ReviewHIV clinical trials
HIV prevention trial design in an era of effective pre-exposure prophylaxis.
Review in HIV clinical trials. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Association between rectal gonorrhoea and HIV incidence in men who have sex with men: a meta-analysis.Sexually transmitted infections · 2022Pooled it
- 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
- Disseminated Effects in Agent-Based Models: A Potential Outcomes Framework and Application to Inform Preexposure Prophylaxis Coverage Levels for HIV Prevention.American journal of epidemiology · 2021Trial
- Brief Report: Routine Use of Oral PrEP in a Phase 2 Rectal Microbicide Study of Tenofovir Reduced-Glycerin 1% Gel (MTN-017).Journal of acquired immune deficiency syndromes (1999) · 2019Trial
- A Population-Based HIV Vaccine Efficacy Trial Design: Statistical Framework and Design Considerations.Vaccines · 2026Review
- Human immunodeficiency virus vaccines: Advances, challenges and future perspectives.World journal of virology · 2026Review
- Counterfactual Groups to Assess Vaccine or Treatment Efficacy in HIV Prevention Trials in High-Risk Populations in Uganda.Vaccines · 2025Article
- Research designs to generate evidence of HIV post-exposure prophylaxis effectiveness for new long-acting agents.Journal of the International AIDS Society · 2025Article
- Challenges in estimating the counterfactual placebo HIV incidence rate from a registration cohort: The PrEPVacc trial.Clinical trials (London, England) · 2025Article
- Perspectives on Design Approaches for HIV Prevention Efficacy Trials.AIDS research and human retroviruses · 2024Article
- Estimating counterfactual placebo HIV incidence in HIV prevention trials without placebo arms based on markers of HIV exposure.Clinical trials (London, England) · 2024Article
- Promising results of HIV prevention trials highlight the benefits of collaboration in global health: The perspective of the Forum HIV Recency Assay Working Group.PLOS global public health · 2024Article
- 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
- Use of propensity score matching to create counterfactual group to assess potential HIV prevention interventions.Scientific reports · 2021Article
- Willingness of female sex workers in Kampala, Uganda to participate in future HIV vaccine trials: a case control study.BMC public health · 2020Article
- Novel Approaches for Development of Human Immunodeficiency Virus Preexposure Prophylaxis Agents.The Journal of infectious diseases · 2020Article
- Advancing Novel PrEP Products - Alternatives to Non-Inferiority.Statistical communications in infectious diseases · 2019Article
- The Connection between the Averted Infections Ratio and the Rate Ratio in Active-control Trials of Pre-exposure Prophylaxis Agents.Statistical communications in infectious diseases · 2019Article
- The averted infections ratio: a novel measure of effectiveness of experimental HIV pre-exposure prophylaxis agents.The lancet. HIV · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
Pre-exposure prophylaxis (PrEP) has demonstrated remarkable effectiveness protecting at-risk individuals from HIV-1 infection. Despite this record of effectiveness, concerns persist about the diminished protective effect observed in women compared with men and the influence of adherence and risk behaviors on effectiveness in targeted subpopulations. Furthermore, the high prophylactic efficacy of the first PrEP agent, tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), presents challenges for demonstrating the efficacy of new candidates. Trials of new agents would typically require use of non-inferiority (NI) designs in which acceptable efficacy for an experimental agent is determined using pre-defined margins based on the efficacy of the proven active comparator (i.e. TDF/FTC) in placebo-controlled trials. Setting NI margins is a critical step in designing registrational studies. Under- or over-estimation of the margin can call into question the utility of the study in the registration package. The dependence on previous placebo-controlled trials introduces the same issues as external/historical controls. These issues will need to be addressed using trial design features such as re-estimated NI margins, enrichment strategies, run-in periods, crossover between study arms, and adaptive re-estimation of sample sizes. These measures and other innovations can help to ensure that new PrEP agents are made available to the public using stringent standards of evidence.
Indexed as
Identifiers
What OpenQuestion holds
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.