ReviewThe lancet. HIV2018
The averted infections ratio: a novel measure of effectiveness of experimental HIV pre-exposure prophylaxis agents.
Review in The lancet. HIV, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 35 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
- Incorporating oral PrEP into standard prevention services for South African women: a nested interrupted time-series study.The lancet. HIV · 2021Trial
- 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
- Pharmacological markers of HIV prevention for oral pre-exposure prophylaxis in men who have sex with men.Nature communications · 2026Article
- Pharmacokinetics, Pharmacodynamics, Efficacy and Drug Resistance Selection of Injectable Long-Acting Lenacapavir Pre-Exposure Prophylaxis (PrEP) Against HIV.CPT: pharmacometrics & systems pharmacology · 2026Article
- Sample size estimation for the averted events ratio.Clinical trials (London, England) · 2026Article
- Pharmacokinetics, pharmacodynamics, efficacy and drug resistance selection of injectable long-acting lenacapavir pre-exposure prophylaxis (PrEP) against HIV.medRxiv : the preprint server for health sciences · 2025Article
- Estimands for Clinical Effectiveness of Risk-Reducing Early Salpingectomy in Women With High Risk of Ovarian Cancer.JAMA network open · 2025Observational
- Counterfactual Groups to Assess Vaccine or Treatment Efficacy in HIV Prevention Trials in High-Risk Populations in Uganda.Vaccines · 2025Article
- Challenges in estimating the counterfactual placebo HIV incidence rate from a registration cohort: The PrEPVacc trial.Clinical trials (London, England) · 2025Article
- Active-Controlled Trial Design for HIV Prevention Trials With a Counterfactual Placebo.Statistics in medicine · 2025Article
- Tackling control risk problems in non-inferiority trials.BMJ medicine · 2025Article
- Study design approaches for future active-controlled HIV prevention trials.Statistical communications in infectious diseases · 2024Article
- Interpretation of active-control randomised trials: the case for a new analytical perspective involving averted events.BMC medical research methodology · 2023Review
- Use of propensity score matching to create counterfactual group to assess potential HIV prevention interventions.Scientific reports · 2021Article
- Confidence limits for the averted infections ratio estimated via the counterfactual placebo incidence rate.Statistical communications in infectious diseases · 2021Article
- A Bayesian averted infection framework for PrEP trials with low numbers of HIV infections: application to the results of the DISCOVER trial.The lancet. HIV · 2020Review
- Novel metric for evaluating pre-exposure prophylaxis programme effectiveness in real-world settings.The lancet. HIV · 2020Review
- Article
- Mathematical modeling to reveal breakthrough mechanisms in the HIV Antibody Mediated Prevention (AMP) trials.PLoS computational biology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Tenofovir disoproxil fumarate combined with emtricitabine is a highly effective oral pre-exposure prophylaxis (PrEP) agent for preventing the acquisition of HIV. This effectiveness has consequences for the design and analysis of trials assessing experimental PrEP regimens, which now generally include an active-control tenofovir disoproxil fumarate plus emtricitabine group, rather than a placebo group, as a comparator. Herein, we describe major problems in the interpretation of the primary measure of effectiveness proposed for these trials, namely the ratio of HIV incidence in the experimental agent group to that in the active-control group. We argue that valid interpretation requires an assumption about one of two parameters: either the incidence among trial participants had they not received PrEP or the effectiveness of tenofovir disoproxil fumarate plus emtricitabine within the trial. However, neither parameter is directly observed because of the absence of a no-treatment group, thus requiring the use of external evidence or subjective judgment. We propose an alternative measure of effectiveness based on the concept of averted infections, which incorporates one of these parameters. The measure is simple to interpret, has clinical and public health relevance, and is a natural preservation-of-effect criterion for assessing statistical non-inferiority. Its adoption could also allow the use of smaller sample sizes, currently a major barrier to the assessment of experimental PrEP regimens.
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.