Using Nevirapine to Prevent Mother-to-Child HIV Transmission During Breastfeeding

This study has been completed.

Sponsor:

Collaborators:

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute on Drug Abuse (NIDA)

National Institute of Mental Health (NIMH)

Information provided by (Responsible Party):

National Institute of Allergy and Infectious Diseases (NIAID)

ClinicalTrials.gov Identifier:

NCT00074412

First received: December 11, 2003

Last updated: July 5, 2013

Last verified: July 2013

History of Changes

Results First Received: May 30, 2013

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver); Primary Purpose: Prevention
Condition:	HIV Infections
Interventions:	Drug: Nevirapine Drug: Nevirapine 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
HIV-infected pregnant women were recruited from antenatal clinics at DAIDS Clinical Trials Sites in Zimbabwe, South Africa, Uganda & Tanzania between May 14, 2008 & January 20th 2010. 1700 mother/infant pairs were enrolled & infants were given daily doses of Nevirapine for 6 weeks at which point there were randomized to placebo or extended NVP.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Infants were excluded from randomization if in first 42 days: had a positive HIV-1 DNA PCR, breastfeeding was discontinued, never initiated or permanently discontinued open-label NVP, certain graded abnormal labs, skin rash grade2B or higher, clinical hepatitis, serious illness/condition that prevented compliance, or use of rifampin/ketoconazole.

Reporting Groups

	Description
Placebo	For infants: extended treatment with NVP placebo
Nevirapine	For infants: extended treatment with NVP

Participant Flow: Overall Study

	Placebo	Nevirapine
STARTED	763 ^[1]	759 ^[1]
Week 8 Visit	759	759
Month 3 Visit	759	755
Month 4 Visit	758	752
Month 5 Visit	756	750
Month 6 Visit	748	748
Month 9 Visit	741	741
Month 12 Visit	733	735
COMPLETED	681 ^[2]	675 ^[2]
NOT COMPLETED	82	84
Death	30	26
Lost to Follow-up	52	58

[1]	Number of infants randomized at 6 weeks.
[2]	Number of infants who completed final 18 month visit: out of 733 infants who were expected.

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
Nevirapine	For infants: extended treatment with NVP
Placebo	For infants: extended treatment with NVP placebo
Total	Total of all reporting groups

Baseline Measures

	Nevirapine	Placebo	Total
Number of Participants [units: participants]	759	763	1522
Age [units: participants]
<=18 years	759	763	1522
Between 18 and 65 years	0	0	0
>=65 years	0	0	0
Gender, Customized [units: participants]
Ambiguous	1	0	1
Male	363	398	761
Female	395	365	760
Region of Enrollment [units: participants]
Tanzania	98	99	197
Uganda	259	261	520
South Africa	171	171	342
Zimbabwe	231	232	463
Categorical Infant Birthweight (g) [units: participants]
Missing	0	1	1
2000-2499	50	52	102
2500-2999	214	211	425
3000-3499	329	336	665
>=3500	166	163	329

Outcome Measures

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1. Primary:

HIV Infection in Infants Determined to be HIV Uninfected at 6 Weeks Enrolled in Each Arm of the Study [ Time Frame: At Month 6 ]

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2. Primary:

Frequency and Severity of Adverse Reactions Among Participating Infants [ Time Frame: 6 weeks through 18 months ]

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Measure Type	Primary
Measure Title	Frequency and Severity of Adverse Reactions Among Participating Infants
Measure Description	For those infants who were randomized at 6 weeks and who initiated study drug we looked at the frequency and severity of adverse reactions through 18 months of study. The severity of all AEs was graded according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. The term severity is described as the intensity grade or level for specific event (i.e. mild, moderate, severe, or life-threatening). Severity is not the same as seriousness.
Time Frame	6 weeks through 18 months
Safety Issue	Yes

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.
A total of 1519 infants, 758 in the NVP arm and 761 in the placebo arm, initiated study product and were thus included in the analysis for the frequency and severity of adverse reactions.

Reporting Groups

	Description
Nevirapine	For infants: extended treatment with NVP
Placebo	For infants: extended treatment with NVP placebo

Measured Values

	Nevirapine	Placebo
Number of Participants Analyzed [units: participants]	758	761
Number of Adverse Events Analyzed [units: Adverse Events]	2014	1964
Frequency and Severity of Adverse Reactions Among Participating Infants [units: Number of Adverse Events]
Death	26	30
Life-Threatening	87	87
Severe	375	332
Moderate	694	677
Mild	832	838

No statistical analysis provided for Frequency and Severity of Adverse Reactions Among Participating Infants

3. Secondary:

Proportion of Infants Who Are Alive and HIV-uninfected in the Two Arms [ Time Frame: At Months 6 and 18 ]

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4. Secondary:

Relative Rates of HIV Infection in the Two Arms [ Time Frame: At Month 18 ]

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5. Secondary:

Infant Survival Rates (Mortality Regardless of HIV Infection) in the Two Arms [ Time Frame: At Month 18 ]

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6. Secondary:

Frequency and Duration of Maternal Plasma and Breast Milk NVP-resistant HIV Strains and the Relationship With HIV Transmission [ Time Frame: Throughout study ]