Evaluating the Safety and Tolerability of Etravirine in HIV-1 Infected Infants and Children

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ClinicalTrials.gov Identifier: NCT01504841

Recruitment Status : Completed

First Posted : January 5, 2012

Results First Posted : September 17, 2019

Last Update Posted : November 2, 2021

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

National Institute of Allergy and Infectious Diseases (NIAID)

Study Type	Interventional
Study Design	Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	HIV Infections
Intervention	Drug: Etravirine (ETR)
Enrollment	26

Participant Flow

Recruitment Details	The first participant was enrolled March 2013, and the final participant was enrolled June 2017. Participants were accrued from a total of 11 sites across Brazil, South Africa, and the USA.
Pre-assignment Details	Participants were stratified into the 3 Cohorts by age group and not randomized. There were no eligibility violations or errors to cohort assignments.


Arm/Group Title	Cohort I: Treatment Experienced, 2 to 6 Years of Age	Cohort II: Treatment Experienced, 1 to 2 Years of Age	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age
Arm/Group Description	Children in this arm were at least ...	Children in this arm were at least ...	Children in this arm were at least ...
Arm/Group Description	Children in this arm were at least 2 but younger than 6 years of age; they received the study drug etravirine (ETR) together with an optimized background regimen (OBR) consisting of one active boosted protease inhibitor (PI) and at least one other active antiretroviral (ARV) drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 1 but younger than 2 years of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 2 months but younger than 1 year of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.
Period Title: Overall Study
Started	20	6	0 ^[1]
Completed	19	5	0
Not Completed	1	1	0
Reason Not Completed
Withdrawal by Subject	1	1	0
[1] No enrollments occurred into Cohort 3 during the study.

Baseline Characteristics

Arm/Group Title		Cohort I: Treatment Experienced, 2 to 6 Years of Age	Cohort II: Treatment Experienced, 1 to 2 Years of Age	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age	Total
Arm/Group Description		Children in this arm were at least ...	Children in this arm were at least ...	Children in this arm were at least ...	Total of all reporting groups
Arm/Group Description		Children in this arm were at least 2 but younger than 6 years of age; they received the study drug etravirine (ETR) together with an optimized background regimen (OBR) consisting of one active boosted protease inhibitor (PI) and at least one other active antiretroviral (ARV) drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 1 but younger than 2 years of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 2 months but younger than 1 year of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Total of all reporting groups
Overall Number of Baseline Participants		11	4	0	15
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Analysis population is defined as having been treated exclusively on the dose determined to be optimal for a given cohort and having either completed 48 weeks of exposure to the study drug or having been classified as a safety failure, due to a study drug related adverse event occurring during the first 48 weeks of treatment.
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	11 participants	4 participants	0 participants	15 participants
		4 (3 to 5)	1 (1 to 1)		3.5 (1 to 5)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	11 participants	4 participants	0 participants	15 participants
	Female	6 54.5%	1 25.0%		7 46.7%
	Male	5 45.5%	3 75.0%		8 53.3%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	11 participants	4 participants	0 participants	15 participants
	Hispanic or Latino	4 36.4%	1 25.0%		5 33.3%
	Not Hispanic or Latino	3 27.3%	1 25.0%		4 26.7%
	Unknown or Not Reported	4 36.4%	2 50.0%		6 40.0%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	11 participants	4 participants	0 participants	15 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%		0 0.0%
	Asian	0 0.0%	0 0.0%		0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%		0 0.0%
	Black or African American	8 72.7%	4 100.0%		12 80.0%
	White	1 9.1%	0 0.0%		1 6.7%
	More than one race	1 9.1%	0 0.0%		1 6.7%
	Unknown or Not Reported	1 9.1%	0 0.0%		1 6.7%
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	11 participants	4 participants	0 participants	15 participants
United States		2	1		3
Brazil		3	1		4
South Africa		6	2		8
Plasma HIV RNA Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	11 participants	4 participants	0 participants	15 participants
	<400 copies/ml	0 0.0%	0 0.0%		0 0.0%
	400 - <5,000 copies/ml	4 36.4%	1 25.0%		5 33.3%
	5,000 - <10,000 copies/ml	0 0.0%	0 0.0%		0 0.0%
	10,000 - < 25,000 copies/ml	2 18.2%	1 25.0%		3 20.0%
	25,000 - < 50,000 copies/ml	1 9.1%	1 25.0%		2 13.3%
	>=50,000 copies/ml	4 36.4%	1 25.0%		5 33.3%
CD4 Count Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	11 participants	4 participants	0 participants	15 participants
	50 - <200 cells/mm^3	1 9.1%	0 0.0%		1 6.7%
	200 - <350 cells/mm^3	1 9.1%	0 0.0%		1 6.7%
	350 - <500 cells/mm^3	1 9.1%	1 25.0%		2 13.3%
	>=500 cells/mm^3	8 72.7%	3 75.0%		11 73.3%
CD4 Percent Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	11 participants	4 participants	0 participants	15 participants
	<= 14 %	1 9.1%	1 25.0%		2 13.3%
	>14 - <25 %	5 45.5%	1 25.0%		6 40.0%
	>= 25 %	5 45.5%	2 50.0%		7 46.7%

Outcome Measures

1.Primary Outcome


Title	Termination From Treatment Due to a Suspected Adverse Drug Reaction (SADR)
Description	Number (%) of participants who discontinued treatment due to a suspect...
Description	Number (%) of participants who discontinued treatment due to a suspected adverse drug reaction (SADR) by Cohort.
Time Frame	From baseline to occurrence of event, up to Week 48.

Outcome Measure Data

Analysis Population Description

Analysis population is defined as having been treated exclusively on the final dose determined to be optimal for a given cohort without adjustments and having either completed 48 weeks of exposure to the study drug or been classified as a safety failure, due to a study drug related adverse event occurring during the first 48 weeks of treatment.


Arm/Group Title	Cohort I: Treatment Experienced, 2 to 6 Years of Age	Cohort II: Treatment Experienced, 1 to 2 Years of Age	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age
Arm/Group Description:	Children in this arm were at least ...	Children in this arm were at least ...	Children in this arm were at least ...
Arm/Group Description:	Children in this arm were at least 2 but younger than 6 years of age; they received the study drug etravirine (ETR) together with an optimized background regimen (OBR) consisting of one active boosted protease inhibitor (PI) and at least one other active antiretroviral (ARV) drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 1 but younger than 2 years of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 2 months but younger than 1 year of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.
Overall Number of Participants Analyzed	11	4	0
Measure Type: Count of Participants Unit of Measure: Participants
Discontinued treatment due to a SADR	1 9.1%	0 0.0%
Did not discontinue treatment due to a SADR	10 90.9%	4 100.0%

2.Primary Outcome


Title	Adverse Events (AEs) of Grade 3 or Higher Severity
Description	Number (%) of participants who experienced a Grade 3 or higher severit...
Description	Number (%) of participants who experienced a Grade 3 or higher severity adverse event through Week 48 by Cohort, with Clopper-Pearson confidence intervals.
Time Frame	From baseline to occurrence of event, up to Week 48.

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Cohort I: Treatment Experienced, 2 to 6 Years of Age	Cohort II: Treatment Experienced, 1 to 2 Years of Age	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age
Arm/Group Description:	Children in this arm were at least ...	Children in this arm were at least ...	Children in this arm were at least ...
Arm/Group Description:	Children in this arm were at least 2 but younger than 6 years of age; they received the study drug etravirine (ETR) together with an optimized background regimen (OBR) consisting of one active boosted protease inhibitor (PI) and at least one other active antiretroviral (ARV) drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 1 but younger than 2 years of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 2 months but younger than 1 year of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.
Overall Number of Participants Analyzed	11	4	0
Measure Type: Count of Participants Unit of Measure: Participants
Experienced a grade 3+ AE	4 36.4%	4 100.0%
Did not experience a grade 3+ AE	7 63.6%	0 0.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort I: Treatment Experienced, 2 to 6 Years of Age
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	%
	Estimated Value	36.4
	Confidence Interval	(2-Sided) 95% 10.9 to 69.2
	Estimation Comments	Exact Binomial (Clopper-Pearson) confidence intervals for Cohort I, percentage of participants who experienced a grade 3+ AE.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cohort II: Treatment Experienced, 1 to 2 Years of Age
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	%
	Estimated Value	100
	Confidence Interval	(2-Sided) 95% 39.8 to 100
	Estimation Comments	Exact Binomial (Clopper-Pearson) confidence intervals for Cohort II, percentage of participants who experienced a grade 3+ AE.

3.Primary Outcome


Title	Death
Description	Number (%) of deaths on study by Cohort.
Description	Number (%) of deaths on study by Cohort.
Time Frame	From baseline to occurrence of event, up to Week 48.

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Cohort I: Treatment Experienced, 2 to 6 Years of Age	Cohort II: Treatment Experienced, 1 to 2 Years of Age	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age
Arm/Group Description:	Children in this arm were at least ...	Children in this arm were at least ...	Children in this arm were at least ...
Arm/Group Description:	Children in this arm were at least 2 but younger than 6 years of age; they received the study drug etravirine (ETR) together with an optimized background regimen (OBR) consisting of one active boosted protease inhibitor (PI) and at least one other active antiretroviral (ARV) drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 1 but younger than 2 years of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 2 months but younger than 1 year of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.
Overall Number of Participants Analyzed	11	4	0
Measure Type: Count of Participants Unit of Measure: Participants
Deaths	0 0.0%	0 0.0%
Live participants	11 100.0%	4 100.0%

4.Primary Outcome


Title	Area Under the Plasma Concentration-Time Curve Over 12 Hours of ETR
Description	Geometric Mean (Standard Deviation) of the area under the plasma conce...
Description	Geometric Mean (Standard Deviation) of the area under the plasma concentration-time curve over 12 hours (AUC12h) of ETR.
Time Frame	Pre-dose, 1, 2, 4, 6, 9, and 12 hours post-dose measured at intensive PK visit (within 7-10 days after last dose of study drug administration)

Outcome Measure Data

Analysis Population Description

Analysis population is defined as having been treated exclusively on the final dose determined to be optimal for a given cohort without adjustments and having either completed 48 weeks of exposure to the study drug or been classified as a safety failure. They must also be considered PK evaluable by the study team; 1 Participant in Cohort 1 is not.


Arm/Group Title	Cohort I: Treatment Experienced, 2 to 6 Years of Age	Cohort II: Treatment Experienced, 1 to 2 Years of Age
Arm/Group Description:	Children in this arm were at least ...	Children in this arm were at least ...
Arm/Group Description:	Children in this arm were at least 2 but younger than 6 years of age; they received the study drug etravirine (ETR) together with an optimized background regimen (OBR) consisting of one active boosted protease inhibitor (PI) and at least one other active antiretroviral (ARV) drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 1 but younger than 2 years of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.
Overall Number of Participants Analyzed	10	4
Geometric Mean (Standard Deviation) Unit of Measure: ng*h/mL
	5512.85 (3615.36)	4821.76 (3167.11)

5.Secondary Outcome


Title	AEs of Grade 3 or Higher Severity Judged to be at Least Possibly Attributable to the Study Medications
Description	Number (%) of Participants with AEs of Grade 3 or higher severity judg...
Description	Number (%) of Participants with AEs of Grade 3 or higher severity judged, by the Study Team, to be at least possibly attributable to the study medications by Cohort, including Clopper-Pearson confidence intervals.
Time Frame	From baseline to occurrence of event, up to Week 48.

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Cohort I: Treatment Experienced, 2 to 6 Years of Age	Cohort II: Treatment Experienced, 1 to 2 Years of Age	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age
Arm/Group Description:	Children in this arm were at least ...	Children in this arm were at least ...	Children in this arm were at least ...
Arm/Group Description:	Children in this arm were at least 2 but younger than 6 years of age; they received the study drug etravirine (ETR) together with an optimized background regimen (OBR) consisting of one active boosted protease inhibitor (PI) and at least one other active antiretroviral (ARV) drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 1 but younger than 2 years of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 2 months but younger than 1 year of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.
Overall Number of Participants Analyzed	11	4	0
Measure Type: Count of Participants Unit of Measure: Participants
Had a grade 3+ AE related to study drug	2 18.2%	0 0.0%
Had no grade 3+ AE related to study drug	9 81.8%	4 100.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort I: Treatment Experienced, 2 to 6 Years of Age
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	%
	Estimated Value	18.2
	Confidence Interval	(2-Sided) 95% 2.5 to 51.8
	Estimation Comments	Exact Binomial (Clopper-Pearson) confidence intervals for Cohort I, percentage of participants who experienced a grade 3+ AE at least possibly related to study medications.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cohort II: Treatment Experienced, 1 to 2 Years of Age
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	%
	Estimated Value	0
	Confidence Interval	(2-Sided) 95% 0 to 60.2
	Estimation Comments	Exact Binomial (Clopper-Pearson) confidence intervals for Cohort II, percentage of participants who experienced a grade 3+ AE at least possibly related to study medication.

6.Secondary Outcome


Title	HIV-1 RNA Virologic Failure Status at Weeks 24 and 48
Description	Number (%) of participants with confirmed Virologic Failure, defined a...
Description	Number (%) of participants with confirmed Virologic Failure, defined as: failure to suppress plasma HIV-1 RNA to fewer than 400 copies/ml and failure to achieve at least a 2-log10 reduction (from baseline) in HIV-1 RNA at Weeks 24 or 48, by Cohort, with Clopper-Pearson confidence intervals. The initial HIV-1 RNA results that met the Virologic Failure definition were each confirmed by a second result obtained within 1 to 4 weeks of the initial result obtained at Week 24 and/or 48.
Time Frame	Baseline, Week 24, and Week 48

Outcome Measure Data

Analysis Population Description


Arm/Group Title		Cohort I: Treatment Experienced, 2 to 6 Years of Age	Cohort II: Treatment Experienced, 1 to 2 Years of Age	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age
Arm/Group Description:		Children in this arm were at least ...	Children in this arm were at least ...	Children in this arm were at least ...
Arm/Group Description:		Children in this arm were at least 2 but younger than 6 years of age; they received the study drug etravirine (ETR) together with an optimized background regimen (OBR) consisting of one active boosted protease inhibitor (PI) and at least one other active antiretroviral (ARV) drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 1 but younger than 2 years of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 2 months but younger than 1 year of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.
Overall Number of Participants Analyzed		11	4	0
Measure Type: Count of Participants Unit of Measure: Participants
Week 24	Virologic Failure	2 18.2%	1 25.0%
Week 24	No Virologic Failure	9 81.8%	3 75.0%
Week 48	Virologic Failure	3 27.3%	3 75.0%
Week 48	No Virologic Failure	8 72.7%	1 25.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort I: Treatment Experienced, 2 to 6 Years of Age
	Comments	Week 24 time point.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	%
	Estimated Value	18.2
	Confidence Interval	(2-Sided) 95% 2.3 to 51.8
	Estimation Comments	Exact Binomial (Clopper-Pearson) confidence intervals for Cohort I Week 24, percentage of participants who experienced Virologic Failure.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cohort II: Treatment Experienced, 1 to 2 Years of Age
	Comments	Week 24 time point.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	%
	Estimated Value	25
	Confidence Interval	(2-Sided) 95% 0.6 to 80.6
	Estimation Comments	Exact Binomial (Clopper-Pearson) confidence intervals for Cohort II Week 24, percentage of participants who experienced Virologic Failure.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cohort I: Treatment Experienced, 2 to 6 Years of Age
	Comments	Week 48 time point.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	%
	Estimated Value	27.3
	Confidence Interval	(2-Sided) 95% 6 to 61
	Estimation Comments	Exact Binomial (Clopper-Pearson) confidence intervals for Cohort I Week 48, percentage of participants who experienced Virologic Failure.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Cohort II: Treatment Experienced, 1 to 2 Years of Age
	Comments	Week 48 time point.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	%
	Estimated Value	75
	Confidence Interval	(2-Sided) 95% 19.4 to 99.4
	Estimation Comments	Exact Binomial (Clopper-Pearson) confidence intervals for Cohort II Week 48, percentage of participants who experienced Virologic Failure.

7.Secondary Outcome


Title	Treatment Discontinued Due to Toxicity or Virologic Failure
Description	Number (%) of participants who discontinued study treatment (ETR) due ...
Description	Number (%) of participants who discontinued study treatment (ETR) due to a toxicity or Virologic Failure (VF), by Cohort.
Time Frame	From baseline to occurrence of event, up to Week 48.

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Cohort I: Treatment Experienced, 2 to 6 Years of Age	Cohort II: Treatment Experienced, 1 to 2 Years of Age	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age
Arm/Group Description:	Children in this arm were at least ...	Children in this arm were at least ...	Children in this arm were at least ...
Arm/Group Description:	Children in this arm were at least 2 but younger than 6 years of age; they received the study drug etravirine (ETR) together with an optimized background regimen (OBR) consisting of one active boosted protease inhibitor (PI) and at least one other active antiretroviral (ARV) drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 1 but younger than 2 years of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 2 months but younger than 1 year of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.
Overall Number of Participants Analyzed	11	4	0
Measure Type: Count of Participants Unit of Measure: Participants
Discontinued Treatment due to VF	1 9.1%	0 0.0%
Did not discontinue treatment due to VF	10 90.9%	4 100.0%

8.Secondary Outcome


Title	Change in Optimized Background Regimen Due to Virologic Failure
Description	Number (%) of participants who initiated a change in their optimized b...
Description	Number (%) of participants who initiated a change in their optimized background regimen (OBR) due to virologic failure, by Cohort.
Time Frame	Measured at entry and at Weeks 8, 12, 24, and 48

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Cohort I: Treatment Experienced, 2 to 6 Years of Age	Cohort II: Treatment Experienced, 1 to 2 Years of Age	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age
Arm/Group Description:	Children in this arm were at least ...	Children in this arm were at least ...	Children in this arm were at least ...
Arm/Group Description:	Children in this arm were at least 2 but younger than 6 years of age; they received the study drug etravirine (ETR) together with an optimized background regimen (OBR) consisting of one active boosted protease inhibitor (PI) and at least one other active antiretroviral (ARV) drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 1 but younger than 2 years of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 2 months but younger than 1 year of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.
Overall Number of Participants Analyzed	11	4	0
Measure Type: Count of Participants Unit of Measure: Participants
Changed OBR due to Virologic Failure	0 0.0%	0 0.0%
Did not change OBR due to Virologic Failure	11 100.0%	4 100.0%

9.Secondary Outcome


Title	New Onset Opportunistic Infection (OI) or AIDS Diagnosis
Description	Number (%) of participants with a new onset opportunistic infection (O...
Description	Number (%) of participants with a new onset opportunistic infection (OI) or AIDS diagnosis, by Cohort.
Time Frame	From baseline to occurrence of event, up to Week 48.

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Cohort I: Treatment Experienced, 2 to 6 Years of Age	Cohort II: Treatment Experienced, 1 to 2 Years of Age	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age
Arm/Group Description:	Children in this arm were at least ...	Children in this arm were at least ...	Children in this arm were at least ...
Arm/Group Description:	Children in this arm were at least 2 but younger than 6 years of age; they received the study drug etravirine (ETR) together with an optimized background regimen (OBR) consisting of one active boosted protease inhibitor (PI) and at least one other active antiretroviral (ARV) drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 1 but younger than 2 years of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 2 months but younger than 1 year of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.
Overall Number of Participants Analyzed	11	4	0
Measure Type: Count of Participants Unit of Measure: Participants
Had a new OI	0 0.0%	0 0.0%
Had no new OIs	11 100.0%	4 100.0%

10.Secondary Outcome


Title	Decline in Absolute CD4 Percent of Greater Than 5 Percent Any Time After 12 Weeks of Therapy
Description	Number (%) of participants with a >5% decline in absolute CD4 perce...
Description	Number (%) of participants with a >5% decline in absolute CD4 percent from baseline at weeks 12, 24, and 48, by Cohort, including Clopper-Pearson confidence intervals.
Time Frame	Measured at baseline and at Weeks 12, 24, and 48

Outcome Measure Data

Analysis Population Description


Arm/Group Title		Cohort I: Treatment Experienced, 2 to 6 Years of Age	Cohort II: Treatment Experienced, 1 to 2 Years of Age	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age
Arm/Group Description:		Children in this arm were at least ...	Children in this arm were at least ...	Children in this arm were at least ...
Arm/Group Description:		Children in this arm were at least 2 but younger than 6 years of age; they received the study drug etravirine (ETR) together with an optimized background regimen (OBR) consisting of one active boosted protease inhibitor (PI) and at least one other active antiretroviral (ARV) drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 1 but younger than 2 years of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 2 months but younger than 1 year of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.
Overall Number of Participants Analyzed		11	4	0
Measure Type: Count of Participants Unit of Measure: Participants
Week 12	>5% decline in CD4 % from baseline	1 9.1%	2 50.0%
Week 12	Increase or <5% decline in CD4 % from baseline	10 90.9%	2 50.0%
Week 24	>5% decline in CD4 % from baseline	1 9.1%	1 25.0%
Week 24	Increase or <5% decline in CD4 % from baseline	10 90.9%	3 75.0%
Week 48	>5% decline in CD4 % from baseline	2 18.2%	2 50.0%
Week 48	Increase or <5% decline in CD4 % from baseline	9 81.8%	2 50.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort I: Treatment Experienced, 2 to 6 Years of Age
	Comments	Week 12 time point.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	%
	Estimated Value	9.1
	Confidence Interval	(2-Sided) 95% 0.2 to 41.3
	Estimation Comments	Exact Binomial (Clopper-Pearson) confidence intervals for Cohort I Week 12, percentage of participants with a >5% decline in absolute CD4 %.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cohort II: Treatment Experienced, 1 to 2 Years of Age
	Comments	Week 12 time point.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	%
	Estimated Value	50
	Confidence Interval	(2-Sided) 95% 6.8 to 93.2
	Estimation Comments	Exact Binomial (Clopper-Pearson) confidence intervals for Cohort II Week 12, percentage of participants with a >5% decline in absolute CD4 %.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cohort I: Treatment Experienced, 2 to 6 Years of Age
	Comments	Week 24 time point.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	%
	Estimated Value	9.1
	Confidence Interval	(2-Sided) 95% 0.2 to 41.3
	Estimation Comments	Exact Binomial (Clopper-Pearson) confidence intervals for Cohort I Week 24, percentage of participants with a >5% decline in absolute CD4 %.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Cohort II: Treatment Experienced, 1 to 2 Years of Age
	Comments	Week 24 time point.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	%
	Estimated Value	25
	Confidence Interval	(2-Sided) 95% 0.6 to 80.6
	Estimation Comments	Exact Binomial (Clopper-Pearson) confidence intervals for Cohort II Week 24, percentage of participants with a >5% decline in absolute CD4 %.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Cohort I: Treatment Experienced, 2 to 6 Years of Age
	Comments	Week 48 time point.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	%
	Estimated Value	18.2
	Confidence Interval	(2-Sided) 95% 2.3 to 51.8
	Estimation Comments	Exact Binomial (Clopper-Pearson) confidence intervals for Cohort I Week 48, percentage of participants with a >5% decline in absolute CD4 %.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Cohort II: Treatment Experienced, 1 to 2 Years of Age
	Comments	Week 48 time point.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	%
	Estimated Value	50
	Confidence Interval	(2-Sided) 95% 6.8 to 93.2
	Estimation Comments	Exact Binomial (Clopper-Pearson) confidence intervals for Cohort II Week 48, percentage of participants with a >5% decline in absolute CD4 %.

Adverse Events

Time Frame	From entry through off study, at an average of 72 weeks.
Adverse Event Reporting Description	At entry, all diagnoses, signs/symptoms and laboratory events were collected. Post-entry, all new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used. All eligible participants who initiated study treatment are included.

Arm/Group Title	Cohort I: Treatment Experienced, 2 to 6 Years of Age	Cohort II: Treatment Experienced, 1 to 2 Years of Age
Arm/Group Description	Children in this arm were at least ...	Children in this arm were at least ...
Arm/Group Description	Children in this arm were at least 2 but younger than 6 years of age; they received the study drug etravirine (ETR) together with an optimized background regimen (OBR) consisting of one active boosted protease inhibitor (PI) and at least one other active antiretroviral (ARV) drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.	Children in this arm were at least 1 but younger than 2 years of age; they received ETR together with an OBR consisting of one active boosted PI and at least one other active ARV drug. Etravirine (ETR): ETR was administered as 25-mg scored tablets and/or 100-mg tablets swallowed whole or dispersed in an appropriate liquid vehicle following a meal. Children took the specified dose orally twice daily within 30 minutes following a meal. Dose was decided according to dosing tables in protocol.
All-Cause Mortality
	Cohort I: Treatment Experienced, 2 to 6 Years of Age	Cohort II: Treatment Experienced, 1 to 2 Years of Age
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/20 (0.00%)	0/6 (0.00%)
Serious Adverse Events Serious Adverse Events
	Cohort I: Treatment Experienced, 2 to 6 Years of Age	Cohort II: Treatment Experienced, 1 to 2 Years of Age
	Affected / at Risk (%)	Affected / at Risk (%)
Total	5/20 (25.00%)	3/6 (50.00%)
Blood and lymphatic system disorders
Anaemia ^† 1	0/20 (0.00%)	1/6 (16.67%)
Injury, poisoning and procedural complications
Forearm fracture ^† 1	1/20 (5.00%)	0/6 (0.00%)
Ligament sprain ^† 1	0/20 (0.00%)	1/6 (16.67%)
Investigations
Lipase increased ^† 1	2/20 (10.00%)	0/6 (0.00%)
Neutrophil count decreased ^† 1	2/20 (10.00%)	1/6 (16.67%)
Platelet count decreased ^† 1	1/20 (5.00%)	1/6 (16.67%)
1 Term from vocabulary, MedDRA 24.0 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Cohort I: Treatment Experienced, 2 to 6 Years of Age	Cohort II: Treatment Experienced, 1 to 2 Years of Age
	Affected / at Risk (%)	Affected / at Risk (%)
Total	20/20 (100.00%)	6/6 (100.00%)
Blood and lymphatic system disorders
Iron deficiency anaemia ^† 1	2/20 (10.00%)	2/6 (33.33%)
Lymphadenopathy ^† 1	7/20 (35.00%)	3/6 (50.00%)
Splenomegaly ^† 1	0/20 (0.00%)	1/6 (16.67%)
Cardiac disorders
Tachycardia ^† 1	0/20 (0.00%)	1/6 (16.67%)
Congenital, familial and genetic disorders
Keratosis follicular ^† 1	1/20 (5.00%)	0/6 (0.00%)
Ear and labyrinth disorders
Ear canal erythema ^† 1	1/20 (5.00%)	0/6 (0.00%)
Ear pain ^† 1	3/20 (15.00%)	1/6 (16.67%)
External ear inflammation ^† 1	1/20 (5.00%)	0/6 (0.00%)
Otorrhoea ^† 1	4/20 (20.00%)	3/6 (50.00%)
Tympanic membrane disorder ^† 1	1/20 (5.00%)	0/6 (0.00%)
Eye disorders
Eye discharge ^† 1	2/20 (10.00%)	0/6 (0.00%)
Eye pruritus ^† 1	1/20 (5.00%)	0/6 (0.00%)
Eyelid disorder ^† 1	1/20 (5.00%)	0/6 (0.00%)
Gastrointestinal disorders
Abdominal distension ^† 1	0/20 (0.00%)	1/6 (16.67%)
Abdominal pain ^† 1	4/20 (20.00%)	0/6 (0.00%)
Abdominal pain upper ^† 1	1/20 (5.00%)	0/6 (0.00%)
Anal pruritus ^† 1	2/20 (10.00%)	0/6 (0.00%)
Constipation ^† 1	2/20 (10.00%)	0/6 (0.00%)
Diarrhoea ^† 1	7/20 (35.00%)	4/6 (66.67%)
Frequent bowel movements ^† 1	1/20 (5.00%)	0/6 (0.00%)
Lip ulceration ^† 1	0/20 (0.00%)	1/6 (16.67%)
Mouth ulceration ^† 1	2/20 (10.00%)	1/6 (16.67%)
Nausea ^† 1	0/20 (0.00%)	1/6 (16.67%)
Odynophagia ^† 1	1/20 (5.00%)	0/6 (0.00%)
Oral disorder ^† 1	2/20 (10.00%)	1/6 (16.67%)
Oral mucosal eruption ^† 1	1/20 (5.00%)	0/6 (0.00%)
Palatal disorder ^† 1	0/20 (0.00%)	1/6 (16.67%)
Parotid gland enlargement ^† 1	1/20 (5.00%)	0/6 (0.00%)
Toothache ^† 1	1/20 (5.00%)	0/6 (0.00%)
Vomiting ^† 1	4/20 (20.00%)	1/6 (16.67%)
General disorders
Chills ^† 1	1/20 (5.00%)	0/6 (0.00%)
Fatigue ^† 1	1/20 (5.00%)	0/6 (0.00%)
Mucosal discolouration ^† 1	0/20 (0.00%)	1/6 (16.67%)
Pyrexia ^† 1	11/20 (55.00%)	3/6 (50.00%)
Hepatobiliary disorders
Hepatomegaly ^† 1	0/20 (0.00%)	1/6 (16.67%)
Infections and infestations
Abscess limb ^† 1	1/20 (5.00%)	1/6 (16.67%)
Acarodermatitis ^† 1	2/20 (10.00%)	0/6 (0.00%)
Acute sinusitis ^† 1	3/20 (15.00%)	0/6 (0.00%)
Adenoiditis ^† 1	0/20 (0.00%)	1/6 (16.67%)
Body tinea ^† 1	1/20 (5.00%)	1/6 (16.67%)
Bronchitis ^† 1	2/20 (10.00%)	0/6 (0.00%)
Enterobiasis ^† 1	1/20 (5.00%)	0/6 (0.00%)
Epstein-Barr virus infection ^† 1	1/20 (5.00%)	0/6 (0.00%)
Gastroenteritis ^† 1	2/20 (10.00%)	1/6 (16.67%)
Helminthic infection ^† 1	1/20 (5.00%)	0/6 (0.00%)
Herpes simplex ^† 1	1/20 (5.00%)	0/6 (0.00%)
Herpes zoster ^† 1	1/20 (5.00%)	0/6 (0.00%)
Impetigo ^† 1	5/20 (25.00%)	2/6 (33.33%)
Latent tuberculosis ^† 1	1/20 (5.00%)	0/6 (0.00%)
Lice infestation ^† 1	3/20 (15.00%)	0/6 (0.00%)
Molluscum contagiosum ^† 1	3/20 (15.00%)	0/6 (0.00%)
Nasopharyngitis ^† 1	1/20 (5.00%)	1/6 (16.67%)
Oral candidiasis ^† 1	1/20 (5.00%)	1/6 (16.67%)
Oral herpes ^† 1	1/20 (5.00%)	0/6 (0.00%)
Otitis externa ^† 1	1/20 (5.00%)	0/6 (0.00%)
Otitis media ^† 1	0/20 (0.00%)	1/6 (16.67%)
Otitis media acute ^† 1	3/20 (15.00%)	3/6 (50.00%)
Otitis media chronic ^† 1	1/20 (5.00%)	0/6 (0.00%)
Parasitic gastroenteritis ^† 1	1/20 (5.00%)	0/6 (0.00%)
Parotitis ^† 1	1/20 (5.00%)	1/6 (16.67%)
Parvovirus B19 infection ^† 1	1/20 (5.00%)	0/6 (0.00%)
Pharyngitis ^† 1	7/20 (35.00%)	1/6 (16.67%)
Pneumonia bacterial ^† 1	2/20 (10.00%)	0/6 (0.00%)
Purulent discharge ^† 1	1/20 (5.00%)	0/6 (0.00%)
Rash pustular ^† 1	1/20 (5.00%)	0/6 (0.00%)
Rhinitis ^† 1	2/20 (10.00%)	0/6 (0.00%)
Sinusitis bacterial ^† 1	1/20 (5.00%)	0/6 (0.00%)
Skin infection ^† 1	1/20 (5.00%)	0/6 (0.00%)
Tinea capitis ^† 1	7/20 (35.00%)	0/6 (0.00%)
Tinea faciei ^† 1	2/20 (10.00%)	0/6 (0.00%)
Tinea manuum ^† 1	1/20 (5.00%)	0/6 (0.00%)
Tonsillitis ^† 1	2/20 (10.00%)	2/6 (33.33%)
Toxocariasis ^† 1	1/20 (5.00%)	0/6 (0.00%)
Upper respiratory tract infection ^† 1	2/20 (10.00%)	1/6 (16.67%)
Urinary tract infection ^† 1	2/20 (10.00%)	0/6 (0.00%)
Varicella ^† 1	2/20 (10.00%)	0/6 (0.00%)
Viral infection ^† 1	1/20 (5.00%)	0/6 (0.00%)
Injury, poisoning and procedural complications
Contusion ^† 1	2/20 (10.00%)	0/6 (0.00%)
Mucosal excoriation ^† 1	1/20 (5.00%)	0/6 (0.00%)
Skin abrasion ^† 1	1/20 (5.00%)	0/6 (0.00%)
Thermal burn ^† 1	1/20 (5.00%)	0/6 (0.00%)
Investigations
Alanine aminotransferase increased ^† 1	5/20 (25.00%)	3/6 (50.00%)
Aspartate aminotransferase increased ^† 1	4/20 (20.00%)	3/6 (50.00%)
Blood albumin decreased ^† 1	1/20 (5.00%)	0/6 (0.00%)
Blood alkaline phosphatase increased ^† 1	7/20 (35.00%)	1/6 (16.67%)
Blood bicarbonate decreased ^† 1	18/20 (90.00%)	5/6 (83.33%)
Blood bilirubin increased ^† 1	3/20 (15.00%)	0/6 (0.00%)
Blood calcium increased ^† 1	1/20 (5.00%)	1/6 (16.67%)
Blood cholesterol increased ^† 1	3/20 (15.00%)	1/6 (16.67%)
Blood creatinine increased ^† 1	1/20 (5.00%)	1/6 (16.67%)
Blood glucose decreased ^† 1	7/20 (35.00%)	1/6 (16.67%)
Blood glucose increased ^† 1	12/20 (60.00%)	3/6 (50.00%)
Blood pH decreased ^† 1	1/20 (5.00%)	0/6 (0.00%)
Blood pH increased ^† 1	1/20 (5.00%)	1/6 (16.67%)
Blood phosphorus decreased ^† 1	2/20 (10.00%)	0/6 (0.00%)
Blood potassium decreased ^† 1	2/20 (10.00%)	0/6 (0.00%)
Blood potassium increased ^† 1	2/20 (10.00%)	3/6 (50.00%)
Blood pressure diastolic increased ^† 1	4/20 (20.00%)	3/6 (50.00%)
Blood pressure systolic increased ^† 1	2/20 (10.00%)	3/6 (50.00%)
Blood sodium decreased ^† 1	14/20 (70.00%)	4/6 (66.67%)
Blood sodium increased ^† 1	1/20 (5.00%)	1/6 (16.67%)
Breath sounds abnormal ^† 1	0/20 (0.00%)	1/6 (16.67%)
Cardiac murmur ^† 1	1/20 (5.00%)	0/6 (0.00%)
Haemoglobin decreased ^† 1	6/20 (30.00%)	5/6 (83.33%)
International normalised ratio increased ^† 1	1/20 (5.00%)	0/6 (0.00%)
Lipase increased ^† 1	4/20 (20.00%)	1/6 (16.67%)
Low density lipoprotein increased ^† 1	1/20 (5.00%)	0/6 (0.00%)
Neutrophil count decreased ^† 1	9/20 (45.00%)	3/6 (50.00%)
Platelet count decreased ^† 1	1/20 (5.00%)	2/6 (33.33%)
Prothrombin time prolonged ^† 1	1/20 (5.00%)	0/6 (0.00%)
Transaminases increased ^† 1	0/20 (0.00%)	1/6 (16.67%)
Weight decreased ^† 1	2/20 (10.00%)	2/6 (33.33%)
Weight increased ^† 1	1/20 (5.00%)	0/6 (0.00%)
White blood cell count decreased ^† 1	1/20 (5.00%)	0/6 (0.00%)
Metabolism and nutrition disorders
Decreased appetite ^† 1	4/20 (20.00%)	2/6 (33.33%)
Failure to thrive ^† 1	2/20 (10.00%)	2/6 (33.33%)
Hypoglycaemia ^† 1	0/20 (0.00%)	1/6 (16.67%)
Vitamin D deficiency ^† 1	1/20 (5.00%)	0/6 (0.00%)
Weight gain poor ^† 1	0/20 (0.00%)	1/6 (16.67%)
Musculoskeletal and connective tissue disorders
Back pain ^† 1	1/20 (5.00%)	0/6 (0.00%)
Clubbing ^† 1	1/20 (5.00%)	0/6 (0.00%)
Myalgia ^† 1	1/20 (5.00%)	0/6 (0.00%)
Neck pain ^† 1	1/20 (5.00%)	0/6 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma ^† 1	2/20 (10.00%)	0/6 (0.00%)
Nervous system disorders
Dizziness ^† 1	1/20 (5.00%)	0/6 (0.00%)
Headache ^† 1	3/20 (15.00%)	0/6 (0.00%)
Hypotonia ^† 1	0/20 (0.00%)	1/6 (16.67%)
Lethargy ^† 1	3/20 (15.00%)	0/6 (0.00%)
Motor developmental delay ^† 1	0/20 (0.00%)	1/6 (16.67%)
Speech disorder developmental ^† 1	0/20 (0.00%)	1/6 (16.67%)
Psychiatric disorders
Insomnia ^† 1	1/20 (5.00%)	0/6 (0.00%)
Irritability ^† 1	1/20 (5.00%)	0/6 (0.00%)
Reproductive system and breast disorders
Breast enlargement ^† 1	0/20 (0.00%)	1/6 (16.67%)
Gynaecomastia ^† 1	0/20 (0.00%)	1/6 (16.67%)
Penile rash ^† 1	1/20 (5.00%)	0/6 (0.00%)
Respiratory, thoracic and mediastinal disorders
Adenoidal hypertrophy ^† 1	1/20 (5.00%)	0/6 (0.00%)
Asthma ^† 1	1/20 (5.00%)	1/6 (16.67%)
Bronchiectasis ^† 1	1/20 (5.00%)	0/6 (0.00%)
Bronchospasm ^† 1	2/20 (10.00%)	1/6 (16.67%)
Cough ^† 1	13/20 (65.00%)	6/6 (100.00%)
Dyspnoea ^† 1	2/20 (10.00%)	1/6 (16.67%)
Nasal congestion ^† 1	14/20 (70.00%)	6/6 (100.00%)
Nasal pruritus ^† 1	1/20 (5.00%)	0/6 (0.00%)
Oropharyngeal pain ^† 1	3/20 (15.00%)	0/6 (0.00%)
Pharyngeal erythema ^† 1	2/20 (10.00%)	0/6 (0.00%)
Pharyngeal inflammation ^† 1	2/20 (10.00%)	1/6 (16.67%)
Rales ^† 1	3/20 (15.00%)	1/6 (16.67%)
Rhinitis allergic ^† 1	1/20 (5.00%)	0/6 (0.00%)
Rhinorrhoea ^† 1	9/20 (45.00%)	6/6 (100.00%)
Rhonchi ^† 1	0/20 (0.00%)	1/6 (16.67%)
Sinus congestion ^† 1	1/20 (5.00%)	0/6 (0.00%)
Sleep apnoea syndrome ^† 1	1/20 (5.00%)	0/6 (0.00%)
Sneezing ^† 1	2/20 (10.00%)	0/6 (0.00%)
Snoring ^† 1	1/20 (5.00%)	0/6 (0.00%)
Tonsillar hypertrophy ^† 1	1/20 (5.00%)	0/6 (0.00%)
Tonsillar inflammation ^† 1	1/20 (5.00%)	0/6 (0.00%)
Upper-airway cough syndrome ^† 1	1/20 (5.00%)	0/6 (0.00%)
Wheezing ^† 1	1/20 (5.00%)	2/6 (33.33%)
Skin and subcutaneous tissue disorders
Dermatitis allergic ^† 1	1/20 (5.00%)	1/6 (16.67%)
Dermatitis atopic ^† 1	1/20 (5.00%)	0/6 (0.00%)
Dermatitis contact ^† 1	1/20 (5.00%)	0/6 (0.00%)
Dry skin ^† 1	5/20 (25.00%)	0/6 (0.00%)
Eczema ^† 1	4/20 (20.00%)	1/6 (16.67%)
Erythema ^† 1	1/20 (5.00%)	0/6 (0.00%)
Hand dermatitis ^† 1	1/20 (5.00%)	0/6 (0.00%)
Macule ^† 1	2/20 (10.00%)	0/6 (0.00%)
Neurodermatitis ^† 1	1/20 (5.00%)	0/6 (0.00%)
Night sweats ^† 1	1/20 (5.00%)	0/6 (0.00%)
Papule ^† 1	3/20 (15.00%)	1/6 (16.67%)
Pruritus ^† 1	1/20 (5.00%)	0/6 (0.00%)
Rash ^† 1	10/20 (50.00%)	3/6 (50.00%)
Rash erythematous ^† 1	1/20 (5.00%)	0/6 (0.00%)
Rash papular ^† 1	2/20 (10.00%)	0/6 (0.00%)
Rash pruritic ^† 1	2/20 (10.00%)	0/6 (0.00%)
Scab ^† 1	1/20 (5.00%)	0/6 (0.00%)
Skin exfoliation ^† 1	0/20 (0.00%)	1/6 (16.67%)
Skin induration ^† 1	0/20 (0.00%)	1/6 (16.67%)
Urticaria ^† 1	1/20 (5.00%)	0/6 (0.00%)
Xeroderma ^† 1	1/20 (5.00%)	0/6 (0.00%)
1 Term from vocabulary, MedDRA 24.0 † Indicates events were collected by systematic assessment

Limitations and Caveats

Due to the slow rate of accrual and the challenging accrual into the youngest cohort, enrollment was stopped early.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and 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 and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Melissa Allen, Director, IMPAACT Operations Center
Organization:	Family Health International (FHI 360)
Phone:	(919) 405-1429
EMail:	mallen@fhi360.org

Publications:

Jittamala P, Puthanakit T, Chaiinseeard S, Sirisanthana V. Predictors of virologic failure and genotypic resistance mutation patterns in thai children receiving non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy. Pediatr Infect Dis J. 2009 Sep;28(9):826-30. doi: 10.1097/INF.0b013e3181a458f9.

Palumbo P, Lindsey JC, Hughes MD, Cotton MF, Bobat R, Meyers T, Bwakura-Dangarembizi M, Chi BH, Musoke P, Kamthunzi P, Schimana W, Purdue L, Eshleman SH, Abrams EJ, Millar L, Petzold E, Mofenson LM, Jean-Philippe P, Violari A. Antiretroviral treatment for children with peripartum nevirapine exposure. N Engl J Med. 2010 Oct 14;363(16):1510-20. doi: 10.1056/NEJMoa1000931.

Layout table for additonal information

Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT01504841
Other Study ID Numbers:	P1090 10850 ( Other Identifier: DAIDS-ES )
First Submitted:	December 30, 2011
First Posted:	January 5, 2012
Results First Submitted:	July 16, 2019
Results First Posted:	September 17, 2019
Last Update Posted:	November 2, 2021

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