Understanding the evidence for ARV-based prevention RESEARCH METHODOLOGY
BACKGROUND
The project used four separate methodologies to access diverse stakeholder perspectives and assess the evidence base, looking specifically at South Africa, India and the USA. A range of outreach and communications approaches include conference presentations and our blog: mappingpathways.blogspot.com.
The world has made great progress in fighting HIV/AIDS since the late 1990s. While incidence rates in sub-Saharan Africa have fallen, most of the world's new infections still occur there. A portfolio of approaches – or 'pathways' – to prevention is needed. Recent trial data shows great promise in four antiretroviral (ARV) prevention strategies: § Testing, Linkage to Care Plus Treatment (TLC+): earlier treatment
for HIV-positive people
POLICY
'''Grass tops' perspectives We conducted semi-structured interviews with stakeholders from health ministries, research and advocacy groups, healthcare providers and others. We sought their views on the strength of the evidence base for different ARV-based prevention strategies, implementation challenges in their countries, and evidence needs, for example on cost-effectiveness or indirect effects.
§ Pre-exposure prophylaxis (PrEP): providing HIV-negative people
with ARVs to prevent HIV § Vaginal and rectal microbicides: topical applications for HIVnegative people to prevent HIV § Post-exposure prophylaxis (PEP): providing ARVs to HIV-negative people with a potential recent exposure to HIV ARV-based prevention strategies raise complex challenges, including access, cost, impact on behaviour and health, implementation and the possibility of drug resistance developing. No single study synthesises clinical, economic and social issues into a single evidence base. Mapping Pathways is a multi-national two year project to: (1) develop this synthesis in a research-driven, community-led way, and (2) draw out implications for future policy and research.
EXPERTLENS
POLICY
EVIDENCE
base We Analysis of the global conducted a systematic literature review to map and analyse existing empirical data on ARV-based prevention strategies. 5,811 articles were retrieved, with 302 selected for analysis and mapped by prevention strategy and findings. A full text review of 100 articles was then summarised in a single comprehensive narrative. The review asks key questions on efficacy, effectiveness, cost-effectiveness, indirect outcomes and socio-economic impacts, and epidemiological modelling. It provides valuable insights into potential pathways and outcomes, highlighting knowledge gaps.
EXPERT LENS
EVIDENCE
COMMUNITY
on the evidence Thirty two An AIDS experts participated in an online Delphi-based discussion (ExpertLens). This harnesses the wisdom of the group in an iterative way: first soliciting individual views, then facilitating online discussion of the answers before statistically determining what the group 'thinks'. Participants included health clinicians, epidemiologists, AIDS policy advocates and policymakers. We asked their views on factors which might alter the effectiveness of different strategies, such as risk groups, socio-economic context and clinical delivery.
COMMUNITY
engagement An online survey engaged ’'Grass Roots' communities, medical professionals, advocates/activists and members of the public (n = 1,069). We asked about the importance of different ARV-based prevention strategies, about implementation challenges, concerns and worries, and what additional evidence they needed.
EARLY FINDINGS FROM SOUTH AFRICA
Generally, South African stakeholders were more sceptical about ARV prevention strategies than those in the US. In particular, they were concerned about adoption and implementation of PrEP and TLC+ in South Africa. Microbicides were viewed with slightly more optimism.
Overall, the evidence base for the efficacy of microbicides, PrEP and TLC+ strategies is weak, based on only a few clinical trials. However, individual trial data is strong in some cases, such as HPTN 052 which found that early ARV treatment reduced transmission by 96%. Modelling studies generally show optimism about TLC+ as a strategy for HIV prevention in developing countries, with caveats that risky behaviours and low adherence could undermine effectiveness. Most PrEP modelling studies focus on sub-Saharan Africa and conclude that it could decrease HIV transmission, particularly for women, though with the same caveats about behaviour and adherence. While modelling studies of PEP show it to be cost-effective for high-risk groups in developed countries, no studies have investigated cost-effectiveness of PEP for developing countries.
POLICY
Most of the literature is about PEP and microbicides
Concerns included the lack of resources required for implementation, the lack of appropriateness of the strategies given political, social and cultural circumstances in South Africa, and little/no scientific data about long term impacts.
“ARV-based prevention strategies may encourage risky behaviour” “… scientifically, TLC+ is a good idea, but in countries like South Africa with a generalised epidemic…it is simply not feasible. … in countries with a lower HIV prevalence it would be easier to allocate funds to this strategy and achieve herd immunity” “… general population PrEP roll-out would be a nightmare … I an concerned about drug resistance, negative impact on treatment later on, South Africa's treatment- illiterate population and the country's bad public health messaging.” Scepticism about microbicides was driven by lack of efficacy and effectiveness data, though there was some optimism relative to the other strategies.
“There are less issues associated with microbicides than PrEP because – 1) less ARVs are used, 2) the intervention is like condoms, although perhaps a bit more complex, and 3) side effects are not such an issue.”
TLC+ (69) PrEP (61) Microbicides (122) PEP (112) There is less empirical data than there are commentaries on that data
EXPERT LENS
EVIDENCE
169 Commentaries 133 Evidence-based papers
Overall there was greater divergence of opinion than convergence in the ExpertLens. However, there was some agreement that TLC+ could be an effective strategy for serodiscordant couples, microbicides might be effective for heterosexual serodiscordant couples, and that PrEP would be effective for MSM, serodiscordant couples and sex workers.
Of the commentaries, 70 were literature reviews. The 135 evidence-based papers included 21 clinical trials, 25 modelling studies and 6 cost studies.
An overwhelming majority of South African respondents felt that TLC+ and microbicides are important prevention strategies and should have lots of attention. PEP is also seen as important, though rarely implemented at any scale. Views on PrEP were mixed.
Q. Do you think [strategy] should be an important part of the HIV prevention plan for your country? % saying very important and should be given lots of attention
TLC+ 89.2%
COMMUNITY
Q. Do you think PEP is an important part of the HIV prevention plan for your country? 8.7%
Microbicides 67.2% 26.6%
% saying very important
PEP 59.2%
PrEP 47%
36.9% say very important and given lots of attention
47%
22.3% say not important, but should be
LOW
HIGH
36%
Concerns about ARV strategies include: Drug resistance (most-cited concern): “The biggest worry is increased resistance to the drugs …” “Not even all HIV-infected people needing Cost-effectiveness and affordability: ARVs are receiving it. Adding more numbers will only strain the healthcare system.” Risk disinhibition: “May decrease condom usage”
South African respondent profile
Most common employers
We also asked experts to compare strategies at a macro-level.TLC+ was ranked as having the most robust evidence base, perhaps because recent research Relative importance confirmed personal experience. One participant commented: “HPTN 052 seems to have the Strength of strongest evidence base because strategy science it confirms much of what we have Cost feasibility observed anecdotally for years.” Readiness for TLC+ was also considered most implementation ready for implementation and Allocation of funds was where the group allocated the most funds. TLC+ PrEP PEP Microbicides
% saying other things more important
% saying other things more important
In South Africa, most respondents were clinicians and/or working for AIDS service organizations, NGOs or the government.
“HIV prevention should be seen as a 'menu' of choices from which an individual can construct a personalised prevention plan that works for them”
Most common jobs
Doctor 51.2% Nurse 16.3%
AIDS service organisation 25.4%
Scientist 9.2%
NGO with AIDS programs 25.4%
Other concerns raised included poor awareness, the potential for ARV black markets, corruption and ethical/moral concerns about implementation.
Program implementer 15.4%
Government 24.3%
Advocate/activist 9.2%
South Africans wanted more evidence on: Implementation challenges: “How [do we] translate knowledge into behavior change?”
The state of the science:
“What are the side effects?”
Mapping Pathways has six partner organisations: AIDS Foundation of Chicago, AIDS United, Baird's CMC, Desmond Tutu HIV Foundation, Naz India and RAND. Funding for year one was provided by Merck & Co.
BAIRD’S CMC
DESMOND TUTU
HIV FOUNDATION