Acyclovir to Treat Patients Co-infected With HIV and Herpes Viruses 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 Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Randomized, Double-Blind, Placebo-Controlled Trial of Acyclovir Prophylaxis Versus Placebo Among HIV-1/HSV-2 Co-Infected Individuals in Uganda|
- Progression to AIDS (CD4+ Less Than 250 Cells/Microliter or World Health Org Stage IV dx, Excluding Esophageal Candidiasis) [ Time Frame: 2 years ] [ Designated as safety issue: No ]Evaluate 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 Org stage IV disease, excluding esophageal candidiasis)
- Difference in Number of Episodes of Genital Ulcer Disease Between Arms [ Time Frame: 2 years ] [ Designated as safety issue: No ]We calculated incidence rate for each treatment arm for episodes of genital ulcer disease, and incidence rate ratio.
- HIV-1 Viral Load Difference Between Arms [ Time Frame: baseline, 6 months, 12 months, 18 months, 24 months ] [ Designated as safety issue: No ]We measured mean annual rate of change in log10 viral load (copies/mL) for each group. We assessed difference in annual rate of change in log10 viral load (copies/mL) between groups.
- Toxicity of Acyclovir [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Adherence to Acyclovir [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Virologic and Immunologic Responses to ART in Those Who Progress to CD+4 Less Than 250cells/mL [ Time Frame: 6 months and 12 moths post ART initiation ] [ Designated as safety issue: No ]
|Study Start Date:||November 2006|
|Study Completion Date:||November 2010|
|Primary Completion Date:||October 2010 (Final data collection date for primary outcome measure)|
|Active Comparator: Acyclovir 400mg tablet twice daily||
400mg twice daily for 24 months
|Placebo Comparator: Placebo tablet twice daily||
Placebo tablet twice daily for 24 months
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.
|Rakai Health Sciences Program, Uganda Virus Research Institute|
|Kalisizo, Rakai District, Uganda|
|Principal Investigator:||Steven J Reynolds, MD||National Institute of Allergy and Infectious Diseases (NIAID)|