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FACILITATING NEXT-GENERATION PRE-EXPOSURE PROPHYLAXIS CLINICAL TRIALS USING HIV RECENT INFECTION ASSAYS: A CONSENSUS STATEMENT FROM THE FORUM HIV PREVENTION TRIAL DESIGN PROJECT
Author
Affilliation
Data First Consulting. Sebastopol, CA, USA.
Fred Hutchinson Cancer Research Center. Seattle, WA, USA.
Vitalant Research Institute, San Francisco, CA, USA / Edward Grebe Consulting. Cape Town, South Africa.
ViiV Healthcare. Research Triangle Park, NC, USA.
Gilead Sciences. Foster City, CA, USA.
Fred Hutchinson Cancer Research Center. Seattle, WA, USA.
Fred Hutchinson Cancer Research Center. Seattle, WA, USA.
Edward Grebe Consulting. Cape Town, South Africa.
University of Washington. Seattle, WA, USA.
Independent Consultant. Washington, DC, USA.
Merck & Co., Inc. Kenilworth, NJ, USA.
Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM). Bonn, Germany.
Forum for Collaborative Research. Washington, DC, USA.
Forum for Collaborative Research. Washington, DC, USA.
Fred Hutchinson Cancer Research Center. Seattle, WA, USA.
Vitalant Research Institute, San Francisco, CA, USA / Edward Grebe Consulting. Cape Town, South Africa.
ViiV Healthcare. Research Triangle Park, NC, USA.
Gilead Sciences. Foster City, CA, USA.
Fred Hutchinson Cancer Research Center. Seattle, WA, USA.
Fred Hutchinson Cancer Research Center. Seattle, WA, USA.
Edward Grebe Consulting. Cape Town, South Africa.
University of Washington. Seattle, WA, USA.
Independent Consultant. Washington, DC, USA.
Merck & Co., Inc. Kenilworth, NJ, USA.
Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM). Bonn, Germany.
Forum for Collaborative Research. Washington, DC, USA.
Forum for Collaborative Research. Washington, DC, USA.
Abstract
Standard-of-care HIV pre-exposure prophylaxis (PrEP) is highly efficacious, but uptake of and persistence on a daily oral pill is low in many settings. Evaluation of alternate PrEP products will require innovation to avoid the unpractically large sample sizes in noninferiority trials. We propose estimating HIV incidence in people not on PrEP as an external counterfactual to which on-PrEP incidence in trial subjects can be compared. HIV recent infection testing algorithms (RITAs), such as the limiting antigen avidity assay plus viral load used on specimens from untreated HIV positive people identified during screening, is one possible approach. Its feasibility is partly dependent on the sample size needed to ensure adequate power, which is impacted by RITA performance, the number of recent infections identified, the expected efficacy of the intervention, and other factors. Screening sample sizes to support detection of an 80% reduction in incidence for 3 key populations are more modest, and comparable to the number of participants in recent phase III PrEP trials. Sample sizes would be significantly larger in populations with lower incidence, where the false recency rate is higher or if PrEP efficacy is expected to be lower. Our proposed counterfactual approach appears to be feasible, offers high statistical power, and is nearly contemporaneous with the on-PrEP population. It will be important to monitor the performance of this approach during new product development for HIV prevention. If successful, it could be a model for preventive HIV vaccines and prevention of other infectious diseases.
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