Published in PLOS One on 2026-08-27, this study is presented as an attributed evidence briefing. The excerpts below are the original researchers’ words, reproduced under their Creative Commons Attribution licence. Health Signal has selected the abstract and, where needed, opening background paragraphs; the complete methods, results, limitations and references remain in the linked paper.
Original authors: Sarah E Stansfield, Mia Moore, Marie-Claude Boily, James P Hughes, Deborah Donnell, Linda-Gail Bekker, Dobromir T Dimitrov
Source: PLOS One • DOI 10.1371/journal.pone.0357094
Read the complete primary study ↗ · Creative Commons Attribution licence
From the researchers
Abstract
On-demand oral tenofovir disoproxil fumarate–emtricitabine (TDF/FTC) pre-exposure prophylaxis (PrEP) has been shown to be effective at preventing HIV acquisition among cisgender men and transgender women but is not recommended for cisgender women. On-demand PrEP may improve PrEP uptake, effective use, and persistence in cisgender women. We utilized published oral PrEP adherence-efficacy curves and data from HPTN 067 study to estimate effectiveness of different non-daily PrEP options when used by cisgender women and investigate which sub-groups may benefit most from on-demand PrEP.
We created a synthetic cohort of PrEP users with data on sex act frequency and pill taking from the HPTN 067 Cape Town site. We simulated PrEP use with three PrEP regimens tested in HPTN 067: daily, time-driven (2 pills/week+1 pill after sex), and event-driven (1 pill before+1 pill after sex) PrEP, and hypothesized 2-1-1 PrEP (2 pills before+1 pill each of the two days after sex) for six months each. We estimated PrEP effectiveness based on the number of pills taken around sex acts. Adherence to 2-1-1 PrEP, which was not tested in the HPTN 067, was informed by observed adherence to event-driven PrEP. Assignment to 2-1-1 PrEP based on daily PrEP adherence and sex act frequency was also analyzed.
We estimated median effectiveness of 86% for daily, 47% for time-driven, 42% for event-driven, and 57% for 2-1-1 PrEP. PrEP users with low adherence to daily PrEP (less than 2.8 pills per week) benefited most from on-demand PrEP. In this subgroup, comprising 8% of the cohort, PrEP effectiveness increased from 41% to 44% when switching from daily to 2-1-1 PrEP while pill taking decreased from 2.2 to 1.4 pills per week; population-level effectiveness was unchanged when this subgroup switched to on-demand PrEP. We found no advantage in assigning 2-1-1 PrEP by sex act frequency.
Our model suggests that on-demand PrEP could benefit women with low daily PrEP adherence by decreasing the number of days when pills need to be taken and modestly increasing effectiveness compared to a daily regimen. This would be a valuable and easy-to-implement additional option in places where daily oral PrEP is already available.
1. Introduction
Multiple types of pre-exposure prophylaxis (PrEP) have shown efficacy in preventing HIV acquisition among cisgender women in randomized-controlled trials including daily oral pills (oral tenofovir disoproxil fumarate/emtricitabine, TDF/FTC), topical (vaginal rings), and long-acting injectable (cabotegravir, CAB-LA, and lenacapavir, LEN) regimens [1–5]. These options should empower more women to find HIV prevention that suits their needs and preferences. Within the oral PrEP options, both daily PrEP and 2-1-1 PrEP (2 pills before and 1 pill each of the following two days after sex) have demonstrated efficacy for cisgender men who have sex with men (MSM) and transgender women (TGW) [6], but only daily PrEP is currently recommended for cisgender women [7].
Reading this evidence
Use the full paper to check the study design, participant selection, comparator and outcome definitions before drawing a practical conclusion. An association does not by itself show cause and effect. A reported performance measure needs its denominator and uncertainty. A finding from a particular facility, sample or time period should retain that scope when it is discussed elsewhere.
This briefing makes the source accessible within the wider research & evidence desk. It does not assess an individual patient or certify a product. When considering relevance to another health system, examine the original authors’ account of context and limitations, then seek local implementation evidence. The related reporting below provides other studies to read alongside this one; it is a topic connection, rather than a claim that their results are directly comparable.
© 2026 Sarah E Stansfield, Mia Moore, Marie-Claude Boily, James P Hughes, Deborah Donnell, Linda-Gail Bekker, Dobromir T Dimitrov. Excerpts reproduced under CC BY. Selection, formatting and contextual notes by Health Signal. The researchers are the authors of the source study, not members of Health Signal’s staff.
Explore connected evidence
- Evidence brief: Awareness of and positive attitudes toward HIV pre-exposure prophylaxis among reproductive-aged women in Ghana: A multilevel analysis of the 2022 Demographic and Health Survey
- Evidence brief: Time to treatment initiation in pregnant women with tuberculosis in Cape Town, South Africa
- Evidence brief: Exploring HIV prevention preferences among key populations in Uganda: A qualitative study
