The advent of newly discovered efficacious tools for the prevention of HIV creates a new challenge and the need for new paradigms: How do we assess the impact of combinations of HIV prevention tools in ethical ways, when we have evidence that individually they work to reduce HIV transmission? How do we roll out efficacious strategies, but assess their effectiveness and cost-effectiveness in real-world settings at scale? In a powerful collaboration between four of the major HIV preventive interventions currently underway - including Harvard's Botswana Community Prevention Project and Familia Salama study of PMTCT, Vanderbilt and Imperial's PopART project, and the Africa Centre's Treatment as Prevention trial, our proposal, entitled "New methods for the design and evaluation of large HIV prevention interventions" will address key gaps in the available methodologies for the design and analysis of these large- scale HIV preventive intervention projects. After extensive dialogue with the Principal Investigators and other key personnel on these projects (three of whom are Co-investigators of this proposal), we have identified our specific aims as: 1) To develop and validate novel network methods to improve the evaluation of large combination prevention clinical trials 2) To develop advanced statistical methods to improve the design and evaluation of large- scale HIV prevention studies. 3) To augment prevention trial designs to adjust for bias due to loss to follow-up and to assess infectiousness and indirect effects. 4) To disentangle and evaluate the effects of specific interventions that comprise a 'package'as in the Harvard-Botswana and HPTN 061/PopART trials
The identification of efficacious tools for the prevention of HIV infection creates new opportunities for disease eradication, as well as the need for new analytical paradigms to make the most of them. In a powerful collaboration among investigators representing four of the major HIV prevention studies currently underway - including the Botswana Combination Prevention Project (BCPP), the Familia Salama study of PMTCT, the HPTN 071/PopART trial, and the Africa Centre's Treatment as Prevention trial, our proposal will address key gaps in the available methodologies for the design and analysis of these large-scale projects. Specifically, we will develop and validate novel network methods to improve the evaluation of the impact of the interventions;we will develop methods for estimating the cost-effectiveness ratio from directly observed project data, and compare the performance of new approaches to those based on model-based simulations currently in use;we will develop methods and software for step wedge designs;we will augment prevention project designs to permit an adjustment for biased loss-to-follow-up and refusal to test;and we will develop modeling strategies for disentangling the effects of specific interventions that comprise a combination prevention 'package', as in the BCPP and HPTN 061/PopART trials.