Trial Outcomes & Findings for Using Nevirapine to Prevent Mother-to-Child HIV Transmission During Breastfeeding (NCT NCT00074412)

NCT ID: NCT00074412

Last Updated: 2023-02-16

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2026 participants

Primary outcome timeframe

At Month 6

Results posted on

2023-02-16

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Placebo For infants: extended treatment with NVP placebo	Nevirapine For infants: extended treatment with NVP
Overall Study STARTED	763	759
Overall Study Week 8 Visit	759	759
Overall Study Month 3 Visit	759	755
Overall Study Month 4 Visit	758	752
Overall Study Month 5 Visit	756	750
Overall Study Month 6 Visit	748	748
Overall Study Month 9 Visit	741	741
Overall Study Month 12 Visit	733	735
Overall Study COMPLETED	681	675
Overall Study NOT COMPLETED	82	84

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo For infants: extended treatment with NVP placebo	Nevirapine For infants: extended treatment with NVP
Overall Study Death	30	26
Overall Study Lost to Follow-up	52	58

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nevirapine n=759 Participants For infants: extended treatment with NVP	Placebo n=763 Participants For infants: extended treatment with NVP placebo	Total n=1522 Participants Total of all reporting groups
Age, Categorical <=18 years	759 Participants n=5 Participants	763 Participants n=7 Participants	1522 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex/Gender, Customized Ambiguous	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Sex/Gender, Customized Male	363 participants n=5 Participants	398 participants n=7 Participants	761 participants n=5 Participants
Sex/Gender, Customized Female	395 participants n=5 Participants	365 participants n=7 Participants	760 participants n=5 Participants
Region of Enrollment Tanzania	98 participants n=5 Participants	99 participants n=7 Participants	197 participants n=5 Participants
Region of Enrollment Uganda	259 participants n=5 Participants	261 participants n=7 Participants	520 participants n=5 Participants
Region of Enrollment South Africa	171 participants n=5 Participants	171 participants n=7 Participants	342 participants n=5 Participants
Region of Enrollment Zimbabwe	231 participants n=5 Participants	232 participants n=7 Participants	463 participants n=5 Participants
Categorical Infant Birthweight (g) Missing	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Categorical Infant Birthweight (g) 2000-2499	50 participants n=5 Participants	52 participants n=7 Participants	102 participants n=5 Participants
Categorical Infant Birthweight (g) 2500-2999	214 participants n=5 Participants	211 participants n=7 Participants	425 participants n=5 Participants
Categorical Infant Birthweight (g) 3000-3499	329 participants n=5 Participants	336 participants n=7 Participants	665 participants n=5 Participants
Categorical Infant Birthweight (g) >=3500	166 participants n=5 Participants	163 participants n=7 Participants	329 participants n=5 Participants

PRIMARY outcome

Timeframe: At Month 6

Population: All infants who were randomly allocated to either treatment or placebo at 6 weeks of age under version 3.0 of the protocol were included in the analysis of the primary endpoint, HIV infection at 6 months. 127/1700 infants were enrolled but excluded from randomization at 6 weeks for various reasons as mentioned in the flow-through.

Outcome measures

Outcome measures
Measure	Nevirapine n=759 Participants For infants: extended treatment with NVP	Placebo n=763 Participants For infants: extended treatment with NVP Placebo
HIV Infection in Infants Determined to be HIV Uninfected at 6 Weeks Enrolled in Each Arm of the Study # of HIV infections at 6 months	8 participants Interval 0.3 to 1.9	18 participants Interval 1.3 to 3.6
HIV Infection in Infants Determined to be HIV Uninfected at 6 Weeks Enrolled in Each Arm of the Study # of Infants at risk for HIV infection at 6 months	700 participants	699 participants

PRIMARY outcome

Timeframe: 6 weeks through 18 months

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Nevirapine n=2014 Adverse Events For infants: extended treatment with NVP	Placebo n=1964 Adverse Events For infants: extended treatment with NVP Placebo
Frequency and Severity of Adverse Reactions Among Participating Infants Death	26 Number of Adverse Events	30 Number of Adverse Events
Frequency and Severity of Adverse Reactions Among Participating Infants Life-Threatening	87 Number of Adverse Events	87 Number of Adverse Events
Frequency and Severity of Adverse Reactions Among Participating Infants Severe	375 Number of Adverse Events	332 Number of Adverse Events
Frequency and Severity of Adverse Reactions Among Participating Infants Moderate	694 Number of Adverse Events	677 Number of Adverse Events
Frequency and Severity of Adverse Reactions Among Participating Infants Mild	832 Number of Adverse Events	838 Number of Adverse Events

SECONDARY outcome

Timeframe: At Months 6 and 18

Population: There were 1522 infants randomized at 6 weeks of birth to either the extended Nevirapine arm (759) or the placebo arm (763).

Outcome measures

Outcome measures
Measure	Nevirapine n=759 Participants For infants: extended treatment with NVP	Placebo n=763 Participants For infants: extended treatment with NVP Placebo
Proportion of Infants Who Are Alive and HIV-uninfected in the Two Arms Number of Infants Alive and HIV-free at 6 months	689 participants	683 participants
Proportion of Infants Who Are Alive and HIV-uninfected in the Two Arms Number of Infants Alive and HIV-free at 18 months	629 participants	616 participants

SECONDARY outcome

Timeframe: At Month 18

Population: A total of 1527 infants were randomized to either placebo or extended NVP. 5 of these infants were later found to be infected at the time of randomization (2 in NVP and 3 in Placebo). Thus, only 1522 infants were included in the analysis.

Outcome measures

Outcome measures
Measure	Nevirapine n=759 Participants For infants: extended treatment with NVP	Placebo n=763 Participants For infants: extended treatment with NVP Placebo
Relative Rates of HIV Infection in the Two Arms # of infants with HIV infection at 18 months	16 participants	23 participants
Relative Rates of HIV Infection in the Two Arms # of infants @ risk for HIV infection at 18 months	664 participants	663 participants

SECONDARY outcome

Timeframe: At Month 18

Outcome measures

Outcome measures
Measure	Nevirapine n=759 Participants For infants: extended treatment with NVP	Placebo n=763 Participants For infants: extended treatment with NVP Placebo
Infant Survival Rates (Mortality Regardless of HIV Infection) in the Two Arms # Infant Deaths at 18 months	26 participants	30 participants
Infant Survival Rates (Mortality Regardless of HIV Infection) in the Two Arms # Infants at risk of death at 18 months	678 participants	684 participants

Adverse Events

Nevirapine

Serious events: 152 serious events

Other events: 614 other events

Deaths: 0 deaths

Placebo

Serious events: 141 serious events

Other events: 618 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Nevirapine n=758 participants at risk For infants: extended treatment with NVP	Placebo n=761 participants at risk For infants: extended treatment with NVP placebo
Blood and lymphatic system disorders Anaemia	5.5% 42/758 • Number of events 48 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.	6.7% 51/761 • Number of events 55 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.
Eye disorders Conjunctivitis	8.2% 62/758 • Number of events 66 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.	5.7% 43/761 • Number of events 53 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.
Infections and infestations Conjunctivitis bacterial	10.0% 76/758 • Number of events 86 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.	9.5% 72/761 • Number of events 80 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.
Skin and subcutaneous tissue disorders Dermatitis atopic	7.3% 55/758 • Number of events 60 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.	4.9% 37/761 • Number of events 44 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.
Gastrointestinal disorders Diarrhoea	7.5% 57/758 • Number of events 63 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.	7.2% 55/761 • Number of events 65 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.
Infections and infestations Gastroenteritis	24.8% 188/758 • Number of events 268 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.	27.3% 208/761 • Number of events 288 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.
Investigations Haemoglobin decreased	9.6% 73/758 • Number of events 76 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.	8.4% 64/761 • Number of events 67 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.
Infections and infestations Malaria	16.1% 122/758 • Number of events 164 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.	14.7% 112/761 • Number of events 160 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.
Investigations Neutrophil count decreased	19.1% 145/758 • Number of events 181 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.	15.9% 121/761 • Number of events 153 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.
Infections and infestations Oral candidiasis	12.8% 97/758 • Number of events 121 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.	10.4% 79/761 • Number of events 93 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.
Infections and infestations Upper respiratory infection	17.8% 135/758 • Number of events 159 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.	24.6% 187/761 • Number of events 223 • Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded. Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.

Additional Information

Statistical Research Associate

Statistical Center for HIV/AIDS Research and Prevention

Phone: 2066677524

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In accordance with the Clinical Trial Agreement between NIAID (DAIDS) \& company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review \& comment. The publication or other disclosure can be delayed for up to thirty additional business days for manuscripts \& five business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER