnosis of HIV infection with the p24 antigen
capture assay or one of the tests for HIV RNA (discussed below). While the
Western blot is an excellent confirmatory test for HIV infection in patients
with a positive or indeterminate EIA, it is a poor screening test. Among
individuals with a negative EIA and PCR for HIV, 2030% may show one or
more bands on Western blot. While these bands are usually faint and represent
cross-reactivity, their presence creates a situation in which other diagnostic
modalities (such as DNA PCR, RNA PCR, the bDNA assay, or p24 antigen
capture) must be employed to ensure that the bands do not indicate early HIV

infection.A guideline for the use of these serologic tests in attempting to make
a diagnosis of HIV infection is depicted in Fig. 182-27. In patients in whom
HIV infection is suspected, the appropriate initial test is the EIA.
If the result is negative, unless there is strong reason to suspect early HIV
infection (as in a patient exposed within the previous 3 months), the diagnosis
is ruled out and retesting should be performed only as clinically indicated. If
the EIA is indeterminate or positive, the test should be repeated. If the repeat
is negative on two occasions, one can assume that the initial positive reading
was due to a technical error in the performance of the assay and that the
patient is negative. If the repeat is indeterminate or positive, one should
proceed to the HIV-1 Western blot. If the Western blot is positive, the
diagnosis is HIV-1 infection. If the Western blot is negative, the EIA can be
assumed to have been a false positive for HIV-1 and the diagnosis of HIV-1
infection is ruled out. It would be prudent at this point to perform specific
serologic testing for HIV-2 following the same type of algorithm. If the
Western blot for HIV-1 is indeterminate, it should be repeated in 46 weeks; in
addition, one may proceed to a p24 antigen capture assay, HIV-1 RNA assay,
or HIV-1 DNA PCR and specific serologic testing for HIV-2. If the p24 and
HIV RNA assays are negative and there is no progression in the Western blot,
a diagnosis of HIV-1 is ruled out. If either the p24 or HIV-1 RNA assay is
positive and/ or the HIV-1 Western blot shows progression, a tentative
diagnosis of HIV-1 infection can be made and later confirmed with a followup Western blot demonstrating a positive pattern. In addition to these standard
laboratory-based assays for detecting antibodies to HIV, a series of point-ofcare tests are also available. Among the most popular of these is the OraQuick
Rapid HIV-1 antibody test that can be run on blood, plasma, or saliva. The
sensitivity and specificity of this test are each ~99%. While negative results
from this test are adequate to rule out a diagnosis of HIV infection, a positive
finding should be considered preliminary and confirmed with standard
serologic testing, as described above. As mentioned above, a variety of

laboratory tests are available for the direct detection of HIV or its components
(Table 182-6; Fig. 182-28).

These tests may be of considerable help in making a diagnosis of HIV

infection when the Western blot results are indeterminate. In addition, the tests
detecting levels of HIV RNA can be used to determine prognosis and to assess
the response to ARV therapies. The simplest of the direct detection tests is the
p24 antigen capture assay. This is an EIA-type assay in which the solid phase
consists of antibodies to the p24 antigen of HIV. It detects the viral protein p24
in the blood of HIV-infected individuals where it exists either as free antigen
or complexed to anti-p24 antibodies. Overall, ~30% of individuals with
untreated HIV infection have detectable levels of free p24 antigen. This
increases to ~50% when samples are treated with a weak acid to dissociate
antigen-antibody complexes.
Throughout the course of HIV infection, an equilibrium exists between p24
antigen and anti-p24 antibodies. During the first few weeks of infection,
before an immune response develops, there is a brisk rise in p24 antigen levels
(Fig. 182-25). After the development of anti-p24 antibodies, these levels
decline. Late in the course of infection, when circulating levels of virus are
high, p24 antigen levels also increase, particularly when detected by
techniques involving dissociation of antigen-antibody complexes. The p24

antigen capture assay has its greatest use as a screening test for HIV infection
in patients suspected of having the acute HIV syndrome, as high levels of p24
antigen are present prior to the development of antibodies. Its use for routine
blood donor screening for HIV infection has been replaced by use of nucleic
acid testing. The ability to measure and monitor levels of HIV RNA in the
plasma of patients with HIV infection has been of extraordinary value in
furthering our understanding of the pathogenesis of HIV infection and in
providing a diagnostic tool in settings where measurements of anti-HIV
antibodies may be misleading, such as in acute infection and neonatal
infection. Three assays are predominantly used for this purpose. They are
reverse transcriptase PCR (RT-PCR; Amplicor); branched DNA (bDNA;
VERSANT); and nucleic acid sequencebased amplification (NASBA;
NucliSens). These tests are of value in making a diagnosis of HIV infection, in
establishing initial prognosis, in determining the need for therapy, and for
monitoring the effects of therapy.

In addition, one may attempt to confirm a diagnosis of HIV infection with the
p24 antigen capture assay or one of the tests for HIV RNA (discussed below).
While the Western blot is an excellent confirmatory test for HIV infection in
patients with a positive or indeterminate EIA, it is a poor screening test.
Among individuals with a negative EIA and PCR for HIV, 2030% may show
one or more bands on Western blot. While these bands are usually faint and

represent cross-reactivity, their presence creates a situation in which other

diagnostic modalities (such as DNA PCR, RNA PCR, the bDNA assay, or p24
antigen capture) must be employed to ensure that the bands do not indicate
early HIV infection. A guideline for the use of these serologic tests in
attempting to make a diagnosis of HIV infection is depicted in Fig. 182-27. In
patients in whom HIV infection is suspected, the appropriate initial test is the
EIA. If the result is negative, unless there is strong reason to suspect early
HIV infection (as in a patient exposed within the previous 3 months), the
diagnosis is ruled out and retesting should be performed only as clinically
indicated. If the EIA is indeterminate or positive, the test should be repeated.
If the repeat is negative on two occasions, one can assume that the initial
positive reading was due to a technical error in the performance of the assay
and that the patient is negative. If the repeat is indeterminate or positive, one
should proceed to the HIV-1 Western blot. If the Western blot is positive, the
diagnosis is HIV-1 infection. If the Western blot is negative, the EIA can be
assumed to have been a false positive for HIV-1 and the diagnosis of HIV-1
infection is ruled out. It would be prudent at this point to perform specific
serologic testing for HIV-2 following the same type of algorithm. If the
Western blot for HIV-1 is indeterminate, it should be repeated in 46 weeks; in
addition, one may proceed to a p24 antigen capture assay, HIV-1 RNA assay,
or HIV-1 DNA PCR and specific serologic testing for HIV-2. If the p24 and
HIV RNA assays are negative and there is no progression in the Western blot,
a diagnosis of HIV-1 is ruled out. If either the p24 or HIV-1 RNA assay is
positive and/or the HIV-1 Western blot shows progression, a tentative
diagnosis of HIV-1 infection can be made and later confirmed with a followup Western blot demonstrating a positive pattern. In addition to these standard
laboratory-based assays for detecting antibodies to HIV, a series of point-ofcare tests are also available. Among the most popular of these is the OraQuick
Rapid HIV-1 antibody test that can be run on blood, plasma, or saliva. The
sensitivity and specificity of this test are each ~99%. While negative results
from this test are adequate to rule out a diagnosis of HIV infection, a positive

finding should be considered preliminary and confirmed with standard

serologic testing, as described above.
As mentioned above, a variety of laboratory tests are available for the direct
detection of HIV or its components (Table 182-6; Fig. 182-28). These tests
may be of considerable help in making a diagnosis of HIV infection when the
Western blot results are indeterminate. In addition, the tests detecting levels
of HIV RNA can be used to determine prognosis and to assess the response to
ARV therapies. The simplest of the direct detection tests is the p24 antigen
capture assay. This
is an EIA-type assay in which the solid phase consists of antibodies to the p24
antigen of HIV. It detects the viral protein p24 in the blood of HIV-infected
individuals where it exists either as free antigen or complexed to anti-p24
antibodies. Overall, ~30% of individuals with untreated HIV infection have
detectable levels of free p24 antigen. This increases to ~50% when samples
are treated with a weak acid to dissociate antigen-antibody complexes.
Throughout the course of HIV infection, an equilibrium exists between p24
antigen and anti-p24 antibodies. During the first few weeks of infection,
before an immune response develops, there is a brisk rise in p24 antigen levels
(Fig. 182-25).
After the development of anti-p24 antibodies, these levels decline. Late in the
course of infection, when circulating levels of virus are high, p24 antigen
levels also increase, particularly when detected by techniques involving
dissociation of antigen-antibody complexes. The p24 antigencapture assay
has its greatest use as a screening test for HIV infection in patients suspected
of having the acute HIV syndrome, as high levels of p24 antigen are present
prior to the development of antibodies. Its use for routine blood donor
screening for HIV infection has been replaced by use of nucleic acid testing.
The ability to measure and monitor levels of HIV RNA in the plasma of
patients with HIV infection has been of traordinary value in furthering our
understanding of the pathogenesis of HIV infection and in providing a

diagnostic tool in settings where measurements of anti-HIV antibodies may be

misleading, such as in acute infection and neonatal infection. Three assays are
predominantly used for this purpose. They are reverse transcriptase PCR (RTPCR; Amplicor); branched DNA (bDNA; VERSANT); and nucleic acid
equencebased amplification (NASBA; NucliSens). These tests are of value in
making a diagnosis of HIV infection, in establishing initial prognosis, in
determining the need for therapy, and for monitoring the effects of therapy. In
addition to these three commercially available tests, the DNA PCR is also
employed by research laboratories for making a diagnosis of HIV infection by
amplifying HIV proviral DNA from peripheral blood mononuclear cells. The
commercially available RNA detection tests have a sensitivity of 4080 copies
of HIV RNA per milliliter of plasma. Research laboratorybased RNA assays
can detect as few as one HIV RNA copy per milliliter, while the DNA PCR
tests can detect proviral DNA at a frequency of one copy per 10,000100,000
cells. Thus, these tests are ex3. Ethical principles applicable to medicine
Ethics is the study of morals. It is concerned with the rights and wrongs of
any particular decision or course of action. For the most part, we are unaware that
there is a moral content to a consultation unless a moral dilemma occurs.
Nevertheless, moral issues are an important influence in decision making in
general practice alongside physical, emotional and psychosocial components.
There are a number of ethical principles fundamental to medicine. These
are expressed in ethical codes, such as the Hippocratic oath, and in good conduct
guidelines, such as those produced by the General Medical Council.
Respect for persons
Respect for persons means treating patients as having rights and involves
finding out what they want and trying to meet these requirements. It recognizes
patients' right to know, their rights to privacy and their rights to treatment - and to

refuse treatment. From the principle of respect for persons follow two important
moral rules - confidentiality and onsent.
Confidentiality.
Confidentiality can be considered to be respecting other peoples' secrets,'7
and is an extension of the patient's right to privacy. Patients' interests are served
by the doctor being
better informed but if patients knew that their secrets were likely to be divulged
then they would be reluctant to give information to the doctor. Although this is an
important moral rule,
it is argued that there are situations when confidence can be broken.
Consent.
Consent can be considered to be an extension of the patient's right to know
and can be defined as 'a voluntary, uncoerced decision made by a sufficiently
competent or autonomous person on the basis of adequate information and
deliberation; to accept rather than reject some proposed course of action that will
affect him or her. This definition emphasizes two things. First, that the patient has
a choice in what happens to him or her, and secondly, that the choice is made after
the necessary information has been provided. Consent in this sense is by
definition informed consent. Within the consultation the patient can be thought to
be disadvantaged because of the doctor's self-interest, by being ill, having limited
medical
knowledge and power, and by being overawed by the doctor. The application of
this moral rule helps to correct any disadvantage by empowering the patient and
respecting the patient's rights.
Duty to do good and avoid harm
Beneficence can be considered to be the doctor's duty to put the patient's
interest before his or her own. It is counterbalanced by non-maleficence, a duty
not to do harm, which is possible with some forms of medical intervention which
are beneficial in themselves.

Fairness to all
Justice demands that there is no discrimination on the basis of age, sex,
religion, sexual orientation or preferred lifestyle, with equal opportunity of access
to resources. In the case of AIDS this principle would demand equal access to
counselling, prevention, assessment and treatment services, including treatment
with azidothymidine. In addition, resources must be distributed fairly and with the
increasing financial burden that AIDS poses to the health service, this is an ethical
issue of great practical importance.
While these are the main ethical principles that can be applied to our
discussion there are also certain themes which run through any discussion of
ethical issues related to AIDS the rights and duties of individuals versus the rights
and duties of society, caring versus judging, and advising and counselling versus
adopting a particular moral posture.

Ethical problems related to AIDS and HIV infection

Some issues, such as the rights of people with HIV-related dementia or the
mentally handicapped with HIV infection, have attracted little attention from
doctors. Other issues, such as making AIDS a notifiable disease, and the
anonymous and voluntary screening of the general population and antenatal
patients, are vigorously debated. In general practice there are three major ethical
issues surrounding AIDS and HIV infection which impinge directly on the
personal relationship between doctor and patient - the duty to care, consent and
confidentiality.
Duty to care
Case study: John is a 22-year-old homosexual who has recently been
diagnosed by his sexually transmitted disease clinic consultant as having AIDS.
He agrees that his general practitioner should be informed and within a few weeks

receives notification from the family practitioner committee that he has been
removed from his doctor's list.
This case raises the issue of the doctor's duty to care for a patient with
AIDS. In this situation the general practitioner exercised the right to remove the
patient from his or her list and hence avoided treating him. Was this a just and fair
thing to do?
The fact that some doctors are unwilling or reluctant to care for people
with AIDS, has led to appeals for doctors to realize that they have a duty to care.
It is often stated that our predecessors treated people with more infectious
diseases, such as tuberculosis, hepatitis B and plague but a closer inspection of
history shows that their responses were varied, with some doctors deciding to care
for patients so as not to be seen to be cowardly and other doctors, including
Sydenham and Galen, fleeing from the epidemic with their private patients. There
are three main reasons for this reluctance to care: a fear of infection, a sense of
hopelessness and powerlessness, and difficulties in dealing with certain groups of
patients.
Fear of infection.
Since HIV was first isolated several studies have shown that the risk to
health care workers is small. The major risk is through penetrating or needle-stick
injuries. The risk of seroconversion after accidental exposure is less than 101, and
so far, only a small number of health workers have acquired HIV infection
occupationally.
A sense of hopelessness and powerlessness.
People who learn that they have become antibody positive often feel
powerless or hopeless in the face of the virus. A diagnosis of AIDS is associated
with inevitable mortality; this is something that we cannot prevent, despite our
knowledge and modern technology, so we can share these feelings of hopelessness
and powerlessness in dealing with people with AIDS. AIDS also reminds us of our
own mortality, perhaps because many of those affected are young people.

Difficulties in dealing with certain groups.

It is important to recognize our own attitudes and prejudices towards
people in high risk groups. Dislike of homosexuals is common even among those
caring for them. A small minority of carers believe that homosexual patients are
'getting what they deserve'. Intravenous drug users are often described as
manipulative, uncooperative and demanding of prescriptions for drugs. In
addition, there has been a tendency to label homosexuals and drug
users as 'guilty victims' with children and haemophiliacs labelled as 'innocent
victims' This creates a hierarchy of blame which reflects our attitudes to these
groups. Can the actions of John's practitioner be justified?
The arguments of those who defend refusal to care include a belief that the
obligations to self and family override obligations to patients, that treating patients
when one is fearful or hostile only compromises their care, and that some doctors
are unable to cope emotionally. If we apply the ethical principle of beneficence
and recognize that the patient is dependent on the knowledge and help of the
doctor, we see that the doctor must efface self interest and care for patients with
AIDS. This decision need not be blind to the real but small risks of infection,
which can be minimized by sensible precautions. It is also not invalidated by any
disapproval the doctor might have for any particular group of patients.
Consent
Case study: Susan is a 24-year-old intravenous drug user. She consents to a
blood test for infectious mononucleosis when she develops swollen glands. Her
general practitioner, knowing she uses drugs intravenously, decides to test the
blood sample for antibodies to the HIV virus. This has not been discussed with
Susan and her consent has not been obtained. A positive result is returned.
This case study illustrates some of the difficulties that can occur when a
blood test is taken without the patient's consent. She may be angry when she finds
out and may react adversely to being told of the positive result. It is recognized
that this can result in adverse psychological reactions, even suicide. What reasons
can be given for not seeking the patient's consent? It is argued that we already take
blood routinely to screen for certain conditions without seeking the patient's

consent for each individual test, for example, blood from antenatal patients is
screened for syphilis.
Few general practitioners seek specific consent for this test and it has been
argued that this establishes a precedent which could be extended to the test for
HIV. However, the test cannot be considered routine because of the serious
implications of a positive result. Furthermore, as consent is such an important
moral rule it would seem desirable to extend this to tests where at present specific
consent is not sought. Another reason given for not seeking consent concerns the
patient's ability to understand what is being said and to make complex decisions.
This assumes that the doctor knows what is best for the patient, but why should
the doctor take responsibility for this choice and the consequences that arise from
it?
Confidentiality
With AIDS and particularly the blood test for HIV there are situations
where it can be argued that a breach in confidence might benefit the patient, the
doctor, nursing staff, other people or society. For example: Should a patient's
confidence be broken in order to try and prevent another patient from acquiring
infection? Should practice and community staff be informed of a positive HIV test
result or of a patient with AIDS? Should information about the blood test for HIV
and the patient's sexual preferences and lifestyle be made available to insurance
companies? Should the results of a blood test for HIV, performed by a sexually
transmitted disease clinic, be made available to a general practitioner without the
consent of the patient?
Protecting the interests of another patient.
Case study: Peter is a 23-year-old intravenous drug user. He is antibody
positive for
the HIV virus and is having regular sexual intercourse with his girlfriend who is
also your patient. She does not know of his positive status. Despite counselling
and persuasion he is adamant that his girlfriend 'must not know. His girlfriend
takes the oral contraceptive pill erratically and Peter will not use a condom.

This is not a new dilemma and is similar to the situation where one partner
has a sexually transmitted disease, and refuses to tell the other partner so that he
or she can receive treatment and advice. Is this a situation where the patient's
confidence can be broken in order to benefit another patient? Initially one should
try to help Peter take responsibility for not passing on the infection to his
girlfriend or anyone else. If this approach fails, it would be justifiable to break
confidence and tell his girlfriend.
In this situation, the greater good has been to try and prevent the girl from
acquiring the virus, especially as she is not using adequate contraception. Peter
should be told of the intended course of action, and given reasons for it. While
breaking confidence in this situation can be justified, the rule of confidentiality is
still an important ethical principle which should only be broken in exceptional
circumstances.

Practice and community staff.

In view of the high level of anxiety, prejudice and fear about people with
AIDS, only those directly involved in the care of patients with AIDS or HIV
infection should be informed. This would include partners, practice nurses and
community nurses, but not receptionists and secretaries. The patient should be told
which members of staff have this confidential information. Any extension beyond
this, for example, to home helps, family members and employers, should be
discussed with the patient prior to disclosure.
In general practice it is unavoidable that staff who are not directly
involved in clinical care, such as receptionists, will come across confidential
information. Therefore, all practice staff should be educated about their duty of
confidentiality towards all medical information, including that related to HIV
infection and every practice must work out procedures for preserving confidential
information, particularly in the written record.
Insurance companies.

Currently general practitioners are asked by insurance companies to

extract information from medical records about whether patients engage in
behaviour which puts
them at risk of HIV infection or have had a blood test for HIV. Should this
information, which was given in confidence, be released to insurance companies?
While patients give written consent for the company to approach their general
practitioner, they are unlikely to be aware that the company is requesting
information about their sexual behaviour, intravenous drug use or the HIV blood
test. The patient is also unlikely to be aware of the nature and extent of
information recorded in the medical record, which may contain impressions about
the patient which have no basis in fact. This is an unsatisfactory situation. The
best solution is for the general practitioner to seek the patient's verbal or written
consent, and if this is refused to return the form uncompleted. More
fundamentally, is it right that information which was collected for medical
purposes should be made available for a commercial purpose which may not serve
the patient's interests? The company can always protect their investment by
arranging an independent medical examination.
HIV blood tests performed by sexually transmitted disease clinics.
At present, these clinics do not release the results of blood tests for HIV to
general practitioners without the patient's consent, unless the patient was referred
by a general practitioner. This is the same as for other sexually transmitted
diseases. It is argued that these results should be made available to the general
practitioner regardless of whether the patient has given consent. This would
protect against a wrong diagnosis and incorrect treatment.
For example, in a consultation for cough and fever in an intravenous drug
user, knowing that the person was HIV antibody positive would suggest the
possibility of Pneumocystis carinii pneumonia, which might be inappropriately
managed if the patient's antibody status were unknown. Knowing who was
antibody positive might also ensure that general practitioners took appropriate self
protective measures during consultations. There are problems with these
arguments. Most importantly they ignore the patient's right to choose for him or

herself. There is also considerable anxiety among patients about general

practitioners receiving confidential HIV blood test results from sexually
transmitted disease clinics,'4 and this might dissuade people from seeking help
and advice from these clinics. There are also problems with the result of the blood
test, which can be negative in someone who has not developed detectable
antibody. The benefits to the doctor in terms of heightening his awareness of risk
and taking self protective measures are also doubtful as there will be patients who,
unknown to the general practitioner, engage in high risk activities and who have
not had a blood test for HIV. It is more logical to employ the same standard of self
protection with all patients.

Why is HIV and AIDS education important?

The expansion and improvement of HIV and AIDS education around the world is
critical to preventing the spread of HIV. There are an estimated 34 million people
living with the virus, and each year millions more people become infected.
Effective HIV and AIDS education can help prevent new infections by providing
people with information about HIV and how it is passed on, and in doing so equip
individuals with the knowledge to protect themselves from becoming infected
with the virus.
HIV and AIDS education also plays a vital role in reducing stigma and
discrimination. Around the world, there continues to be a great deal of fear and
stigmatisation of people living with HIV, which is fuelled by misunderstanding
and misinformation. This not only has a negative impact on people living with
HIV, but can also fuel the spread of HIV by discouraging people from seeking
testing and treatment.

Who needs HIV and AIDS education?

HIV and AIDS education can be effective when targeted at specific groups who
are particularly at risk of HIV infection. The groups that HIV and AIDS education
needs to target vary depending on the nature of the epidemic in an area. High risk
groups can also change over time. For example, in the early years of the AIDS
epidemic in America, men who have sex with men and injecting drug users were
most at risk of HIV infection. Today, heterosexual African Americans and the
Hispanic/Latino population are also identified as groups particularly vulnerable to
HIV infection in America.
AIDS affects many parts of society, and so everyone needs to be aware of HIV
and AIDS.
However, it is important that such a focus does not lead to groups who are
considered not at risk missing out on HIV and AIDS education. This can lead to
a rise in HIV infection rates amongst groups who are often neglected by HIV and
AIDS education, for example older people. Providing the general population with
basic AIDS education contributes to the spread of accurate information;
promoting awareness and tackling stigma and discrimination.
It is also important that people who are already infected with HIV receive HIV
and AIDS education. This can help people to live positively without passing on
the virus to anyone else; to prevent themselves becoming infected with a different
strain of the virus; and to ensure a good quality of life by informing them about
medication and the support that is available to them.

Where does HIV and AIDS education take place?

HIV and AIDS education can take place in many different environments, from
classes at school to families and friends sharing knowledge at home. It is
important that this education is provided in a variety of settings to ensure that the

most vulnerable and marginalised groups in society are reached, and that accurate
information about HIV and AIDS is reinforced from different sources.

HIV and AIDS education in schools

The most common place for people to learn about HIV and AIDS is at school.
Due to their capacity and universality, schools are a crucial setting for educating
young people about AIDS. As young people are at a high risk of becoming
infected with HIV, it is vital that they are educated about HIV transmission before
they are exposed to situations that put them at risk of HIV infection (for example,
before they are sexually active). Schools play a major role in shaping the attitudes,
opinions and behaviour of young people and so are ideal environments for
teaching the social as well as the biological aspects of HIV and AIDS.
Members of the wider community can also increase their knowledge about HIV
and AIDS through the school environment. Teachers who expand their
understanding of the subject while planning lessons and receiving teacher training
can pass this information on to adults as well as pupils, and the same can be said
for children themselves; once informed about AIDS, they can tell their parents or
their friends what they have learned.

HIV and AIDS education in the workplace

Educating people at work is an important way of providing people with vital
prevention information, and can reach people who have previously missed out on
HIV and AIDS education. Furthermore, it is estimated that nine out of ten people
living with HIV are working. Providing education in the workplace is important
for protecting those at work living with HIV, and for helping them to live healthily
and stay in work.
Some occupations carry an increased risk of HIV infection, making HIV and
AIDS education in the workplace even more important for preventing the spread
of the virus. Health care workers may be at a higher risk of HIV transmission, for
example from needles and other medical instruments, while at work. HIV and

AIDS education needs to be a priority in such environments, to ensure that

healthcare workers take precautions that will protect them from HIV infection.
Some people may be more vulnerable to HIV and AIDS because of the lifestyle of
their work. For example, workers who spend time away from home may be more
involved in risky sexual behaviour than those who spend the majority of the time
at home with their families.
The International Labour Organisation (ILO) works throughout the world on
HIV/AIDS policies and programmes in the workplace. The organisation aims to
protect against discrimination in labour laws, promote prevention initiatives
within the workplace, and supports those living with HIV by ensuring access to
social protection, treatment and care. In 2012 they launched the Getting to Zero
at Work campaign to promote the rights of people living with HIV in the
workplace.12 However, workplace HIV and AIDS education is not universal and
as a result, people are still unaware of the dangers of HIV, and those living with
the virus are still subject to HIV related stigma and discrimination at work.

How can HIV and AIDS education be delivered?

There are a great variety of methods and materials that can be used to educate
people about HIV and AIDS, including radio & television, booklets, billboards,
comic strips, street theatre, fundraising events and many more. The form in which
HIV and AIDS education should be delivered depends on those who are being
educated. In order to reach the target group, it needs to be considered which
environments they will be most receptive in, and what media is most relevant to
them.
How HIV and AIDS education should be delivered also depends on the principal
aims of the education programme. Sometimes education on HIV and AIDS is
about giving people information which they will remember on a long term basis,
about how to protect themselves; the difference between HIV and AIDS; and
helping to reduce discrimination. Other education strategies are intended to have

more immediate effects, and may target people when they are most likely to take
part in risky behaviour in nightclubs or holiday resorts, for example.
There is no set or prescribed form that HIV and AIDS education should take, but
there are certain things that need to be considered when carrying out or producing
resources for HIV and AIDS education. The following questions have significant
implications for the way in which HIV and AIDS education should be delivered:

Is the education programme targeted at a specific risk-group or more

generally at the population as a whole?

What age are the people to be educated?

Are the people to be educated already sexually aware?

Have they been exposed to HIV and AIDS education before?

Are they literate?

What language or local dialect do they speak?

Are there cultural issues to be considered? For example, attitudes to

sexuality, or laws against portrayal of explicit images or language.

Are people able to do what you're suggesting? There's no point in advising

people to use condoms if none are available to them, or to use clean
needles if needle exchanges are illegal.

HIV and AIDS education through the mass media

The mass media has played a central role in many countries responses to AIDS
since the very early days of the epidemic. In the UK, as a response to the growing
number of new HIV infections during the 1980s, a leaflet about AIDS was
delivered to every household and a major advertising campaign carrying the
slogan AIDS: Dont Die of Ignorance, was launched. The UK governments use
of the media for broadly targeted or blanket education was successful in

promoting widespread awareness of HIV and AIDS amongst the general

population.
Although media-based HIV and AIDS education is considered effective for raising
general awareness, its overall impact is difficult to measure. It is essential that
education goes beyond promoting general awareness and instigates behaviour
change to reduce the risk of HIV transmission.
If constructed badly, HIV and AIDS education can have the detrimental affect of
increasing stigma and discrimination towards people living with HIV. Some media
messages try to change peoples behaviour by making the audience afraid of the
consequences of becoming infected with HIV. This not only has the potential of
making the target audience afraid of people infected with HIV but also carries the
risk of portraying HIV positive people as at fault for becoming infected.
Media based HIV and AIDS education can be particularly harmful when targeted
at specific risk groups, such as men who have sex with men or injecting drug
users. Not only can this fuel stigmatisation of these groups, but it can also hinder
HIV prevention. By not representing the broad face of the epidemic, and instead
focusing on risks to specific groups, the media encourages the attitude that AIDS
is somebody elses problem and that if you are not part of a risk group you dont
need to worry about HIV and AIDS.

Peer education
It is not just teachers who can provide education; peoples knowledge about HIV
and AIDS can be influenced by a variety of different people, including family,
friends, and the wider community. Peer education is education provided by
somebody who is either directly part of the group receiving the information, or
who is from a similar social background.
Peer education is a less formal method of educating, which can be more accessible
to people who are not used to or dislike a formal classroom environment. At the
same time, peer educators are trained on the subject, ensuring that the information

they provide is accurate and reliable. This makes peer education a very effective
way of reaching marginalised groups. For example, peer education programmes
have been found to work well in prisons, where authority figures are often
distrusted.

What information needs to be included in HIV and

AIDS education?
Although HIV and AIDS education needs to be tailored to the context in which it
takes place and to the people who are being educated, there are some key areas
that HIV and AIDS education programmes need to cover. It is important that the
information provided is a balance of the social and emotional aspects of
HIV/AIDS as well as biological and medical information.
Comprehensive HIV and AIDS education includes:
How to protect and promote ones health

Basic knowledge of HIV and AIDS including how to protect oneself

from HIV infection.

Learning about treatment and care - including an understanding of

voluntary counselling and testing (VCT) and antiretroviral drugs.

Social and emotional aspects

How to maintain a healthy level of self-confidence and self esteem.

Coping with difficult and risky situations.

Coping with loss.

Sexuality

Learning about different sexual orientations and the development of

sexuality.

Promotion of equity, including gender issues

Understanding that social, biological, economic and cultural factors affect

vulnerability to HIV.

Understanding that men and women have similar rights in society and
family.

Overcoming stigma and discrimination and promoting human rights

How to show support for HIV positive people and how not to discriminate
against or stigmatise people living with HIV.

Understanding the importance of confronting HIV and AIDS in the

community.

Providing the right information is only part of carrying out comprehensive HIV
and AIDS education. For the education to be effective, this information needs to
be absorbed and remembered. Active learning encourages people to engage with
information by giving them the opportunity to apply it.
4. HIV PROPHYLAXIS
Post Exposure Prophylaxis
Post-exposure prophylaxis (PEP) is short-term antiretroviral treatment to reduce
the likelihood of HIV infection after potential exposure, either occupationally or
through sexual intercourse. Within the health sector, PEP should be provided as
part of a comprehensive universal precautions package that reduces staff exposure
to infectious hazards at work.
The use of ARVs for HIV post-exposure prophylaxis (HIV-PEP) following
occupational exposure to HIV, and the recent expansion of HIV-PEP to nonoccupational situations, have raised numerous areas of uncertainty for policy
makers and healthcare providers caring for potentially exposed individuals. Key
issues among these are the appropriate indications for HIV-PEP, ART choices, and
management strategies to accompany use of PEP for HIV. With the expanding

availability of ART in resource-poor settings, issues of provision of HIV-PEP

require policy decision that can be implemented in programme and services
delivery planning.
The risk of transmission of HIV from an infected patient through a needlestick
where the skin is punctured by a sharp is less than 1%. The risk for
transmission from exposure to infected fluids or tissues is believed to be lower
than for exposure to infected blood.
The risk of exposure from needlesticks and other means exists in many settings
where protective supplies are limited and the rates of HIV infection in the
patient population are high. The availability of PEP may reduce the occurrence
of occupationally acquired HIV infection in health care workers. It is believed
that the availability of PEP for health workers will serve to increase staff
motivation to work with people infected with HIV, and may help to retain staff
concerned about the risk of exposure to HIV in the workplace.
There is significant debate on the need to use PEP after sexual exposure. The
UN offers PEP to its staff in cases of rape when the likelihood of HIV exposure
is considered high.
How it is done
The proper use of supplies, staff education and supervision needs should be
outlined clearly in institutional policies and guidelines.
Regular supervision in health care settings can help to deter or reduce risk of
occupational hazards in the workplace. If injury or contamination result in
exposure to HIV infected material, post exposure counselling, treatment,
follow-up and care should be provided. Post-exposure prophylaxis (PEP) with
antiretroviral treatment may reduce the risk of becoming infected.
Prevention of exposure
Prevention of exposure remains the most effective measure to reduce the risk
of HIV transmission to health workers. The priority must be to train health
workers in prevention methods (universal precautions) and to provide them
with the necessary materials and protective equipment. Staff should as well be

knowledgeable about risks of acquiring HIV sexually, and be easily able to

access condoms and confidential STI treatment services.
Managing occupational exposure to HIV

First AID should be given immediately after the injury: wounds and

skin sites exposed to blood or body fluids should be washed with soap and
water, and mucous membranes flushed with water.

The exposure should be evaluated for potential to transmit HIV

infection (based on body substance and severity of exposure).

The exposure source should be evaluated for HIV infection. Testing of

source persons should only occur after obtaining informed consent, and should
include appropriate counselling and care referral. Confidentiality must be
maintained.

Clinical evaluation and baseline testing of the exposed health care

worker should proceed only after informed consent.

Exposure risk reduction education should occur with counsellors

reviewing the sequence of events that preceded the exposure in a sensitive and
non-judgmental way.

Since the early 1990s, in many countries antiretroviral medicines have been
prescribed for postexposure prophylaxis (PEP) following occupational exposure
to the human immunodeficiency virus (HIV). This practice has since been
extended to non-occupational situations, primarily for cases of sexual assault.
Increasingly, however, both policy-makers and health care providers have been
raising questions about certain aspects of the use of HIV PEP: in particular, about
the indications for post-exposure prophylaxis, the most suitable antiretroviral
medicines to use and various issues relating to prescribing protocols and clinical
management. Awareness of these areas of uncertainty has been further heightened
by the expanding availability of antiretroviral therapy in more resourceconstrained
settings and has led to calls for clear operational guidance on providing PEP.
In September 2005, a Joint WHO/ILO Expert Consultation for the Development
of Policy and Guidelines on Occupational and Non-occupational HIV Post-

exposure Prophylaxis was held in Geneva. The objectives of this Consultation

were (1) to review scientific evidence and programmatic experience in relation to
providing PEP in occupational and non-occupational settings and (2) to
recommend a consensus approach to formulating policy and operational
guidelines for HIV PEP. Although the needs of workers and people who have been
sexually assaulted provided the focus of the Consultation, consideration was given
to other types of nonoccupational exposure for which PEP might be indicated:
specifically, those arising from isolated or episodic injecting drug use and
consensual sexual exposure. The Consultation recommendations, which are based
on current understanding of the efficacy of PEP and available data for comparing
different PEP strategies, represent the collective opinion of experts working in this
field and form the basis of the present policy guidelines and service delivery
recommendations.
The term post-exposure prophylaxis is generally understood to mean the medical
response given to prevent the transmission of blood-borne pathogens following a
potential exposure to HIV.i In the context of HIV, post-exposure prophylaxis
refers to the set of services that are provided to manage the specific aspects of
exposure to HIV and to help prevent HIV infection in a person exposed to the risk
of getting infected by HIV. These services might comprise first aid,
counselling including the assessment of risk of exposure to the infection, HIV
testing, and depending on the outcome of the exposure assessment, the
prescription of a 28-day course ofantiretroviral drugs, with appropriate support
and follow-up. For the purposes of these guidelines on providing PEP, individuals
sustain potential occupational exposure to HIV in the course of their work.
However, the term occupational post-exposure prophylaxis should not be assumed
to be solely related to health care. Other workers, such asmay be exposed to blood
and other potentially infectious body fluids while performing
Individuals can also face potential non-occupational exposure to HIV outside the
work setting. In these guidelines, this term predominantly refers to potential
exposure through sexual assault. Other forms of potential non-occupational

exposure include those arising from needle-sharing among injecting drug users
and potential exposure through consensual sex. The exposed person is the person
who has been potentially at risk of acquiring HIV infection through exposure to
blood or body fluids in his or her occupation or in another non-occupational
situation.
The source person is the person who is (either identified or not identified as) the
possible source of contamination through potentially infectious blood or body
fluid. If the serostatus of the source person is unknown, he or she may be asked to
provide informed consent to HIV testing. The source person may
Worldwide, in 2007, an estimated 33.2 million people were infected with HIV.
Post-exposure prophylaxis, which by definition includes the prevention of motherto-child transmission, is currently the only way of reducing the risk of
development of HIV infection in an individual who has been exposed to the virus,
and as such, is widely considered to be an integral part of the
overall strategy for preventing the transmission of HIV. Strong ethical arguments
support providing PEP for HIV infection. Each day, thousands of people around
the world experience accidental exposure to blood and other body fluids or tissues
while performing their work duties. Health care workers are especially
vulnerable. Moreover, in many parts of the world, the potential for workplace
accidents that may expose workers to HIV-infected blood and other body fluids is
increasing. Several factors are contributing to the increased risk of occupational
HIV exposure. First, more people are living with HIV infection. At the same time,
antiretroviral medicines are becoming increasingly available for treating AIDS,
including in many resource-constrained settings, with the result that more people
with HIV are coming into contact with health care services. Second, as people
receiving antiretroviral therapy accrue its benefits and live longer, they are more
likely to survive, and the numbers of people living with HIV in contact with
health services is increasing, both as health care providers and as
people receiving treatment.

Given that sexual exposure is associated with the risk of HIV transmission, there
are also ethical reasons to support providing PEP to people who have been
sexually assaulted. Although data on the efficacy of HIV PEP are fairly limited,
good evidence suggests that a short course of antiretroviral therapy effectively
reduces HIV transmission rates following needlestick exposure. This comes
largely from a single casecontrol study involving health care workers.
HIV PEP can preserve life and health. Providing post-exposure prophylaxis is an
important component of compliance with protection obligations deriving from
national and international human rights laws. In the context of HIV PEP, the key
human rights obligations are to ensure the right to the highest attainable standard
of health, to protect against violence and its consequences and to protect rights to
privacy and bodily integrity. In developing PEP policies, the goal is to strike a
balance
between protecting population health and protecting individual human rights.
Non-discrimination
A non-discriminatory approach to service accessibility, information provision and
education is critical and must underpin any policy or operational guidelines on
HIV PEP. The ILO code of practice on HIV/AIDS and the world of work4 and
several other international human rights instruments provide detailed guidance
regarding consent, confidentiality and access to
information and health care services on a non- discriminatory basis. The policy for
eligibility for PEP should always be founded on the principle of equity. Decisions
about whether or not to offer post-exposure prophylaxis should be based purely on
clinical considerations of risk and should not be tied in any way to a persons
decision to file a police report or to pursue legal action. Individuals should be
assessed for PEP regardless of their involvement in any activities considered to be
illegal by national legislation, such as injecting drug use, sex work or men having
sex with men. Nor should there be any barriers to access for financial or
administrative reasons. Non-citizens (such as refugees, asylum-seekers and
stateless people) should have equal access to health care, including PEP, in the
country in which they are currently residing or staying

Confidentiality
Personal information relating to PEP, such as the reasons for seeking it, having it
provided and for HIV testing, needs to be confidential. Privacy and confidentiality
considerations are the same as those for HIV testing (see the section on HIV
testing and counselling . In the case of children, the rights of the child should be
protected. The confidentiality of HIV test
results should be consistent with the obligation to protect the right of children to
privacy.
Informed consent
Informed consent for HIV PEP needs to be obtained in the same way as for any
other health care procedure. Consent to any HIV testing in the context of PEP
must also be obtained, in accordance with standard guidelines for HIV testing and
counselling testing and counselling guidelines in further reading section). HIV
testing and counselling is often referred to as voluntary counselling and testing,
when initiated by the beneficiary, or provider-initiated testing and counselling,
when proposed by the services provider. In special situations in which the
individual has limited or no capacity to consent (such as
children and unconscious or mentally ill adults), a parent or responsible person
can provide consent. Depending on national or regional legislation, unreasonable
refusal to consent may be overridden in cases where it is considered to be in the
persons best interest.
An individual or a small team needs to take responsibility for implementing
services. At the local level, certain categories of health care workers, such as
infection control professionals, would be appropriate candidates for assuming
responsibility for implementing PEP policy.
Operational guidelines
A code of practice, protocols and standard operating procedures for PEP services
need to be formulated as part of the process of developing policy.

Post-exposure prophylaxis services

The comprehensive package of post-exposure prophylaxis services offered
depends on the setting and context in which the exposure occurs. This needs to be
resourced and should include mechanisms for linking all potential service
providers.
HIV PEP services would include, as a core package:reporting assistance and
possible referral capacity;risk assessment;
ervices for:
providing consent to PEP
pre- and post-HIV test counselling (for both the exposed person and the source
person)
drug adherence and managing side effects
preventing the risk of transmission;
HIV testing, to include:
initial testing of exposed individuals
testing of the source person, when possible;
providing PEP medication, which includes:
the initial dose (as soon as possible following exposure and preferably within 72
hours)
the full course (28 days of treatment);
support and follow-up; and
appropriate record-keeping and documentation.
Support services that are highly desirable but not necessarily essential to
providing PEP include:
follow-up HIV testing at three and six months;
medication to manage side effects (such as medication for nausea, diarrhoea or
headache);
monitoring of adherence;
additional in-person clinical follow-up or 24-hour on-call advice from a provider
with
expertise in HIV PEP;

 hepatitis B and C testing;

hepatitis B PEP and vaccination;
pregnancy testing at baseline and follow-up (for all women of childbearing age);
in case of exposure through sexual assault:
forensic examination;
trauma counselling and management including psychosocial support;
prophylaxis and management of sexually transmitted infections;
emergency contraception;
needle and syringe exchange schemes (for injecting drug users).
Service components may be delivered at different points or levels of the health
care system (primary, secondary or tertiary settings). Any written information for
health care providers and/or patients should be readily accessible and written in
simple and clear language. Annexes 2 and 3 provide sample scripts for service
providers and information sheets for patients, respectively.The special needs of
certain population subgroups, especially children and pregnant or breastfeeding
women, should be taken into account and catered for (see section 3.3.6). Service
prerequisites that is, functions and resources that ideally would already be in
place before services are provided are as follows:
a multidisciplinary
committee would usually develop local protocols);
a written algorithm for risk assessment;
prompt access to and clear protocols for delivering the first dose of PEP;
adequate availability of PEP medication;
HIV testing and counselling services;
a supply of condoms;
protocols governing counselling services (which would cover risk reduction,
side effects of PEP medication and the importance of adherence and HIV testing);
and
links to local clinical and referral services (including for people who are not
eligible for or
decline PEP)

Evaluating client eligibility for HIV post-exposure prophylaxis involves assessing

the following:
the timing of the potential exposure;
the persons HIV status;
the nature and risk of the exposure; and
the HIV status of the source of the potential exposure.
Timing of post-exposure prophylaxis initiation
PEP should be initiated as soon as possible after exposure, within the first hours
and no later than 72 hours after exposure. PEP should not be offered beyond 72
hours after exposure. Animal studies indicate that PEP is not effective when given
more than 72 hours after exposure. They are the basis of the recommendation that
PEP should not be given to people who present more than 72 hours after
exposure . Thus, to maximize its benefits, PEP to prevent HIV infection should
always be started as soon as possible following exposure and within 72 hours of
the potential exposure. A first dose or, even better, a starter pack of PEP drugs
should be made readily available to potentially exposed individuals and given
according to national policy and local protocols. An HIV test should normally not
be a condition of initiating PEP, nor should PEP be delayed until the results of an
HIV test become available (unless rapid testing is used).
Pre-existing HIV infection
Post-exposure prophylaxis is intended for HIV-negative individuals only. The
possibility that the exposed individual has pre-existing HIV infection should
always be explored as part of the process of assessing eligibility. PEP providers
should be aware that both occupationally exposed workers and people who have
been sexually assaulted may have other
ongoing risks for HIV infection. Potentially exposed people who are known or
found to be HIV infected should not receive PEP. They should, however, be
offered counselling and given appropriate information about how to prevent

further transmission. They should also be referred for clinical and laboratory
assessment to determine their eligibility for antiretroviral therapy.
Assessment of the exposure to HIV
Post-exposure prophylaxis should be provided following significant exposure of
mucous membranes (through sexual exposure or splashes to the eyes, nose or oral
cavity) or non-intact skin (through percutaneous sharps or skin abrasion) to a
potentially infectious body fluid from a source that is HIV infected or has
unknown status. The nature of the exposure should be assessed in detail to
determine the risk of transmission and thus eligibility for PEP. Clinicians can
apply a risk assessment algorithm to assist in the process of determining eligibility
. Annex 6 provides the currently accepted recommendations governing PEP use
according to thenature of the exposure. Chapters 4 and 5, respectively, discuss in
more detail the risks associated with occupational exposure and exposure from
sexual assault.
Assessment of the sources HIV status
Knowing the HIV status of the source of the exposure is extremely helpful. In
case of sexual assault, identifying the perpetrator and obtaining informed consent
to be tested is difficult. If the source tests negative, PEP need not be started (or
can be discontinued) unless a clinician with expertise in diagnosing acute HIV
infection suspects that the source may be acutely infected and in the window
period. However, because PEP needs to be started as soon as possible after
exposure, initiation it where indicated should not be delayed until the results of
HIV testing of the source person are known.
Standard HIV testing and counselling protocols should be followed in testing the
source of theexposure (see the section on HIV testing and counselling guidelines
in the further reading). This includes obtaining informed consent prior to
performing the test for HIV infection and keeping the results confidential. No
simple mechanism or formula can be applied to determine the likelihood that an
unknown or untested source is infected with HIV. Assessment of the HIV status of
the source, and thus

decisions about the eligibility for PEP, must therefore be based on available
epidemiological data.
The definition of what constitutes a high-risk source varies both within and
between counties. In settings with a high prevalence of HIV infection, assuming
that all sources of unknown HIV status are infected is reasonable. Elsewhere,
local and community epidemiology and knowledge of the demographic
characteristics of the source can be used to predict the likelihood that the source is
infected.
People who have been exposed should receive counselling about specific aspects
of postexposure prophylaxis, ideally at the time when they present following
exposure. The counselling should include information about the importance of
adherence and the possibility of side effects as well as advice about the risk of
transmission as part of their counselling.
The PEP service provider should provide counselling on adherence and side
effects. The samplescripts attached in Annex 2 provide guidance on both of these
aspects of counselling. Thepeople receiving PEP must comprehend the dosing
instructions, and the counselling should include assessing their understanding.
Counselling must be backed up with appropriate followup support services to
maximize adherence to the PEP regimen and to manage any side effects.
Counselling to reduce risk is also necessary to prevent the transmission of HIV to
sexual partners,to children of breastfeeding mothers and to recipients of blood
donations, if the exposed person has become infected. Risk reduction counselling
should be given during the initial visit and reinforced in later visits. Condom use
and/or other protective preventive measures should be encouraged until a HIV test
after six months is negative. Discussing the risk of HIV transmission associated
with consensual sex after a person has been occupationally exposed or sexually
assaulted may be difficult given the sensitive nature of the issue, but this dialogue
is essential. Service providers need to be aware that some of the exposed people

may not welcome the prospect of having to talk to sexual partners about the need
to use a condom, and this can create barriers to follow-up and PEP adherence.
Offering exposed individuals assistance in talking to their sexual partners about
using condoms may be appropriate. Counselling women of childbearing age about
getting pregnant during post-exposure prophylaxis is critical. Whereas most drugs
prescribed for PEP are regarded as safe during pregnancy, women should be told
of the possible risk of transmitting HIV during pregnancy,especially at the initial
stage of infection.
In the process of seeking informed consent for HIV post-exposure prophylaxis,
people who have been exposed to HIV must be made fully aware of the following:
the risk of acquiring HIV infection f rom the specific exposure;
what is known and not known about the efficacy of PEP;
the importance of taking a HIV test and of receiving appropriate post-test
counselling (although testing may be delayed if necessary);
the possibility that they might already be infected with HIV will need to be
assessed if they have not already had an HIV test;
people already living with HIV should be referred to a local clinic for treatment
of theirinfection, and if they had started PEP the medicine should be stopped when
the diagnosis is confirmed;
people with discordant rapid HIV test results should be offered PEP while
waiting for pending laboratory-based confirmatory testing;
that PEP medication will be discontinued if their initial HIV test is positive: this
medication does not work for people living with HIV and could increase the risk
of drug resistance among people already infected;
the importance of adhering to medicine;
the duration of the course of medicine (four weeks);
the common side effects that may be experienced while taking PEP medicine;
that they can stop taking PEP medicine at any time, but if they do so, they will
probably not get the full benefit of PEP if the source to which they were exposed
was HIV positive;

 PEP medicine can be taken during pregnancy and may protect the mother
fromgetting HIV infection after exposure;
that continuing to breastfeed while taking PEP is safe, although if women get
infected by HIV while breastfeeding, the risk of transmitting HIV through
breastfeeding is higher at the early stage of infection; appropriate counselling
should discuss safe alternatives to breastfeeding if they are acceptable, feasible,
affordable and sustainable; and
exclusive breastfeeding is strongly recommended whenever alternatives are not
possible
Criteria for recommending treatment with two nucleoside-analogue reversetranscriptase inhibitors
A regimen comprising two nucleoside-analogue reverse-transcriptase inhibitors
isrecommended if:
the HIV status of the source person is unknown;
the background prevalence of resistance to antiretroviral therapy in the
communityis less than 15%;
the source person has never used antiretroviral therapy;
the source person is unlikely to have HIV infection resistant to antiretroviral
therapy,
based on antiretroviral therapy and adherence history.
Recommended
prophylaxis

two-drug

combination

therapies

for

HIV

post-exposure

A regimen comprising two nucleoside-analogue reverse-transcriptase inhibitors

plus aboosted protease inhibitor can be considered if:
the source person is HIV positive, taking antiretroviral t herapy and is known to
have signs of, personal history of or proven antiretroviral therapy resistance; or
the source persons HIV status is unknown;and
the background prevalence of resistance to antiretroviral therapy in the
community exceeds 15% (where this is known).
If drug resistance is suspected and a third drug is considered necessary, it should
be a boostedprotease inhibitor, not a non-nucleoside reverse-transcriptase
inhibitor. In addition, nevirapine is not recommended for PEP due to the risk of
toxicity and efavirenz should not be given to women who are pregnant or are of
childbearing age because it is teratogenic. If the resistance profile of the source
person is known, the selection of PEP medicines should take account of that
profile.

Appropriate information must be given to everyone exposed to HIV and therefore

considering PEP about the risks and benefits of taking it in the context of pre-

existing HIV infection. Of particular concern is the risk of developing

antiretroviral therapy resistance to lamivudine.
Adherence
Studies in high-income countries have demonstrated that in people living with
HIV, higher levels of drug adherence are associated with improved viral, immune
and clinical outcomes. Adherence rates of 95% or greater are required to
maximize the benefits of antiretroviral therapy. Although parallel data are not
available for PEP, the magnitude of the positive effects of high levels of adherence
is generally assumed to be similar. Although PEP is taken for a relatively short
time period (four weeks), providing adherence information and support is still
important to maximize the efficacy of medicines.
Side effects
The most commonly reported side effects are nausea and fatigue12. Side effects
can be reduced by prescribing a dual nucleoside-analogue reverse-transcriptase
inhibitor rather than three-drug regimen, by prescribing medicine to reduce side
effects (such as antiemetic for nausea) and by advising people on how to reduce
side effects (for instance, by taking medicines with food). People should
understand that side effects may be expected so that any symptoms experienced
are not confused with symptoms of HIV seroconversion.
The recommended duration of PEP for HIV infection is 28 days. The first dose of
it should always be offered as soon as possible after exposure. Once commenced,
the full PEP should be taken unless there are specific reasons to stop. Starter packs
with incremental full 28 days of dosing can be used. To reduce waste, some
countries have adopted a strategy whereby supplies are swappedbetween low-use
areas and high-use areas to ensure that medicines are used before they
expire.
Initial dose

The first dose of PEP should always be offered as soon as possible after exposure,
and if necessary, without waiting for HIV testing and counselling or the HIV test
results of the source person (unless rapid testing, which provides results within
one hour, is available) or, in the case of sexual assault, for the full forensic
examination. The initial provision of PEP (starter packs) may be limited to the
first dose or may consist of the necessary drugs for 57 or more days. This
strategy is often used when non-experts provide the initial care, with referral to
PEP experts or a post-exposure prophylaxis clinic within the next few days.
When PEP has been initiated, facilitating access to a full 28-day supply of
medicines is the next step. Several dispensing strategies can be used to achieve
this. Strategies for dispensing drugs should aim to maximize access and adherence
yet minimize drug waste. A key factor governing the choice of strategy is the
ability of the person potentially exposed to HIV to return to collect further doses
of medicine. This is something that should be evaluated as part of the process of
assessing the risk of the potential exposure to HIV.
The options for dispensing PEP at the initial consultation are as follows:
starter packs: an initial supply of medicine to last 17 days;
incremental dosing: providing medicine every week or two weeks to encourage
follow-up and to minimize possible waste of medicine; and
full 28-day dosing: supplying the full 28-day course of medicine at the initial
visit, which may maximize the likelihood of completing the course if follow-up is
a concern.
Starter packs
Starter packs are suited for use in emergency department settings. They usually
contain sufficient medicine to cover the first few days of the PEP course (17
days) and are prescribed under the condition that the person receiving the
medicine return to a designated clinic within 13 days to undergo complete risk
assessment and HIV testing and counselling and to collect the rest of the course of
medicine. Using starter packs is often favoured as it generally means that less

medicine is wasted. For example, if the person decides for whatever reason not to
continue with PEP, the rest of the course that might otherwise have been
prescribed is not wasted. In addition, using starter packs means that non-specialist
facilities need only stock small amounts of medicine, and thus less stock is wasted
if it is not used by the expiry date. A second advantage of this dispensing strategy,
which requires timely follow-up to obtain the remainder of the medicine, is that it
affords an experienced clinician the opportunity to discuss adherence, thus
maximizing the likelihood that the course of medicine will be completed as
prescribed. It also allows the decision to take PEP to be re-evaluated in light of
results of testing the source person (if available) and risk assessment by an
experienced clinician who may be less likely to prescribe it inappropriately (such
as for low-risk exposure).
The primary concern associated with initiating PEP before the result of an HIV
test is known is the risk of developing resistance to antiretroviral therapy among
people who are not aware that they are infected with HIV and who are given a
two-drug regimen. Resistance is unlikely to develop with starter packs given the
short duration of treatment. PEP is discontinued if the exposed person is later
found to be HIV-positive. Incremental dosing
Many PEP programmes opt to dispense two weeks worth of medicine at any one
visit. In much the same way as starter packs do, incremental dispensing strategies,
which mean that people have to return during the course, facilitate monitoring of
adherence and side effects and provideopportunities for additional counselling and
support.
Full 28-day dosing In some instances, providing the full 28-day dosing of PEP
medicine maximizes the likelihood of
completing the course. In emergency settings, for refugees or internally displaced
people and individuals who do not have ready access to health care facilities (such
as those living in rural areas) and/or have dependants (such as children), there are
valid reasons for dispensing a full 28-day course of PEP at the initial visit,

whether the individual consents to HIV testing or not. The main disadvantage of
supplying a full course of this medicine at the initial visit is that it reduces
motivation to attend follow-up. For this reason, this strategy is often the least
preferred of the three options listed above. Differentiating between those who
have and those who have not had a baseline HIV test may be weighted when
deciding how much medicine to prescribe at the initial visit versus theneed for
follow-up and support and the risk of developing drug resistance when a two-drug
regimen containing lamivudine is prescribed to a person who is already infected
with HIV.

The Bibliography

Abbas AK, Lichtman AH, Pillai, S. 2007. Cellular and Molecular Immunology.
6th ed.

Philadelphia : Saunders Elsevier.

Bloch KC. Infectious Diseases In : Mc Phee SJ, Ganong WF. Pathophysiology of

Disease. Fifth Edition. New York.
Kasper, Braunwald, Fauci, Hauser, Longo, Jameson(Editors). Sepsis and Septic
Shock. Harrisons Manual Of Medicine, 16 th Edition, Mc Graw Hill,
2005