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

HIV Infections Clinical Trial

Official title:

A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Acyclovir for the Reduction of HIV Acquisition Among High-Risk HSV-2 Seropositive, HIV Seronegative Individuals

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00076232
• Other study ID #: HPTN 039
• Secondary ID: 1R01AI0520545U01
• Status: Completed
• Phase: Phase 3
• First received: January 15, 2004
• Last updated: December 29, 2010
• Start date: April 2005
• Est. completion date: November 2007

Study information

• Verified date: August 2009
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Other known NCT identifiers

• NCT00068965

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3682
• Est. completion date: November 2007
• Est. primary completion date: June 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria For All Participants:

• 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

Inclusion Criteria for MSM:

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

Inclusion Criteria for WSM:

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

Exclusion Criteria For All Participants:

• 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

Exclusion Criteria for MSM:

• In a mutually monogamous relationship with an HIV uninfected partner throughout the past 2 years

• Reported sex at birth as female

Exclusion Criteria for WSM:

• Pregnancy at screening or enrollment

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Herpes Genitalis
• HIV Infections
• HIV Seronegativity

Intervention

Drug:
• Acyclovir
400 mg tablet taken orally twice daily
• Acyclovir placebo
Oral tablet taken twice daily

Locations

Country	Name	City	State
United States	New York Blood Center	New York City	New York
United States	San Francisco Department of Public Health, AIDS Office, Research Section	San Francisco	California
United States	University of Washington	Seattle	Washington

Sponsors (4)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Mental Health (NIMH), National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

References & Publications (10)

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

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 s — View Citation

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 Ja — View Citation

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 preven — View Citation

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. Review. — View Citation

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 — View Citation

Sánchez 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. — View Citation

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

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. Epub 2001 Dec 14. — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serologically confirmed HIV infection		Throughout study	No
Secondary	Occurrence and frequency of genital ulcers		Throughout study	Yes
Secondary	Proportion of doses missed by study participants assigned to twice-daily acyclovir and twice-daily placebo		Throughout study	No

External Links

•   Click here for more information about acyclovir
•   Haga clic aquí para ver información sobre este ensayo clínico en español.