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Ending the HIVAIDS Pandemic Follow the Science

Anthony S. Fauci, M.D., and Hilary D. Marston, M.D., M.P.H.


N Engl J Med 2015; 373:2197-2199December 3, 2015DOI: 10.1056/NEJMp1502020
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In July 1996, researchers, policymakers, and activists involved in the fight against HIVAIDS met in Vancouver,
Canada, for the 11th International Conference on AIDS. During that historic meeting, practitioners and patients heard
evidence regarding a powerful weapon to stop the relentless onslaught of the human immunodeficiency virus (HIV):
combination antiretroviral therapy (ART), with a protease inhibitor as the centerpiece of the regimen. In the nearly 20
years since that watershed meeting, the early promise of durable effects from combination therapy has been realized
for many patients: between 2000 and 2014, the rollout of ART saved an estimated 7.8 million lives worldwide.
Despite this success, the timing of ART initiation has remained the subject of intense debate. As with any therapy,
clinicians and their patients weighed ART's benefits against its risks, and the results of that calculus seemed to depend
on the patient's stage of illness. Specifically, evidence supporting treatment later in the course of HIV infection, when the
CD4+ T-cell count fell below a certain critical level, seemed far stronger than that supporting early treatment (particularly
given the toxic effects associated with the first approved antiretroviral drugs). Today, a series of well-designed efficacy
studies conducted over a period of more than a decade has fundamentally changed this discussion.
In addition, researchers continue to accrue promising data on the concept of using ART for HIV prevention in HIVnegative persons preexposure prophylaxis (PrEP). Findings from the landmark Intervention Prventive de
l'Exposition aux Risques avec et pour les Gays (IPERGAY) study, now reported in the Journal (pages 22372246),
demonstrate the safety and efficacy of on-demand PrEP for men who have sex with men and transgender women
(persons who are born male but identify as female), who are at high risk for HIV infection. In this study, persons who
took PrEP in an event-driven manner around the time of sexual activity were 86% less likely to acquire HIV infection
than those taking placebo.
Taken together, these studies have shown definitively that the benefits of prompt initiation of ART regardless of the
CD4+ T-cell count outweigh the risks, for both the infected person and uninfected sexual partners and that PrEP can
be implemented in a way that is both acceptable to patients and safe and effective in blocking HIV transmission.
With regard to ART initiation, three critical questions were asked and answered by a trifecta of large international
randomized, controlled trials over the course of a decade. First, practitioners, including ourselves, and patients had
worried about the risks of toxic effects of long-term ART, particularly on the cardiovascular system, and wondered
whether long-term treatment was worse than the virus itself for some patients. Moreover, practical concerns about the
cost and inconvenience of ART loomed large, as did the related risks of poor adherence and the potential emergence of
resistant virus.
The first of the relevant seminal studies, the Strategies for Management of Antiretroviral Therapy (SMART) study
published in 2006,1 was designed to answer the clinical question about toxic effects. Researchers randomly assigned
5472 HIV-infected participants in 33 countries with initial CD4+ counts above 350 cells per cubic millimeter to receive
continuous therapy (viral-suppression group) or episodic therapy (drug-conservation group); treatment was initiated
when CD4+ T-cell counts fell below 250 per cubic millimeter and stopped when counts rose above 350 per cubic
millimeter. The study's primary analysis found a 160% higher risk of death, opportunistic illness, or both in the drugconservation group (P<0.001). Moreover, the risk of grade 4 toxic drug effects did not differ significantly between
groups, and cardiovascular events were actually more common in the drug-conservation group. The SMART study thus
demonstrated that the benefits of therapy far outweighed the risks of toxic effects. 1 The virus was worse than the drugs.

A second critical question was whether viral suppression could prevent forward transmission. If so, the benefits of
treatment would extend beyond the infected person to his or her uninfected sexual partners (and in the case of people
who inject drugs, potentially to those with whom they shared needles). Observational cohort studies among
serodiscordant couples strongly suggested that lower viral loads were associated with a reduced likelihood of forward
transmission.2 At the same time, surveillance studies demonstrated that the majority of transmissions could be traced to
persons with uncontrolled viremia. So the question arose whether therapy that suppressed the plasma viral load would
also result in lower transmission.
This question was definitively answered by a controlled, prospective clinical trial, the HIV Prevention Trials Network
(HPTN) 052 study, published in 2011.2 Its investigators enrolled 1763 HIV-serodiscordant, predominantly heterosexual
couples in nine countries with CD4+ T-cell counts between 350 and 550 per cubic millimeter, assigning half the infected
volunteers to immediate ART and half to deferred therapy (delayed until the CD4+ T-cell count fell below 250 per cubic
millimeter, or until development of an AIDS-related illness). Uninfected partners were tested quarterly for
seroconversion. The study documented a 96% reduction in HIV transmission in the immediate-therapy group as
compared with the deferred-therapy group.2 Combined with PrEP, taken regularly or possibly in an event-driven manner
by certain high-risk persons (as reported in the IPERGAY study), treatment as prevention could dramatically reduce the
incidence of HIV infection.
Although these findings regarding treatment as prevention clearly demonstrated the public health benefit of early
treatment, a third critical question was whether initiating treatment at normal or near-normal CD4+ T-cell counts actually
benefited the person being treated. It is true that many practitioners and a variety of treatment guidelines, particularly in
higher-resource environments, suggested consideration of treatment at higher CD4+ T-cell counts. However, conclusive
scientific evidence in the form of results from randomized, controlled clinical trials was limited. The answer to this third
question was therefore eagerly awaited.
In July 2015, the international AIDS community convened once again in Vancouver for another watershed moment
during which they heard the answer. In the Strategic Timing of Antiretroviral Treatment (START) study, which opened in
March 2011 in 35 countries, investigators randomly assigned 4685 patients with CD4+ T-cell counts of more than 500
per cubic millimeter to therapy initiated immediately or deferred until their CD4+ T-cell count fell below 350 per cubic
millimeter (or until AIDS-defining illness emerged).3 The study revealed that patients in the immediate-initiation group
were 57% less likely to develop serious illness (AIDS-related or otherwise) or die than those in the deferred-initiation
group. Risks of grade 4 toxic drug effects did not differ significantly between groups. Patients receiving immediate
therapy were more than 70% less likely to develop an AIDS-related illness and 40% less likely to develop severe non
AIDS-related illness (e.g., myocardial infarction). The TEMPRANO study conducted in Ivory Coast added weight to
these findings, also demonstrating the benefits of early treatment. 4
As a triad of critical clinical trials, SMART, HPTN 052, and START settle the debate concerning early initiation of ART.
Clinicians and patients can now be assured that ART's benefits outweigh the risks for the infected person, regardless of
CD4+ T-cell count. Public health officials can confidently support early treatment, recognizing the spillover public health
benefits for HIV prevention. Moreover, IPERGAY provides important new data that support the use of PrEP for
preventing HIV infection in high-risk populations.
Taken together, these studies provide an evidence-based blueprint for effective treatment and prevention of HIV
infection and will serve as critical tools in the fight to end the HIVAIDS pandemic. However, in order to realize that
promise, the political will must be mobilized to match the scientific evidence and provide the financial and human
resources necessary to dramatically scale up HIV testing and treatment around the world. The science has spoken.
There can now be no excuse for inaction.

TREATMENT AS PREVENTION (TASP)


TasP.jpg

Treatment as prevention (TasP) refers to HIV prevention methods that use antiretroviral treatment (ART) to
decrease the risk of HIV transmission. Antiretroviral treatment reduces the HIV viral load in the blood, semen,
vaginal fluid and rectal fluid to very low levels ('undetectable'), reducing the risk of onwards HIV
transmission.1
For a number of years now, there has been growing evidence of the benefits of HIV treatment as a prevention
method. In 2011 a landmark study, HPTN 052, showed early initiation of antiretroviral treatment in people
living with HIV with a CD4 count between 350 and 550, reduced HIV transmission to HIV-negative partners by
96%.2
A number of follow-up studies since have also reported significant reductions in HIV transmission, with new
infections averted as a result.3 4 5 6
This has led to the idea that treatment as prevention could be used as part of a 'test and treat' strategy increasing testing and treatment coverage to decrease community viral load and reduce the rate of new HIV
infections.7 8
Following the results of HPTN 052, Executive Director of UNAIDS Michel Sidib, commented:
"This breakthrough is a serious game changer and will drive the prevention revolution forward. It makes
HIV treatment a new priority prevention option." 9

HIV treatment is already being used as prevention


Prevention of mother-to-child transmission (PMTCT)
Treatment as prevention has been used since the mid-1990s to prevent mother-to-child transmission (PMTCT)
of HIV. In 1994, research showed how zidovudine reduced the vertical transmission of HIV from HIV-infected
mothers to their babies from 25% to 8%.10
Since then, testing pregnant women and treating HIV-positive mothers with antiretroviral drugs (ARVs) during
pregnancy, delivery and breastfeeding has been found to reduce the risk of a mother transmitting HIV to her
child by up to 90%.11
One study from the United Kingdom (UK) and Ireland found that pregnant women who received at least 14
days of treatment reduced the risk of transmitting HIV to their babies to less than 1%.12
Pre-exposure prophylaxis (PrEP)
Pre-exposure prophylaxis (PrEP) uses antiretroviral drugs to protect HIV-negative people from HIV before
potential exposure. Trials have shown that when taken consistently and correctly, PrEP is very effective.13 14
As a result, like TasP, it potentially has population-wide benefits. However, if not taken routinely and
consistently, PrEP is much less effective. It is important that PrEP is offered as part of a combination package of
prevention initiatives, and does not replace other, more effective methods like condoms.15
In 2015, the World Health Organization released new guidelines and a policy brief recommending that PrEP
should be offered as a choice to people who are at substantial risk of HIV infection. Previously, it was only
recommended for certain key affected populations such as sex workers, men who have sex with men and people
who inject drugs.16 17
Microbicides
Microbicides are gels or creams containing antiretroviral drugs that are applied to the vagina to help prevent
HIV infection. Vaginal microbicides are effective, so long as they are used consistently and correctly. One study
observed 39% fewer infections, but its findings have not been replicated.18

The main challenge is adherence in other words, creating a product that women who are at high risk of HIV
infection are able to use regularly. In this respect, the issues for microbicides and PrEP are comparable. In fact,
a microbicide gel is essentially a different way to deliver PrEP and is sometimes referred to as topical PrEP.19
There is also ongoing work into rectal microbicides suitable for use during anal sex.20
Post-exposure prophylaxis (PEP)
Post-exposure prophylaxis (PEP) is short-term antiretroviral treatment taken after possible exposure to HIV.
Since 1998, it has been used by healthcare workers who may have been exposed to HIV-infected fluids.21 More
recently, it has been used to treat those who may have been exposed during a single event (for example sexual
assault, unprotected sex or sharing drug injecting equipment).22
More research is needed into the effectiveness of PEP as an HIV prevention strategy. One trial from the mid1990s, which gave zidovudine to healthcare workers exposed to HIV, prevented transmission in 81% of
cases.23However, its use in PEP has since been replaced by tenofovir as a component of a three-drug
combination.24

Test and treat strategies


'Test and treat' programmes are based on the premise that the rate of new HIV infections can be reduced by
rolling out universal HIV testing in order to diagnose all people living with HIV, and initiate antiretroviral
treatment regardless of CD4 count or viral load.25
One study from South Africa estimated that the implementation of universal voluntary HIV testing for adults
over 15 years old would decrease HIV prevalence to 1% within 50 years.26
Trials testing the effectiveness of treatment as prevention for the general population in high HIV prevalence
settings are currently ongoing. The HPTN 071 study, known as PopART, is currently carrying out a large scale
trial in 21 communities across South Africa and Zambia.27
The trial aims to measure the costs and benefits of a combination package of interventions that includes door-todoor voluntary HIV testing and immediate treatment for HIV-positive individuals regardless of CD4 count. The
five-year project runs until 2017.28
A 2016 study in India among men who have sex with men and people who inject drugs found a clear correlation
between treatment, viral suppression and HIV incidence in large populations - although long-term follow up is
needed.29

Limitations of treatment as prevention


TasP is not 100% effective
Following the results of the HPTN 052 study, in 2013, the World Health Organization recommended that
antiretroviral treatment be offered to all people living with HIV who have uninfected partners to reduce HIV
transmission.30

However, even if all mixed status couples had access to treatment, it is widely agreed that this would not bring
an end to the epidemic. If the preventative benefits of treatment are overstated, people are more likely to engage
in high-risk behaviours. Research from Switzerland showed how increased access to antiretroviral treatment can
lead to a reduction in other HIV prevention measures such as condom use.31
Furthermore, a 2013 study from China of 38,000 mixed status couples reported that treating the HIV-infected
partners reduced the risk of HIV transmission to the uninfected partner by a comparatively low 26%.32 In the
HPTN 052 study, 30% of HIV-positive people had an external partner.33
More recently however, results from a four-year study conducted across 14 European countries, which observed
HIV serodifferent couples (where the HIV-positive partner was taking suppressive ART), found zero
transmissions after couples had sex 58,000 without a condom. The study, which included both straight and gay
couples, provides good evidence for the effectiveness of TasP. 34
Adherence is vital to its success
The success of treatment as prevention is highly dependent upon people adhering to their treatment. It is widely
agreed that once treatment is initiated it should not be interrupted, as incomplete viral suppression causes the
more sensitive strains of HIV to be suppressed and the resistant strains to become dominant. Resistant strains
are harder to treat.35
Adherence is an issue even where treatment is widely available. In 2011, one study from the United States of
America (USA) reported that 15 years after the initiation of highly active antiretroviral therapy (HAART), and
four years after the introduction of combination prevention, only 19% of 1.1 million people living with HIV in
the country had an undetectable viral load.36
In South Africa, which has the largest treatment programme in the world, a study found that only 64% of people
who were initiated on treatment between 2002 and 2007 were still in care three years on.37
Multidrug-resistant HIV
There are also concerns that the widespread use of antiretroviral treatment at a population level to reduce the
number of new HIV infections could lead to a significant increase in levels of multidrug-resistant HIV.
The dramatic scaling up of treatment could see increases in non-adherence resulting in the development of
resistant strains of the virus.38 One study from Los Angeles County, USA, reported that the use of 'test and treat'
among men who have sex with men could almost double the prevalence of multidrug-resistant HIV cases from
4.8% to 9.1% by 2023 among this group.39
Despite legitimate arguments about treatment adherence and drug resistance, many argue that interventions
should be implemented regardless given the prevention benefits and how existing combination treatment has
proved effective in suppressing viral load. Moreover, there remains a lot of scope to improve the current
delivery of treatment through improved monitoring of treatment adherence as well as strengthening the links
between treatment and care.40

The future of treatment as prevention


Treatment as prevention has a lot of potential in reducing population level rates of HIV transmission by
increasing uptake of HIV testing, offering treatment and linking people to care.41

However, its effectiveness relies, at least in part, on the willingness and ability of people on treatment to remain
in care and follow their prescribed course of antiretroviral drugs correctly. A number of studies have promoted a
combination of cognitive, behavioural and mixed interventions including emotional support as a means of
improving adherence.42 43 44
Others have suggested that more research is needed in order to identify the most effective way of delivering
TasP. Research from Botswana has modelled the benefits of targeting such a strategy at people with the lowest
CD4 counts.45
Bigger challenges and questions remain around its implementation in resource-limited settings. Its success
depends much upon the ability of a country's healthcare service to deliver these services.46 47 However, with
trials ongoing, the burden of adding treatment-based prevention to already strained healthcare systems remains
unknown.48
Ethical and public health concerns have also been raised about how limited supplies of antiretroviral drugs in
resource-limited countries are distributed - for treatment, prevention or both. One study concludes it is
"unethical to watch patients with treatable AIDS worsen and die, even with supportive care, so that medications
for treatment can be diverted for prevention."49 However, others maintain that while TasP requires large
financial investments and poses significant implementation challenges, it is potentially a highly cost-effective
approach to reducing both new HIV infections and the overall global HIV burden.50
Overall, there is wide support for treatment as an HIV prevention measure, especially in those with CD4 counts
under 350. Treatment for this group must be scaled up, with healthcare systems working to increase adherence
and retention in care.
It is widely acknowledged that treatment alone will not end the global HIV epidemic. In order to be effective,
treatment needs to be delivered as part of a comprehensive package of prevention methods including HIV and
sexual and reproductive health education, condom use and behaviour change.51
References
1.World Health Organization (WHO) (2012) 'Antiretroviral treatment as prevention (TASP) of HIV and TB'
2.Cohen, M.S. et al (2011) 'Prevention of HIV-1 Infection with Early Antiretroviral Therapy' The New England Journal
of Medicine 365(5):493-505
3.Baeten, J.M. et al (2012) 'Antiretroviral Prophylaxis for HIV Prevention in Heterosexual Men and Women' The New
England Journal of Medicine 367(5):399-410
4.Thigpen, M.C. et al (2012) 'Antiretroviral Preexposure Prophylaxis for Heterosexual HIV Transmission in
Botswana' The New England Journal of Medicine 367:423-434
5.Das, M. et al (2010) 'Decreases in Community Viral Load Are Accompanied by Reductions in New HIV Infections
in San Francisco' PLOS One 5(6):e11068
6.Rodger, A.J. et al (2016) 'Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent Couples
When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy', The Journal of the American Medical
Association, Vol 316, No.2
7.CATIE (2013) 'Treatment as prevention: do the individual prevention benefits translate to the population level?'

8.Solomon, S.S et al (2016) 'Community viral load, antiretroviral therapy coverage, and HIV incidence in India: a
cross-sectional, comparative study' The Lancet HIV 3(4): 183-190
9.UNAIDS (2011, 12 May) 'Groundbreaking trial results confirm HIV treatment prevents transmission of HIV'
10.Connor, E.M. et al (1994) 'Reduction of Maternal-Infant Transmission of Human Immunodeficiency Virus Type 1
with Zidovudine Treatment' The New England Journal of Medicine 331:1173-1180
11.Centers for Disease Control and Prevention (CDC) (2006) 'Achievements in Public Health: Reduction in Perinatal
Transmission of HIV Infection --- United States, 1985--2005' Morbidity and Mortality Weekly Report 55(21):582-597
12.Townsend, C.L. et al (2008) 'Low rates of mother-to-child transmission of HIV following effective pregnancy
interventions in the United Kingdom and Ireland, 2000-2006' AIDS 22(8):973-981
13.McCormack, S., et al (2014) Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD):
effectiveness results from the pilot phase of a pragmatic open-label randomised trial The Lancet 387(10013):53-60
14.San Francisco Department of Public Health, Population Health Division (2015) 'HIV Epidemiology Annual Report
2014'
15.UNAIDS (2015) Oral pre-exposure prophylaxis: putting a new choice in context
16.World Health Organization (WHO) (2015) 'Guideline on when to start antiretroviral therapy and on pre-exposure
prophylaxis for HIV'
17.World Health Organization (WHO) (2015) 'Policy brief: WHO expands recommendation on oral pre-exposure
prophylaxis of HIV infection (PrEP)'
18.Abdool Karim, S. et al (2010) Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the
Prevention of HIV Infection in Women Science 329(5996):1168-1174
19.Shattock, R.J. and Rosenberg, Z. (2012) 'Microbicides: Topical Prevention against HIV' Cold Spring Harbor
Perspectives in Medicince 2(2):a007385
20.Microbicide Trials Network (MTN) (2013, 2 October) 'Researchers Launch First-Ever Phase II Safety Study of a
Rectal Microbicide to Prevent HIV'
21.Henderson, D.K. and Gerberding, J.L. (1989) 'Prophylactic zidovudine after occupational exposure to the human
immunodeficiency virus: an interim analysis' The Journal of Infectious Diseases 160(2):321-327
22.Smith, D.K. et al (2005) 'Antiretroviral Postexposure Prophylaxis After Sexual, Injection-Drug Use, or Other
Nonoccupational Exposure to HIV in the United States' Morbidity and Mortality Weekly Report 54(2):1-20
23.Cardo, D.M. et al (1997) 'A CaseControl Study of HIV Seroconversion in Health Care Workers after
Percutaneous Exposure' The New England Journal of Medicine 337:1485-1490
24.British HIV Association (BHIVA) (2014, 10 September) 'Change to the recommended regimen for post-exposure
prophylaxis (PEP)'
25.World Health Organization (WHO) (2015) 'Guideline on when to start antiretroviral therapy and on pre-exposure
prophylaxis for HIV'
26.Granich, M.D. et al (2009) 'Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for
elimination of HIV transmission: a mathematical model' The Lancet 373(9657):48-57

27.Cori, A. et al (2014) 'HPTN 071 (PopART): A Cluster-Randomized Trial of the Population Impact of an HIV
Combination Prevention Intervention Including Universal Testing and Treatment: Mathematical Model' PLOS One
9(1):e84511
28.London School of Hygiene & Tropical Medicine 'HPTN 071 (PopART)' [accessed 12 April 2017]
29.Solomon, S.S et al (2016) 'Community viral load, antiretroviral therapy coverage, and HIV incidence in India: a crosssectional, comparative study' The Lancet HIV 3(4): 183-190
30.World Health Organization (2013) 'Consolidated guidelines on the use of antiretroviral drugs for treating and
preventing HIV infection'
31.Hasse, B. et al (2010) 'Frequency and determinants of unprotected sex among HIV-infected persons: the Swiss
HIV cohort study' Clinical Infectious Diseases 51(11):1314-1322
32.Jia, Z. et al (2013) 'Antiretroviral therapy to prevent HIV transmission in serodiscordant couples in China (200311): a national observational cohort study' Lancet 382(9899):1195-1203
33.Cohen, M.S. et al (2011) 'Prevention of HIV-1 Infection with Early Antiretroviral Therapy' The New England
Journal of Medicine 365(5):493-505
34.Rodger, A.J. et al (2016) 'Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent
Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy', The Journal of the American
Medical Association, Vol 316, No.2
35.AIDSinfo (2014) 'Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents'
36.Gardner, E.M. et al (2011) 'The Spectrum of Engagement in HIV Care and its Relevance to Test-and-Treat
Strategies for Prevention of HIV Infection' Clinical Infectious Diseases 52(6):793-800
37.Cornell, M. et al (2010) 'Temporal changes in programme outcomes among adult patients initiating antiretroviral
therapy across South Africa, 2002-2007' AIDS 24(14):2263-2270
38.Shelton, J.D. (2011) 'ARVs as HIV Prevention: A Tough Road to Wide Impact' Science 334:1645-1646
39.ScienceDaily (2013, 18 March) 'Widespread 'test-and-treat' HIV policies could increase dangerous drug
resistance'
40.Gupta, R.K. et al (2013) 'Oral Antiretroviral Drugs as Public Health Tools for HIV Prevention: Global Implications
for Adherence, Drug Resistance, and the Success of HIV Treatment Programs' The Journal of Infectious Diseases
207(Supplement 2):101-106
41.Smith, L. et al (2011) 'HIV-1 treatment as prevention: the good, the bad, and the challenges' Current Opinion in
HIV and AIDS 6(4):315-325
42.Dewing, S. et al (2014) 'Antiretroviral adherence interventions in Southern Africa: implications for using HIV
treatments for prevention' Current HIV/AIDS Reports 11(1):63-71
43.Scheurer, D. et al (2012) 'Association between different types of social support and medication adherence' The
American Journal of Managed Care 18(12):461-467
44.Jones, D.L. et al (2007) 'Efficacy of a Group Medication Adherence Intervention Among HIV Positive Women:
The SMART/EST Womens Project' AIDS and Behaviour 11(1):79-86
45.Novitsky, V. et al (2010) 'HIV-1 Subtype C-Infected Individuals Maintaining High Viral Load as Potential Targets
for the Test-and-Treat Approach to Reduce HIV Transmission' PLOS One 5(4):e10148

46.Sigaloff, K.C.E. et al (2014) 'Global Response to HIV: Treatment as Prevention, or Treatment for Treatment?'
Clinical Infectious Diseases 59(Supplement 1):7-11
47.Harries, A.D. et al (2010) 'The HIV-associated tuberculosis epidemicwhen will we act?' The Lancet
375(9729):1906-1919
48.Padian, N.S. et al (2011) 'HIV prevention transformed: the new prevention research agenda' Lancet
378(9787):269-278
49.Macklin, R. et al (2012) 'Given Resource Constraints, It Would Be Unethical To Divert Antiretroviral Drugs From
Treatment To Prevention' Health Affairs (Project Hope) 31(7):1537-1544
50.Wilson, D. et al (2014) 'The economics, financing and implementation of HIV treatment as prevention: What will it
take to get there?' African Journal of AIDS Research 13(2):109-119
51.Venkatesh, K.A. et al (2011) 'Is expanded HIV treatment preventing new infections? Impact of antiretroviral
therapy on sexual risk behaviors in the developing world' AIDS 25(16):1939-1949

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HIV PREVENTION PROGRAMMES


OVERVIEW

Prevention-Programmes-overview.jpg

HIV prevention programmes are interventions that aim to halt the transmission of HIV. They are implemented
to either protect an individual and their community, or are rolled out as public health policies.
Initially, HIV prevention programmes focused primarily on preventing the sexual transmission of HIV through
behaviour change. For a number of years, the ABC approach - "Abstinence, Be faithful, Use a Condom" - was
used in response to the growing epidemic in sub-Saharan Africa.
However, by the mid-2000s, it became evident that effective HIV prevention needs to take into account
underlying socio-cultural, economic, political, legal and other contextual factors.1 As the complex nature of the
global HIV epidemic has become clear, forms of 'combination prevention' have largely replaced ABC-type
approaches.

Combination prevention

Combination prevention advocates for a holistic approach whereby HIV prevention is not a single intervention
(such as condom distribution) but the simultaneous use of complementary behavioural, biomedical and
structural prevention strategies.2
Combination prevention programmes consider factors specific to each setting, such as levels of infrastructure,
local culture and traditions as well as populations most affected by HIV. They can be implemented at the
individual, community and population levels.3
UNAIDS has called for combined approaches to HIV prevention to be scaled-up, to reinvigorate the global
response and make a sustained impact on global HIV incidence rates.
UNAIDS defines combination prevention as:
"rights-based, evidence-informed, and community-owned programmes that use a mix of biomedical,
behavioural, and structural interventions, prioritised to meet the current HIV prevention needs of particular
individuals and communities, so as to have the greatest sustained impact on reducing new infections." 4
'Know your epidemic, know your response'
Developing a clear and evidence-informed picture of a specific HIV epidemic is needed before deciding on a
package of HIV prevention interventions.
The know your epidemic, know your response approach is the starting point for combination prevention
programming, and is comprised of a series of exercises to help categorise an epidemic (such as generalised or

concentrated). This involves looking at factors such as modes of HIV transmission, key affected populations
and key epidemiological trends (such as the number of new HIV infections among young people).5 6
The planning process that programmers and policy makers are recommended to follow is described below:

A planning process that is inclusive and based on evidence.

Ensure the participation of all relevant stakeholders, including government officials, cultural leaders, civil
society organisations, donors, and most importantly, individuals and communities affected by HIV and AIDS.

Identify modes of transmission and the most affected populations.

Understand how HIV is spread in an epidemic. Identify the most common modes of transmission, and the most
affected populations.

Identify geographic variations in HIV prevalence.

Identify geographic difference in HIV prevalence, such as urban vs rural areas.

Know the size of key affected populations.

Ensure that the appropriate tools are available to collect, monitor and evaluate data about key populations.

Identify and understand structural factors that might fuel HIV prevalence.

Analyse social, legal, economic and cultural drivers of HIV prevalence. For example, punitive laws or gender
inequalities.
Upon completion of the know your epidemic, know your response planning process, a package of coordinated
biomedical, behavioural and structural HIV prevention interventions can be developed and implemented.7
Behavioural interventions

Behavioural interventions seek to reduce the risk of HIV transmission by addressing risky behaviours. A
behavioural intervention may aim to reduce the number of sexual partners individuals have; improve treatment
adherence among people living with HIV; increase the use of clean needles among people who inject drugs; or
increase the consistent and correct use of condoms. To date, these types of interventions have proved the most
successful.8
Examples of behavioural interventions include:

information provision (such as sex education)

counselling and other forms of psycho-social support

safe infant feeding guidelines

stigma and discrimination reduction programmes

cash transfer programmes.9

Biomedical interventions

Biomedical interventions use a mix of clinical and medical approaches to reduce HIV transmission. One
example of a biomedical intervention - male circumcision - is a simple medical procedure that has been shown
to reduce the risk of HIV transmission by up to 60% during unprotected heterosexual sex.10
In order to be effective, biomedical interventions are rarely implemented independently and are often used in
conjunction with behavioural interventions. For example, when a man is circumcised, he will often be tested for
HIV and receive counselling and education about condom use and safer sex.11
Examples of biomedical interventions include:

male and female condoms

sex and reproductive health services

voluntary medical male circumcision

antiretroviral drugs for the prevention of mother-to-child transmission, pre-exposure


prophylaxis, post-exposure prophylaxis and treatment as prevention

HIV testing and counselling

testing and treatment of sexually transmitted infections

needle and syringe programmes

opioid substitution therapy

blood screening.12

Structural interventions

Structural interventions seek to address underlying factors that make individuals or groups vulnerable to HIV
infection. These can be social, economic, political or environmental.
"For many people, the simple fact that 90% of the world's HIV infections occur in developing countries is
evidence that social, economic and political structures drive risk behaviours and shape vulnerability." 13
Structural interventions are much more difficult to implement because they attempt to deal with deep-rooted
socio-economic issues such as poverty, gender inequality and social marginalisation. They can also be reliant on
the cooperation of governments to achieve law or policy reforms.
For example, laws that criminalise same-sex relationships often hinder men who have sex with men from
accessing condoms. A womans subordinate status can affect her ability to negotiate condom use while a lack of

infrastructure such as transport, prevents many people from accessing health clinics. By successfully addressing
these structural barriers, individuals are empowered and able to access HIV prevention services.14
Examples of structural interventions include:

interventions addressing gender, economic and social inequality

decriminalising sex work, homosexuality, drug use and the use of harm reduction services

interventions to protect individuals from police harassment and violence

laws protecting the rights of people living with HIV.15

A public health approach to combination prevention


More recently, some people have advocated for a public health approach to combination prevention. This
involves using a combination of biomedical, behavioural and structural strategies to target currently available
resources at high prevalence regions or 'hot spots' and high-risk groups.16
For example, a combination of needle and syringe programmes, antiretroviral treatment, HIV testing and opioid
substitution therapy in Tallinn, Estonia, was found to reduce HIV prevalence among people who inject drugs
from 20.7% to 7.5% between 2005 and 2011.17
Likewise, a study from South Africa has suggested that pre-exposure prophylaxis together with test and treat
programmes could reduce HIV transmission among sex workers and their clients by 40% over a 10-year
period.18
It is thought that targeting combination prevention initiatives at high-risk groups together with a scale-up in
antiretroviral treatment has the potential to reduce HIV prevalence from pandemic levels to low-endemic
levels.19

Fast-tracking combination prevention


In order to end the HIV epidemic as a public health threat by 2030, in 2014, UNAIDS launched a Fast-Track
strategy to greatly step up the HIV response in low- and middle-income countries.20
The strategy re-emphasises the need for interventions to target key locations and key affected populations.21 It
also identifies a number of other ways to increase the effectiveness of combination prevention efforts, a few of
which are discussed below.
Increasing political and financial commitment
A UNAIDS modelling exercise suggests that nearly 25% of future HIV investments should go into effective
combination prevention initiatives, while the rest should support efforts to achieving the 90-90-90 targets and
reducing new infections by 75%.22
Getting the support of political leaders, religious leaders and other influential figures in society can help to raise
awareness and influence norms regarding HIV prevention.23

Using new tools and technology


Over the past decade, a number of new HIV prevention tools have emerged that increase the effectiveness of
these services. For example, even in low-income countries, mobile phone ownership and internet access have
grown considerably and have changed how people interact and receive information.24
Taking advantage of this shift, Young Africa Live enables young people to talk about topics that affect their
daily lives including sex, HIV, rape and gender issues, as well as where to get tested for HIV. The platform now
has 1.8 million users across South Africa and is expanding to Tanzania and Kenya.25

1.UNAIDS (2010) 'Combination HIV Prevention: Tailoring and Coordinating Biomedical,


Behavioural and Structural Strategies to Reduce New HIV Infections'
2.UNAIDS (2010) 'Combination HIV Prevention: Tailoring and Coordinating Biomedical,
Behavioural and Structural Strategies to Reduce New HIV Infections'
3.UNAIDS (2010) 'Combination HIV Prevention: Tailoring and Coordinating Biomedical,
Behavioural and Structural Strategies to Reduce New HIV Infections'
4.UNAIDS (2010) 'Combination HIV Prevention: Tailoring and Coordinating Biomedical,
Behavioural and Structural Strategies to Reduce New HIV Infections'
5.UNAIDS (2012, 15 May) '30th Meeting of the UNAIDS Programme Coordinating Board'
6.UNAIDS (2007) 'Practical Guidelines for Intensifying HIV Prevention'
7.UNAIDS (2010) 'Combination HIV Prevention: Tailoring and Coordinating Biomedical,
Behavioural and Structural Strategies to Reduce New HIV Infections'
8.Coates, T.J. et al (2008) 'Behavioural strategies to reduce HIV transmission: how to make
them work better' The Lancet 372(9639):669-684
9.UK Consortium on AIDS and International Development (2013) 'Working Group Briefing
Paper: Combination Prevention'
10.Auvert, B. et al (2005) 'Randomized, controlled intervention trial of male circumcision for
reduction of HIV infection risk: the ANRS 1265 Trial' PLOS Medicine 2(11):e298
11.Padian, N.S. et al (2008) 'Biomedical interventions to prevent HIV infection: evidence,
challenges, and way forward' The Lancet 372(9638):585-599
12.UK Consortium on AIDS and International Development (2013) 'Working Group Briefing
Paper: Combination Prevention'
13.Rao, G. et al (2008) 'Structural approaches to HIV prevention' The Lancet 372(9640):764775
14.Rao, G. et al (2008) 'Structural approaches to HIV prevention' The Lancet 372(9640):764775
15.UK Consortium on AIDS and International Development (2013) 'Working Group Briefing
Paper: Combination Prevention'

16.Jones, A. et al (2014) 'Transformation of HIV from pandemic to low-endemic levels: a public


health approach to combination prevention' The Lancet 384(9939)272-279
17.Uuskula, A. et al (2014) 'Combined prevention for persons who inject drugs in the HIV
epidemic in a transitional country: the case of Tallinn, Estonia' AIDS Care 23:1-7
18.Bekker, L.G. et al (2015) 'Combination HIV prevention for female sex workers: what is the
evidence?' The Lancet 385(9962):72-87
19.Jones, A. et al (2014) 'Transformation of HIV from pandemic to low-endemic levels: a public
health approach to combination prevention' The Lancet 384(9939)272-279
20.UNAIDS (2014) 'Fast Track Strategy'
21.UNAIDS (2015) Fast-Tracking combination prevention
22.UNAIDS (2015) Fast-Tracking combination prevention
23.UNAIDS (2015) Fast-Tracking combination prevention
24.UNAIDS (2015) Fast-Tracking combination prevention
25.Social Tech Guide (2014) 'Young Africa Live'
26.Johnson, L.F. et al (2012) The effect of changes in condom usage and antiretroviral
treatment coverage on human immunodeficiency virus incidence in South Africa: a model-based
analysis Journal of the Royal Society Interface 9(72):1544-1554
27.United Nations Population Fund (UNFPA) (2011) Comprehensive Condom Programming: A
guide for resource mobilization and country programming
28.Sandoy, I.F. et al (2012) Condom availability in high risk places and condom use: a study
at district level in Kenya, Tanzania and Zambia BMC Public Health 12:1030

29.Sweat, M.D. et al (2012) Effects of condom social marketing on condom use in developing countries: a
systematic review and meta-analysis, 19902010 Bulletin of the World Health Organization 90:613-622A[/f]

Achieving full coverage


HIV prevention coverage is currently fragmented. Implementing programmes with sufficient intensity and
coverage over a long enough period of time is critical to their success.
Condom programmes show how where high coverage has been achieved, they have had a significant impact. In
South Africa, data reveals how condom use increased with an increase in the distribution of condoms leading to
a decline in new infections between 2000 and 2008.26
By contrast, condom distribution has not been scaled up enough in many countries despite the low
cost.27Availability also varies greatly between countries as well as within countries with many health facilities
experiencing stock-outs. Young peoples access to condoms is also restricted by social norms and the negative
attitudes of healthcare workers.28

South Africas condom programme utilised social marketing to increase condom use. Specifically, condom
brands are designed to be appealing and reflect local cultural values. Condoms are also sold at an affordable
price or are distributed for free in impoverished areas.29

THE HIV TREATMENT CASCADE


HIV treatment cascade

The HIV treatment cascade is a model that outlines the steps of care that people living with HIV go through
from initial diagnosis to achieving viral suppression (a very low level of HIV in the body), and shows the
proportion of individuals living with HIV who are engaged at each stage.
In most parts of the world, large gaps exist between the number of people who have HIV, those who are aware
of their infection, those attending medical services, and those receiving effective treatment.
The treatment cascade can identify weaknesses at different stages or unacceptable variations between different
groups or countries. They can focus the attention of policy makers or help persuade political leaders that more
needs to be done.
The ultimate aim for an HIV treatment programme is for people living with HIV to be virally suppressed. For
this to happen, people living with HIV need to be diagnosed promptly, quickly receive antiretroviral treatment
(ART), continuously engage with medical services, adhere to medication, and have any difficulties with
treatment appropriately managed. If any of these steps are missed, the benefits of treatment for the individual,
and the prevention benefits for their sexual partners and for the wider population can be lost.

For weak health systems, maintaining a strong treatment cascade is challenging. Notably, it is poor in the United
States of America (USA), a very rich country with a health system that is not accessible to all (only 30% of
Americans living with HIV achieve viral suppression).1 In fact, a number of programmes in much lowerincome countries have had significantly better results.

The link between testing and treatment


Testing and diagnosis
The first step in the treatment cascade is for individuals who are living with HIV to be diagnosed and be made
aware of their infection. However, only 53% of people with HIV are thought to be diagnosed, with wide
variations between countries - 86% in Australia, 71% in Canada, 51% in sub-Saharan Africa and 44% in
Ukraine.2
Services that test and diagnose people need to be more accessible. However, testing programmes often rely on
individuals being aware of the need to test for HIV and to seek out testing themselves.
One study discovered a big difference in the number of people agreeing to an HIV test depending on the
wording of offers of testing. 38% of patients offered opt-in testing agreed to a test, compared to 51% of people
actively given the choice whether to test or not and 66% of people given an opt-out offer. This strongly
highlights the need for the way in which tests are offered to be reconsidered in favour of more opt-out
approaches.3
Experience also shows that when individuals are attending a health facility for another purpose and are advised
that HIV testing is routine there, most people are happy to be tested.4 This is the approach frequently taken in
antenatal services, tuberculosis clinics and sexual health clinics and could be extended to other health services.
Community-based testing
Several approaches that can boost the proportion of people diagnosed with HIV aim to take HIV testing services
out of health facilities and into communities. These approaches include:

self-testing (tests completed by the person rather than a health worker)

outreach testing in diverse settings including villages, workplaces and venues used by key
affected populations (often delivered by peers of those being tested)

multi-disease campaigns (offering tests for less stigmatised conditions such as diabetes or
high blood pressure alongside HIV)

home-based testing (health workers going door to door).5

Services may also propose HIV testing to both members of a couple, or seek out sexual partners of individuals
who have themselves been recently diagnosed. Similarly, it is important to provide testing for the infants
and children of people living with HIV.

Linking testing and treatment services


In order to strengthen the treatment cascade, services offering HIV testing and treatment need to be closely
linked. An increasing number of these testing facilities are offering immediate ART to those individuals they
diagnose, in line with the most recent World Health Organisation (WHO) treatment guidelines.
In contrast, in situations where testing and treatment services are provided at separate locations and without
effective communication channels, individuals newly diagnosed with HIV may not engage with treatment
services or delay doing so.
When people are not given support to adjust to an HIV-positive diagnosis or there are practical barriers to
accessing health services, people may not get prompt access to treatment.6 Even when initial contact with a
service providing HIV treatment is made, if a person is told that they do not need medication yet they may
disengage with care. The risk is that by the time they do make contact again, their health has considerably
deteriorated. Delayed treatment is something the most recent WHO guidelines aims to prevent.
Offering immediate treatment
Immediately offering treatment to newly diagnosed individuals can plug a gap in the HIV treatment cascade,
reducing the number of people lost between diagnosis and treatment initiation. Past experience
with programmes to prevent the mother to child transmission of HIV has shown that the immediate offer of HIV
treatment can lead to high levels of uptake and prevent dangerous delays. If only an HIV diagnosis is required
to start ART, it is possible to provide treatment at the smallest and most remote health centres.7
Maintaining a continuum of care at sites where women are diagnosed rather than referring them to specialised
ART facilities elsewhere has improved uptake.8

Engagement and retention in care


Many of the same barriers that may discourage an individual from engaging with healthcare in the first place
can also make on-going retention in care challenging, including HIV stigma, distrust of health services,
concerns about confidentiality, the time and cost of transport to a clinic, loss of income due to attending
healthcare, waiting times in clinics, lack of support from partners and family as well as other personal
priorities.9 10

As a result, many people receiving HIV treatment drop out of care the World Health Organisation estimates
that the average retention rate was 81% 12 months after initiating ART, 75% at 24 months, and 67% at 60
months.11
Retention of children and adolescents is often poor and heavily influenced by the attitudes of families,
caregivers and the wider community.12 Gaps between child and adult services, and inadequate support for
young people moving from one to the other, can result in loss to follow up.
The World Health Organisations guidelines include recommendations on how to organise services in order to
promote engagement and retention in care.
They state that HIV programmes should provide people-centred services that are organised around the health
needs and preferences of people living with HIV. Some examples of this include decentralisation, reduction in
clinic visits and clinic waiting times, and upholding individual dignity and respect, especially for vulnerable
populations.13
Adherence
The WHO also make recommendations on how to support adherence to medication. Antiretroviral treatment
requires tablets to be taken at the same time once or twice daily, but if doses are missed or taken late it can
become ineffective. Adherence may be affected by individual factors (such as changes in daily routines,
depression), medication-related factors (like side-effects, complex dosing regimens) and health system factors
(including requiring the patient to visit facilities frequently to receive medication, asking the patient for out-ofpocket payments).
The WHO recommends interventions such as support on adherence from peer counsellors, mobile phone text
messages to remind individuals to take doses, other reminder devices such as alarms, cognitive behavioural
therapy, behavioural skills training, and medication adherence training. Moreover, they recommend simpler
once-a-day regimens which combine several drugs in one pill.14
Innovative programmes in specific settings may also bolster adherence. Community and peer groups can
support people to adhere to their medications. Food and nutrition support, including cash transfers, may help
individuals on low incomes.15
Adherence interventions can also tackle health system factors. To ensure a continued supply of medication and
prevent stock-outs, the WHO recommends that pharmaceutical supply management systems used to forecast,
procure and deliver ARV drugs are optimised.16

Achieving viral suppression


The aim of HIV treatment and the final step on the treatment cascade is viral suppression.
Individuals who have an undetectable viral load are responding well to HIV treatment and are highly unlikely to
pass HIV on to others. This underscores the need to ensure that every person living with HIV has access to viral
load monitoring the test that provides information on viral suppression.
The WHO recommends that viral load testing should be carried out six and twelve months after starting
antiretroviral treatment, and for patients stable on ART, every twelve months after that.17 However, while point-

of-care and dried blood spot versions of these tests are now available and their price is falling, they remain
inaccessible for many health services and clinics.
Viral load tests are important because they give an early indication of difficulties with adherence and/or
treatment failure, allowing patients to be switched promptly to an alternative treatment so long as effective
second-line treatments or third-line treatments are available. Delays in switching treatment risks allowing drug
resistance to develop. While the WHO treatment guidelines recommend HIV drug resistance testing when
assessing first-line ARV failures, laboratory facilities for these complex tests are even less readily available than
viral load tests in low- and middle- income countries.
Viral suppression around the world
When provided appropriately, modern HIV treatment is highly effective as shown by the treatment cascades in
several high-income countries in which over 90% of those receiving treatment are virally suppressed. For
example, Switzerland has one of the strongest treatment cascades in the world, with an undetectable viral load
achieved in 95% of people taking treatment.18 However, around the world the percentage of all people living
with HIV with an undetectable viral load is lower (68%) due to people remaining undiagnosed or not receiving
treatment.19
Moreover, a number of low- and middle-income countries have been able to achieve good rates of viral
suppression in those who receive treatment. This is the case for 72% in Brazil, 77% in Georgia and 82% in
Rwanda.20
Nonetheless it is important to look at the overall treatment cascades in these countries to get a fuller picture. For
example, in Brazil only 80% of people living with HIV have been diagnosed and only 60% of those diagnosed
receive treatment. This means just 40% of HIV-positive Brazilians are actually virally suppressed. The picture
in Georgia is comparable.
Attention to each step in the treatment cascade and high-quality health services throughout are needed for HIV
treatment programmes to be successful. In the face of extremely challenging circumstances , the results
achieved in Rwanda are inspiring around 90% of those living with HIV are diagnosed and linked with care,
70% of this group receive antiretroviral treatment and 82% of those on treatment are virally suppressed.
Overall, 52% of HIV-positive Rwandans are virally suppressed a figure comparable to that in many much
higher-income countries.21
References

1.Levi, J. et al (2015) 'Can the UNAIDS 90-90-90 target be achieved? Analysis of 12 national
level HIV treatment cascades' Eighth International AIDS Society Conference on HIV
Pathogenesis, Treatment and Prevention, Vancouver, Abstract MOAD0102

2.Levi, J. et al (2015) 'Can the UNAIDS 90-90-90 target be achieved? Analysis of 12 national
level HIV treatment cascades' Eighth International AIDS Society Conference on HIV
Pathogenesis, Treatment and Prevention, Vancouver, Abstract MOAD0102

3.Montoy, JCC, et al (2015) 'Patient choice in opt-in, active choice, and opt-out HIV screening:
randomized clinical trial', BMJ 2016, 352:h6895

4.World Health Organisation (WHO) (2015) 'Consolidated guidelines on HIV testing services'

5.World Health Organisation (WHO) (2015) 'Consolidated guidelines on HIV testing services'

6.Musheke, M. et al (2013) 'A systematic review of qualitative findings on factors enabling and
deterring uptake of HIV testing in sub-Saharan Africa' BMC Public Health 13:220

7.Schouten, E.J. et al (2011) 'Prevention of mother-to-child transmission of HIV and the healthrelated Millennium Development Goals: time for a public health approach' The Lancet
378(9787):282284

8.Suthar, A.B. et al (2013) 'Integrating antiretroviral therapy into antenatal care and maternal
and child health settings: a systematic review and meta-analysis' Bulletin of the World Health
Organization 91:46-56

9.Suthar, A.B. et al (2013) 'Integrating antiretroviral therapy into antenatal care and maternal
and child health settings: a systematic review and meta-analysis' Bulletin of the World Health
Organization 91:46-56

10.Musheke, M. et al (2013) 'A systematic review of qualitative findings on factors enabling


and deterring uptake of HIV testing in sub-Saharan Africa' BMC Public Health 13:220

11.World Health Organisation (WHO) (2013) 'Consolidated guidelines on the use of


antiretroviral drugs for treating and preventing HIV infection'

12.World Health Organisation (2011) 'Retention in HIV programmes: Defining the challenges
and identifying solutions'

13.World Health Organisation (2015) 'Policy brief: Consolidated guidelines on the use of
antiretroviral drugs for treating and preventing HIV infection: Whats new'

14.World Health Organisation (2015) 'Policy brief: Consolidated guidelines on the use of
antiretroviral drugs for treating and preventing HIV infection: Whats new'

15.UNAIDS (2015) 'On the Fast-Track to end AIDS by 2030: Focus on location and population'

16.World Health Organisation (WHO) (2013) 'Consolidated guidelines on the use of


antiretroviral drugs for treating and preventing HIV infection'

17.World Health Organisation (2015) 'Policy brief: Consolidated guidelines on the use of
antiretroviral drugs for treating and preventing HIV infection: Whats new'

18.Levi, J. et al (2015) 'Can the UNAIDS 90-90-90 target be achieved? Analysis of 12 national
level HIV treatment cascades' Eighth International AIDS Society Conference on HIV
Pathogenesis, Treatment and Prevention, Vancouver, Abstract MOAD0102

19.UNAIDS (2014) '909090 - An ambitious treatment target to help end the AIDS epidemic'

20.Levi, J. et al (2015) 'Can the UNAIDS 90-90-90 target be achieved? Analysis of 12 national
level HIV treatment cascades' Eighth International AIDS Society Conference on HIV
Pathogenesis, Treatment and Prevention, Vancouver, Abstract MOAD0102

21.Farmer, P.E. et al (2013) 'Reduced premature mortality in Rwanda: lessons from success'
British Medical Journal 346:f65

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Pre-exposure prophylaxis

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PRE-EXPOSURE PROPHYLAXIS (PREP)


FOR HIV PREVENTION

PrEP protesters

Pre-exposure prophylaxis (PrEP) uses antiretroviral drugs (ARVs) to protect HIV-negative


people from HIV before potential exposure to the virus.
Trials have shown that when taken consistently and correctly, PrEP is very
effective.1 2 3 Truvada is currently the only drug approved for use as PrEP. Truvada is a
single pill that is a combination of two ARVs, tenofovir and emtricitabine.
Recognising that PrEP potentially has population-wide benefits, in 2015 the World Health
Organization (WHO) released new guidelines and a policy brief recommending that PrEP
should be offered as a choice to people who are at substantial risk of HIV infection.4
Previously, PrEP was only recommended for certain key affected populations such as sex
workers, men who have sex with men (sometimes referred to as MSM) and people who
inject drugs (sometimes referred to as PWID).5However, it was recognised that this
excluded people who are at substantial risk but do not belong to one of these groups.
If not taken routinely and consistently, PrEP is much less effective. Therefore, it is
important that any programme offering PrEP provides the service as part of a
combination package of prevention initiatives, and does not replace other, more effective
methods like condoms.

The case for PrEP


It works
PrEP has been shown to reduce the risk of HIV infection from unprotected sex by over
90%, and from injecting drugs by more than 70%.6 A number of high profile trials have
shown how PrEP can be an effective HIV prevention option in a number of different
settings.
Started in 2007, the iPrEx study was the first to offer PrEP. PrEP was provided to 2,500
men who have sex with men at 11 sites in six countries on four continents. It found that
the HIV infection rate in HIV-negative gay men who were given PrEP was reduced by 44%
compared with men taking a placebo. Among those who took PrEP seven days a week,
the risk of infection was reduced by 99%.7 Similarly, the IPERGAY study, which offered
PrEP at six hospitals in France and Canada, reported an 86% reduction in the HIV
infection rate compared to those taking a placebo.8
The Partners PrEP trial recruited 4,758 heterosexual couples in which one partner was
living with HIV across Kenya and Uganda. The risk of HIV infection was reduced by 62%
among those who took tenofovir and 73% among those who received
Truvada.9 Additionally, a number of trials have shown the effectiveness of PrEP in
preventing HIV infection among women at a high risk of HIV.10
Moreover, there is no evidence that PrEP leads to a reduction in condom use and other
safer sex behaviour. For example, the PROUD Study conducted in the United Kingdom
(UK) reported no difference in condom usage or levels of sexually transmitted infections
between the group given PrEP and the group that didnt take the drug.11
It is cost effective
PrEP is estimated to be cost-effective where HIV incidence is greater than 3 per 100
person-years and possibly in places with lower HIV prevalence levels. This level of HIV
prevalence remains common among young women in some settings in Southern Africa,
some sex workers in Africa and men who have sex with men in many countries.12
PrEP drug costs are lower than HIV treatment costs, both per-dose and for the duration of
use. Moreover, PrEP is used as needed as opposed to lifelong for treatment.13 With an
estimated cost of less than 5% of an HIV programmes total budget, PrEP is considered
by UNAIDS to be a key component of a Fast-Tracked response.14
There is a demand
Demand for PrEP is rising among people at substantial risk of infection. A multi-country
survey of people at higher risk of HIV infection found that 61% of respondents would
definitely use PrEP if it was available.15 Up to 92% of men who have sex with men
surveyed in India said that they were likely to use PrEP.16
In the UK, around half of men who have sex with men have shown an interest in taking
PrEP.17 One study has predicted that providing PrEP with annual HIV testing alongside

improved treatment services to just a quarter of men who have sex with men in the UK
with a high risk of HIV infection, could prevent over 7,000 new HIV infections by 2020.18

PrEP pilot programmes


There are also a growing number of countries with pilot programmes that are
demonstrating the potential impact of PrEP as an effective HIV prevention tool. Just a few
are outlined below.
The San Francisco experience
San Francisco in the United States of America (USA) was one of the first places to
implement PrEP, rolling out the service in 2012.19 Between a quarter and one third of at
risk men who have sex with men in San Francisco are now thought to be on PrEP.
In November 2014, roughly 600 men who have sex with men enrolled on PrEP at the Magnet
sexual health clinic in the Castro neighbourhood of San Francisco. After one year, there
were no new HIV infections among the group. Adherence remained high over time 95%
after one month, and 94% in the seventh month reported that they had missed fewer
than three doses during the past week.20
Steve Gibson, Director of the Magnet clinic, said:
"The bottom line is that there were no new HIV infections. We've found that
the combination of clinical services combined with benefits navigation is what
helps insure that people can start taking the medication the same day, often
costing the client nothing." 21
In order to increase PrEP coverage, a website has been launched that sends SMS
reminders to new clients to help them adhere to their medication and links them to
health professionals and peers via an online social network if they have any questions.
They are also supported to select health insurance plans that cover at least a portion of
their PrEP costs.22
The PrEP Brazil Study
The PrEP Brazil Study focuses on men who have sex with men and transgender women.
It uses a number of innovative ways to increase PrEP adherence, including SMS
reminders and engagement through social media.23
Preliminary results of the study are promising with uptake of PrEP over 50%, and notable
increases in awareness of the service and knowledge of high-risk sexual behaviour
among participants.24
Growing awareness and demand for PrEP is expected to increase its rollout. In 2011, only
22% of men who have sex with men in Brazil had heard about PrEP.25 By 2015, PrEP
awareness among this group was 60% in Sao Paulo and Rio de Janeiro, and nearly 95%
said that they would like to use PrEP to prevent HIV.26

The SAPPH-IRe project, Zimbabwe


In 2009, the Sister with a Voice programme was launched to strengthen Zimbabwes HIV
response among sex workers. Within this programme, the SAPPH-Ire project is trialling
offering antiretroviral treatment (ART) to women who test positive for HIV and PrEP to
women who test negative for HIV.27
Offered at 14 locations, community-based adherence support is provided to both groups
where each woman in the programme selects a 'sister', another woman in the
programme with whom she attends monthly peer group sessions.28
Their HIV status is kept confidential unless they choose to disclose it, and the
programme sisters support each other with medication adherence. SMS reminders are
used to encourage women to attend both clinic and medication refill appointments.29
Another key component of the programme is legal advice provided to participants by
peer educators. The peer educators inform sex workers of their basic rights and how they
can legally protect themselves against violations of those rights.30
"The argument is over about PrEP. If you take the drug, it works, not only in a
clinical trial but in the field." - Anthony Fauci, Director, US National Institute of
Allergy and Infectious Diseases (NIAID) 31
Scale up of PrEP in Kenya
Kenya and South Africa are the first African countries to begin implementing a PrEP
strategy, and to date, have employed small-scale pilot projects to start introducing PrEP.
The Bridge to Scale project has now been established in Kenya to scale-up PrEP for HIV
prevention.
Awarded US$ 22.3 million in funding in September 2016, the project aims to reach
20,000 people who are at high risk of HIV, including adolescent girls and young women.
The project will examine barriers to accessing PrEP and other HIV prevention services for
those at highest risk of HIV and aims to find the most effective strategies for
implementing PrEP so that it reaches these groups.32

Challenges of PrEP
Access
Availability of PrEP is currently extremely limited, with less than 1% of people at
substantial risk of HIV infection having access to it.33
PrEP is slowly being approved by countries. The USA approved PrEP in 2012, and since
then Canada, France, South Africa, Kenya and Israel have also rolled out the service. The
European Commission approved the use of Truvada for PrEP in August 2016. 34 Other
countries are also working towards including PrEP in their national HIV programmes. 35

To increase access to PrEP in California USA, a company called Nurx is allowing people to
get a prescription for PrEP via a mobile app without having to see a doctor. The
information put into this app is reviewed by a doctor remotely who decides whether the
treatment is suitable for the person. Before they can receive their prescription, they must
also have blood and urine tests.36
Though there has been significant progress in rolling out PrEP for certain groups like men
who have sex with men, young people and adolescents in high prevalence settings are
being left behind.37
Attempts to address this include two pilot programmes called Pluspills and UChoose in
Cape Town, South Africa. Pluspills is looking into the acceptability and use of PrEP among
girls and boys between 15 and 19 years of age, while UChoose is examining PrEP
delivery through different contraceptive options among girls aged 16 to 17 years.38
PEPFARs DREAMS initiative also includes a PrEP component for young women and
adolescent girls.39
Awareness
Where knowledge of PrEP is high, demand is also high. However, many people who could
benefit from PrEP are still unaware of the service.
One study surveying awareness and acceptability of PrEP among men who have sex with
men in Scotland, Wales, Northern Ireland and the Republic of Ireland, found that only one
third (34.5%) were aware of PrEP. Men who tested for HIV every six months were most
likely to be aware of PrEP.40
Likewise, research from the USA among young men who have sex with men aged 18 to
24, found that only 27% of the sample had heard about PrEP. They were more likely to
have heard about PrEP if they were older, better educated, had no permanent residence,
had health insurance, or reported having at least one sexually transmitted infection (STI)
in their lifetime.41
PrEP needs to be offered as part of a package of HIV prevention services
PrEP is not 100% effective, and therefore it needs to be delivered as part of a
comprehensive package of HIV prevention services. These include condoms and
lubricant, safer sex counselling, frequent STI check-ups and treatment, and regular HIV
testing.42
A range of models for delivering PrEP have been proposed, including STI clinics, primary
care clinics, and community-based organisations with links to clinics.43 44 45 However,
each of these options presents challenges.
For example, while STI clinics serve a population at risk of HIV infection, most operate on
a drop-in or urgent care basis and do not provide ongoing care and monitoring.

Conversely, primary care clinics are experienced with ongoing care, but need to be able
to identify people eligible for PrEP and offer risk reduction and adherence counselling. 46
Adherence
If not taken routinely and consistently, PrEP is much less effective. People with high
levels of adherence have high levels of protection, while lower adherence leads to low or
no protection.
One study of three cities in the USA reported very different levels of PrEP adherence
among men who have sex with men. In San Francisco, 52% of participants took PrEP
daily compared to 35% in Washington DC and just 13.5% in Miami.47
A further 27% of those from Miami, 18% from Washington and 4% from San Francisco
only took two doses a week - offering about 70% protection (compared to over 90% if
taken daily). Moreover, 11%, 2% and 4% respectively took just one dose a week, offering
very little protection; and 4.5%, 2% and 0% of participants had no detectable tenofovir in
their blood.48
A number of factors were attributed to this difference in adherence levels including
knowledge and awareness of PrEP, its availability and the participants' lifestyle.49
Another factor which can affect adherence is exposure to abuse and violence within a
relationship. A study carried out among HIV-serodiscordant couples accross Africa found
that women who had experienced verbal, physical, or economic abuse from a partner
were more likely to have low PrEP adherence. The reasons given included stress and
forgetting, leaving home without pills, and partners throwing pills away.50
To address PrEP adherence issues, two trials, ECLAIR and HPTN 077, are currently
investigating the use of long-acting injectable (LAI) antiretrovirals to prevent reliance on
daily pill-taking.51
Stigma and discrimination
As with other HIV services, stigma and discrimination can negatively impact upon uptake
and adherence to PrEP.
In some settings, PrEP is associated with high-risk sexual activity. It also has the stigma
of being related to HIV (which may also relate to other stigmas, such as homosexuality,
sex work, and/or drug use) and the stigma of PrEP being an alternative to condoms (as
condom use is often associated with responsible sexual activity).52
PrEP-related stigma has been reported by trial participants at a range of sites among
different key affected populations spanning several countries.
For example, in consultations, sex workers have expressed concerns that if people know
they are taking PrEP, third parties (such as brothel owners, clients and managers) would

pressure them to reduce condom use. Authorities may also persecute sex workers for the
possession of PrEP pills as evidence of sex work.53
Experience with PrEP use among sex workers remains limited, but involving third parties
early in planning PrEP programmes is important, as is continuing to promote condoms
and lubrication as a critical component of combination prevention.54
References

1.McCormack, S. et al (2014) Pre-exposure prophylaxis to prevent the acquisition of HIV-1


infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label
randomised trial The Lancet 387(10013):53-60
2.Baeten, J.M. et al (2012) 'Antiretroviral Prophylaxis for HIV-1 Prevention among Heterosexual
Men and Women' New England Journal of Medicine 367(5):399-410
3.Grant, R.M. et al (2010) 'Preexposure Chemoprophylaxis for HIV Prevention in Men Who
Have Sex with Men' New England Journal of Medicine 363:2587-2599
4.World Health Organisation (WHO) (2015) 'Policy brief: WHO expands recommendation on
oral pre-exposure prophylaxis of HIV infection (PrEP)'
5.San Francisco Department of Public Health, Population Health Division (2015) 'HIV
Epidemiology Annual Report 2014'
6.Centers for Disease Control and Prevention (CDC) PrEP [accessed February 2016]
7.Anderson, P.L. et al (2012) Emtricitabine-tenofovir concentrations and pre-exposure
prophylaxis efficacy in men who have sex with men Science Translational Medicine
4(151):151ra125
8.Molina, J.M. et al (2015) On Demand PrEP With Oral TDF-FTC in MSM: Results of the ANRS
Ipergay Trial Conference on Retroviruses and Opportunistic Infections (CROI), Seattle, USA,
Abstract 23LB
9.Baeten, J. et al (2012) Antiretroviral Prophylaxis for HIV-1 Prevention among Heterosexual
Men and Women New England Journal of Medicine 367(5):399-410
10.Thomson, K.A. et al (2016) Tenofovir-based oral preexposure prophylaxis prevents HIV
infection among women Current Opinion in HIV and AIDS 11(1):18-26
11.McCormack, S. et al (2015) Pre-exposure prophylaxis to prevent the acquisition of HIV-1
infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label
randomised trial The Lancet 387(10013):53-60
12.Ong, K.J. et al (2015) 'Cost andcost-effectiveness of an HIV pre-exposure prophylaxis (PrEP)
programme for high-risk men who have sex with men in England: results of a static decision
analytical model 386:S16
13.World Health Organisation (WHO) (2015) 'Policy brief: WHO expands recommendation on
oral pre-exposure prophylaxis of HIV infection (PrEP)'

14.UNAIDS (2015) On the Fast-Track to end AIDS by 2030: Focus on location and population
15.Eisingerich, A.B. et al (2012) Attitudes and acceptance of oral and parenteral HIV
preexposure prophylaxis among potential user groups: a multinational study PLoS One
7(1):e28238
16.Wheelock, A. et al (2013) 'Are Thai MSM Willing to Take PrEP for HIV Prevention? An
Analysis of Attitudes, Preferences and Acceptance' PLoS One 8(1):e54288
17.Young, I. et al (2013) 'Awareness and Willingness to Use HIV Pre-Exposure Prophylaxis
amongst Gay and Bisexual Men in Scotland: Implications for Biomedical HIV Prevention' PLoS
ONE 8(5):e64038
18.Punyacharoensin, N. et (2016) Effect of pre-exposure prophylaxis and combination HIV
prevention for men who have sex with men in the UK: a mathematical modelling study The
Lancet HIV
19.aidsmap (2015, 18 December) 'Evidence for PrEP efficacy grows, but implementation
presents challenges'
20.aidsmap (2015, 18 December) 'Evidence for PrEP efficacy grows, but implementation
presents challenges'
21.aidsmap (2015, 18 December) 'Evidence for PrEP efficacy grows, but implementation
presents challenges'
22.UNAIDS (2015) On the Fast-Track to end AIDS by 2030: Focus on location and population
23.UNAIDS (2015) On the Fast-Track to end AIDS by 2030: Focus on location and population
24.Hoagland, B. et al (2015) Pre-exposure prophylaxis (PrEP) uptake and associated factors
among MSM and TGW in the PrEP Brasil demonstration project. Eighth IAS Conference on HIV
Pathogenesis, Treatment and Prevention, Vancouver. Abstract TUAC0205LB
25.Perisse, A.R.S. et al (2013) Knowledge about HIV preventative measures among MSM
using internet-based social networks in Brazil. Presented at IAS 2013, Kuala Lumpur, Malaysia, 30
June3 July 2013
26.Hoagland, B. et al (2015) Pre-exposure prophylaxis (PrEP) uptake and associated factors
among MSM and TGW in the PrEP Brasil demonstration project. Eighth IAS Conference on HIV
Pathogenesis, Treatment and Prevention, Vancouver. Abstract TUAC0205LB
27.AVAC 'Sisters Antiretroviral therapy Programme for Prevention of HIV an Integrated
Response (SAPPH-Ire) [accessed February 2016]
28.UNAIDS (2015) On the Fast-Track to end AIDS by 2030: Focus on location and population
29.UNAIDS (2015) On the Fast-Track to end AIDS by 2030: Focus on location and population
30.UNAIDS (2015) On the Fast-Track to end AIDS by 2030: Focus on location and population
31.aidsmap (2015, 18 December) 'Evidence for PrEP efficacy grows, but implementation
presents challenges'

32.PRNewswire (2016) 'Kenya Expands Bold HIV Prevention Strategy; Jhpiego Chosen to
Reach Vulnerable Kenyans with Daily Pill' (Accessed on: 20/09/2016
33.UNAIDS (2015) On the Fast-Track to end AIDS by 2030: Focus on location and population
34.Gilead (2016) 'European Commission Grants Marketing Authorization for Gileads OnceDaily Truvada For Reducing the Risk of Sexually Acquired HIV-1' (Accessed on: 20/09/2016)
35.PrEPWatch 'National Policies & Strategies' [accessed 29 March 2016]
36.The Guardian (2016, 29 March) 'Uber for birth control' service to deliver HIV prevention
drug Truvada
37.UNAIDS (2015) On the Fast-Track to end AIDS by 2030: Focus on location and population
38.UNAIDS (2015) On the Fast-Track to end AIDS by 2030: Focus on location and population
39.The United States Presidents Emergency Plan for AIDS Relief (PEPFAR) Innovation
Challenge Fact Sheet[accessed 1 January 2016]
40.Frankis, J.S. et al (2015) Towards preparedness for PrEP: PrEP awareness and acceptability
among MSM at high risk of HIV transmission who use sociosexual media in four Celtic nations:
Scotland, Wales, Northern Ireland and The Republic of Ireland: an online survey Sexually
Transmitted Infections
41.Bauermeister, J.A. et al (2013) 'PrEP awareness and perceived barriers among single young
men who have sex with men' Current HIV Research 11(7):520-527
42.The American Foundation for AIDS Research (amfAR) (2013) 'Fact Sheet: Pre-Exposure
Prophylaxis (PrEP)
43.Norton, W.E. et al (2013) Primary care and public health partnerships for implementing
pre-exposure prophylaxis American Journal of Preventive Medicine 44: S7779
44.Cohen, S.E. et al (2013) Preparing for HIV Pre-Exposure Prophylaxis: Lessons Learned from
Post-Exposure Prophylaxis American Journal of Preventive Medicine 44:S8085
45.Hosek, S.G. (2013) HIV pre-exposure prophylaxis diffusion and implementation issues in
nonclinical settings American Journal of Preventive Medicine 44:S129-132
46.Norton, W.E. et al (2013) Primary care and public health partnerships for implementing
pre-exposure prophylaxis American Journal of Preventive Medicine 44: S7779
47.Cohen, S.E. et al (2014) 'Implementation of PrEP in STD Clinics: High Uptake and Drug
Detection Among MSM in the Demonstration Project' 21st Conference on Retroviruses and
Opportunistic Infections (CROI), Abstract 954
48.Cohen, S.E. et al (2014) 'Implementation of PrEP in STD Clinics: High Uptake and Drug
Detection Among MSM in the Demonstration Project' 21st Conference on Retroviruses and
Opportunistic Infections (CROI), Abstract 954
49.Cohen, S.E. et al (2014) 'Implementation of PrEP in STD Clinics: High Uptake and Drug
Detection Among MSM in the Demonstration Project' 21st Conference on Retroviruses and
Opportunistic Infections (CROI), Abstract 954

50.Roberts, S.T., et al (2016) Intimate partner violence and adherence to HIV pre-exposure
prophylaxis (PrEP) in African women in HIV serodiscordant relationships: A prospective cohort
study, Journal of Acquired Immune Deficiency Syndromes
51.AVAC (2016) AVACs Take PxWire: A Quarterly Update on HIV Prevention Research 9(1)
52.Haire, B.H (2015) 'Preexposure prophylaxis-related stigma: strategies to improve uptake and
adherence a narrative review' HIV/AIDS - Research and Palliative Care 7:241-249

53.UNAIDS (2015) Oral pre-exposure prophylaxis: Questions and answers


54.UNAIDS (2015) Oral pre-exposure prophylaxis: Questions and answers

HIV TREATMENT PROGRAMMES


OVERVIEW
Women waiting outside clinic

How does antiretroviral treatment work?


Drugs used to treat HIV, known as antiretrovirals or antiretroviral therapy (ART), prevent HIV from replicating
and infecting new immune system cells in the body. ART therefore reduces the levels of HIV in an individuals
body to extremely low levels as well as preventing damage to his or her immune system. In contrast, when HIV
is left untreated, it is the depletion of immune function that leaves the body vulnerable to a wide range of
infections and which eventually leads to serious illness and death.

Individuals who are diagnosed soon after HIV infection and begin ART without delay are able to remain in
good health for decades, with a life expectancy similar to that of people who dont have HIV.1 However, less
than half of people living with HIV in the world have good enough access to high quality health services for
that potential to be realised.

Global uptake of treatment


Of the 37 million people living with HIV, only 41% of adults and 32% of children living with HIV were
receiving ART in 2014.2
Nonetheless these figures are highly impressive when compared with those of only a few years ago. In 2002 the
World Health Organisation (WHO) announced a plan that appeared to some at the time to be over-ambitious their 3 by 5 initiative aimed for three million people to be on treatment by 2005. It accelerated access to
treatment (to 2.2 million people) without quite meeting its objective in time.
The movement then gained momentum, with 7.5 million people receiving treatment in 2010. By the middle of
2015, 15.8 million people were receiving HIV treatment.3
Men are less likely than women to receive treatment; children and adolescents are also underserved.4 Although
the availability of treatment has improved in all parts of the world, the proportion of people living with HIV
receiving ART varies considerably between regions. There are particular gaps in low- and middle-income
countries, especially those in Eastern Europe and the Middle East.5
However, as the burden of HIV is concentrated in a few key countries, improvements in the availability of
treatment in specific countries can have a significant impact on the overall global situation. For example, South
Africa has the largest population of people living with HIV in the world (6.9 million). A radical turn-around in
its governments health policy resulted in the number of South Africans receiving treatment jumping from 4,000
to 3.1 million between 2000 and 2014. The country now has the largest HIV treatment programme in the
world.6
Globally, 61% of all people with HIV live in just ten countries South Africa, Nigeria, India, Kenya,
Mozambique, Uganda, Tanzania, Zimbabwe, the United States of America, and Zambia.7 While this means that
efforts can be focused, these are mostly low-income countries, adding to the challenge.

Ambitious targets and guidelines


Despite rapid progress, the Joint United Nations Programme on HIV and AIDS (UNAIDS) and the World
Health Organisation (WHO) have set global targets that are far more ambitious.
90-90-90 targets
UNAIDS is encouraging countries to work towards targets known as 90-90-90.8 The aim is that by 2020, 90%
of all people living with HIV will know their status, 90% of those diagnosed will be on treatment, and 90% of
those on treatment will be virally suppressed (an undetectable viral load, indicating successful treatment). This
would mean that 73% of the global population of people living with HIV would be virally suppressed by 2020.
If this is achieved, then models predict the end of HIV as an epidemic disease by 2030.

Current guidelines
Consistent with those targets, the World Health Organisation now recommends that everybody living with HIV,
of all ages and in all parts of the world, should receive antiretroviral therapy.9
Previously, guidelines were more cautious, only recommending treatment to certain groups for example,
individuals with a more depleted immune system (as shown by clinical symptoms or a lower CD4 cell count),
people with tuberculosis co-infection or pregnant women who needed to prevent transmission to an unborn
child. However the evidence of the benefit of prompt HIV treatment for all has now become overwhelming.
Studies have conclusively demonstrated that delaying HIV treatment10 and taking breaks11 from HIV treatment
results in greater morbidity and mortality. Research has also shown that effective HIV treatment prevents
onward transmission to sexual partners12 and unborn children.
The guidelines have therefore become simpler. WHO recommends that all people living with HIV should begin
antiretroviral therapy as soon as possible after diagnosis and continue to take it indefinitely. Assessment of an
individuals clinical stage or CD4 cell count is not required before initiating HIV treatment.
Nonetheless in situations where resources prevent full implementation of the guidelines, treatment should be
prioritised for individuals with severe or advanced HIV clinical disease (WHO clinical stage 3 or 4) and

individuals with a CD4 cell count below 350 cells/mm3. This is to ensure that people who urgently need
treatment are not displaced by people whose need is less pressing.
The AIDSFree Guidance Database details current HIV testing and treatment guidelines for many countries
around the world.13
Achieving the targets
These changes to the treatment guidelines dramatically affect the scale of HIV treatment programmes and the
financial resources required. An analysis based on 2014 figures showed that if only those with a CD4 cell count
below 200 were eligible for treatment (as had been recommended in 2002), then 11 million people would need
treatment. Based on the 2010 recommendation to offer treatment to those with a CD4 cell count below 350, 15
million require treatment. With 2013s shift to recommend treatment for all those below CD4 500, 28 million
require treatment. Finally, with the 2015 recommendation for treatment for everyone diagnosed, almost 37
million need antiretroviral therapy.14
Only a limited number of countries (all upper-middle-income or high-income) have updated their national
guidelines to recommend treatment for all.15 This means that treatment is usually only begun when patients
already have a low CD4 cell count and a weakened immune system. As a result their medical care is often more
complicated and expensive. Delaying treatment also contributes to extra HIV infections increasing future
costs - as the potential of earlier treatment to prevent onward transmission has been missed.16

Global challenges
Funding
With the global burden of HIV concentrated in low and lower-middle income countries, funding from
international donors has been essential to the scale-up of HIV treatment. The contribution of the American
government, primarily channelled through the Presidents Emergency Plan for AIDS Relief (PEPFAR) and the
Global Fund to Fight AIDS, Tuberculosis and Malaria, has been particularly important.
A rapid scale-up of international funding from $1.2 billion in 2002 to $7.8 billion in 2008 allowed many
countries treatment programmes to expand in that period.17 But international donors have curtailed or capped
their contributions since the 2008 financial crash. With $8.6 billion provided in 2014, funding is little different
to that available six years earlier. A scale-up in line with either WHO treatment guidelines or UNAIDS 90-9090 targets is extremely challenging in this context.18
In response, funding from domestic governments has become increasingly important for HIV programmes in
many countries. By 2014, domestic funding comprised about 57% of total resources available for HIV
programmes in low- and middle- income countries. In the five previous years, 84 countries increased their
domestic spending on AIDS, including 35 which more than doubled it.19
Such shifts are dependent on countries economic growth and on political leadership. In too many countries,
leaders are unwilling to fully support HIV programmes or they limit their support to specific elements.
Provision for key affected populations such as sex workers or people who inject drugs is often seen as
politically unpalatable.

Drug prices and generics


While staffing and infrastructure costs are important, the biggest single element influencing the affordability of
HIV treatment programmes is the price of antiretroviral drugs. Generic manufacturers now supply more than
95% of all ARVs in low- and middle- income countries, at a cost of less than US$ 150 per person per year for a
persons first treatment regimen.20 But if a person needs to switch to an alternative regimen, its price may be
around $300 a year and third-line regimens (rarely available from generic manufacturers) may cost 15 times
more than the standard first-line regimen. Further patent restrictions and a weakening of competition from
generic manufacturers could restrict access to newer medicines.
Moreover economic growth in many countries may move them into the middle-income bracket, meaning that
they are no longer permitted to use generic drugs and may also become ineligible for international donor
funding.
Weak healthcare systems
The effective scale-up of HIV treatment is made more challenging by weak health services and health systems
in many countries. In places where health services are difficult to access, understaffed or poorly organised,
uptake of testing and treatment is suboptimal, with too many people dropping out of care when faced with
difficulties.
A very concrete example is stock-outs, when antiretrovirals or other medical supplies cease to be available in
clinics. Poor planning, forecasting and budgeting; delivery delays; and corruption are described as the most
common reasons for stock-outs.21 When stock-outs occur, individuals may simply take a forced break from
their treatment and wait for supplies to be replenished, risking the development of drug resistance, treatment
failure and a switch to a more expensive drug combination.

Improving access to treatment


The role of civil society
Civil society movements have been vital in placing HIV high up on the public health agenda and in finding
solutions to challenging problems. Further pressure from civil society may be needed for the next scale-up of
treatment to be achieved.
To look at an historical example, South Africas treatment access movement linked street protests and
community activism with court challenges and high-level lobbying.22 Campaigners focused on social justice
and linked with activists across the world, ultimately achieving a relaxation of intellectual property restrictions.
Campaigning eventually led to a change in the South African governments approach to HIV and the worlds
largest HIV treatment programme.
The changing role of healthcare providers
Activism has also spurred innovations in the health sector. For example, task-shifting involves redistributing
human resources so that, for example, a nurse rather than a doctor initiates patients on antiretroviral therapy.
This means that shortages of qualified doctors do not stop people from receiving treatment as nurses can be
trained for specific tasks and are less costly.
People living with HIV have also been involved in delivering care to their peers sometimes as a counsellor,
but sometimes with a more extensive role. For example rather than requiring patients to make a lengthy visit to

the clinic each month, they may be seen inbetween clinic visits by a trained peer who assesses adherence and
conducts basic health checks, referring patients to the clinic in the case of any abnormalities.23 In southern
Africa, patients who are stable on therapy sometimes form groups in which members distribute medication to
each other.24
Such projects particularly respond to the challenge of an ever increasing number of people who are stable on
HIV treatment and will need an ongoing supply of ARVs for the rest of their lives.25 Without innovation, they
will fill up existing health facilities and reduce capacity for patients who are unwell or newly diagnosed.
Decentralisation of HIV care to a wider range of health services can also make HIV treatment more accessible.
HIV treatment may be integrated with services for tuberculosis, maternal and child health, hepatitis, or other
health conditions. For example South Africa made ART available at virtually every public health facility in the
country.26
Improving the efficiency of treatment services will mean that more patients can be treated for the same financial
resources. Wide variations in the cost of providing treatment between facilities demonstrate that some facilities
are less efficient whereas others may be benefiting from economies of scale (providing ART to more patients
while fixed costs remain the same) or economies of scope (integrating ART delivery with other health services).
Other efficiency gains are possible through improving procurement systems so as to lower the cost of
commodities and introducing new technologies (such as point-of-care diagnostic tests).27
Addressing stigma and discrimination
Finally, addressing the stigma and discrimination faced by people living with HIV especially that which
occurs in health services - may encourage more people to test and to start treatment. Many people living with
HIV, especially those who belong to key populations such as people who use drugs or men who have sex with
men, report stigmatising attitudes from health workers which discourage them from using health services.
Revising laws which discriminate against key populations, protecting the rights of people living with HIV and
making legal services available so that people can seek redress may ultimately have an impact on the uptake of
antiretroviral therapy.
REFERENCES

Sabin, C.A., (2013) 'Do people with HIV infection have a normal life expectancy in the era of
combination antiretroviral therapy?' BMC Medicine 11:251

2.UNAIDS (2015) 'Fact sheet 2015'

3.UNAIDS (2015) 'On the Fast-Track to end AIDS by 2030: Focus on location and population'

4.UNAIDS (2015) 'On the Fast-Track to end AIDS by 2030: Focus on location and population'

5.World Health Organization (2014) 'Global update on the health sector response to HIV'

6.World Health Organization (2015) 'Global health response to HIV, 2000-2015, focus on
innovations in Africa'

7.UNAIDS (2014) 'The Gap Report'

8.UNAIDS (2014) '909090 - An ambitious treatment target to help end the AIDS epidemic'

9.World Health Organization (2015) 'Guideline on when to start antiretroviral therapy and on
pre-exposure prophylaxis for HIV'

10.INSIGHT START Study Group (2015) 'Initiation of Antiretroviral Therapy in Early


Asymptomatic HIV Infection' New England Journal of Medicine 27;373(9):795-807

11.SMART Study Group (2006) 'CD4+ count-guided interruption of antiretroviral treatment'


New England Journal of Medicine 30;355(22):2283-96

12.Cohen MS et al (2011) 'Prevention of HIV-1 infection with early antiretroviral therapy' New
England Journal of Medicine 11;365(6):493-505

13.USAID, PEPFAR & AIDSFree 'AIDSFree Guidance Database' [accessed March 2016]
14.D Cooper (2015) 'Antiretroviral Therapy: Past, Present, and Future' 2015 Conference on
Retroviruses and Opportunistic Infections, Seattle, NGaly-Mann Lecture
15.Health GAP (2015) 'Towards Treatment on Demand for All'

16.Tanser F et al (2013) 'High coverage of ART associated with decline in risk of HIV acquisition
in rural KwaZulu-Natal, South Africa', Science Feb 22;339(6122):966-71

17.Kaiser Family Foundation and UNAIDS (2015) 'Financing the Response to AIDS in Low- and
Middle-Income Countries: International Assistance from Donor Governments in 2014'

18.Dutta A et al (2015) 'The HIV Treatment Gap: Estimates of the Financial Resources Needed
versus Available for Scale-Up of Antiretroviral Therapy in 97 Countries from 2015 to 2020'. PLOS
Medicine Nov; 12(11): e1001907

19.UNAIDS (2015) 'How AIDS changed everything: MDG 6: 15 years, 15 lessons of hope from
the AIDS response'

20.World Health Organization (2015) 'Global health response to HIV, 2000-2015, focus on
innovations in Africa'

21.International Treatment Preparedness Coalition (2014) 'Global policy, local disconnects: a


look into the implementation of the 2013 HIV treatment guidelines'

22.World Health Organization (2015) 'Global health response to HIV, 2000-2015, focus on
innovations in Africa'

23.Selke HM et al (2010) 'Task-Shifting of Antiretroviral Delivery From Health Care Workers to


Persons Living With HIV/AIDS: Clinical Outcomes of a Community-Based Program in Kenya' JAIDS
55:4

24.Decroo T et al (2011) 'Distribution of antiretroviral treatment through self-forming groups of


patients in Tete province, Mozambique' JAIDS 56:2

25.Bekker LG et al (2014) 'Provision of antiretroviral therapy in South Africa: the nuts and bolts'
Antiviral Therapy 19 Suppl 3:105116

26.World Health Organization (2015) 'Global health response to HIV, 2000-2015, focus on
innovations in Africa'

27.PEPFAR (2011) 'PEPFAR: Making Smart Investments to Increase Impact and Efficiency and
Save More Lives'

ORIGIN OF HIV & AIDS


Origins

Since the 1980s, there has been a lot of debate around the origin of HIV. So where did HIV and AIDS come
from?
Here we discuss evidence about the origin of HIV, and find out how, when and where HIV first began to cause
illness in humans. There are two types of HIV, known as HIV-1 and HIV-2, which have different origins and
causes.

The link between HIV and SIV


HIV is a type of lentivirus, which means it attacks the immune system. In a similar way, the SIV virus (simian
immunodeficiency virus) attacks the immune systems of monkeys and apes.1
Research found that HIV is related to SIV and there are many similarities between the two viruses. HIV-1 is
closely related to a strain of SIV found in chimpanzees, and HIV-2 is closely related to a strain of SIV found in
sooty mangabeys.2

Did HIV come from monkeys?


In 1999, a strain of SIV (called SIVcpz) was found in a chimpanzee that was almost identical to HIV in humans.
The researchers who discovered this connection concluded that it proved chimpanzees were the source of HIV1, and that the virus had at some point crossed species from chimps to humans.3
The same scientists then conducted more research into how SIV could have developed in the chimps. They
discovered that the chimps had hunted and eaten 2 smaller species of monkeys (red-capped mangabeys and
greater spot-nosed monkeys) and became infected with 2 different strains of SIV.
The two different SIV strains then joined together to form a third virus (SIVcpz) that could be passed on to
other chimps. This is the strain that can also infect humans.4
How did HIV cross from chimps to humans?
The most commonly accepted theory is that of the 'hunter'. In this scenario, SIVcpz was transferred to humans
as a result of chimps being killed and eaten, or their blood getting into cuts or wounds on the human
hunter.5Normally, the hunter's body would have fought off SIV, but on a few occasions it adapted itself within
its new human host and became HIV-1.
There are four main groups of HIV strains (M, N O and P), each with a slightly different genetic make-up. This
supports the hunter theory because every time SIV passed from a chimpanzee to a human, it would have
developed in a slightly different way within the human body, and produced a slightly different strain. This
explains why there is more than one strain of HIV-1.6
How did HIV-2 get passed to humans?
HIV-2 comes from SIVsmm in sooty mangabey monkeys rather than chimpanzees.7 The crossover to humans is
believed to have happened in a similar way (through the butchering and consumption of monkey meat).
It is far rarer, and less infectious than HIV-1. As a result, it infects far fewer people, and is mainly found in a
few countries in West Africa like Mali, Mauritania, Nigeria and Sierra Leone.8

When and where did HIV start in humans?


Studies of some of the earliest known samples of HIV provide clues about when it first appeared in humans and
how it evolved. The most studied strain of HIV is HIV-1 Group M, which is the strain that has spread
throughout the world and is responsible for the vast majority of HIV infections today.
Did HIV start in Africa?
Using the earliest known sample of HIV, scientists have been able to create a 'family-tree' ancestry of HIV
transmission, allowing them to discover where HIV started.
Their studies concluded that the first transmission of SIV to HIV in humans took place around 1920 in Kinshasa
in the Democratic Republic of Congo (DR Congo).9
The same area is known for having the most genetic diversity in HIV strains than anywhere else, reflecting the
number of different times SIV was passed to humans. Many of the first cases of AIDS were recorded there too.

How did HIV spread from Kinshasa?


The area around Kinshasa is full of transport links, such as roads, railways and rivers. It also had a growing sex
trade around this time. The high population of migrants and sex trade might explain how HIV spread along
these infrastructure routes, firstly to Brazzaville by 1937.
The lack of transport routes into the North and East of the country accounts for the significantly fewer reports of
infections there at the time.10
By 1980, half of all infections in DR Congo were in locations outside of the Kinshasa area, reflecting the
growing epidemic.11
Why is Haiti significant?
In the 1960s, the 'B' subtype of HIV-1 (a subtype of strain M) had made its way to Haiti. At this time, many
Haitian professionals who were working in the colonial Democratic Republic of Congo during the 1960s
returned to Haiti.12 Initially, they were blamed for being responsible for the HIV epidemic, and suffered severe
racism, stigma and discrimination as a result.
HIV-1 subtype B is now the most geographically spread subtype of HIV internationally, with 75 million
infections to date.13

What happened in the 1980s in the USA?


People sometimes say that HIV started in the 1980s in the United States of America (USA), but in fact this was
just when people first became aware of HIV and it was officially recognised as a new health condition.
In 1981, a few cases of rare diseases were being reported among gay men in New York and California, such as
Kaposi's Sarcoma (a rare cancer) and a lung infection called PCP.14 15 No one knew why these cancers and
opportunistic infections were spreading, but that there must be an infectious 'disease' causing them.
At first the disease was called all sorts of names relating to the word 'gay'.16 It wasn't until mid-1982 that it was
realised the 'disease' was also spreading among other populations such as haemophiliacs and heroin
users.17 18By September that year, the 'disease' was finally named AIDS.19

What is the 'Four-H-Club'?


When cases of AIDS started to emerge in the USA the majority of cases were among men who have sex with
men(homosexuals), haemophiliacs and heroin users. Adding Haitians to this list made the 'Four-H Club' of
groups at high risk of AIDS.20
REFERENCES

1.Worobey, M. et al (2010) 'Island biogeography reveals the deep history of SIV' Science
329(5998):1487
2.Sharp, P.M. & Hahn, B.H. (2011) 'Origins of HIV and the AIDS pandemic' Cold Spring Harbour
Perspectives in Medicine 1(1):a006841

3.Gao, F. et al (1999) 'Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes' Nature
397(6718):436-441
4.Bailes, E. et al (2003) 'Hybrid Origin of SIV in Chimpanzees' Science 300(5626):1713
5.Sharp, P.M. and Hahn, B.H. (2011) 'Origins of HIV and the AIDS pandemic' Cold Spring
Harbour Perspectives in Medicine 1(1):a006841
6.Sharp, P.M. & Hahn, B.H. (2011) 'Origins of HIV and the AIDS pandemic' Cold Spring Harbour
Perspectives in Medicine 1(1):a006841
7.Chen, Z. et al (1997) 'Human Immunodeficiency Virus Type 2 (HIV-2) Seroprelavence and
Characterization of a Distinct HIV-2 Genetic Subtype from the Natural Range of Simian
Immunodeficiency Virus-Infected Sooty Mangebeys' Journal of Virology 71(5):3953-3960
8.Sharp, P.M. & Hahn, B.H. (2011) 'Origins of HIV and the AIDS pandemic' Cold Spring Harbour
Perspectives in Medicine 1(1):a006841
9.Faria, N.R. et al (2014) 'The early spread and epidemic ignition of HIV-1 in human
populations' Science 346(6205):56-61
10.BBC News (2014, 3 October) 'Aids: Origin of pandemic 'was 1920s Kinshasa'
11.Faria, N.R. et al (2014) 'The early spread and epidemic ignition of HIV-1 in human
populations' Science 346(6205):56-61
12.Faria, N.R. et al (2014) 'The early spread and epidemic ignition of HIV-1 in human
populations' Science 346(6205):56-61
13.University of Oxford News (2014, 3 October) 'HIV pandemic's origins located'
14.Hymes, K.B. et al (1981) 'Kaposi's sarcoma in homosexual men: A report of eight cases'
Lancet 2(8247):598-600
15.Centers for Disease Control (CDC) (1981, 4 July) 'Kaposi's Sarcoma and Pneumocystis
Pneumonia among Homosexual Men- New York City and California' MMWR Weekly 30(4):305-308
16.Brennan, R.O. & Durack, D.T. (1981) 'Gay compromise syndrome' Lancet 2(8259):13381339
17.Centers for Disease Control (CDC) (1982, 9 July) 'Opportunistic infections and Kaposi's
Sarcoma among Haitians in the United States' 31(26):353-4,360-1
18.Centers for Disease Control (CDC) (1982, 16 July) 'Epidemiologic notes and Reports
Pneumocystis carinii Pneumonia among persons with hemophilia A' MMWR Weekly 31(27):365367
19.Centers for Disease Control (CDC) (1982, 24 September) 'Current Trends Update on
Acquired Immune Deficiency Syndrome (AIDS)- United States' MMWR Weekly 31(37):507508,513-514
20.Farmer, P. (1992) 'AIDS and Accusation: Haiti and the Geography of Blame' University of
California Press

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HIV strains and types

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HIV STRAINS AND TYPES


Strains and types

Each time HIV replicates (by infecting a new cell), small changes or mutations may
occur.1 This means there are many different forms of HIV, including within the body of a
single person living with HIV.

HIV-1 and HIV-2


HIV type 1 and HIV type 2 are two distinct viruses. Worldwide, the predominant virus is
HIV-1, and generally when people talk about HIV without specifying the type of virus they
are referring to HIV-1.
The relatively uncommon HIV-2 virus is concentrated in West Africa, but has been seen in
other countries. It is less infectious and progresses slower than HIV-1. While commonly
used antiretroviral drugs are active against HIV-2, optimum treatment is poorly
understood.2 3

Groups within HIV-1

The strains of HIV-1 can be classified into four groups.4 The most important group, M, is
the major group and is responsible for the majority of the global HIV epidemic.
The other three groups are N, O and P. They are quite uncommon and only occur in
Cameroon, Gabon and Equatorial Guinea.

Subtypes within HIV-1 group M


Within group M there are known to be at least nine genetically distinct subtypes of HIV-1.
These are subtypes A, B, C, D, F, G, H, J and K.
Additionally, different subtypes can combine genetic material to form a hybrid virus,
known as a circulating recombinant form (CRFs), of which quite a few have been
identified.5
The dominant HIV subtype in the Americas, Western Europe and Australasia is subtype B.
As a result, the great majority of HIV clinical research has been conducted in populations
where subtype B predominates. However this subtype represents only 12% of global HIV
infections.

In contrast, less research is available for subtype C, although just under half of all people
living with HIV have subtype C. It is very common in the high prevalence countries of
Southern Africa, as well as in the horn of Africa and India.
The greatest diversity of subtypes is found in Cameroon and the Democratic Republic of
Congo - the region where the HIV-1 epidemic originated.
However, these geographical patterns in the distribution of subtypes are changing over
time, due to migration and the mixing of populations.6

Do differences in subtypes matter?


Some studies suggest that certain subtypes have a greater risk of transmission or faster
disease progression than others.7 On the other hand, antiretroviral drugs (ARVs),
although largely developed in relation to subtype B, have generally proven to be
effective against a wide range of subtypes.8 9
Nonetheless, comparative research on these important issues is relatively limited, partly
because individuals with different subtypes are found in distinct geographical locations.
A more practical concern are the tests used to diagnose HIV and monitor the level of
virus in the body (viral load). Tests that are sensitive to the full range of subtypes (and to
group O and HIV-2) do exist but may not be readily available in all settings. This is a
concern in places where diverse subtypes are prevalent.

SEARCHING FOR A CURE FOR HIV AND


AIDS

Scientist looks down a microscope

Curing HIV and AIDS means clearing HIV from the body. The virus replicates by inserting its genetic code into
CD4 cells, an important part of the immune system. Antiretroviral drugs (ARVs) interfere with this replication
process, which is why they are very effective at reducing the amount of HIV in a persons body to low levels.
However, existing treatments cannot completely remove HIV from the body. Even if someone takes ARVs for
many years, HIV will still be hiding in various parts of their body, known as viral reservoirs. If treatment stops
or is interrupted, HIV can re-establish itself by leaking out of these reservoirs.
Researchers talk about two different types of cure for HIV. One is called a sterilising cure, in which the virus
is completely eradicated from the body. They also talk about a functional cure, where HIV remains in the body
but is kept under control by treatment.1

How close are we to a functional cure for HIV?


A lot of cure research has been focussed on the idea of a functional cure. A functional cure means HIV is not
eradicated from the body (as it still survives in the viral reservoirs) but removes HIV from the blood and
prevents negative effects like progression to AIDS, or transmission to others.
The most well-known case of a potential functional cure occurred in a man called Timothy Brown, also known
as the Berlin Patient. In 2008, he had a bone marrow transplant to treat leukaemia that also seemed to have
cured his HIV. However, the procedure is not an option for most people with HIV as it is very dangerous. It is
only really an option for patients living with HIV who need a bone marrow transplant for other reasons.2
There has been more success with treating people very soon after they become infected with HIV. In a 2012
study, 14 French people living with HIV known as the Visconti cohort, started taking ARVs very soon after
they became infected. After three years of medication, they stopped taking ARVs, which would normally result

in the HIV infection re-emerging. They remained with low levels of virus in their systems for an average of
seven years.3
The potential benefits of this approach has also been seen in two newly born babies. In March 2014, it was
reported that a nine-month-old baby born in California with HIV may have been functionally cured as a result
of ARVs that doctors administered just four hours after birth. Similarly, in March 2013, researchers announced
that a Mississippi baby born with HIV and given high doses of three ARVs shortly after delivery, still appeared
to be functionally cured two years on.4 However, in July 2014, progress towards a functional cure took a
significant blow with detectable levels of HIV found in the Mississippi baby.5
Most recently in July 2015, researchers announced that a French teenager who was infected with HIV at birth
was still in good health 12 years after she last took ARVs. However, it is not yet known why she has fared better
than the Visconti cohort or the Mississippi baby. Moreover, some scientists say that in all of these cases it is still
unknown whether they could have controlled the virus on their own if they had never been treated.6
Many have pointed out the similarities between HIV and cancer, in that it is impossible in both cases to
definitely prove they have been removed from the body. This has led some to suggest that in the HIV field,
remission should be used to describe the absence of HIV (viral replication) when someone is not on treatment
instead of cure to avoid confusion.7
"I am personally convinced that remission is achievable. When? I don't know. But it is feasible. We have
'proof of concept'. We have the famous Visconti patients, treated very early on. Now it is more than 10 years
since they stopped their treatment and they are still doing very well, most of them." - Francoise BarreSinoussi, virologist and Director of the Regulation of Retroviral Infections, Institut Pasteur 8

Flushing HIV out of its hiding places


Many researchers believe that the best hope for curing HIV infection lies in combining antiretroviral treatment
with drugs that flush HIV from its hiding places. The idea is to force the dormant, infected cells to become
active so that the body's own immune system or ARVs can destroy the last remnants of the virus. This approach
is called 'shock and kill'.9
There have been a number of attempts to employ this technique. Most recently, in July 2015, researchers at the
University of California, United States of America (USA) announced that a compound called PEP005 in the
anti-cancer drug Picato, is effective at waking up dormant HIV. The researchers also tested other compounds
capable of reactivating dormant HIV. They found that a substance called JQ1, when used in combination with
Picato, boosts the activation of HIV more than seven-fold.10
Satya Dandekar, lead author of the study said:
"We are excited to have identified an outstanding candidate for HIV reactivation and eradication that is
already approved and is being used in patients." 11
In another study published in the same journal, researchers at the Free University of Brussels reported that they
had found two more drug combinations that are effective at flushing HIV out of its hiding places.12

However, so far, these drug combinations have only been shown to work on infected tissue and blood samples
in the laboratory, not in people living with HIV. Moreover, these drug combinations have only been approved to
prevent cancer in sun-damaged skin. Clinical trials are needed to prove that the drugs are safe and effective for
people living with HIV.13

What about a vaccine?


A vaccine to prevent HIV infection remains an important, but challenging priority for researchers. The history
of smallpox and polio shows that when highly effective, affordable vaccines are available, mass vaccination
programmes can eradicate infectious diseases.
To be effective, a vaccine would require a substance that teaches the immune system how to create protective
immune responses against HIV. While scientists have discovered a great deal about the immune systems
response to HIV in over 30 years of research, they have not yet identified a fully effective substance.
The development of a vaccine to prevent HIV infection is especially challenging because:

the diversity of HIV subtypes and the frequency with which the virus mutates means that a
vaccine would need to prevent infection from multiple strains. But in general, antibodies
are not effective against multiple strains

HIV attacks and uses the same CD4 cells that are needed for an effective immune
response.

The most exciting recent progress in vaccine research concerns the Thai RV144 trial, which reported its results
in 2009. Individuals who received a vaccine were 31% less likely to become infected with HIV than people who
received a placebo.14
Individuals received two vaccines with different modes of action; a prime vaccine called ALVAC and a boost
vaccine that was modelled on the gp120 protein on the outer surface of HIV. Several groups of researchers are
now trying to refine and improve this approach.15
Vaccine researchers are also excited by the discovery that some individuals living with HIV produce antibodies
that work against multiple strains of HIV. These are called broadly neutralising antibodies (bnAbs).
Researchers are attempting to manufacture bnAbs to see whether they could protect HIV-negative people from
infection.16

Other cure research


Antibodies
All people living with HIV naturally respond to the virus by producing antibodies. While most people's
antibodies are unable to kill HIV, the immune systems of a small minority produce broadly neutralising
antibodies (bnAbs), which can kill or neutralise a wide range of HIV strains.17
In 2014, one study detailed how a research team found and identified these antibodies in a South African
woman before cloning them in a laboratory. Despite providing hope for gene therapy in other people, these
antibodies were unable to destroy the HIV virus within her own body because the virus mutates too quickly. She
is currently on ART.18

Abdool Karim, one of the scientists working on the study said:


When a person develops broadly neutralising antibodies it actually has no benefit to the individual who
develops it; [they are] not able to neutralise their own virus." 19
Gene therapy
Gene therapy has also been explored as a potential option for eliminating HIV infection. This involves injecting
genetically modified white blood cells into people living with HIV to build their resistance to the virus.
1% of people naturally produce bnAbs that make them resistant to the most common strains of HIV. In 2014, 12
people living with HIV were given these genetically modified CD4 cells.20
At the start of the trial, all of the patients were on ART but were taken off treatment after they received the
modified cells. As expected, the HIV levels in their bodies began to rise but as the modified cells multiplied and
circulated, they pushed levels of the virus back down.21
However, the number of modified cells fell over time, halving roughly once a year. The trial has been running
since 2009 and all of the participants are now back on treatment.22 A 2015 study that used a similar technique
in mice reported an 80% to 95% decrease in HIV levels.23
Most recently, researchers reported success in using this technique to remove HIV genes completely from
infected cells. Once the virus was gone, the cells continued to function normally with no signs of damage, and
appeared to be protected from reinfection. So far, this technique has only been used on cells in the laboratory.24
Despite promising trials, it isnt yet clear whether gene therapy could be an effective treatment for HIV.