Trial Outcomes & Findings for Safety, Tolerance and Pharmacokinetics of Raltegravir-Containing Antiretroviral Therapy in Infants, Children Infected With HIV and TB (NCT NCT01751568)

Last Updated: 2021-11-05

Results Overview

Number (Frequency) of participants who permanently discontinued raltegravir study treatment due to an adverse event(s) of greater than or equal to Grade 3, deemed at least possibly related to raltergravir.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

40 participants

Primary outcome timeframe

Measured from the first dose of raltegravir through the participant's last study visit (median of 34 weeks)

Results posted on

2021-11-05

Participant Flow

Accrual occurred between November 2014 and April 2019 in four (4) sites from South Africa.

Participant milestones

Participant milestones
Measure	Cohort 1: ≥ 2 to < 6 Years of Age on TB Treatment Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 2: ≥ 6 to < 12 Years of Age on TB Treatment Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 3: : ≥ 4 Weeks to < 2 Years of Age on TB Treatment Participants in this cohort received chewable raltegravir tablets (as a dispersible tablet), starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.
Overall Study STARTED	13	14	13
Overall Study COMPLETED	12	14	13
Overall Study NOT COMPLETED	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: ≥ 2 to < 6 Years of Age on TB Treatment Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 2: ≥ 6 to < 12 Years of Age on TB Treatment Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 3: : ≥ 4 Weeks to < 2 Years of Age on TB Treatment Participants in this cohort received chewable raltegravir tablets (as a dispersible tablet), starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.
Overall Study Participant never started treatment of raltegravir, was taken off-study.	1	0	0

Baseline Characteristics

Safety, Tolerance and Pharmacokinetics of Raltegravir-Containing Antiretroviral Therapy in Infants, Children Infected With HIV and TB

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: ≥ 2 to < 6 Years of Age on TB Treatment n=12 Participants Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 2: ≥ 6 to < 12 Years of Age on TB Treatment n=14 Participants Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 3: : ≥ 4 Weeks to < 2 Years of Age on TB Treatment n=13 Participants Participants in this cohort received chewable raltegravir tablets (as a dispersible tablet), starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Total n=39 Participants Total of all reporting groups
Age, Continuous	3.55 years n=5 Participants	8.55 years n=7 Participants	1.00 years n=5 Participants	3.70 years n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	7 Participants n=7 Participants	5 Participants n=5 Participants	17 Participants n=4 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	22 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=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 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=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants	14 Participants n=7 Participants	13 Participants n=5 Participants	39 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Black Non-Hispanic	11 participants n=5 Participants	14 participants n=7 Participants	13 participants n=5 Participants	38 participants n=4 Participants
Race/Ethnicity, Customized Hispanic (Regardless of Race)	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Region of Enrollment South Africa	12 participants n=5 Participants	14 participants n=7 Participants	13 participants n=5 Participants	39 participants n=4 Participants
Log10 RNA	4.91 log10(copies/ml) n=5 Participants	4.55 log10(copies/ml) n=7 Participants	5.13 log10(copies/ml) n=5 Participants	4.97 log10(copies/ml) n=4 Participants
CD4 Count	559 cells/mm^3 n=5 Participants	575 cells/mm^3 n=7 Participants	1513 cells/mm^3 n=5 Participants	808 cells/mm^3 n=4 Participants
CD4 Percent	15.25 percentage n=5 Participants	21.35 percentage n=7 Participants	16.80 percentage n=5 Participants	16.80 percentage n=4 Participants
Weight	13.60 kilograms n=5 Participants	21.30 kilograms n=7 Participants	8.03 kilograms n=5 Participants	13.80 kilograms n=4 Participants

PRIMARY outcome

Timeframe: Measured from the first dose of raltegravir through the participant's last study visit (median of 34 weeks)

Population: Includes all participants who received at least one dose of raltegravir at the final recommended dose for the cohort.

Outcome measures

Outcome measures
Measure	Cohort 1: ≥ 2 to < 6 Years of Age on TB Treatment n=12 Participants Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 2: ≥ 6 to < 12 Years of Age on TB Treatment n=14 Participants Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 3: : ≥ 4 Weeks to < 2 Years of Age on TB Treatment n=13 Participants Participants in this cohort received chewable raltegravir tablets (as a dispersible tablet), starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.
Number of Participants Who Permanently Discontinued Treatment Due to Adverse Event(s) of Greater Than or Equal to Grade 3 Deemed at Least Possibly Related to Raltegravir	0 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Measured from the first dose of raltegravir through a participant's last study visit (median of 34 weeks)

Population: Includes all participants who received at least one dose of raltegravir at the final recommended dose for the cohort.

Number (Frequency) of participants who experienced Death, Grade 4 life-threatening adverse events deemed at least possibly related to raltegravir

Outcome measures

Outcome measures
Measure	Cohort 1: ≥ 2 to < 6 Years of Age on TB Treatment n=12 Participants Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 2: ≥ 6 to < 12 Years of Age on TB Treatment n=14 Participants Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 3: : ≥ 4 Weeks to < 2 Years of Age on TB Treatment n=13 Participants Participants in this cohort received chewable raltegravir tablets (as a dispersible tablet), starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.
Number of Participants Who Experienced Death, Grade 4 Life-threatening Adverse Events Deemed at Least Possibly Related to Raltegravir	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Measured from the first dose of raltegravir through a participant's last study visit (median of 34 weeks)

Population: Includes all participants who received at least one dose of raltegravir at the final recommended dose for the cohort.

Number (Frequency) of Participants who experienced Grade 4 non-life threatening adverse event(s) deemed as probably or definitely related to raltegravir

Outcome measures

Outcome measures
Measure	Cohort 1: ≥ 2 to < 6 Years of Age on TB Treatment n=12 Participants Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 2: ≥ 6 to < 12 Years of Age on TB Treatment n=14 Participants Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 3: : ≥ 4 Weeks to < 2 Years of Age on TB Treatment n=13 Participants Participants in this cohort received chewable raltegravir tablets (as a dispersible tablet), starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.
Number of Participants Who Experienced Grade 4 Non-life Threatening Adverse Event(s) Deemed as Probably or Definitely Related to Raltegravir	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Measured from the first dose of raltegravir through a participant's last study visit (median of 34 weeks)

Population: Includes all participants who received at least one dose of raltegravir at the final recommended dose for the cohort.

Number (Frequency) of Participants who experienced Adverse event(s) of greater than or equal to Grade 3 deemed at least possibly related to raltegravir

Outcome measures

Outcome measures
Measure	Cohort 1: ≥ 2 to < 6 Years of Age on TB Treatment n=12 Participants Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 2: ≥ 6 to < 12 Years of Age on TB Treatment n=14 Participants Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 3: : ≥ 4 Weeks to < 2 Years of Age on TB Treatment n=13 Participants Participants in this cohort received chewable raltegravir tablets (as a dispersible tablet), starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.
Number of Participants Who Experienced Adverse Event(s) of Greater Than or Equal to Grade 3 Deemed at Least Possibly Related to Raltegravir	1 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: At the study visit between days 5 and 8 of raltegravir initiation; A (0.5) mL of blood sample was drawn at each time point: pre-dose (0), 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post dosing.

Population: Participants with intensive pharmacokinetic (PK) results at the final recommended dose in each Age Cohort

Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods (Phoenix WinNonlin 8.1, Certara, Princeton, New Jersey). AUC12h (area-under-the-curve from 0 to 12 hours) were determined using the linear-log trapezoidal rule. Geometric Means (GM) for AUC12h were calculated for each cohort.

Outcome measures

Outcome measures
Measure	Cohort 1: ≥ 2 to < 6 Years of Age on TB Treatment n=12 Participants Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 2: ≥ 6 to < 12 Years of Age on TB Treatment n=14 Participants Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 3: : ≥ 4 Weeks to < 2 Years of Age on TB Treatment n=13 Participants Participants in this cohort received chewable raltegravir tablets (as a dispersible tablet), starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.
Pharmacokinetic (PK) Parameter: Area Under the Curve (AUC12h)	12.8 h*mg/L Interval 4.0 to 25.8	17.2 h*mg/L Interval 10.1 to 31.3	14.6 h*mg/L Interval 6.4 to 29.7

PRIMARY outcome

Timeframe: At the study visit between days 5 and 8 of raltegravir initiation; A (0.5) mL of blood sample was drawn at each time point: pre-dose (0), 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post dosing.

Population: Participants with intensive pharmacokinetic (PK) results at the final recommended dose in each Age Cohort

Outcome measures

Outcome measures
Measure	Cohort 1: ≥ 2 to < 6 Years of Age on TB Treatment n=12 Participants Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 2: ≥ 6 to < 12 Years of Age on TB Treatment n=14 Participants Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 3: : ≥ 4 Weeks to < 2 Years of Age on TB Treatment n=13 Participants Participants in this cohort received chewable raltegravir tablets (as a dispersible tablet), starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.
Pharmacokinetic (PK) Parameter: Concentration at 12h (C12)	101.8 ng/mL Interval 18.8 to 334.9	101.2 ng/mL Interval 48.3 to 354.6	47.3 ng/mL Interval 19.6 to 131.4

SECONDARY outcome

Timeframe: Measured at Week 8

Population: Includes all participants who received at least one dose of raltegravir at the final recommended dose for the cohort. Please note that an as-Treated (AT) analysis was carried out, such that participants who permanently discontinued treatment before week 8, without evaluable data were not included in the analyses.

Number (Frequency) of Participants who failed to respond virologically at Week 8, which includes HIV RNA (copies/mL) greater than 400 copies/mL AND less than 1-log10 drop from baseline. Please note that the protocol definition of virologic response was: achieving at least a 1-log10 reduction from baseline in HIV-1 RNA (copies/mL) or HIV-1 RNA ≤ 400 copies/mL at week 8. An As-Treated (AT) analysis was carried out, such that participants who permanently discontinued treatment before week 8, without evaluable data were not included in the analyses.

Outcome measures

Outcome measures
Measure	Cohort 1: ≥ 2 to < 6 Years of Age on TB Treatment n=12 Participants Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 2: ≥ 6 to < 12 Years of Age on TB Treatment n=12 Participants Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 3: : ≥ 4 Weeks to < 2 Years of Age on TB Treatment n=12 Participants Participants in this cohort received chewable raltegravir tablets (as a dispersible tablet), starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.
Number of Participants Who Failed to Respond Virologically at Week 8, Which Means Having HIV RNA (Copies/mL) Greater Than 400 Copies/mL AND Less Than 1-log10 Drop From Baseline	1 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Measured from the first dose of raltegravir through a participant's last study visit (median of 34 weeks)

Population: Includes all participants who received at least one dose of raltegravir at the final recommended dose for the cohort.

Number (Frequency) of participants who developed of new opportunistic infection(s) (OIs)

Outcome measures

Outcome measures
Measure	Cohort 1: ≥ 2 to < 6 Years of Age on TB Treatment n=12 Participants Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 2: ≥ 6 to < 12 Years of Age on TB Treatment n=14 Participants Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 3: : ≥ 4 Weeks to < 2 Years of Age on TB Treatment n=13 Participants Participants in this cohort received chewable raltegravir tablets (as a dispersible tablet), starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.
Number of Participants Who Developed of New Opportunistic Infection(s) (OIs)	1 Participants	0 Participants	1 Participants

Adverse Events

Cohort 1: ≥ 2 to < 6 Years of Age on TB Treatment

Serious events: 8 serious events

Other events: 12 other events

Deaths: 0 deaths

Cohort 2: ≥ 6 to < 12 Years of Age on TB Treatment

Serious events: 5 serious events

Other events: 14 other events

Deaths: 0 deaths

Cohort 3: : ≥ 4 Weeks to < 2 Years of Age on TB Treatment

Serious events: 5 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1: ≥ 2 to < 6 Years of Age on TB Treatment n=12 participants at risk Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 2: ≥ 6 to < 12 Years of Age on TB Treatment n=14 participants at risk Participants in this cohort received chewable raltegravir tablets, starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.	Cohort 3: : ≥ 4 Weeks to < 2 Years of Age on TB Treatment n=13 participants at risk Participants in this cohort received chewable raltegravir tablets (as a dispersible tablet), starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen. Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.
Hepatobiliary disorders Hepatotoxicity	16.7% 2/12 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	0.00% 0/14 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	0.00% 0/13 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.
Immune system disorders Drug hypersensitivity	0.00% 0/12 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	7.1% 1/14 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	0.00% 0/13 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.
Infections and infestations Gastroenteritis	8.3% 1/12 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	0.00% 0/14 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	0.00% 0/13 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.
Infections and infestations Pneumonia bacterial	0.00% 0/12 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	0.00% 0/14 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	7.7% 1/13 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.
Investigations Amylase increased	16.7% 2/12 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	0.00% 0/14 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	15.4% 2/13 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.
Investigations Bilirubin conjugated increased	16.7% 2/12 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	0.00% 0/14 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	7.7% 1/13 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.
Investigations Blood potassium increased	0.00% 0/12 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	7.1% 1/14 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	0.00% 0/13 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.
Investigations Blood pressure diastolic increased	0.00% 0/12 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	0.00% 0/14 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	7.7% 1/13 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.
Investigations Neutrophil count decreased	16.7% 2/12 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	21.4% 3/14 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	7.7% 1/13 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.
Investigations Transaminases increased	0.00% 0/12 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	0.00% 0/14 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	7.7% 1/13 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.
Metabolism and nutrition disorders Hyponatraemia	8.3% 1/12 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	0.00% 0/14 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	0.00% 0/13 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.
Nervous system disorders Generalised tonic-clonic seizure	0.00% 0/12 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	7.1% 1/14 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.	0.00% 0/13 • Measured from the first dose of raltegravir through the participant's last study visit (up to 64 weeks). 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. Adverse events (AE) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.

Other adverse events

Additional Information

Melissa Allen, Director, IMPAACT Operations Center

Family Health International (FHI 360)

Phone: (919) 544-7040

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

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