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Cited by 524HIV/AIDS Research and InterventionsHerpesvirus Infections and TreatmentsHIV Research and Treatment

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

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Celum, C., Wald, A., Lingappa, J.R., Magaret, A.S., Wang, R.S., Mugo, N., Mujugira, A., Baeten, J.M. +37 more·2010·New England Journal of Medicine
DOI 10.1056/nejmoa0904849PMC PMC2838503
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Abstract

BACKGROUND: Most 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. METHODS: We 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. RESULTS: A 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. CONCLUSIONS: Daily 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.)

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  • Use of acyclovir had no effect on HIV transmission in a large randomized controlled trial of mixed-status heterosexual couples where the partner with HIV was also HSV-2 seropositive.

    “Use of acyclovir had no effect on HIV transmission.”

    From Sexually Transmitted Infections Treatment Guidelines, 2021 (2021) · cites this paper as [88]

  • Providing HSV treatment to persons with HIV and HSV infection has not demonstrated benefit in reducing HIV acquisition among uninfected partners.

    “Providing HSV treatment to persons with HIV and HSV infection has not demonstrated benefit in reducing HIV acquisition among uninfected partners.”

    From Sexually Transmitted Infections Treatment Guidelines, 2021 (2021) · cites this paper as [88]

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Authors
Celum, C., Wald, A., Lingappa, J. R., Magaret, A. S., Wang, R. S., Mugo, N., Mujugira, A., Baeten, J. M., Mullins, J. I., Hughes, J. P., Bukusi, E. A., Cohen, C. R., Katabira, E., Ronald, A., Kiarie, J., Farquhar, C., Stewart, G. J., Makhema, J., Essex, M., Were, E., Fife, K. H., de Bruyn, G., Gray, G. E., McIntyre, J. A., Manongi, R., Kapiga, S., Coetzee, D., Allen, S., Inambao, M., Kayitenkore, K., Karita, E., Kanweka, W., Delany, S., Rees, H., Vwalika, B., Stevens, W., Campbell, M. S., Thomas, K. K., Coombs, R. W., Morrow, R., Whittington, W. L. H., McElrath, M. J., Barnes, L., Ridzon, R., & Corey, L.
Affiliations
  • University of Washington (US)
  • Kenya Medical Research Institute (KE)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2010-02-04
Volume
362
Issue
5
Pages
427-439
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa0904849
PMC
PMC2838503
OpenAlex
W2167876918
Cited by
524
References
36
Citations by year
2026: 9 · 2025: 11 · 2024: 8 · 2023: 15 · 2022: 12 · 2021: 11 · 2020: 11 · 2019: 19 · 2018: 17 · 2017: 33 · 2016: 28 · 2015: 47 · 2014: 35 · 2013: 57 · 2012: 67
FWCI
54.56
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • University of Nairobi Research Archive (University of Nairobi) (submittedVersion)
Funders
  • Emory University
  • London School of Hygiene and Tropical Medicine
  • University of Cape Town
  • National Institute of Mental Health (R01MH066767)
  • National Institute of Allergy and Infectious Diseases (AI38858, AI 27757, P01AI030731, U01AI038858, P30AI027757)
Topics
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
  • Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Keywords
acyclovir, HIV-1 transmission, herpes simplex virus type 2, suppressive antiviral therapy, serodiscordant couples, HIV-1 seroconversion, genital ulcers, HIV-1 viral load, antiretroviral therapy
MeSH terms
Acyclovir, Adolescent, Adult, Antiviral Agents, Female, Follow-Up Studies, Herpes Genitalis, Humans, Male, Patient Compliance, Pregnancy, RNA, Viral, HIV-1, HIV Infections, AIDS-Related Opportunistic Infections, Herpesvirus 2, Human, CD4 Lymphocyte Count, Unsafe Sex, Kaplan-Meier Estimate, Young Adult, Intention to Treat Analysis

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