Trial Outcomes & Findings for Evaluating the Safety and Tolerability of Etravirine in HIV-1 Infected Infants and Children (NCT NCT01504841)

NCT ID: NCT01504841

Last Updated: 2021-11-02

Results Overview

Number (%) of participants who discontinued treatment due to a suspected adverse drug reaction (SADR) by Cohort.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

26 participants

Primary outcome timeframe

From baseline to occurrence of event, up to Week 48.

Results posted on

2021-11-02

Participant Flow

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.

Participants were stratified into the 3 Cohorts by age group and not randomized. There were no eligibility violations or errors to cohort assignments.

Participant milestones

Participant milestones
Measure	Cohort I: Treatment Experienced, 2 to 6 Years of Age 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.	Cohort II: Treatment Experienced, 1 to 2 Years of Age 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 Study STARTED	20	6
Overall Study COMPLETED	19	5
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort I: Treatment Experienced, 2 to 6 Years of Age 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.	Cohort II: Treatment Experienced, 1 to 2 Years of Age 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.	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age 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 Study Withdrawal by Subject	1	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort I: Treatment Experienced, 2 to 6 Years of Age n=11 Participants 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.	Cohort II: Treatment Experienced, 1 to 2 Years of Age n=4 Participants 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.	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age 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 n=15 Participants Total of all reporting groups
Age, Continuous	4 years n=5 Participants	1 years n=7 Participants	—	3.5 years n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	1 Participants n=7 Participants	—	7 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	3 Participants n=7 Participants	—	8 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	1 Participants n=7 Participants	—	5 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	1 Participants n=7 Participants	—	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	2 Participants n=7 Participants	—	6 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	4 Participants n=7 Participants	—	12 Participants n=4 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	0 Participants n=7 Participants	—	1 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	—	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	—	1 Participants n=4 Participants
Region of Enrollment United States	2 participants n=5 Participants	1 participants n=7 Participants	—	3 participants n=4 Participants
Region of Enrollment Brazil	3 participants n=5 Participants	1 participants n=7 Participants	—	4 participants n=4 Participants
Region of Enrollment South Africa	6 participants n=5 Participants	2 participants n=7 Participants	—	8 participants n=4 Participants
Plasma HIV RNA <400 copies/ml	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Plasma HIV RNA 400 - <5,000 copies/ml	4 Participants n=5 Participants	1 Participants n=7 Participants	—	5 Participants n=4 Participants
Plasma HIV RNA 5,000 - <10,000 copies/ml	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Plasma HIV RNA 10,000 - < 25,000 copies/ml	2 Participants n=5 Participants	1 Participants n=7 Participants	—	3 Participants n=4 Participants
Plasma HIV RNA 25,000 - < 50,000 copies/ml	1 Participants n=5 Participants	1 Participants n=7 Participants	—	2 Participants n=4 Participants
Plasma HIV RNA >=50,000 copies/ml	4 Participants n=5 Participants	1 Participants n=7 Participants	—	5 Participants n=4 Participants
CD4 Count 50 - <200 cells/mm^3	1 Participants n=5 Participants	0 Participants n=7 Participants	—	1 Participants n=4 Participants
CD4 Count 200 - <350 cells/mm^3	1 Participants n=5 Participants	0 Participants n=7 Participants	—	1 Participants n=4 Participants
CD4 Count 350 - <500 cells/mm^3	1 Participants n=5 Participants	1 Participants n=7 Participants	—	2 Participants n=4 Participants
CD4 Count >=500 cells/mm^3	8 Participants n=5 Participants	3 Participants n=7 Participants	—	11 Participants n=4 Participants
CD4 Percent <= 14 %	1 Participants n=5 Participants	1 Participants n=7 Participants	—	2 Participants n=4 Participants
CD4 Percent >14 - <25 %	5 Participants n=5 Participants	1 Participants n=7 Participants	—	6 Participants n=4 Participants
CD4 Percent >= 25 %	5 Participants n=5 Participants	2 Participants n=7 Participants	—	7 Participants n=4 Participants

PRIMARY outcome

Timeframe: From baseline to occurrence of event, up to Week 48.

Population: 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.

Number (%) of participants who discontinued treatment due to a suspected adverse drug reaction (SADR) by Cohort.

Outcome measures

Outcome measures
Measure	Cohort I: Treatment Experienced, 2 to 6 Years of Age n=11 Participants 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.	Cohort II: Treatment Experienced, 1 to 2 Years of Age n=4 Participants 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.	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age 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.
Termination From Treatment Due to a Suspected Adverse Drug Reaction (SADR) Discontinued treatment due to a SADR	1 Participants	0 Participants	—
Termination From Treatment Due to a Suspected Adverse Drug Reaction (SADR) Did not discontinue treatment due to a SADR	10 Participants	4 Participants	—

PRIMARY outcome

Timeframe: From baseline to occurrence of event, up to Week 48.

Number (%) of participants who experienced a Grade 3 or higher severity adverse event through Week 48 by Cohort, with Clopper-Pearson confidence intervals.

Outcome measures

Outcome measures
Measure	Cohort I: Treatment Experienced, 2 to 6 Years of Age n=11 Participants 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.	Cohort II: Treatment Experienced, 1 to 2 Years of Age n=4 Participants 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.	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age 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.
Adverse Events (AEs) of Grade 3 or Higher Severity Experienced a grade 3+ AE	4 Participants	4 Participants	—
Adverse Events (AEs) of Grade 3 or Higher Severity Did not experience a grade 3+ AE	7 Participants	0 Participants	—

PRIMARY outcome

Timeframe: From baseline to occurrence of event, up to Week 48.

Number (%) of deaths on study by Cohort.

Outcome measures

Outcome measures
Measure	Cohort I: Treatment Experienced, 2 to 6 Years of Age n=11 Participants 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.	Cohort II: Treatment Experienced, 1 to 2 Years of Age n=4 Participants 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.	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age 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.
Death Deaths	0 Participants	0 Participants	—
Death Live participants	11 Participants	4 Participants	—

PRIMARY outcome

Timeframe: 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)

Population: 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.

Geometric Mean (Standard Deviation) of the area under the plasma concentration-time curve over 12 hours (AUC12h) of ETR.

Outcome measures

Outcome measures
Measure	Cohort I: Treatment Experienced, 2 to 6 Years of Age n=10 Participants 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.	Cohort II: Treatment Experienced, 1 to 2 Years of Age n=4 Participants 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.	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age 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.
Area Under the Plasma Concentration-Time Curve Over 12 Hours of ETR	5512.85 ng*h/mL Standard Deviation 3615.36	4821.76 ng*h/mL Standard Deviation 3167.11	—

SECONDARY outcome

Timeframe: From baseline to occurrence of event, up to Week 48.

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.

Outcome measures

Outcome measures
Measure	Cohort I: Treatment Experienced, 2 to 6 Years of Age n=11 Participants 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.	Cohort II: Treatment Experienced, 1 to 2 Years of Age n=4 Participants 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.	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age 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.
AEs of Grade 3 or Higher Severity Judged to be at Least Possibly Attributable to the Study Medications Had a grade 3+ AE related to study drug	2 Participants	0 Participants	—
AEs of Grade 3 or Higher Severity Judged to be at Least Possibly Attributable to the Study Medications Had no grade 3+ AE related to study drug	9 Participants	4 Participants	—

SECONDARY outcome

Timeframe: Baseline, Week 24, and Week 48

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.

Outcome measures

Outcome measures
Measure	Cohort I: Treatment Experienced, 2 to 6 Years of Age n=11 Participants 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.	Cohort II: Treatment Experienced, 1 to 2 Years of Age n=4 Participants 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.	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age 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.
HIV-1 RNA Virologic Failure Status at Weeks 24 and 48 Week 24 · Virologic Failure	2 Participants	1 Participants	—
HIV-1 RNA Virologic Failure Status at Weeks 24 and 48 Week 24 · No Virologic Failure	9 Participants	3 Participants	—
HIV-1 RNA Virologic Failure Status at Weeks 24 and 48 Week 48 · Virologic Failure	3 Participants	3 Participants	—
HIV-1 RNA Virologic Failure Status at Weeks 24 and 48 Week 48 · No Virologic Failure	8 Participants	1 Participants	—

SECONDARY outcome

Timeframe: From baseline to occurrence of event, up to Week 48.

Number (%) of participants who discontinued study treatment (ETR) due to a toxicity or Virologic Failure (VF), by Cohort.

Outcome measures

Outcome measures
Measure	Cohort I: Treatment Experienced, 2 to 6 Years of Age n=11 Participants 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.	Cohort II: Treatment Experienced, 1 to 2 Years of Age n=4 Participants 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.	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age 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.
Treatment Discontinued Due to Toxicity or Virologic Failure Did not discontinue treatment due to VF	10 Participants	4 Participants	—
Treatment Discontinued Due to Toxicity or Virologic Failure Discontinued Treatment due to VF	1 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Measured at entry and at Weeks 8, 12, 24, and 48

Number (%) of participants who initiated a change in their optimized background regimen (OBR) due to virologic failure, by Cohort.

Outcome measures

Outcome measures
Measure	Cohort I: Treatment Experienced, 2 to 6 Years of Age n=11 Participants 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.	Cohort II: Treatment Experienced, 1 to 2 Years of Age n=4 Participants 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.	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age 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.
Change in Optimized Background Regimen Due to Virologic Failure Changed OBR due to Virologic Failure	0 Participants	0 Participants	—
Change in Optimized Background Regimen Due to Virologic Failure Did not change OBR due to Virologic Failure	11 Participants	4 Participants	—

SECONDARY outcome

Timeframe: From baseline to occurrence of event, up to Week 48.

Number (%) of participants with a new onset opportunistic infection (OI) or AIDS diagnosis, by Cohort.

Outcome measures

Outcome measures
Measure	Cohort I: Treatment Experienced, 2 to 6 Years of Age n=11 Participants 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.	Cohort II: Treatment Experienced, 1 to 2 Years of Age n=4 Participants 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.	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age 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.
New Onset Opportunistic Infection (OI) or AIDS Diagnosis Had a new OI	0 Participants	0 Participants	—
New Onset Opportunistic Infection (OI) or AIDS Diagnosis Had no new OIs	11 Participants	4 Participants	—

SECONDARY outcome

Timeframe: Measured at baseline and at Weeks 12, 24, and 48

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.

Outcome measures

Outcome measures
Measure	Cohort I: Treatment Experienced, 2 to 6 Years of Age n=11 Participants 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.	Cohort II: Treatment Experienced, 1 to 2 Years of Age n=4 Participants 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.	Cohort III: Treatment Experienced, 2 Months to 1 Year of Age 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.
Decline in Absolute CD4 Percent of Greater Than 5 Percent Any Time After 12 Weeks of Therapy Week 12 · >5% decline in CD4 % from baseline	1 Participants	2 Participants	—
Decline in Absolute CD4 Percent of Greater Than 5 Percent Any Time After 12 Weeks of Therapy Week 12 · Increase or <5% decline in CD4 % from baseline	10 Participants	2 Participants	—
Decline in Absolute CD4 Percent of Greater Than 5 Percent Any Time After 12 Weeks of Therapy Week 24 · >5% decline in CD4 % from baseline	1 Participants	1 Participants	—
Decline in Absolute CD4 Percent of Greater Than 5 Percent Any Time After 12 Weeks of Therapy Week 24 · Increase or <5% decline in CD4 % from baseline	10 Participants	3 Participants	—
Decline in Absolute CD4 Percent of Greater Than 5 Percent Any Time After 12 Weeks of Therapy Week 48 · >5% decline in CD4 % from baseline	2 Participants	2 Participants	—
Decline in Absolute CD4 Percent of Greater Than 5 Percent Any Time After 12 Weeks of Therapy Week 48 · Increase or <5% decline in CD4 % from baseline	9 Participants	2 Participants	—

Adverse Events

Cohort I: Treatment Experienced, 2 to 6 Years of Age

Serious events: 5 serious events

Other events: 20 other events

Deaths: 0 deaths

Cohort II: Treatment Experienced, 1 to 2 Years of Age

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort I: Treatment Experienced, 2 to 6 Years of Age n=20 participants at risk 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.	Cohort II: Treatment Experienced, 1 to 2 Years of Age n=6 participants at risk 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.
Blood and lymphatic system disorders Anaemia	0.00% 0/20 • From entry through off study, at an average of 72 weeks. 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.	16.7% 1/6 • From entry through off study, at an average of 72 weeks. 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.
Injury, poisoning and procedural complications Forearm fracture	5.0% 1/20 • From entry through off study, at an average of 72 weeks. 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.	0.00% 0/6 • From entry through off study, at an average of 72 weeks. 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.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/20 • From entry through off study, at an average of 72 weeks. 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.	16.7% 1/6 • From entry through off study, at an average of 72 weeks. 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.
Investigations Lipase increased	10.0% 2/20 • From entry through off study, at an average of 72 weeks. 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.	0.00% 0/6 • From entry through off study, at an average of 72 weeks. 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.
Investigations Neutrophil count decreased	10.0% 2/20 • From entry through off study, at an average of 72 weeks. 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.	16.7% 1/6 • From entry through off study, at an average of 72 weeks. 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.
Investigations Platelet count decreased	5.0% 1/20 • From entry through off study, at an average of 72 weeks. 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.	16.7% 1/6 • From entry through off study, at an average of 72 weeks. 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.

Other adverse events

Additional Information

Melissa Allen, Director, IMPAACT Operations Center

Family Health International (FHI 360)

Phone: (919) 405-1429

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER