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

History of Changes

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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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 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 ]

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3. Secondary:

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

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4. Secondary:

Toxicity of Acyclovir [ Time Frame: 2 years ]

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: Yes

5. Secondary:

Adherence to Acyclovir [ Time Frame: 2 years ]

Results not yet posted. Anticipated Posting 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 posted. Anticipated Posting Date: No text entered. Safety Issue: No

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

All Principal Investigators ARE employed by the organization sponsoring the study.

Limitations and Caveats

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
No text entered.

Results Point of Contact:

Name/Title: Steven Reynolds
Organization: NIAID
phone: 256-772-220-087
e-mail: sjreynolds@niaid.nih.gov

Publications:

Moriuchi M, Moriuchi H, Williams R, Straus SE. Herpes simplex virus infection induces replication of human immunodeficiency virus type 1. Virology. 2000 Dec 20;278(2):534-40.

Serwadda D, Gray RH, Sewankambo NK, Wabwire-Mangen F, Chen MZ, Quinn TC, Lutalo T, Kiwanuka N, Kigozi G, Nalugoda F, Meehan MP, Ashley Morrow R, Wawer MJ. Human immunodeficiency virus acquisition associated with genital ulcer disease and herpes simplex virus type 2 infection: a nested case-control study in Rakai, Uganda. J Infect Dis. 2003 Nov 15;188(10):1492-7. Epub 2003 Oct 28.

Stein DS, Graham NM, Park LP, Hoover DR, Phair JP, Detels R, Ho M, Saah AJ. The effect of the interaction of acyclovir with zidovudine on progression to AIDS and survival. Analysis of data in the Multicenter AIDS Cohort Study. Ann Intern Med. 1994 Jul 15;121(2):100-8.

Publications automatically indexed to this study:

Reynolds SJ, Makumbi F, Newell K, Kiwanuka N, Ssebbowa P, Mondo G, Boaz I, Wawer MJ, Gray RH, Serwadda D, Quinn TC. Effect of daily aciclovir on HIV disease progression in individuals in Rakai, Uganda, co-infected with HIV-1 and herpes simplex virus type 2: a randomised, double-blind placebo-controlled trial. Lancet Infect Dis. 2012 Jun;12(6):441-8. Epub 2012 Mar 19.

Responsible Party:	Steven Reynolds, 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

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