The following is a summary of “Estimating counterfactual placebo HIV incidence in HIV prevention trials without placebo arms based on markers of HIV exposure,” published in the October 2023 issue of Infectious Disease by Zhu et al.
Developing new ways to evaluate the effectiveness of HIV prevention interventions is a priority since active-controlled trials are becoming more common. Researchers performed a retrospective study to develop alternative methods for evaluating the efficacy of new HIV prevention interventions in active-controlled trials.
The study proposed an approach for estimating the effectiveness of HIV prevention by using an HIV exposure marker, like incident rectal gonorrhea, to estimate what HIV incidence would be without the prevention method (counterfactual placebo HIV incidence). They established a statistical framework, outlined regression and likelihood-based estimation methods, identified 3 crucial assumptions for valid inferences, assessed its performance with real data, and demonstrated the approach using a recent HIV prevention trial with active controls.
The study obtained highly accurate and precise counterfactual placebo incidence and prevention efficacy estimates with the right assumptions in finite samples. Using data from the DISCOVER trial in men and transgender women who had sex with men and assuming correctly specified assumptions, the estimated prevention efficacy for tenofovir alafenamide plus emtricitabine is 98.1% (95% CI: 96.4%–99.4%) using the working model approach and 98.1% (95% CI: 96.4%–99.7%) using the likelihood-based approach.
The study found that before the HIV exposure marker approach can be used in practice, more research is needed to assess its assumptions, evaluate its performance in trials with placebo arms, and develop improved exposure markers.