CoChat
Sign Up
Cited by 1,878HIV/AIDS Research and InterventionsHIV/AIDS drug development and treatmentHIV, Drug Use, Sexual Risk

The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.

Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial.

Open access
McCormack, Sheena, Dunn, David T, Desai, Monica, Dolling, David I, Gafos, Mitzy, Gilson, Richard, Sullivan, Ann K, Clarke, Amanda, Reeves, Iain, Schembri, Gabriel, Mackie, Nicola, Bowman, Christine, Lacey, Charles J, Apea, Vanessa, Brady, Michael, Fox, Julie, Taylor, Stephen, Antonucci, Simone, Khoo, Saye H, Rooney, James, Nardone, Anthony, Fisher, Martin, McOwan, Alan, Phillips, Andrew N, Johnson, Anne M, Gazzard, Brian, Gill, Owen N·2016·The Lancet
DOI 10.1016/s0140-6736(15)00056-2PMC PMC4700047
Open this paper in CoChat — free accountOpen PDF

Abstract

BACKGROUND: Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir-emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. METHODS: PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). FINDINGS: We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64-96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3-11·3). 13 men (90% CI 9-23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients. INTERPRETATION: In this high incidence population, daily tenofovir-emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection. FUNDING: MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/s0140-6736(15)00056-2

Cites

24 of 24 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 Trial profile *First to deferred and subsequently to immediate; considered in the deferred group for analyses but continued on pre-exposure prophylaxis. †19 pairs of partners were allocated to the same group (14 to immediate, five to deferred) including six pairs (all assigned to the immediate group) not enrolled concurrently. ‡One participant who was allocated to the deferred group was prescribed immediate pre-exposure prophylaxis in error; he was included in the deferred group for analyses but continued on pre-exposure prophylaxis. §Includes unable to contact, moved away, and non-attendance as no longer at risk. ¶HIV status ascertained if confirmed HIV-positive or HIV-negative test after 48 weeks or after Oct 13, 2014.
Figure 1 Trial profile *First to deferred and subsequently to immediate; considered in the deferred group for analyses but continued on pre-exposure prophylaxis. †19 pairs of partners were allocated to the same group (14 to immediate, five to deferred) including six pairs (all assigned to the immediate group) not enrolled concurrently. ‡One participant who was allocated to the deferred group was prescribed immediate pre-exposure prophylaxis in error; he was included in the deferred group for analyses but continued on pre-exposure prophylaxis. §Includes unable to contact, moved away, and non-attendance as no longer at risk. ¶HIV status ascertained if confirmed HIV-positive or HIV-negative test after 48 weeks or after Oct 13, 2014.CC BY · PubMed Central
Figure 2 Incident HIV infections Left bound for each HIV case represents last non-reactive HIV test; right bound represents first reactive HIV test. The dotted line represents time when participants in the deferred group became eligible for pre-exposure prophylaxis under the original protocol. *Had a stored enrolment sample that tested positive for HIV RNA but was retained in the analysis.
Figure 2 Incident HIV infections Left bound for each HIV case represents last non-reactive HIV test; right bound represents first reactive HIV test. The dotted line represents time when participants in the deferred group became eligible for pre-exposure prophylaxis under the original protocol. *Had a stored enrolment sample that tested positive for HIV RNA but was retained in the analysis.CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 24 references

Research works printed but not linked: 2

  1. Antonucci S, Desai M, Dolling D, et al. The UK PROUD PrEP Pilot study: a baseline analysis. 20th International AIDS Conference; July 20–25, 2014; Melbourne, Australia. Abstract THPE197.
  2. Molina J-M, Capitant C, Charreau I, et al. On demand PrEP with oral TDF-FTC in MSM: results of the ANRS Ipergay trial. Conference on Retroviruses and Opportunistic Infections; Feb 23–26, 2015; Seattle, WA, USA. Abstract 23LB.

Cited by

Sorted by citations

Items 401–500 of 1,000

Related

See all

Metadata

Authors
McCormack, S., Dunn, D. T., Desai, M., Dolling, D. I., Gafos, M., Gilson, R., Sullivan, A. K., Clarke, A., Reeves, I., Schembri, G., Mackie, N., Bowman, C., Lacey, C. J., Apea, V., Brady, M., Fox, J., Taylor, S., Antonucci, S., Khoo, S. H., Rooney, J., Nardone, A., Fisher, M., McOwan, A., Phillips, A. N., Johnson, A. M., Gazzard, B., & Gill, O. N.
Affiliations
  • Chelsea and Westminster Hospital NHS Foundation Trust (GB)
  • MRC Clinical Trials Unit at UCL (GB)
  • Public Health England (GB)
  • Central and North West London NHS Foundation Trust (GB)
  • Royal Sussex County Hospital (GB)
  • Homerton University Hospital NHS Foundation Trust (GB)
  • Imperial College Healthcare NHS Trust (GB)
  • Sheffield Teaching Hospitals NHS Foundation Trust (GB)
  • University of York (GB)
  • Barts Health NHS Trust (GB)
  • King's College Hospital NHS Foundation Trust (GB)
  • Guy's and St Thomas' NHS Foundation Trust (GB)
  • Heart of England NHS Foundation Trust (GB)
  • University of Liverpool (GB)
  • Gilead Sciences (United States) (US)
  • University College London (GB)
Corresponding author
McCormack, Sheena
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2016-01
Volume
387
Issue
10013
Pages
53-60
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(15)00056-2
PMC
PMC4700047
OpenAlex
W1413161224
Cited by
1,878
References
24
Citations by year
2026: 61 · 2025: 122 · 2024: 136 · 2023: 163 · 2022: 174 · 2021: 201 · 2020: 181 · 2019: 240 · 2018: 207 · 2017: 213 · 2016: 152
FWCI
154.11
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • National Institute for Health and Care Research (ACF-2008-20-002, NF-SI-0508-10244)
  • Public Health England
Topics
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
  • Health Sciences › Medicine › Epidemiology › HIV, Drug Use, Sexual Risk
Keywords
tenofovir disoproxil fumarate, emtricitabine, risk compensation, men who have sex with men, post-exposure prophylaxis, trial retention, PrEP adherence, sexual health clinics
MeSH terms
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination, Adult, Bisexuality, England, Humans, Male, Pilot Projects, HIV-1, HIV Infections, Treatment Outcome, Condoms, Homosexuality, Male, Anti-HIV Agents, Unsafe Sex, Pre-Exposure Prophylaxis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review