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
Results First Received: July 18, 2012  
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
Conditions: HIV Infections
Herpes Genitalis
Interventions: Drug: Acyclovir
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
440 HIV+ subjects recruited in rural Rakai, Uganda within the Rakai Health Sciences Program mobile medical clinic during May 2007 thru November 2008

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
All subjects were randomized to study arm, and initiated study treatment at the time of enrollment.

Reporting Groups
  Description
Acyclovir 400mg Tablet Twice Daily No text entered.
Placebo Tablet Twice Daily No text entered.

Participant Flow:   Overall Study
    Acyclovir 400mg Tablet Twice Daily     Placebo Tablet Twice Daily  
STARTED     220     220  
COMPLETED     198     198  
NOT COMPLETED     22     22  
Death                 5                 7  
Lost to Follow-up                 7                 7  
Protocol Violation                 1                 0  
initiated ART                 9                 8  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Acyclovir 400mg Tablet Twice Daily No text entered.
Placebo Tablet Twice Daily No text entered.
Total Total of all reporting groups

Baseline Measures
    Acyclovir 400mg Tablet Twice Daily     Placebo Tablet Twice Daily     Total  
Number of Participants  
[units: participants]
  220     220     440  
Age, Customized  
[units: participants]
     
20-29 years     46     44     90  
30-39 years     94     93     187  
40-49 years     54     53     107  
50+ years     26     30     56  
Gender  
[units: participants]
     
Female     150     161     311  
Male     70     59     129  



  Outcome Measures
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1.  Primary:   Progression to AIDS (CD4+ Less Than 250 Cells/Microliter or World Health Org Stage IV dx, Excluding Esophageal Candidiasis)   [ Time Frame: 2 years ]
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Measure Type Primary
Measure Title Progression to AIDS (CD4+ Less Than 250 Cells/Microliter or World Health Org Stage IV dx, Excluding Esophageal Candidiasis)
Measure Description 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)
Time Frame 2 years  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat analysis of all subjects randomized on the trial meeting the primary endpoint

Reporting Groups
  Description
Acyclovir 400mg Tablet Twice Daily No text entered.
Placebo Tablet Twice Daily No text entered.

Measured Values
    Acyclovir 400mg Tablet Twice Daily     Placebo Tablet Twice Daily  
Number of Participants Analyzed  
[units: participants]
  220     220  
Progression to AIDS (CD4+ Less Than 250 Cells/Microliter or World Health Org Stage IV dx, Excluding Esophageal Candidiasis)  
[units: participants]
  95     110  


Statistical Analysis 1 for Progression to AIDS (CD4+ Less Than 250 Cells/Microliter or World Health Org Stage IV dx, Excluding Esophageal Candidiasis)
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] <0.05
Hazard Ratio (HR) [4] 0.75
95% Confidence Interval ( 0.58 to 0.99 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Intent-to-treat analysis used Cox proportional hazards (CPH) models, adjusting for baseline log10 viral load (VL), CD4 cell count, gender and age to assess the risk of disease progression
[2] Other relevant method information, such as adjustments or degrees of freedom:
  adjusted for baseline log10 viral load, baseline CD4 count, gender, and age
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value was adjusted to include multiple looks at data including an interim efficacy review at 50% and 75% accrual of person-years on study
[4] Other relevant estimation information:
  No text entered.



2.  Secondary:   Difference in Number of Episodes of Genital Ulcer Disease Between Arms   [ Time Frame: 2 years ]

3.  Secondary:   HIV-1 Viral Load Difference Between Arms   [ Time Frame: baseline, 6 months, 12 months, 18 months, 24 months ]

4.  Secondary:   Toxicity of Acyclovir   [ Time Frame: 2 years ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   Yes

5.  Secondary:   Adherence to Acyclovir   [ Time Frame: 2 years ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

6.  Secondary:   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 ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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