A Study of Acyclovir to Help Prevent HIV Infection in People With Genital Herpes

NCT ID: NCT00076232

Last Updated: 2010-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

3682 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-04-30

Study Completion Date

2007-11-30

Brief Summary

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Genital herpes (HSV-2) is the most common cause of genital sores worldwide, and the presence of genital sores is a significant risk factor for becoming infected with HIV. This study will test the effectiveness of twice-daily dosing of acyclovir, a commonly prescribed anti-herpes drug, in preventing HIV infection in HSV-2 infected women who sleep with men (WSM) and men who sleep with men (MSM).

Study hypothesis: Given that genital herpes is a significant risk factor to HIV acquisition, twice-daily HSV-2 suppressive therapy - 400 mg of acyclovir - will prevent HIV infection among high risk, HSV-2 seropositive WSM and MSM.

Detailed Description

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Many studies have shown that prior HSV-2 infection is associated with an increased risk for HIV infection. Acyclovir is the most widely studied and clinically utilized antiviral for the suppression of HSV-2 infection. This study will evaluate the efficacy of twice-daily dosing of acyclovir in preventing HIV infection in both WSM and MSM with genital herpes. For this study, WSM will be enrolled in Lusaka, Zambia; Harare, Zimbabwe; and Johannesburg, South Africa; MSM will be enrolled in Lima and Pucallpa, Peru; Seattle, Washington, USA; New York City, New York, USA; and San Francisco, California, USA.

Participants will be enrolled for 12 months in this study and will be randomly assigned to one of two study arms. The first arm will receive 400 mg acyclovir twice daily; the second arm will receive placebo. Follow-up visits will occur monthly. Participants will be tested for STDs, including HIV and syphilis, at each visit and treated as necessary; participants will also be given adherence and condom counseling, risk behavior and sexual history questionnaires, and genital symptoms questionnaires at all study visits. Medical history will be assessed and participants will undergo blood work at Months 3, 6, 9, and 12.

Conditions

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HIV Infections HIV Seronegativity Herpes Genitalis

Keywords

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HIV Seronegativity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Caregivers

Study Groups

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1

Participants will receive acyclovir for the duration of the study

Group Type EXPERIMENTAL

Acyclovir

Intervention Type DRUG

400 mg tablet taken orally twice daily

2

Participants will receive acyclovir placebo for the duration of the trial

Group Type PLACEBO_COMPARATOR

Acyclovir placebo

Intervention Type DRUG

Oral tablet taken twice daily

Interventions

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Acyclovir

400 mg tablet taken orally twice daily

Intervention Type DRUG

Acyclovir placebo

Oral tablet taken twice daily

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* HIV-uninfected
* HSV-2 infected
* Plans to stay in the area for the duration of study participation
* Willing and able to provide consent, undergo clinical evaluations, take study drugs, adhere to follow-up schedule, and provide adequate locator information


* At least 1 episode of anal intercourse with another man within 6 months of study entry


* At least 1 episode of unprotected vaginal sex within 6 months of study entry

Exclusion Criteria

* Current enrollment in another HIV vaccine or prevention trial
* History of adverse reaction to acyclovir
* Current or planned use of famiciclovir, valacyclovir, or acyclovir for genital HSV. Use of short-course antiviral therapy for herpes zoster after enrollment is allowed.
* Known plans for travel away from study site for more than 2 months


* In a mutually monogamous relationship with an HIV uninfected partner throughout the past 2 years
* Reported sex at birth as female


* Pregnancy at screening or enrollment
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role collaborator

National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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DAIDS

Principal Investigators

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Connie Celum, MD, MPH

Role: STUDY_CHAIR

University of Washington

Anna Wald, MD, MPH

Role: STUDY_CHAIR

University of Washington

Locations

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San Francisco Department of Public Health, AIDS Office, Research Section

San Francisco, California, United States

Site Status

New York Blood Center

New York, New York, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Bruisten SM. Genital ulcers in women. Curr Womens Health Rep. 2003 Aug;3(4):288-98.

Reference Type BACKGROUND
PMID: 12844451 (View on PubMed)

Mbopi-Keou FX, Robinson NJ, Mayaud P, Belec L, Brown DW. Herpes simplex virus type 2 and heterosexual spread of human immunodeficiency virus infection in developing countries: hypotheses and research priorities. Clin Microbiol Infect. 2003 Mar;9(3):161-71. doi: 10.1046/j.1469-0691.2003.00550.x.

Reference Type BACKGROUND
PMID: 12667248 (View on PubMed)

Schacker T. The role of HSV in the transmission and progression of HIV. Herpes. 2001 Jul;8(2):46-9.

Reference Type BACKGROUND
PMID: 11867018 (View on PubMed)

Wald A, Link K. Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: a meta-analysis. J Infect Dis. 2002 Jan 1;185(1):45-52. doi: 10.1086/338231. Epub 2001 Dec 14.

Reference Type BACKGROUND
PMID: 11756980 (View on PubMed)

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; HPTN 039 Protocol Team. 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. Lancet. 2008 Jun 21;371(9630):2109-19. doi: 10.1016/S0140-6736(08)60920-4.

Reference Type RESULT
PMID: 18572080 (View on PubMed)

Reid SE, Dai JY, Wang J, Sichalwe BN, Akpomiemie G, Cowan FM, Delany-Moretlwe S, Baeten JM, Hughes JP, Wald A, Celum C. Pregnancy, contraceptive use, and HIV acquisition in HPTN 039: relevance for HIV prevention trials among African women. J Acquir Immune Defic Syndr. 2010 Apr;53(5):606-13. doi: 10.1097/QAI.0b013e3181bc4869.

Reference Type RESULT
PMID: 19838129 (View on PubMed)

Watson-Jones D, Wald A, Celum C, Lingappa J, Weiss HA, Changalucha J, Baisley K, Tanton C, Hayes RJ, Marshak JO, Gladden RG, Koelle DM. Use of acyclovir for suppression of human immunodeficiency virus infection is not associated with genotypic evidence of herpes simplex virus type 2 resistance to acyclovir: analysis of specimens from three phase III trials. J Clin Microbiol. 2010 Oct;48(10):3496-503. doi: 10.1128/JCM.01263-10. Epub 2010 Aug 11.

Reference Type RESULT
PMID: 20702659 (View on PubMed)

Curlin ME, Cassis-Ghavami F, Magaret AS, Spies GA, Duerr A, Celum CL, Sanchez JL, Margolick JB, Detels R, McElrath MJ, Corey L. Serological immunity to adenovirus serotype 5 is not associated with risk of HIV infection: a case-control study. AIDS. 2011 Jan 14;25(2):153-8. doi: 10.1097/QAD.0b013e328342115c.

Reference Type RESULT
PMID: 21150554 (View on PubMed)

Jacob ST, Baeten JM, Hughes JP, Peinado J, Wang J, Sanchez J, Reid SE, Delany-Moretlwe S, Cowan F, Fuchs JD, Koblin B, Griffith S, Wald A, Celum C. A post-trial assessment of factors influencing study drug adherence in a randomized biomedical HIV-1 prevention trial. AIDS Behav. 2011 Jul;15(5):897-904. doi: 10.1007/s10461-010-9853-2.

Reference Type RESULT
PMID: 21104007 (View on PubMed)

Sanchez J, Sal Y Rosas VG, Hughes JP, Baeten JM, Fuchs J, Buchbinder SP, Koblin BA, Casapia M, Ortiz A, Celum C. Male circumcision and risk of HIV acquisition among MSM. AIDS. 2011 Feb 20;25(4):519-23. doi: 10.1097/QAD.0b013e328340fd81.

Reference Type RESULT
PMID: 21099672 (View on PubMed)

Fuchs J, Celum C, Wang J, Hughes J, Sanchez J, Cowan F, Reid S, Delany-Moretlwe S, Corey L, Wald A; HIV Prevention Trials Network 039 Protocol Team. Clinical and virologic efficacy of herpes simplex virus type 2 suppression by acyclovir in a multicontinent clinical trial. J Infect Dis. 2010 Apr 15;201(8):1164-8. doi: 10.1086/651381.

Reference Type DERIVED
PMID: 20214474 (View on PubMed)

Other Identifiers

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1R01AI052054

Identifier Type: NIH

Identifier Source: secondary_id

View Link

5U01AI047981-05

Identifier Type: NIH

Identifier Source: secondary_id

View Link

DAIDS-ES ID 10066

Identifier Type: -

Identifier Source: secondary_id

HPTN 039

Identifier Type: -

Identifier Source: org_study_id

NCT00068965

Identifier Type: -

Identifier Source: nct_alias