Our Lady of Fatima University

College of Medicine
Department of Biochemistry

Written Report on Laboratory Conference:

Acquired Immunodeficiency Syndrome (AIDS)

1st Year, Section B1 Group 10

Sacabin, Ivy
Tinonas, Apple Gay
Ty, Crestherose
Uy, Ann Renette
Valero, Cherry Anne
Yaco, Joyce Ann
Learning Objectives:

1. Describe Human Immunodeficiency Virus (HIV)

2. Describe the genome of HIV
3. Differentiate HIV from other viruses
4. Discuss the life cycle of HIV
5. Discuss the significance of co-receptors in HIV infection
6. Enumerate the different diagnostic tests used to detect HIV infection
7. Define Acquired Immunodeficiency Syndrome
8. Discuss the different stages of HIV infection
9. Identify drugs used to treat AIDS and describe the mechanism of activity at molecular level
10. Discuss other possible approaches at the molecular level that can be utilized for the prevention
and management of AIDS
11. Determine availability of vaccine against AIDS

Topic Outline

A. Human Immunodeficiency Virus

1. Description of the virus and its genome
2. HIV Replication
3. Significance of Co-receptors of HIV
4. Diagnostic tests for HIV infection
B. Acquired Immunodeficiency Syndrome
1. Definition
2. Stages of HIV infection
3. Drugs used to treat HIV/AIDS and their mechanism
4. Possible approaches for the prevention and management of AIDS
5. Vaccine against AIDS
A. Human Immunodeficiency Virus (HIV)

1. Description of the virus and its genome

Human Immunodeficiency Virus (HIV) can lead to the disease AIDS (acquired
immunodeficiency syndrome). HIV attacks the bodys immune system, specifically the CD4 cells (T
cells), which help the immune system fight off infections. If left untreated, HIV reduces the number of
CD4 cells (T cells) in the body, making the person more likely to get infections or infection-related
cancers. Over time, HIV can destroy so many of these cells that the body cant fight off infections and
disease. These opportunistic infections or cancers take advantage of a very weak immune system and
signal that the person has AIDS, the last state of HIV infection.

The HIV-1 virion (Fig. 1) is an enveloped structure containing 72 external spikes.These

spikes are formed by the two major viral envelope proteins, gp120 and gp41. (gp stands for
glycoproteinproteins linked to sugarsand the number refers to the mass of the protein, in
thousands of daltons.) The HIV-1 lipid bilayer is also studded with various host proteins, including
class I and class II major histocompatibility complex molecules, acquired during virion budding.The
cone-shaped core of HIV-1 contains four nucleocapsid proteins (p24, p9, p7) each of which is
proteolytically cleaved from a 53 kDa gag precursor by the HIV-1 protease.The phosphorylated p24
polypeptide forms the chief component of the inner shell of the nucleocapsid, whereas the p17 protein
is associated with the inner surface of the lipid bilayer and stabilizes the exterior and interior
components of the virion.The p7 protein binds directly to the genomic RNA through a zinc finger
structural motif and together with p9 forms the nucleoid core.The retroviral core contains two copies
of the single stranded HIV-1 genomic RNA that is associated with the various preformed viral
enzymes, including the reverse transcriptase, integrase, ribonuclease, and protease.

Fig.1 HIV virion

HIV Genome
The HIV RNA genome contains three major genes: gag, pol, and env (Fig. 2).
The gag gene encodes p17 (MA), p24 (CA), and p7 (NC) (core and matrix proteins). The pol
gene encodes reverse transcriptase, protease, integrase, and ribonuclease. Finally, the env gene
encodes gp41 (TM) and gp120 (SU) (transmembrane and surface proteins).
Genes for additional regulatory and accessory proteins of diverse function are located
between the pol and env genes. Listed below are the accessory genes and its functions:
 Fig.2 HIV genome

Table 1. Accessory genes and functions

Accessory Genes
tat (transcriptional activator)
rev (regulation of gene expression)
vif (viral infectivity factor)
nef (negative effector)
vpr (viral protein r)
vpu (viral protein u)
Function
Required for elongation of viral transcripts
Promotes nuclear export of incompletely spliced viral RNAs
Promotes viral replication;
Overcomes inhibitory effect of host cell enzyme
(APOBEC3G)
Downregulates host cell CD4 and class 1 MHC expression;
Enhances release of infectious virus factor tetherin
Increases viral replication;
Promotes HIV infection of macrophages;
Blocks cell cycle progression
Downregulates host cell CD4 expression; Enhances virus
release from host cell; Counteracts host restriction

HIV difference from other viruses

HIV belongs to the primitive Lentivirus (genus of Retroviridae) group consisting of ss RNA,
enveloped icosahedral nucleocapsid, glycoprotein envelope and reverse transcriptase. Retroviruses
store their genetic information in molecules of ribonucleic acid (RNA). However, unlike other RNA
viruses, retroviruses use RNA as a template (master pattern) for forming deoxyribonucleic acid
(DNA), the genetic material that puts viral replication instructions into effect. This process, called
reverse transcription, is the exact opposite of the normal flow of genetic information in living things
in which DNA serves as the template for RNA formation. Lentiviruses has the ability to integrate into
the host chromosome and evade the host immunity causing ability to infect immune cells
(macrophages, and in case of HIV, T cells). HIV glycoprotein molecules are specific for CD4 in the
host cell membrane, attacking CD4+ T-cells.
 2. HIV Replication

The first phase of HIV replication, which includes viral entry, reverses transcription and
integration of the virus into the host genome, is accomplished by proteins provided by the virus.
The second phase of replication, which includes the synthesis and processing of viral
genomes, mRNAs, and structural proteins, uses the host cell machinery for transcription and protein
synthesis. The end result of HIV replication in most cell types is cell death (Fig. 3).

1. Attachment to a specific cell surface receptor: Attachment is accomplished via the gp120
fragment of the env gene product on the HIV surface, which preferentially binds to a CD4
receptor molecule therefore; the virus infects helper T cells, Lymphocytes, Monocytes, And
Dendritic Cells, which contain this protein in their cell membranes.
2. Entry of virus into the cell: An additional co-receptor, a Chemokine receptor, is required for
entry of the viral core into the cell. Two Chemokine receptors that are in work by HIV as co-
receptors are CCR5 and CXCR4, which are expressed differentially on different cell types.
Binding to a co-receptor activates the viral gp41 gene product, triggering synthesis between
the viral envelope and the cell membrane (Fig. 4).
3. Reverse transcription of viral RNA: After entering the host cell, the HIV RNA is
transcribed into DNA by reverse transcriptase. An RNA-directed DNA polymerase that enters
host cells as part of the viral nucleocapsid. A host cellular transfer RNA is hydrogen-bonded
to a specific site on each viral RNA molecule for initiation of reverse transcription.
4. Integration of the provirus into host cell DNA: The provirus is Virion Core associated
components and transported to the nucleus with the aid of p17 (MA). In the nucleus, viral
integrase cleaves the chromosomal DNA and covalently inserts the provirus randomly with
respect to the site of integration in the recipient DNA that becomes a stable part of the cell
genome and can never be eliminated. Therefore, HIV has two genomic forms: namely,
single-stranded RNA present in the extracellular virus and pro-viral double-stranded DNA
within the cell.
5. Transcription and translation of integrated viral DNA sequences: The provirus is
transcribed into a full-length mRNA by the cell RNA polymerase II. In all retroviruses, one of
the spliced mRNAs is translated into the envelope proteins. In the complex viruses, such as
HIV and HTLV, additional spliced molecules produce accessory proteins that are important in
regulating transcription and other aspects of replication.
6. Assembly and maturation of infectious progeny: Assembly begins as the genomes and
uncleaved Gag and Gag-Pol polyproteins associate with the TM-modified plasma membrane.
As the virion buds from the surface, viral protease is activated and cleaves the polyproteins
into their component proteins, which then assemble into the mature virion. Cleavage is a
necessary step in the maturation of infectious virus.

Tropicity of HIV to CD4 T Cells

The HIV glycoprotein molecules in its outer membrane, gp41 and gp120, are specific for their
specific receptors on a human cell membrane. These receptors are CD4 and a co-receptor called
CCR5 that permits docking with the host cell and fusion with the cell membrane. One of them, the
gp120 envelope protein, participates in HIV-1 attachment to CD4 cells: Macrophages, Dendritic
Cells, and Monocytes. Dendritic cells are present throughout the bodys mucosal surfaces and bear the
CD4 protein.
 Fig.3 HIV Replication

Fig.4 Entry of HIV into Host Cell

3. Significance of Co-receptors of HIV

A co-receptor is a cell surface receptor that binds a signalling molecule in addition to a

primary receptor in order to facilitate ligand recognition and initiate biological processes, such as
entry of a pathogen into a host cell (Fig. 5).

The primary cellular receptor for HIV entry is CD4. However, expression of CD4 on a target
cell is necessary but not sufficient for HIV entry and infection. Several chemokine receptors act as co-
factors that allow HIV entry when co-expressed with CD4 on a cell surface, such as CCR5 and
CXCR4 appear to be the two major co-receptors for HIV entry into cells. The first of these to be
identified was CXCR4, or fusin, which is expressed on T cells. Co-expression of CXCR4 and CD4 on
a cell allow T-tropic HIV isolates to fuse with and infect the cell. HIV gp120 interacts with both CD4
and CXCR4 to adhere to the cell and to effect conformational changes in the gp120/gp41 complex
that allow membrane fusion by gp41. CXCR4 is expressed on many T cells, but usually not on
macrophages and does not allow fusion by macrophage-tropic (M-tropic) HIV isolates. CCR5 is
expressed on both Macrophages and T cells and may be infected by the macrophage-trophic HIV
isolate. This is the HIV isolate seen in most cases.

Fig.5 Chemokine Receptors/ Co-receptors

4. Diagnostic tests for HIV infection

Blood tests are the most common way to diagnose HIV. These tests look for antibodies to the
virus that the body creates in an attempt to fight the virus.
People exposed to the virus should get tested immediately, although it can take the body
anywhere from six weeks to a year to develop antibodies to the virus. Follow-up tests may be needed
depending on the initial time of exposure.
Early testing is crucial. If you test positive for the virus, you and your doctor will discuss and
develop a treatment plan that can help fight HIV and ward off complications. Early testing also can
alert you to avoid high-risk behavior that can spread the virus to others.

WHO has defined five key componentsthe 5 Csthat must be respected and adhered to by all
HTC services. These components are:

Consent
Confidentiality
Counselling
Correct test results
Connection/linkage to prevention, care and treatment.

It should also include sufficient and appropriate information and access to prevention services
for individuals who test HIV negative or HIV positive. HTC services should also include referrals to
medical and psychosocial support services for people diagnosed as HIV positive. Testing for HIV
without informed consent is unethical and violates human rights.
Specific Guidelines

1. Conduct of Pre - HIV Test Counseling

i. Client - Initiated Counseling and Testing

a) All clients who want to be tested for HIV shall be provided with pre - HIV test
counseling in a space where privacy could be observed and confidentiality ensured.

b) Pre- HIV test counseling shall either be conducted in individual or group settings.
Clients shall be strongly encouraged to bring their confidants during the pre- and post-
HIV test counseling.

c) The same counselor is highly recommended to conduct both pre and post-test
counseling and, if needed, follow- up session for a client.

d) Adult clients shall be counseled in a setting that is safe and secure for both councelor
and client.

e) Pre- and post-HIV test counseling of children shall take into consideration the
maturity of the client and when necessary, responsible parents or a legal guardian,
including any registerd social worker, shall be involved.

f) Counselors shall ensure that clients understand the information printed on the consent
form. All necessary and correct information that clients need to make decisions
for themselves shall be provided.

g) Counselors shall strongly encourage follow-up counseling sessions and ensure that
clients utilize referral networks that are in place and functional.

h) All counselors shall have basic knowledge on voluntary blood donation and
incorporate facts on the blood donation and incorporate facts on blood donation when
appropriate.

ii. Provider-Initiated Counseling and Testing

a) As part of medical management, HIV testing shall be offered by health care provider
to all the following;
1) Clients assesed for STI in an STI clinic or elsewhere;
2) Pregmant woman with one or more of the following HIV risk;
i. Multiple sex partners
ii. Person who inject drugs (PWID)
iii. History of STI, including a diagnosis of syphilis
iv. Husband or partner has multiple sex partners, history of STI or
is a known PWD
3) People assesing community-based services designated for males
having sex with males, people in prostitution and those who inject drugs
 4) Diagnosed TB patients, as discussed in AO 2008-00022, otherwise
known as Policies and Guidelines in the Colaborative Approach of
TB and HIV Prevention and Control,
5) Patients showing signs and symptoms consistent with HIV-related
diseases or AIDS seen by attending physician.
6) Parents/Guardian of all children born to HIV infected mothers (or
those with possible exposure)

b) Basic conditions on confidentiality, informed consent, and counseling shall be

adhered to.
c) Pre-HIV counseling shall be limited to basic information-giving that would help the
patient decide whether to accept HIV testing.

d) Post-HIV test counseling shall be provided to all clients tested by trained personnel.

e) Counselors providing post test counseling services shall emphasize prevention for
those that tested negative and, medical and psychosocial support to those that tested
positive.

f) The capacities for pre and post HIV test counseling including the capacity to
provide medical and psychosocial support shall be enhanced and the referral
networks between and among these providers shall be functional.

2. Conduct of HIV Testing

Only registered medical technologist with HIV proficiency training shall perform the
HIV test using Food and Drug Administration (FDA) registered test kits. Other screening
tests may be performed including but not limited to Enzyme Immunoassay (EIA), Particle
Agglutination (PA) and Rapid Assay (RA), Reactive samples from clients/patients shall be
brought to the STD/AIDS Central Cooperative Laboratory (SACCL) at the San Lazaro
Hospital for confirmatory testing. For reactive blood units (not person) from blood banks,
samples shall be referred to the Research Institute for Tropical Medicine (RITM) for
confirmatory testing.

3. Release and Reporting of Test Result

Samples reactive to screening test shall not be reportedly directly to the client/patient.
All reactive samples shall be referred for confirmatory testing. The reference laboratories
namely SACCL and RITM shall not release the result of the confirmatory test directly to the
patient/client under any circumstance but must send the result to the referring HIV testing
facility. This is to ensure that the release of the HIV test shall be accompanied by post-test
counseling especially if the result is positive. SACCL and RIITM are required to report the
confirmed positive samples to the National Epidemiology Center (NEC).

It is the responsibility of the BSF to ensure that donors have been screened properly and
pre-donation counseling has been provided to all potential blood donors in order to prevent
the occurence of reactive and positive samples by eliminating those individual with high risk
behaviors. For confirmed positive blood units, tracing the donor and informing her/him of
 the result is not recommended. Providing result to a free HIV test can put the blood supply
at risk as high risk individuals within the window period may avail of this free services.
Information campaign on HIV services available and stigma reduction activities will be
intensified by CHD in areas where positive blood units are identified.

4. Conduct of Post - HIV test Counseling

Post-HIV test counseling shall be provided together with the release of the test result
whether the test is negative or positive. It shall be done in an enclosed space where
counseling can be done in privacy. It is recommended that the trained counselor who
performed the pre-test counseling shall also provide the post-test counseling.

HIV Testing Protocol in the Philippines

A. Take the HIV Test.

1. If the result is Non-Reactive (Negative), repeat the test after 3 months. If still non- reactive,
you can repeat the test after 1 year.
2. If the result is Reactive (Positive):
a. Go to the nearest HIV Treatment Hub
b. Take the initial lab tests required including CD4. Most hubs wont require the initial
Viral Load (VL) but it is best that you get it for baseline information.

B. Result of Labs
1. If you have infections, get treatment
2. If your CD4 is above 350, come back after 6 months.
3. If your CD4 is below 350, ARV's will be prescribed:
a. You will undergo a 2 week trial period. If there are no adverse effects (side effects),
you will continue with the ARV's. If there are adverse effects, your HIV doctor will
change your ARV's.
b. Prophylaxis is usually given if CD4 is below 200.

C. ARV Treatment
1. If you don't have adverse effects from your ARV's after the trial period, you will be given 1
to 3 month supply of your ARV's.
2. Come back to the treatment hub for your refill of your ARV's a week before you run out

D. CD4 and VL Testing

1. CD4 test is repeated every 6 months (after the last CD4 count)
2. Viral Load Test is repeated every year. The VL test should be taken together with the initial
CD4 test and should be taken a year after the last VL.
Primary Tests for Diagnosing HIV & AIDS

1. Home Tests

The first type of home testing kit involves pricking the finger to collect a blood sample, sending
the sample to a licensed laboratory, and then calling in for results as early as the next business day.
This test is anonymous. If the test is positive, a follow-up test is performed right away, and the
results include the follow-up test. The manufacturer provides confidential counseling and referral to
treatment. The tests conducted on the blood sample collected at home find infection later after
infection than most lab-based tests using blood from a vein, but earlier than tests conducted with oral
fluid.
Another testing procedure involves swabbing the mouth for an oral fluid sample and using a kit
to test it. Results are available in 20 minutes. If tested positive, a follow up test will be needed. The
manufacturer provides confidential counseling and referral to follow-up testing sites. Because the
level of antibody in oral fluid is lower than it is in blood, oral fluid tests find infection later after
exposure than do blood tests. Up to 1 in 12 infected people may test false-negative with this test.

2. ELISA Test

ELISA, which stands for enzyme-linked immunosorbent assay, is used to detect HIV infection.
If an ELISA test is positive, the Western blot test is usually administered to confirm the diagnosis. If
an ELISA test is negative, but you think you may have HIV, you should be tested again in one to
three months.

ELISA is quite sensitive in chronic HIV infection, but because antibodies aren't produced
immediately upon infection, you may test negative during a window of a few weeks to a few months
after being infected. Even though your test result may be negative during this window, you may have
a high level of the virus and be at risk of transmitting infection.

The blood sample will be sent to a laboratory for analysis. For the ELISA test, a lab technician
adds the sample to a petri dish containing HIV antigen. An antigen is any foreign substance, such as
a virus, that causes your immune system to respond. If your blood contains antibodies to HIV, it will
bind with the antigen. The technician will check this by adding an enzyme (a protein that helps speed
up chemical reactions) to the petri dish and watching how your blood and the antigen react. If the
contents of the dish change color, you may have HIV.

3. Western Blot

This is a very sensitive blood test used to confirm a positive ELISA test result. The general
process of a Western blot test is similar to the ELISA. However, the Western blot method is more
complicated. It involves separating the HIV sample into its component proteins using an electrical
current. Then, these proteins are transferred to a special kind of paper (blotting), and reacted with your
blood sample. An enzyme is used to cause color change and detect antibodies.
 The Western blot assay is a method in which individual proteins of an HIV-1 lysate are
separated according to size by polyacrylamide gel electrophoresis. The viral proteins are then
transferred onto nitrocellulose paper and reacted with the patient's serum. Any HIV antibody from the
patient's serum is detected by an antihuman immunoglobulin G (IgG) antibody conjugated with an
enzyme that in the presence of substrate will produce a colored band. Positive and negative control
serum specimens are run simultaneously to allow identification of viral proteins (Fig. 6).

Fig.6 Procedures done in creating a western blot

strips.

HIV, like any other virus, is composed of a number of different proteins. The Western blot
positive control lane contains proteins from a patient sera as well as HIV proteins. HIV positivity can
therefore only be confirmed by the presence of the following types of proteins:

Table 2. Viral Proteins

gp160 viral envelope precursor (env)
gp120 viral envelope protein (env) binds to CD4
p24 viral core protein (gag)
p31 reverse transcriptase (pol)

Band Pattern Interpretation

Background information on the HIV Western blot test. In 1987 the Centers for Disease Control
along with several others organizations established criteria for serologic interpretation of HIV
Western blot tests. The criteria are listed below:
Table 3. Band Pattern Interpretation

No bands present Negative

Bands at either p31 OR p24 AND bands present at either gp160 Positive
OR gp120
Bands present, but pattern does not meet criteria for positivity Indeterminate

Band pattern Interpretation

(Fig. 7)
1. Lane 1, HIV+
serum (positive control)
2. Lane 2, HIV- serum
(negative control)
3. Lane A, Patient A
4. Lane B, Patient B
5. Lane C, Patient C

Fig.7 HIV Western Blot Banding Pattern

4. Viral Load Test

This test measures the amount of HIV in your blood. Generally, it's used to monitor
treatment progress or detect early HIV infection. Three technologies measure HIV viral load In the
blood:

The PCR (polymerase chain reaction) method uses an enzyme to multiply the HIV in the
blood sample. Then a chemical reaction marks the virus. The markers are measured and used to
calculate the amount of virus. This is the most widely used viral load test.
The bDNA (branched DNA) method combines a material that gives off light with the
sample. This material connects with the HIV particles. The amount of light is measured and
converted to a viral count. Bayer produces this test.
The NASBA (nucleic acid sequence based amplification) method amplifies viral proteins
to derive a count
The basic principles of these tests are similar. HIV is detected using DNA sequences that
bind specifically to those in the virus. It is important to note that results may vary between tests.
Viral load results are reported as copies of HIV in one milliliter of blood. The lower the number, the
less virus there is in your blood. Numbers can range from about one million copies to as few as 50
copies. If you have less than 50 copies, your health care provider may tell you that your results are
undetectable. Being undetectable is the best result because it means your virus is under control.
However, undetectable does not mean that you have been cured of HIV; it just means that there is not
enough virus for the test to measure (below 50 copies).
B. Acquired Immunodeficiency Syndrome (AIDS)

1. Definition

Acquired Immunodeficiency syndrome (AIDS) is a term which applies to the most advanced
stages of HIV Infection. It is defined as occurrence of any or more than 20 opportunistic infections or
HIV-related cancer. The CD4 count of an uninfected adult / adolescent who is generally in good
health ranges from 500 cells/mm3 to 1,600 cells/mm3.

2. Stages of HIV Infection

Table 4. Categorization of HIV / AIDS is based on the lowest documented CD4 Cell Count

Stages CD4 Values

Primary HIV Infection 500 cells/l

Clinical Stage 1 Acute/ Early/ Mild 350 499 cells/l

Clinical Stage 2 Intermediate/ Latent/ Chronic 200 - 349 cells/l

Clinical Stage 3 - Advanced/ Crisis (AIDS) <200 cells/l

The clinical course of HIV infection is divided into 3 phases: Acute Phase, Chronic Phase, & Crisis
Phase (Fig. 8).

The acute phase represents the initial response of an immunocompetent adult to HIV
infection. Clinically, this phase typically manifests as a self-limited illness that develops in 50% to
70% of affected persons 3 to 6 weeks after infection; it is characterized by nonspecific symptoms
including sore throat, myalgia, fever, rash, and sometimes aseptic meningitis. This phase is also
characterized by high levels of virus production, viremia, and widespread seeding of the peripheral
lymphoid tissues, typically with a modest reduction in CD4 + T cells. Soon, however, a virus-specific
immune response develops, evidenced by seroconversion (usually within 3 to 17 weeks of exposure)
and by the development of virus-specifi CD8 + CTLs. As viremia abates, CD4 + T cells return to
nearly normal numbers. However, the reduction in plasma virus does not signal the end of viral
replication, which continues within CD4 + T cells and macrophages in the tissues (particularly
lymphoid organs).

The middle, chronic phase represents a stage of relative containment of the virus. The
immune system is largely intact at this point, but there is continued HIV replication that may last for
several years. Patients either are asymptomatic or develop persistent lymphadenopathy, and minor
opportunistic infections such as thrush (Candida) or herpes zoster. During this phase, viral replication
in the lymphoid tissues continues unabated; thus, there is no true microbiologic latency in HIV
infection. The extensive viral turnover is associated with continued loss of CD4 + cells, but a large
proportion of the CD4 + cells is replenished and the decline of CD4 + cells in the peripheral blood is
modest. After an extended and variable period, the number of CD4 + cells begins to decline, the
proportion of the surviving CD4 + cells infected with HIV increases, and host defenses begin to
wane. Persistent lymphadenopathy with signifiant constitutional symptoms (fever, rash, fatigue)
reflcts the onset of immune system decompensation, escalation of viral replication, and the onset of
the crisis phase.

The final, crisis phase is characterized by a catastrophic breakdown of host defenses, a

marked increase in viremia, and clinical disease. Typically, patients present with fever of more than 1
months duration, fatigue, weight loss, and diarrhea; the CD4 + cell count is reduced below 500 cells/
L. After a variable interval, serious opportunistic infections, secondary neoplasms, and/or neurologic
manifestations (so-called AIDS-defiing conditions) emerge, and the patient is said to have fullblown
AIDS. Even if the usual AIDS-defiing conditions are not present, Centers for Disease Control and
Prevention (CDC) guidelines defie any HIV-infected person with CD4 + counts of 200 cells/ L or
less as having AIDS. In the absence of treatment, most patients with HIV infection develop AIDS
after a chronic phase lasting 7 to 10 years.

Fig.8 Clinical Course of Infection

Clinical Staging of HIV/AIDS for Adults and Children (WHO)

Table 5. Clinical Staging of HIV / AIDS based on WHO.

STAGE MANIFESTATION

Primary HIV Infection Asymptomatic

Acute Retroviral Syndrome

Clinical Stage 1 Asymptomatic

Persistent Generalized Lymphadenopathy

Clinical Stage 2 Moderate unexplained weight loss (10% of BW)

Recurrent respiratory tract infections (sinusitis, bronchitis, otitis
media, pharyngitis)
Herpes zoster
Angular cheilitis
Recurrent oral ulcerations
Papular pruritic eruptions
Secorrhoeic dermatitis
Fungal nail infections of fingers

Clinical Stage 3 Severe weight loss (>10% of BW)

Unexplained chronic diarrhea >1 month
Unexplained persistent fever
Oral candidiases
Oraal hairy leukoplakia
Pulmonary tuberculosis for the last 2 years
Severe presumed bacterial infections (pneumonia, empyema,
pyomyositis, bone/joint infection, meningitis, bacteremia)
Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis

Clinical Stage 4 HIV wasting syndrome

Pneumocystis pneumonia
Recurrent severe or radiological bacterial pneumonia
Chronic herpes simplex infection
Esophageal candidiasis
Extrapulmonary Tuberculosis
Kaposis Sarcoma
CNS Toxoplasmosis
HIV encephalopathy
 3. Drugs used to treat HIV/AIDS and their mechanism

Drugs to inhibit infection and replication by the AIDS virus have been an intense focus of
research. More than 200 drugs are in development or clinical trials, and approximately 60 drugs have
been formally approved by the Food and Drug Administration for HIV therapy. There are 4 classes of
anti-retroviral drugs that are classified according to the enzyme they are blocking in order to inhibit
HIV replication/maturation (Fig. 9).

Early Inhibitors
CCR5 Antagonist- Inhibits the binding of glycoprotein (gp120) to CCR5. Blocks HIV
glycoprotein from binding with CCR5 chemokine receptor.
Example: Maraviroc
Fusion Inhibitor- Inhibits the fusion of HIV to host cell. Blocks gp120 receptor in HIV
envelope from fusing with the CD4 in host cell.
Ex. Fuzeon

Nucleoside Analogs/Reverse Transcriptase Inhibitors

Inhibits the Reverse Transcriptase Enzyme. Interrupt the HIV multiplication cycle by either
mimicing the structure of actual nucleosides (NRTI) or binding to enzyme and restructures it
(NNRTI). As a result, viral replication and the viral cycle are terminated

Integrase Inhibitors
Inhibits the Integrase Enzyme. Attaches to the integrase enzyme preventing the formation of
the provirus and block future virus multiplication in that cell.
Ex. Raltegravir, Elvitegravir, Dolutegravir

Protease Inhibitors (PIs)

Inhibits the Protease Enzyme. Blocks the cleavage of long immature proteins to smaller
functional viral proteins.
Ex. Tipranavir, Indinavir, Saquinavir, Fosamprenavir, Ritonavir, Darunavir,
Atazanavir, Nelfinavir, Lopinavir + Ritonavir

Highly Active Anti-Retroviral Therapy (HAART)

The most effective regimen in controlling AIDS and inevitable drug resistance. Uses two
reverse transcriptase inhibitors plus one protease inhibitor in a cocktail. The virus is
interrupted in two different phases of its cycle
 Fig.9 Mechanism of Action of Anti-retroviral Drugs.

4. Possible approaches for the prevention and management of AIDS

Killing and Inactivation

1. Heat in solution at 56C within 10-20 mins

2. Lyophilize protein at 68C after 2 hrs

3. Disinfection extreme pH (1.0 & 13.0); 50% ethanol, 35% isopropanol,

0.5% paraformaldehyde, 0.3% H202, & 0.5% Lysol

4. Drying - HIV dried in a salt solution on stainless steel surfaces

 5. Vaccine Against AIDS

From the very first years of the AIDS epidemic, the potential for a vaccine has been regarded
warily, because the virus presents many seeming insurmountable problems.

Factors affecting difficulty of vaccine development

HIV becomes latent in cells

HIV cell surface antigens mutate rapidly
HIV infection is not completely controlled by immune responses
Absence of useful small animal model
HIV vaccine cannot consist of attenuated virus
High degree of variation in viral isolates from different patients

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