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

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ClinicalTrials.gov Identifier: NCT00405821
Recruitment Status : Completed
First Posted : November 30, 2006
Results First Posted : September 28, 2012
Last Update Posted : September 28, 2012
Sponsor:
Collaborators:
University of Washington
Johns Hopkins University
Translational Genomics Research Institute
Information provided by (Responsible Party):
Steven Reynolds, National Institutes of Health Clinical Center (CC)

Tracking Information
First Submitted Date  ICMJE November 29, 2006
First Posted Date  ICMJE November 30, 2006
Results First Submitted Date  ICMJE July 18, 2012
Results First Posted Date  ICMJE September 28, 2012
Last Update Posted Date September 28, 2012
Study Start Date  ICMJE November 2006
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 28, 2012)
Progression to AIDS (CD4+ Less Than 250 Cells/Microliter or World Health Org Stage IV dx, Excluding Esophageal Candidiasis) [ Time Frame: 2 years ]
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)
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00405821 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 28, 2012)
  • Difference in Number of Episodes of Genital Ulcer Disease Between Arms [ Time Frame: 2 years ]
    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 ]
    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 ]
  • Adherence to Acyclovir [ Time Frame: 2 years ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Acyclovir to Treat Patients Co-infected With HIV and Herpes Viruses in Uganda
Official Title  ICMJE A Randomized, Double-Blind, Placebo-Controlled Trial of Acyclovir Prophylaxis Versus Placebo Among HIV-1/HSV-2 Co-Infected Individuals in Uganda
Brief Summary

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.

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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • HIV Infections
  • Herpes Genitalis
Intervention  ICMJE
  • Drug: Acyclovir
    400mg twice daily for 24 months
  • Drug: Placebo
    Placebo tablet twice daily for 24 months
Study Arms  ICMJE
  • Active Comparator: Acyclovir 400mg tablet twice daily
    Intervention: Drug: Acyclovir
  • Placebo Comparator: Placebo tablet twice daily
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 28, 2012)
440
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE November 2010
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Uganda
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT00405821
Other Study ID Numbers  ICMJE 999907032
07-I-N032 ( Other Identifier: NIAID Intramural IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Steven Reynolds, National Institutes of Health Clinical Center (CC)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE
  • University of Washington
  • Johns Hopkins University
  • Translational Genomics Research Institute
Investigators  ICMJE
Principal Investigator: Steven J Reynolds, MD National Institute of Allergy and Infectious Diseases (NIAID)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP