Evidence map›Paper›PMID 20089951›Full record

Trial reportThe New England journal of medicine2010

Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2.

C Celum, A Wald, J R Lingappa, A S Magaret, R S Wang, N Mugo, A Mujugira, J M Baeten, J I Mullins, J P Hughes and 36 more

Registry-linked trialOpen access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00194519 (Phase III Randomized Placebo-Controlled Trial of HSV-2 Suppression to Prevent HIV Transmission Among HIV-Discordant Couples), which is not on this map. Cited by 307 papers, 18 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
307citing papers in PubMed, 18 pooled it
50.7field-weighted citation impact, top 1% 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.

NCT00194519 phase3completednot on this map

Phase III Randomized Placebo-Controlled Trial of HSV-2 Suppression to Prevent HIV Transmission Among HIV-Discordant Couples

TypeinterventionalSponsorUniversity of WashingtonRan2004 to 2010Enrolled3,408ConditionsHIV Infection, Herpes Simplex, Genital, Sexually Transmitted DiseasesArmsGeneric acyclovir, Placebo
3 · Its place in the literature

Who cites it

307 citing papers in PubMed, 18 syntheses or guidelines pooled it, 525 citations in OpenAlex.

  1. 2024 European guidelines for the management of genital herpes.Journal of the European Academy of Dermatology and Venereology : JEADV · 2025
    Guideline
  2. Guideline
  3. Pooled it
  4. Sexually Transmitted Infections Treatment Guidelines, 2021.MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports · 2021
    Guideline
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Interventions for men and women with their first episode of genital herpes.The Cochrane database of systematic reviews · 2016
    Pooled it
  10. Sexually transmitted diseases treatment guidelines, 2015.MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports · 2015
    Guideline
  11. Pooled it
  12. Pooled it
  13. Pooled it
  14. Pooled it
  15. Pooled it
  16. Pooled it
  17. Guideline
  18. Pooled it
  19. Trial
  20. Trial

247 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

46 authors at 1 institution in 2 countries.

C CelumDepartment of Global Health, University of Washington, Harborview Medical Center, 325 Ninth Ave., Box 359927, Seattle, WA 98104, USA.
A Wald
J R Lingappa
A S Magaret
R S Wang
N Mugo
A Mujugira
J M Baeten
J I Mullins
J P Hughes
E A Bukusi
C R Cohen
E Katabira
A Ronald
J Kiarie
C Farquhar
G J Stewart
J Makhema
M Essex
E Were
K H Fife
G de Bruyn
G E Gray
J A McIntyre
R Manongi
S Kapiga
D Coetzee
S Allen
M Inambao
K Kayitenkore
E Karita
W Kanweka
S Delany
H Rees
B Vwalika
W Stevens
M S Campbell
K K Thomas
R W Coombs
R Morrow
W L H Whittington
M J McElrath
L Barnes
R Ridzon
L Corey
Partners in Prevention HSV/HIV Transmission Study Team
University of Namur · BE

Funding

WOMEN'S HEALTH AGENDAU01AI038858 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI BENSON, CONSTANCE ANN · 1996 to 2008
$157.5M
University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI Kenneth Sherr · 1988 to 2026
$104.9M
THE PERINATAL COMPLICATIONS OF ASYMPTOMATIC GENITAL HERPES SIMPLEX VIRUSP01AI030731 · NIAID · UNIVERSITY OF WASHINGTON · PI ZHU, JIA · 1991 to 2017
$34.3M
Couples HIV Counseling &Testing in two African capitalsR01MH066767 · NIMH · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ALLEN, SUSAN A · 2002 to 2006
$6.1M
NIAID NIH HHS AI-27757NIAID NIH HHS AI-38858NIAID NIH HHS P01 AI030731NIAID NIH HHS P01 AI30731NIAID NIH HHS P30 AI027757NIAID NIH HHS U01 AI038858NIMH NIH HHS R01 MH066767NIMH NIH HHS R01 MH66767
6 · The paper itself

Abstract

backgroundMost persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1.

methodsWe conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, > or = 250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses.

resultsA total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P=0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log(10) copies per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2-positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir were observed.

conclusionsDaily acyclovir therapy did not reduce the risk of transmission of HIV-1, despite a reduction in plasma HIV-1 RNA of 0.25 log(10) copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2. (ClinicalTrials.gov number, NCT00194519.)

Indexed as

Herpesvirus 2, HumanHIV-1AcyclovirAdolescentAdultAIDS-Related Opportunistic InfectionsAntiviral AgentsCD4 Lymphocyte CountFemaleFollow-Up StudiesHerpes GenitalisHIV InfectionsHumansIntention to Treat AnalysisKaplan-Meier EstimateMaleAcyclovirAntiviral AgentsRNA, Viral

Identifiers

PMID20089951
PMCPMC2838503
OpenAlexW2167876918

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.