Acyclovir to Treat Patients Co-infected With HIV and Herpes Viruses in Uganda

This study has been completed.
Sponsor:
Collaborators:
University of Washington
Johns Hopkins University
Translational Genomics Research Institute, Phoenix, Arizona.
Information provided by (Responsible Party):
Steven Reynolds, National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00405821
First received: November 29, 2006
Last updated: August 28, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Herpes Genitalis
Drug: Acyclovir
Drug: Placebo
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • 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)


Secondary Outcome Measures:
  • 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 ]

Enrollment: 440
Study Start Date: November 2006
Study Completion Date: November 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Acyclovir 400mg tablet twice daily Drug: Acyclovir
400mg twice daily for 24 months
Placebo Comparator: Placebo tablet twice daily Drug: Placebo
Placebo tablet twice daily for 24 months

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • 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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00405821

Locations
Uganda
Rakai Health Sciences Program, Uganda Virus Research Institute
Kalisizo, Rakai District, Uganda
Sponsors and Collaborators
University of Washington
Johns Hopkins University
Translational Genomics Research Institute, Phoenix, Arizona.
Investigators
Principal Investigator: Steven J Reynolds, MD National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Steven Reynolds, Scientific Director NIH-Uganda ICER, National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00405821     History of Changes
Other Study ID Numbers: 999907032, 07-I-N032
Study First Received: November 29, 2006
Results First Received: July 18, 2012
Last Updated: August 28, 2012
Health Authority: United States: Federal Government
Uganda: Research Ethics Committee
Uganda: National Council for Science and Technology

Keywords provided by National Institutes of Health Clinical Center (CC):
AIDS
HIV Disease Progression
Quality of Life
HIV Viral Load
Genital Ulcers
HIV
Treatment Naive

Additional relevant MeSH terms:
Herpes Genitalis
Herpes Simplex
Acquired Immunodeficiency Syndrome
HIV Infections
DNA Virus Infections
Genital Diseases, Female
Genital Diseases, Male
Herpesviridae Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Acyclovir
Anti-Infective Agents
Antiviral Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014