Estimating HIV incidence in the era of long-acting PrEP

SY05

Symposium

Track C - Epidemiology and prevention science

Plaza Ballroom/Channel 3

24 July 14:45 - 15:45

Moderators

Nyaradzo Mavis MGODI
University of Zimbabwe, Zimbabwe
Veronica MILLER
Forum for Collaborative Research, United States

As access to PrEP continues to expand, we have seen the design and conduct of HIV prevention trials change. Increasingly, trials of new HIV prevention agents are including an active control arm. This has implications for measuring HIV incidence as a primary endpoint. Alternative approaches to HIV incidence estimation are being explored, including the use of recency testing and estimates of cross-sectional incidence.

14:45 5 min	Introduction Nyaradzo Mavis MGODI University of Zimbabwe, Zimbabwe Veronica MILLER Forum for Collaborative Research, United States

14:50 10 min	Novel scientific approaches for establishing efficacy of new biologics in the era of long-acting PrEP Deborah DONNELL Fred Hutchinson Cancer Research Center, United States

15:00 10 min	Experience with using recency assays to estimate HIV incidence in an HIV prevention trial Moupali DAS Gilead Sciences, United States

15:10 10 min	Experience with using a registrational cohort to estimate HIV incidence: Lessons from PREPVAcc Eugene RUZAGIRA MRC/UVRI and LSHTM Uganda Research Unit, Uganda

15:20 25 min	Live Q&A Veronica MILLER Forum for Collaborative Research, United States Nyaradzo Mavis MGODI University of Zimbabwe, Zimbabwe Moupali DAS Gilead Sciences, United States Deborah DONNELL Fred Hutchinson Cancer Research Center, United States Eugene RUZAGIRA MRC/UVRI and LSHTM Uganda Research Unit, Uganda

AUTHOR

Richard Gray

SUMMARY

This symposium focused on estimating HIV incidence for use as a primary endpoint in clinical trials now that highly effective prevention interventions are available and it is no longer ethical to use a placebo control in most studies. This is highly relevant for future trials of new HIV prevention agents.

HIGHLIGHTS

Deborah Donnell started the session by providing an overview of the use of a "counterfactual placebo" to estimate the background HIV incidence and calculate the efficacy of new agents when the HIV incidence in the control and experimental arms are similar. Incidence estimates could come from other trials, registration cohorts, recency assays, reliable predictors of HIV risk, or from adherence or immune biomarkers. These approaches all rely on significant assumptions. The two presentations that followed provided examples of the application of recency assays and registration cohorts. Moupali Das presented on the use of Recent Infection Testing Algorithms to estimate the background HIV incidence for the Purpose studies of Lenacapavir for PrEP and the prevention of vaginal and rectal HIV. Eugene Ruzagira then described the application of a registration cohort to estimate the background HIV incidence for the PrEPVacc trial. The estimated HIV incidence showed a decline over time and was affected by a cluster of seroconversions and COVID-19 restrictions highlighting the challenges when using these estimation methods. The panel discussion highlighted the complexities and practicalities of conducting trials in an era of highly effective treatments, prevention agents, and in an era of combination prevention.

CRITICAL ASSESSMENT

It is important for innovative trial designs to be developed so that the efficacy of new PrEP and other prevention agents can be evaluated robustly, efficiently, and ethically. The various approaches described in this season show promise, but they all rely on assumptions that could affect the robustness of trial results and there are several practical challenges that will need to be overcome. This includes the ability to obtain regulatory approval for the roll-out of new agents. It is likely that several approaches will be needed for application in trials which could vary for different settings and populations.