Trial reportJournal of the International AIDS Society2021
Using the adherence-efficacy relationship of emtricitabine and tenofovir disoproxil fumarate to calculate background hiv incidence: a secondary analysis of a randomized, controlled trial.
Trial report in Journal of the International AIDS Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02842086 (A Phase 3, Randomized, Double-blind Study to Evaluate the Safety and Efficacy of Emtricitabine and Tenofovir Alafenamide), which is not on this map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 3, Randomized, Double-blind Study to Evaluate the Safety and Efficacy of Emtricitabine and Tenofovir Alafenamide (F/TAF) Fixed-Dose Combination Once Daily for Pre-Exposure Prophylaxis in Men and Transgender Women Who Have Sex With Men and Are At Risk of HIV-1 Infection
Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- Evaluating adherence in an active-controlled HIV pre-exposure prophylaxis trial (PrEPVacc) to inform the estimation of HIV incidence in a counterfactual placebo arm.HIV research & clinical practice · 2025Trial
- HIV Prevention Among Men Who Have Sex With Men: Tenofovir Alafenamide Combination Preexposure Prophylaxis Versus Placebo.The Journal of infectious diseases · 2024Trial
- Using the adherence-efficacy relationship of emtricitabine and tenofovir disoproxil fumarate to calculate background hiv incidence: a secondary analysis of a randomized, controlled trial.Journal of the International AIDS Society · 2021Trial
- Comparing Approaches for Estimating Counterfactual HIV Incidence Among Populations With High Vulnerability to HIV in Lima, Peru: A Multi-Study Comparative Analysis.Journal of the International AIDS Society · 2026Article
- Sample size estimation for the averted events ratio.Clinical trials (London, England) · 2026Article
- Background HIV Incidence in PURPOSE 1 and 2 PrEP Trials.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Article
- Bridged treatment comparisons: an illustrative application in HIV treatment.American journal of epidemiology · 2025Article
- Challenges in estimating the counterfactual placebo HIV incidence rate from a registration cohort: The PrEPVacc trial.Clinical trials (London, England) · 2025Article
- Dosing forgiveness of oral PrEP for cisgender women remains uncertain.Journal of the International AIDS Society · 2025Article
- Active-Controlled Trial Design for HIV Prevention Trials With a Counterfactual Placebo.Statistics in medicine · 2025Article
- Estimating counterfactual placebo HIV incidence in HIV prevention trials without placebo arms based on markers of HIV exposure.Clinical trials (London, England) · 2024Article
- Generalizing the intention-to-treat effect of an active control from historical placebo-controlled trials: A case study of the efficacy of daily oral TDF/FTC in the HPTN 084 study.Journal of the American Statistical Association · 2024Article
- Study design approaches for future active-controlled HIV prevention trials.Statistical communications in infectious diseases · 2024Article
- Efficacy estimates of oral pre-exposure prophylaxis for HIV prevention in cisgender women with partial adherence.Nature medicine · 2023Article
- Interpretation of active-control randomised trials: the case for a new analytical perspective involving averted events.BMC medical research methodology · 2023Review
- Counterfactual estimation of efficacy against placebo for novel PrEP agents using external trial data: example of injectable cabotegravir and oral PrEP in women.Journal of the International AIDS Society · 2023Article
- Estimating HIV Incident Diagnoses Among Men Who Have Sex With Men Eligible for Pre-exposure Prophylaxis but Not Taking It: Protocol and Feasibility Assessment of Data Sources and Methods.JMIR research protocols · 2023Article
- Clinical Considerations in the Selection of Preexposure Prophylaxis for HIV Prevention in Canada.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2022Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
introductionRandomized trials of new agents for HIV pre-exposure prophylaxis (PrEP) compare against emtricitabine and tenofovir disoproxil fumarate (F/TDF), without a placebo group. We used the well-characterized adherence-efficacy relationship for F/TDF to back-calculate the (non-PrEP) counterfactual background HIV incidence (bHIV) in a randomized trial of a novel PrEP agent and estimate comparative efficacy (to counterfactual bHIV).
methodsThe DISCOVER trial (ClinicalTrials.gov: NCT02842086) randomized 5387 men who have sex with men (MSM) and transgender women who have sex with men and demonstrated non-inferiority of emtricitabine and tenofovir alafenamide (F/TAF) to F/TDF (HIV incidence rate ratio [IRR] 0·47, 95% CI: 0·19 to 1.15). Tenofovir diphosphate (TFV-DP) levels in dried blood spots (DBS) were assessed for all diagnosed with HIV and in a random 10% of the cohort. We used a Bayesian model with a diffuse prior distribution, derived from established data relating tenofovir diphosphate levels to HIV prevention efficacy. This prior, combined with the F/TDF seroconversion rate and tenofovir diphosphate levels in DISCOVER, yielded Bayesian inferences on the counterfactual bHIV.
resultsThere were six versus 11 postbaseline HIV infections (0.14 vs. 0.25/100 person-years [PY]) on F/TAF and F/TDF respectively. Of the 11 on F/TDF, 10 had low, none had medium and one had high tenofovir diphosphate levels; among HIV-negative controls, 5% of the person-time years had low, 9% had medium and 86% had high TFV-DP levels. A non-informative prior distribution for counterfactual bHIV, combined with the prior for TFV-DP level-efficacy relationship, yielded a posterior counterfactual bHIV of 3·4 infections/100 PY (0.80 Bayesian credible interval [CrI] 1·9 to 5·9), which suggests a median HIV efficacy of 96% (0.95 CrI [88% to 99%]) for F/TAF and 93% (0.95 CrI [87% to 96%]) for F/TDF compared to bHIV.
conclusionsBased on the established connection of drug concentrations to PrEP prevention efficacy, a Bayesian framework can be used to estimate a synthetic non-PrEP control group in randomized, active-controlled PrEP trials that include a F/TDF-comparator group.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.