Evidence map›Paper›PMID 25300863›Full record

Trial reportThe Lancet. Infectious diseases2014

Single-agent tenofovir versus combination emtricitabine plus tenofovir for pre-exposure prophylaxis for HIV-1 acquisition: an update of data from a randomised, double-blind, phase 3 trial.

Jared M Baeten, Deborah Donnell, Nelly R Mugo, Patrick Ndase, Katherine K Thomas, James D Campbell, Jonathan Wangisi, Jordan W Tappero, Elizabeth A Bukusi, Craig R Cohen and 17 more

Registry-linked trialAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Infectious diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00557245 (Parallel Comparison of Tenofovir and Emtricitabine/Tenofovir Pre-Exposure Prophylaxis to Prevent HIV-1 Acquisition Within HIV-1 Discordant Couples), which is not on this map. Cited by 82 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 9 pooled it
8.1field-weighted citation impact, top 2% of its field
1 · What the graph read from 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.

2 · The registry

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.

NCT00557245 phase3completednot on this map

Parallel Comparison of Tenofovir and Emtricitabine/Tenofovir Pre-Exposure Prophylaxis to Prevent HIV-1 Acquisition Within HIV-1 Discordant Couples

TypeinterventionalSponsorUniversity of WashingtonRan2008 to 2013Enrolled4,758ConditionsHIV-1 Infections, HIV InfectionsArmsTenofovir Disoproxil Fumarate (TDF), Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF), Placebo
3 · Its place in the literature

Who cites it

82 citing papers in PubMed, 9 syntheses or guidelines pooled it, 119 citations in OpenAlex.

  1. Canadian guideline on HIV pre- and postexposure prophylaxis: 2025 update.CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2025
    Guideline
  2. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2025
    Guideline
  3. Pooled it
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  6. Risk of sexual transmission of human immunodeficiency virus with antiretroviral therapy, suppressed viral load and condom use: a systematic review.CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2018
    Pooled it
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  8. Canadian guideline on HIV pre-exposure prophylaxis and nonoccupational postexposure prophylaxis.CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2017
    Guideline
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22 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors at 14 institutions in 4 countries.

Jared M BaetenDepartment of Global Health, University of Washington, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA. Electronic address: jbaeten@uw.edu.
Deborah DonnellDepartment of Global Health, University of Washington, Seattle, WA, USA; Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Nelly R MugoDepartment of Global Health, University of Washington, Seattle, WA, USA; Centres for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.
Patrick NdaseDepartment of Global Health, University of Washington, Seattle, WA, USA.
Katherine K ThomasDepartment of Global Health, University of Washington, Seattle, WA, USA.
James D CampbellCenters for Disease Control and Prevention, Entebbe, Uganda.
Jonathan WangisiAIDS Support Organization, Kampala, Uganda.
Jordan W TapperoCenters for Disease Control and Prevention, Atlanta, GA, USA.
Elizabeth A BukusiDepartment of Global Health, University of Washington, Seattle, WA, USA; Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya; Department of Obstetrics and Gynecology, University of Nairobi and Kenyatta National Hospital, Nairobi, Kenya; Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA, USA.
Craig R CohenDepartment of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA, USA.
Elly KatabiraInfectious Disease Institute, Makerere University, Kampala, Uganda.
Allan RonaldInfectious Disease Institute, Makerere University, Kampala, Uganda; Department of Medicine, University of Manitoba, Winnipeg, Canada.
Elioda TumwesigyeKabwohe Clinical Research Center, Kabwohe, Uganda.
Edwin WereDepartment of Reproductive Health, Moi University, Eldoret, Kenya.
Kenneth H FifeDepartment of Medicine, Indiana University, Indianapolis, IN, USA.
James KiarieDepartment of Global Health, University of Washington, Seattle, WA, USA; Department of Obstetrics and Gynecology, University of Nairobi and Kenyatta National Hospital, Nairobi, Kenya.
Carey FarquharDepartment of Global Health, University of Washington, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA.
Grace John-StewartDepartment of Global Health, University of Washington, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA.
Lara KidoguchiDepartment of Global Health, University of Washington, Seattle, WA, USA.
Robert W CoombsDepartment of Medicine, University of Washington, Seattle, WA, USA; Department of Laboratory Medicine, University of Washington, Seattle, WA, USA.
Craig HendrixDepartment of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Mark A MarzinkeDepartment of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Lisa FrenkelDepartment of Laboratory Medicine, University of Washington, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA; Seattle Children's Hospital Research Institute, Seattle, WA, USA.
Jessica E HabererMassachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
David BangsbergMassachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Connie CelumDepartment of Global Health, University of Washington, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA.
Partners PrEP Study Team
University of Washington · USHarvard University · USJohns Hopkins University · USMakerere University · UGUniversity of California, San Francisco · USCenters for Disease Control and Prevention · UGCenters for Disease Control and Prevention · USFred Hutch Cancer Center · USIndiana University – Purdue University Indianapolis · USJoint Clinical Research Centre · UGKenyatta National Hospital · KEMoi University · KESeattle Children's Hospital · USThe AIDS Support Organization · UG

Funding

University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI Kenneth Sherr · 1988 to 2026
$104.9M
Ujima Mentoring ProgramP30MH062246 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Sheri Ann Lippman · 2001 to 2026
$57.4M
Pediatric HIV-1 in Africa: Pathogenesis and ManagementK24HD054314 · NICHD · UNIVERSITY OF WASHINGTON · PI JOHN-STEWART, GRACE C. · 2006 to 2016
$1.2M
NIAID NIH HHS P30 AI027757NICHD NIH HHS K24 HD054314NIMH NIH HHS P30 MH062246
6 · The paper itself

Abstract

backgroundAntiretroviral pre-exposure prophylaxis (PrEP), with daily oral tenofovir disoproxil fumarate or tenofovir disoproxil fumarate in combination with emtricitabine, has been shown to be efficacious for HIV-1 prevention. Although the use of more than one antiretroviral agent is essential for effective HIV-1 treatment, more than one agent might not be required for effective prophylaxis. We assessed the efficacy of single-agent tenofovir disoproxil fumarate relative to combination emtricitabine plus tenofovir disoproxil fumarate as PrEP.

methodsWe did a randomised, double-blind, placebo-controlled three-group phase 3 trial of daily oral tenofovir disoproxil fumarate and emtricitabine plus tenofovir disoproxil fumarate PrEP in HIV-1 uninfected individuals in heterosexual HIV-1 serodiscordant couples from Kenya and Uganda. After an interim review, the trial's placebo group was discontinued and thereafter the active groups were continued, and participants initially randomly assigned to placebo were offered rerandomisation in a 1:1 ratio to tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate as PrEP. The primary endpoints were HIV-1 seroconversion and safety. This trial is registered with ClinicalTrials.gov, number NCT00557245.

findings4410 (99·6%) of 4427 couples received tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate and were followed up for HIV-1 acquisition. Of 52 incident HIV-1 infections, 31 occurred in individuals assigned tenofovir disoproxil fumarate (incidence 0·71 cases per 100 person-years) and 21 were in those assigned emtricitabine plus tenofovir disoproxil fumarate (0·48 cases per 100 person-years); HIV-1 incidence in the placebo group until discontinuation was two cases per 100 person-years. HIV-1 prevention efficacy with emtricitabine plus tenofovir disoproxil fumarate was not significantly different from that of tenofovir disoproxil fumarate alone (hazard ratio [HR] 0·67, 95% CI 0·39-1·17; p=0·16). Detection of tenofovir in plasma samples, compared with no detection and as measured in seroconverters and a subset of non-seroconverters, was associated with an 85% relative risk reduction in HIV-1 acquisition for the tenofovir disoproxil fumarate group (HR 0·15, 95% CI 0·06-0·37; p<0·0001) and 93% for the emtricitabine plus tenofovir disoproxil fumarate group (0·07, 0·02-0·23; p<0·0001). No significant differences were noted in the frequency of deaths, serious adverse events, or serum creatinine and phosphorus abnormalities between the two groups.

interpretationThese results do not rule out the potential for a slight difference in HIV-1 protection with tenofovir disoproxil fumarate compared with emtricitabine plus tenofovir disoproxil fumarate, but show that once-daily oral tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate regimens both provide high protection against HIV-1 acquisition in heterosexual men and women.

fundingBill & Melinda Gates Foundation and US National Institutes of Health.

Indexed as

AdenineAdultAnti-HIV AgentsDeoxycytidineDouble-Blind MethodDrug Therapy, CombinationEmtricitabineFemaleHIV-1HIV InfectionsHumansKenyaMaleOrganophosphonatesPlacebosPre-Exposure ProphylaxisAdenineAnti-HIV AgentsDeoxycytidineEmtricitabineOrganophosphonatesPlacebosTenofovir

Identifiers

PMID25300863
PMCPMC4252589
OpenAlexW2134966461

What OpenQuestion holds

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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.