Rapporteur report
Track C: Biomedical Prevention report by Rebecca Guy
This symposium provided an overview of current HIV prevention research, and the future challenges in trial design and implementation.
Quarrisha Abdool Karim, South Africa Current implementation challenges of HIV prevention.
A range of prevention trials are underway: microbicides, barrier methods, behaviour, treatment, prevention of mother to child transmission and vaccine. However prevention works has not been scale-up adequately: There are a number of prevention challenges – diversity of the epidemic, no single solution, scientific uncertainty – no surrogate markers of protection (most reliable is HIV infection of uninfected people), public health imperative to respond to the epidemic, stakeholder demand for communication at all stages and synergy between science & activism. Slow scaling up of ART in sub-Saharan Africa: health care services are struggling with additional burden of AIDS care (shortage of skilled health care personnel, overworked and stressed staff) and the “brain drain” phenomenon: over the last 35 years, 44% of WITS Medical School graduates (Johannesburg) have emigrated. There is a need for strengthening health care delivery systems. Male circumcision may provide an opportunity to impact HIV trajectories in low circumcision and high HIV prevalence settings; involves consenting adult men in response, integrate safe male circumcision services with other sexual and reproductive health services for men, promote greater male responsibility, reduce HIV incidence in adult men by 50-60%. However lack of consensus in scientific community and ambivalence to make policy decision at a country level. Translating RCT findings to policy and practice is complex and RCT evidence is often not sufficient for policy formulation. Combination interventions such as biomedical and behavioural/social may be requited to impact on the pandemic– need panoply of options to address complex and diverse pandemic!
Willard Cates Jr, United States HIV Prevention Research. The optimist’s view
HIV prevention research in the past decade: two new biomedical approaches (nevirapine for prevention of mother to child transmission and male circumcision) and five lessons learned –adherence (social desirability bias but new approaches to improve accuracy, e.g. Carraguard study – blue dye applicator assay (top five breakthroughs in microbiocide studies), prevention standards – traditional approaches (prevention counselling, provision of male condoms, STI treatment). Male circumcision – the next ethical frontier. How do we counsel participants about the benefits and risks of male circumcision? Must we offer male circumcision to all participants (or their partners)? Require controls to be circumcised? Stratify enrollment by male circumcision status? Cost considerations: Preparatory work, product expenses, community activities, communications support, central vs. field costs, monitoring visits. Costs involved vary according to trial type. For example phase 2b/3, microbicide trials: 2.9K - $ 21.6K per participant, circumcision trials – 1,1K to 3.8K per participants (variability much lower). Cost per endpoint most important for effectiveness. HIV prevention best buy – male circumcision. Community engagement lessons learned: must begin engagement early, requires resources and specialised skill set, must extend beyond local community, formative research necessary but not sufficient, research literacy in the community. Communications planning: power of communications, site/staff selection/preparation (established relationships with local health authorities and opinion leaders and personnel with proven ability to interact effectively with activists, media, public officials), communication plans in protocol, rapid response time, media training for researchers, prepare, prepare, prepare!
Andrew Nunn, United Kingdom Challenges in microbicide trial design.
Biomarkers: Are most likely to help identify potentially unsafe microbicides. There are no intermediate markers of activity (such as those used in treatment of active disease). Phase 11b. The case for: a way to select from multiple products, the opportunity to eliminate ineffective products, a fast answer for a highly effective product, a substantial cost reduction – but only if no further trials are indicated, insights on trial design and site preparedness. The case against; a longer, more costly process – for moderately effective microbicides a subsequent, phase III trial will be required, risk of eliminating potentially effective microbicides, a positive finding (whether statistically significant or not) could make it more difficult to conduct a pivotal Phase III trial – participants and possibly ethics committees might consider it unethical to conduct another placebo controlled trial. Prevention trials - “To date, of 25 randomised controlled trials for HIV prevention, four have shown a protective effect (three trials of circumcision and one trial of treating STIs to prevent HIV); whereas 19 showed no effect and two had potentially a deleterious effect.” Padian et al, Lancet July 13 2007. Improving trial efficiency - Selection of population: high incidence population group, limit age range to those most sexually active, stable, i.e. non-mobile, consider the option of DOT. Minimise loss to follow-up: shorten follow-up duration, involve male partners at time of enrolment, and ensure participants are aware of the commitment expected and that they can be contacted. Collect data to better understand participants’ behaviour. Learn from experiences of completed trials
Veronica Miller What needs to be done to move prevention research forward?
Effective research requires the effective translation of research results into implementation at the community level. We are not starting from zero, completion of the following trials (prevention of mother to child transmission, malaria oral prophylaxis, malaria bed nets, HPV vaccine etc). Therefore don’t ignore lesson learned. Research on combination approaches is missing from the landscape. Cooperation and coordination among prevention research programs. Need for a mechanism for critical but collegial protocol discussions and need for (transparent) review process for prevention clinical trials. Good prevention research practice requires resources and high-incidence sites. It is important to sustainability research sites and build up capacity. Confidence in research – requires buy in from communities absolute necessity, community involvement and community ownership. Translation into policy: demonstration that research results translate into effectiveness at the community level, implementation research for efficacious interventions and planning for implementation. Behavioral issues in biomedical research can’t be left out of the equation, even if complex.
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