Official Title: “A Randomized, Double-Blind, Placebo-Controlled Trial of Acyclovir Prophylaxis Versus Placebo Among HIV-1/HSV-2 Co-Infected Individuals in Uganda”

This study will determine whether acyclovir, a medicine used to treat herpes simplex virus 2 (HSV-2), can slow down the progression (worsening) of HIV disease in people with both HIV and HSV-2 infections. HSV-2 increases the amount of HIV virus in the blood of infected people and may make HIV progress faster. The study will evaluate: "Whether people who take acyclovir can avoid antiretroviral treatment until later in their lives "Whether people who take acyclovir get fewer genital ulcers "How well people are able to take acyclovir and any side effects they experience from it "Differences in the amount of HIV virus in the blood of patients who are and are not taking acyclovir, and how HIV/AIDS is different in these patients.

People 18 years of age and older living in the Rakai district of Uganda who are infected with both HIV (early stage disease) and HSV-2 may be eligible for this study. Participants are randomly assigned to take the study drug, acyclovir, or a placebo (look-alike pill with no active ingredient) daily for 2 years. During this time, they visit the clinic once a month for a routine physical examination. Patients who develop genital ulcers or complications of HIV are treated for the problem, and patients whose HIV disease progresses, requiring them to begin antiretroviral therapy, are treated accordingly.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control

Study Primary Completion Date: August 2009

Interventions that slow HIV-1 disease progression among persons with CD4+ counts above 250 cells/microliter could postpone the need for antiretroviral therapy (ART) and prolong life-expectancy for HIV-infected persons. Herpes simplex virus type 2 (HSV-2) has been shown to up-regulate HIV-1 replication at the cellular level. (1) This finding has been supported by clinical evidence that individuals who are HSV-2 seropositive at the time of HIV-1 seroconversion had higher HIV viral loads at 5 and 15 months post-seroconversion. (2) Earlier studies during the era of zidovudine (Retrovir) monotherapy showed a survival advantage when acyclovir (ACV, Zovirax) was added to the treatment of patients with HIV. (3) Acyclovir prophylaxis has been shown to decrease herpes simplex virus infections and varicella-zoster virus infections among HIV infected patients in a meta-analysis of randomized trials from North America and Europe. This analysis also found a reduced risk of mortality among patients treated with acyclovir. The potential of acyclovir to slow HIV-1 disease progression has not been assessed in a randomized trial in Africa where high rates of HSV-2 infection have been observed among HIV-1 infected individuals. This study proposes to assess the benefits of acyclovir prophylaxis among HIV-1 infected individuals dually infected with HSV-2 who are not on ART through a randomized double-blind placebo controlled trial.

Intervention(s) in this Clinical Trial

• Drug: Acyclovir
  • N/A
• Drug: Placebo
  • N/A

Primary Measures

• To eval the effect of acyclovir prophylaxis vs placebo among HIV-1/HSV-2 co-infected individuals on the progression to AIDS (CD4+ less than 250 cells/microliter or World Health Organization [WHO] stage III/IV dx) and requirement for ART.
  • Time Frame: November 2010
    Safety Issue?: No

Secondary Measures

• Meas diff in # of episodes of genital ulcer dx btw interv and placebo arms;HIV-1 viral load btw interv and placebo arms;Toxicity of acyclovir;Adherence to acyclovir; virologic/immun resp to ART in those who progress to CD+4 less than 250cells/microliter.
  • Time Frame: November 2010
    Safety Issue?: No

INCLUSION CRITERIA:

• 1. Documentation of HIV-1 infection, by either two positive ELISAs or two discrepant
• ELISAs with a confirmatory positive Western Blot
• 2. Documentation of prior HSV-2 infection by Focus Kalon ELISA
• 3. Absolute CD4+ T-cell count of greater than or equal to 300 and less than or equal to 400 cells/microliter within 30 days prior to randomization
• 4. All participants must be receiving Cotrimoxazole prophylaxis as part of standard care unless contraindicated
• 5. Age at least 18 years and above
• 6. Laboratory values (within 30 days prior to randomization)
• 1. Aspartate transaminase (AST) no more than five times (5X) the upper limit of normal (ULN)
• 2. Total bilirubin no more than 2 times ULN
• 3. Creatinine no more than 2.0 mg/dL
• 4. Platelet count at least 50 000/microliter
• 5. Hemoglobin at least 8g/dL
• 7. Written informed consent

EXCLUSION CRITERIA:

• 1. Concurrent malignancy or any other disease state requiring cytotoxic chemotherapy
• 2. Symptomatic for significant HIV-related illnesses (WHO stage III or IV), such as opportunistic infections and malignancies other than mucocutaneous Kaposi's sarcoma.
• A history of AIDS defining opportunistic infections other than mucocutaneous Kaposi's sarcoma or candida or treated tuberculosis
• 3. Active HSV-2 disease as suggested by painful genital ulcer disease at time of screening or enrollment
• 4. Current use of antiretroviral medications or Preventing Mother-to-Child Transmission (PMTCT) use of antiretrovirals within the previous 6 months
• 5. Significant cardiac, pulmonary, kidney, rheumatologic, gastrointestinal, or CNS disease as detectable on routine medical history, physical examination, or screening laboratory studies.
• 6. Psychiatric illness that, in the opinion of the PI, might interfere with the study compliance.
• 7. Active substance abuse or history of prior substance abuse that may interfere with protocol compliance or patient safety.
• 8. CD4+ count less than 300 or more than 400 cells/microliter.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Overall Clinical Trial Officials and Contacts

Overall Contact: Thomas C. Quinn, M.D. (410) 955-7635 tquinn@mail.nih.gov

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00405821

Study ID Number: 999907032

ClinicalTrials.gov Identifier: NCT00405821

Health Authority: United States: Federal Government