After years of limited and fragile successes in preventing new HIV infections, it is now recognised that one-size fits all approaches do not work and that only a combination of prevention strategies can bring the HIV epidemic under control. As a result, the concept of Combination Prevention has arisen as the new paradigm at the heart of prevention programmes such as those put forward by UNAIDS in its 2011–2015 Strategy: Getting to zero report.
Combination Prevention includes the provision of proven prevention methods, such as condoms, male circumcision and prevention of mother-to-child transmission (PMTCT), but also a range of behavioral and biomedical interventions specially targeted at those most susceptible to HIV infection, even if partially efficacious in clinical trials, such as vaccines and pre-exposure prophylaxis. Finally, Combination Prevention has at its heart expanded testing and antiretroviral treatment for individuals found to be HIV-positive to reduce transmission to their sexual partners. This is in line with the goal of achieving universal access to ART by 2015 and represent a real paradigm shift when extended to entire population.
While such prevention strategies are based on sound epidemiological principles, results in the field are mixed or still undetermined and the impact of these approaches on the course of the epidemic is difficult to assess, particularly if they are to be used in combination. But beyond their intrinsic efficacy the success of each of these approaches is very much contingent on their potential impact at population level.
Impact has been previously pictured as the pyramid below (for example by Kevin de Cock at the recent Treatment as Prevention Workshop held in Vancouver under the auspices of Julio Montaner from the British Columbia Centre for Excellence in HIV/AIDS). The effectiveness of each of the strategy currently envisaged has to be considered in relation to its impact. To date, the reference in matter of effectiveness is a systematic review by Nancy Padian of late phases RCTs for prevention of sexual transmission of HIV in which 39 unique interventions have been examined in 37 HIV prevention RCTs and of which only six, all evaluating biomedical interventions, demonstrated definitive effects on HIV incidence.
In the pyramid above, each strategy and its effectiveness has been aligned with its corresponding potential impact. For the sake of argument, the result of the FEM-PREP trial recently closed due to futility has been added to illustrate that one approach may well work in a particular context (oral use/anal intercourse) but not in another (oral use/vaginal intercourse) even if this result is still too preliminary to draw definitive conclusions.
Remarkably the approaches currently effective are the one with the lowest impact. The main reason being that they require behavioural changes which are most difficult to achieve at population level for a number of complex reasons. This does not mean that these strategies do not have an impact but that despite being efficacious they are struggling to achieve an impact on a scale large enough to make a difference.
By contrast, approaches that could have a higher impact have a lower or unknown effectiveness, because they have not been tested or because they are poorly and badly implemented, if at all (consider sex education at school, or human rights for men-who have sex with men).
This points to a critical aspect of Combination Prevention which is that combining different prevention approaches will not be enough if they all rely on the same “mechanics” and share the same weaknesses. Promoting PrEP may be based on a different rational than promoting condoms but its actual use will have to face problem similar in scope to that of condom use. At the end of the day they both require a change in beahviour and sticking to it. This aspect of combination applies both to highly efficacious approaches which rely on behavior change and to intervention whose impact rely on political and financial commitment. What’s needed is a “pick and mix” combination.
“At this pivotal moment in the global response, we must courageously face up to the challenges presented by” new Combination Prevention and ensure that more research is done on approaches that have not been assessed yet (such as Test and Treat) and that the overall strategy combines a diversity of approaches. To be successful, Combination Prevention will have to include a number of approaches drawn from the different levels of the impact pyramid.
|Notes:Condoms effectiveness is that provided by the WHO.
Effectiveness is provided as the set point effectiveness with the 95% Confidence Interval which provides the range of value between which the true effectiveness resides. FEM-PREP data are not definitive and will be updated in the coming months.
The final quote originates from the UNAIDS strategy report 2011-2015.