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Cited by 449Herpesvirus Infections and TreatmentsHIV/AIDS Research and InterventionsHIV Research and Treatment

Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial.

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Celum, Connie, Wald, Anna, Hughes, James, Sanchez, Jorge, Reid, Stewart, Delany-Moretlwe, Sinead, Cowan, Frances, Casapia, Martin +8 more·2008·The Lancet
DOI 10.1016/s0140-6736(08)60920-4PMC PMC2650104
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Abstract

Background Across many observational studies, herpes simplex virus type 2 (HSV-2) infection is associated with two-fold to three-fold increased risk for HIV-1 infection. We investigated whether HSV-2 suppression with aciclovir would reduce the risk of HIV-1 acquisition.Methods We undertook a double-blind, randomised, placebo-controlled phase III trial in HIV-negative, HSV-2 seropositive women in Africa and men who have sex with men (MSM) from sites in Peru and the USA. Participants were randomly assigned by block randomisation to twice daily aciclovir 400 mg (n=1637) or matching placebo (n=1640) for 12-18 months, and were seen monthly for dispensation of study drug, adherence counselling and measurement by pill count and self-reporting, and risk reduction counselling, and every 3 months for genital examination and HIV testing. The primary outcome was HIV-1 acquisition and secondary was incidence of genital ulcers. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00076232.Findings 3172 participants (1358 women, 1814 MSM) were included in the primary dataset (1581 in aciclovir group, 1591 in control group). The incidence of HIV-1 was 3.9 per 100 person-years in the aciclovir group (75 events in 1935 person-years of follow-up) and 3.3 per 100 person-years in the placebo group (64 events in 1969 person-years of follow-up; hazard ratio 1.16 [95% CI 0.83-1.62]). Incidence of genital ulcers on examination was reduced by 47% (relative risk 0.53 [0.46-0.62]) and HSV-2 positive genital ulcers by 63% (0.37 [0.31-0.45]) in the aciclovir group. Adherence to dispensed study drug was 94% in the aciclovir group and 94% in the placebo group, and 85% of expected doses in the aciclovir group and 86% in the placebo group. Retention was 85% at 18 months in both groups (1028 of 1212 in aciclovir group, 1030 of 1208 in placebo group). We recorded no serious events related to the study drug.Interpretation Our results show that suppressive therapy with standard doses of aciclovir is not effective in reduction of HIV-1 acquisition in HSV-2 seropositive women and MSM. Novel strategies are needed to interrupt interactions between HSV-2 and HIV-1.

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  • A previous trial reported no benefit of acyclovir in preventing HIV acquisition among persons seropositive for HSV-2.

    “These findings are consistent with a previous trial that reported no benefit of acyclovir in preventing HIV acquisition among persons seropositive for HSV-2 (89).”

    From Sexually Transmitted Infections Treatment Guidelines, 2021 (2021) · cites this paper as [89]

  • 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 [89]

    The Methods describe treatment of HIV-negative, HSV-2-seropositive participants to test whether it reduced their own HIV acquisition. The Discussion explicitly says the study has no bearing on whether HSV-2 suppression reduces HIV transmission from people coinfected with HIV and HSV-2—the claim's population and outcome. (LLM, conf=0.78)

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Research works printed but not linked: 2

  1. [28]Delany S, Mayaud P, Clayton T, et al. Impact of HSV-2 suppressive therapy on genital and plasma HIV-1 RNA in HIV-1 and HSV-2-seropostive women not taking ART: a randomized, placebo-controlled trial in Johannesburg, South Africa. 14th Conference on Retroviruses and Opportunistic Infections; Los Angeles, CA, USA. Foundation for Retrovirology and Human Health; 2007. abstract number 154LB. [Google Scholar]
  2. [29]Dunne E, Whitehead S, Sternberg M, et al. The effect of suppressive acyclovir therapy on HIV cervicovaginal shedding in HIV- and HSV-2-infected women, Chiang Rai, Thailand. 14th Conference on Retroviruses and Opportunistic Infections; Los Angeles, CA, USA. Foundation for Retrovirology and Human Health; 2007. abstract number 30. [Google Scholar]

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Authors
Celum, C., Wald, A., Hughes, J., Sanchez, J., Reid, S., Delany-Moretlwe, S., Cowan, F., Casapia, M., Ortiz, A., Fuchs, J., Buchbinder, S., Koblin, B., Zwerski, S., Rose, S., Wang, J., & Corey, L.
Affiliations
  • University of Washington (US)
  • Centre for Infectious Disease Research in Zambia (ZM)
  • The Royal Free Hospital (GB)
  • Asociación Civil Impacta Salud y Educación (PE)
  • San Francisco Department of Public Health (US)
  • New York Blood Center (US)
  • National Institutes of Health (US)
  • Family Health International 360 (US)
  • Fred Hutch Cancer Center (US)
Corresponding author
Celum, Connie
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2008-06
Volume
371
Issue
9630
Pages
2109-2119
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(08)60920-4
PMC
PMC2650104
OpenAlex
W2097301807
Cited by
449
References
32
Citations by year
2026: 3 · 2025: 3 · 2024: 11 · 2023: 5 · 2022: 8 · 2021: 3 · 2020: 4 · 2019: 10 · 2018: 8 · 2017: 23 · 2016: 15 · 2015: 26 · 2014: 28 · 2013: 34 · 2012: 43
FWCI
55.67
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • National Institute of Child Health and Human Development
  • National Institute of Mental Health
  • Office of AIDS Research
  • National Institute on Drug Abuse
  • University of Washington (U01 AI46749, U01 AI52054)
  • National Institute of Allergy and Infectious Diseases
Topics
  • Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Keywords
acyclovir, HIV-1 acquisition, herpes simplex virus type 2, HIV prevention, men who have sex with men, women, genital ulcers, antiviral therapy
MeSH terms
Acyclovir, Adolescent, Adult, Aged, Antiviral Agents, Double-Blind Method, Female, Herpes Genitalis, Humans, Male, Middle Aged, Sexual Behavior, Sexually Transmitted Diseases, HIV-1, HIV Infections, Proportional Hazards Models, Herpesvirus 2, Human, Homosexuality, Male

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