Steven G. Self

The HIV epidemic continues to grow worldwide despite major advances in understanding the pathogenesis of HIV infection and in our ability to treat the disease. Control of the epidemic requires improved methods and strategies for preventing HIV infection. An HIV vaccine that is simple to administer, inexpensive and that induces long-lasting immunity to all known HIV strains would be the optimal preventive measure. The thorough and efficient clinical evaluation of HIV vaccine candidates presents many scientific and operational challenges. There are multiple mechanisms through which an HIV vaccine might be effective and clinical trials must be designed to assess each potential mechanism; there are significant global heterogeneities in human and viral populations for which an HIV vaccine is needed and a program of clinical trials must be designed to assess the impact of these heterogeneities on vaccine effectiveness; the most appropriate settings for clinical evaluation of HIV vaccines are ones which typically lack existing infrastructure to support rigorous clinical research so that such infrastructure must be developed as part of the clinical evaluation program.

The focus of my research is: 1) the design, coordination and analysis of a clinical trials program to evaluate promising candidate HIV vaccines and 2) the development of new statistical study designs and analytic techniques that will increase the efficiency of those evaluations. The coordination of field trials is performed largely throughactivities of the Statistical Center for HIV/AIDS Research and Prevention (SCHARP). SCHARP is composed of statistical coordinating centers for international NIH-funded clinical research networks including the HIV Vaccine Trials Network (HVTN) and the HIVPrevention Trials Network (HPTN. I serve as Co-Director of SCHARP. There are also methodological research groups working on biomathematical modeling of HIV infection dynamics and development of new statistical methods within SCHARP. Topics of current methodologic research include the use of interacting branching processes to model the early events of HIV infection and the potential for vaccines to impact the course of infection by changes in the dynamics of these processes, the development of efficient designs of Phase I/II vaccine trials for optimization of vaccination regimens over dose, schedule and route of administration, the development of statistical methods for the analysis and interpretation of new assays for cellular immune response, the development of new statistical methods for the analysis of effects of human and viral heterogeneity on vaccine efficacy and the use of post-infection biomarker data to assess potential vaccine effects on disease progression and secondary transmission.