“There is no silver bullet” is a common mantra in AIDS prevention, and Dr. Robin Shattock of the Imperial College in London provided a plenary talk in that vein on combination prevention and the need for scientific evaluation Monday at the 2011 International AIDS Conference in Rome.
Shattock defined combination prevention as comprised of four elements—behavior change, treatment, structural interventions and biomedical strategies. Devoted to biomedical strategies, his talk included an outline of interventions that could be implemented prior to HIV exposure—medical male circumcision, oral pre-exposure prophylaxis (PrEP), topical PrEP and preventive vaccines and those interventions relevant subsequent to HIV exposure— antiretroviral therapy (ART), immediate treatment of infected partners and treatment for prevention.
Prevention clinical trials continue to focus on a single intervention, Shattock said, and called for clinical trials to evaluate combination prevention strategies to maximize impact. Some possible combinations include oral PrEP and topical PrEP for intermittent use; PrEP for women combined with medical male circumcision plus oral PrEP for men; treatment for prevention combined with PrEP for the HIV-negative partner; and vaccines plus PrEP. He acknowledged that all of these combinations would need to be underpinned with behavioral and structural interventions.
The remainder of Shattock’s talk addressed his particular interest – vaccine and PrEP combinations. The Thai RV 144 trial, which demonstrated the feasibility of an HIV vaccine with 34 percent efficacy, was at its most effective one-year post vaccination. Revaccination would likely be required to have a real impact on HIV incidence. Co-implementation of PrEP and medical male circumcision could increase vaccine efficacy.
A combination prevention strategy using a vaccine and PrEP could enhance efficacy by providing protection during the immunization period, reducing the infectious challenges, boosting local immunity, providing protection between revaccination campaigns, and offering immunological coverage of intermittent PrEP adherence. Shattock highlighted the potential of a vaginal ring that could be formulated with both ART and a vaccine.
Shattock acknowledged the challenges to conducting combination prevention trials from the increased complexity and the need for larger numbers of trial participants, to a more challenging informed consent process and the possibility of risk compensation and adherence, which may vary according to the perceived efficacy of the different interventions. Nevertheless, he said, we need combination trials because of potential additive or synergistic effects that could stimulate incremental reductions in HIV incidence.