HIV Infections
Conditions
Keywords
Integrase Inhibitors, Infant, Child, Adolescent
Brief summary
Dolutegravir (DTG) is an HIV drug in the integrase inhibitor drug class. This study evaluated the pharmacokinetics (PK), safety, tolerability of and immune response to DTG when used concurrently with optimized background therapy (OBT) in HIV-1 infected infants, children, and adolescents.
Detailed description
DTG is an HIV medicine in the integrase inhibitor drug class. The purpose of this study was to evaluate the pharmacokinetics, safety, tolerability, and antiviral activity of DTG when used concurrently with OBT in HIV-1 infected infants, children, and adolescents. Participants in this study were evaluated for PK, safety and tolerability through 48 weeks, followed by additional long-term study follow-up that lasted for approximately 144 weeks (3 years), for a total of 192 weeks on study. This study had two stages. Stage I provided pharmacokinetics, short-term tolerability and safety data on DTG on a limited number of participants to permit dose selection for further study in Stage II. Once a Stage I dose was accepted, enrollment to Stage II began to complete enrollment to the cohort. Stage II provided longer-term safety and antiviral activity data among a larger number of participants. Infants, children and adolescents with HIV-1, aged ≥ 4 weeks to \< 18 years enrolled in the age and formulation cohorts specified below: * Cohort I: Adolescents ≥ 12 to \<18 years of age (film-coated tablets) * Cohort IIA: Children ≥ 6 to \<12 years of age (film-coated tablets) * Cohort IIB: Children ≥ 6 to \<12 years of age (granules for suspension) * Cohort III: Children ≥ 2 to \< 6 years of age (granules for suspension) * Cohort IV: Children ≥ 6 months to \< 2 years of age (granules for suspension) * Cohort III-DT: Children ≥ 2 to \< 6 years of age (dispersible tablets) * Cohort IV-DT: Children ≥ 6 months to \< 2 years of age (dispersible tablets) * Cohort V-DT: Infants ≥ 4 weeks to \< 6 months (dispersible tablets) Cohorts were opened sequentially according by age group (starting with the older age group), DTG formulation, and study stage, i.e. Initial study enrollment was for Cohort I and progressed to Cohort IIA once Cohort I Stage I met the PK and safety criteria, followed by opening of Cohort IIB. Each cohort enrolled in two sequential stages: Stage I and II (the only exception is Cohort IIB, which only enrolled through Stage I). Sequential enrollment for Cohort III and IV proceeded in the same manner. Cohort V never enrolled because of the recommended changes in dosing and inclusion of enrollment weight band in the criteria for dose finding. Stage I participants had physical examinations and had blood draws for safety assessments at study visits: Day 0; Day 5 (+5 days); and Weeks 4, 8, 12, 16, 24, 32, 40, and 48. Stage I participants also had intensive PK sampling with blood samples collected at time 0 (pre-dose), and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing. Once a Stage I treatment dose was accepted, enrollment to Stage II began to complete enrollment to the cohort. Stage II participants had physical examinations and blood draws for safety assessment at study visits: Day 0; Day 10; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48. Blood, plasma, and urine were collected and tested to measure immune response. Females of childbearing potential underwent pregnancy testing at screening and at every study visit. After 48 weeks, all Stage I and Stage II participants entered the long-term study follow-up and continued to receive DTG. During this time, participants had safety and/or antiviral activity assessments every 12 weeks for up to 3 years. The study was able to determine a proposed dose (i.e. optimal dose) for Cohorts I, IIA, III-DT, IV-DT, and V-DT but not for Cohorts IIB, III, and IV. Participants on the proposed dose had intensive PK sampling between days 5 and10 of DTG initiation with blood samples collected at time 0 (pre-dose), and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing. The study is closed to accrual and study follow-up was completed on Oct 18, 2023.
Interventions
DRUGDTG film-coated tablets
DTG film-coated tablets initial starting dose at \ 1 mg/kg with a maximum dose of 50 mg; orally once daily. Participants weighing ≥ 35kg received the proposed dose of 50 mg of DTG film-coated tablets.
DRUGDTG granules for suspension
DTG granules for suspension initial starting dose at \ 0.64 mg/kg with a maximum dose of 32 mg; orally once daily.
DRUGDTG dispersible tablets
DTG dispersible tablets initial starting dose of \ 0.8 mg/kg with a maximum dose of 30 mg; orally once daily. The proposed weight-band dosing was: Weight band 3 to \<6 kg: 5 mg DTG dispersible tablets; Weight band 6 to \<10 kg: 15 mg DTG dispersible tablets; Weight band 10 to \<14 kg: 20 mg DTG dispersible tablets; Weight band 14 to \<20 kg: 25 mg DTG dispersible tablets; Weight band ≥20 kg: 30 mg DTG dispersible tablets.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Weeks to 17 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed HIV-1 infection, defined as positive results from two samples collected at different time points (see protocol for more information) * Participant belonged to one of the ARV exposure groups below: 1. ARV-treatment experienced (not including receipt of ARVs as prophylaxis or for prevention of perinatal transmission) * Previously took ARVs for treatment, but not taking ARVs at study screening. * Had been off treatment for greater than or equal to 4 weeks prior to screening, OR * At screening, taking ARVs for treatment but failing. * Was on an unchanged, failing therapeutic regimen within the 4 to 12 weeks prior to screening (less than or equal to 1 log drop in HIV-1 RNA within the 4 to 12 weeks prior to screening). OR * For participants less than 2 years of age, initiated ARVs for treatment less than 4 weeks prior to screening. 2. ARV treatment naive (no exposure to ARVs for treatment; could have received ARVs for prophylaxis or prevention of perinatal transmission) * If an infant had received nevirapine (NVP) as prophylaxis to prevent perinatal transmission, he or she did not receive NVP for at least 14 days prior to enrollment into Stage I or II. * HIV-1 RNA viral load greater than 1,000 copies/mL of plasma at screening. * Demonstrated ability or willingness to swallow assigned study medications. * Parent or legal guardian were able and willing to provide signed informed consent. * Female participants of reproductive potential, defined as having reached menarche, and who were engaging in sexual activity that could lead to pregnancy, agreed to use two contraceptive methods while on study and for two weeks after stopping study drug. * Males engaging in sexual activity that could lead to HIV-1 transmission agreed to use a condom. * Agreed to stay on optimized background therapy (OBT) while on study: * Participants who at screening were greater than or equal to 2 years of age and ARV-treatment experienced, had at screening at least one fully active drug for the OBT. * Participants who were greater than or equal to 2 years of age and ARV-treatment naïve, had genotype testing at screening/entry even with results pending. * Participants less than 2 years of age (either ARV-treatment experienced or ARV treatment naïve), had genotype testing at screening/entry even with results pending.
Exclusion criteria
* Presence of any active AIDS-defining opportunistic infection * At enrollment, participant less than 3.0 kg * Known Grade 3 or greater of any of the following laboratory toxicities within 30 days prior to study entry: neutrophil count, hemoglobin, platelets, aspartate aminotransferase (AST), alanine transaminase (ALT), lipase, serum creatinine and total bilirubin. A single repeat within the 30 days is allowed for eligibility determination. NOTE: Grade 3 total bilirubin was allowable, if the participant was on atazanavir (ATV). * ANY known Grade 4 laboratory toxicities within 30 days prior to study entry. NOTE: Grade 4 total bilirubin was allowable, if the participant was on ATV. * The following liver toxicities within 30 days prior to study entry: ALT greater than 3x the upper limit of normal (ULN) AND direct bilirubin was greater than 2x ULN * Any prior history of malignancy, with the exception of localized malignancies such as squamous cell or basal cell carcinoma of the skin * Clinical or symptomatic evidence of pancreatitis, as determined by the clinician * Use of any disallowed medications at time of screening (see the protocol for a complete list of disallowed medications) * Known history of exposure to integrase inhibitor treatment by the participant or participant's mother prior to delivery/cessation of breastfeeding * Known resistance to an integrase inhibitor * Women who were pregnant or breastfeeding * At screening/entry, participating in or had participated in a study with a compound or device that was not commercially available within 30 days of signing informed consent, unless permission from both Protocol Teams was granted * Participant was unlikely to adhere to the study procedures, keep appointments, or was planning to relocate during the study to a non-IMPAACT study site * Any clinically significant diseases (other than HIV infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator's opinion, would compromise the outcome of this study * At screening/entry had used, or anticipated using, chronic systemic immunosuppressive agents or systemic interferon (e.g., for treatment of hepatitis C virus \[HCV\] infection) within 30 days prior to beginning DTG study treatment. Systemic corticosteroids (e.g., prednisone or equivalent up to 2 mg/kg/day) for replacement therapy or short courses (less than or equal to 30 days) were permitted. (See protocol for more information on disallowed medications.) * Any condition that in the opinion of the site investigator, placed the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol. * Active tuberculosis (TB) disease and/or requirement for treatment that included rifampin at the time of the screening visit. However, participants who needed rifampin treatment while on DTG were allowed to continue in P1093 provided the DTG dose was adjusted according to the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | From treatment initiation through Weeks 24 and 48 | All grade 3 or higher signs/symptoms, diagnoses, and laboratory AEs were included. AE grading was based on DAIDS AE Grading Table, Version 1.0, December 2004 (Clarification, August 2009). A 2-sided 95% Confidence Interval (CI) was calculated for the percentage using the binominal exact method. |
| Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | From treatment initiation through Weeks 24 and 48 | All grade 3 or higher signs/symptoms, diagnoses, and laboratory AEs were included. AE grading was based on DAIDS AE Grading Table, Version 1.0, December 2004 (Clarification, August 2009). A 2-sided 95% Confidence Interval (CI) was calculated for the percentage using the binominal exact method. |
| Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | From treatment initiation through Weeks 24 and 48 | Number of participants with permanent discontinuation of study drug due to AEs assessed by the site investigator as related to the study drug. |
| Number of Participants Who Died | From treatment initiation through Weeks 24 and 48 | Number of participants who died were summarized |
| PK Parameter: Area-under-the-curve From 0 to 24 Hours (AUC0-24) | One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing | Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). AUC0-24 was determined using linear up-log down estimation in WinNonlin. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/ml | Week 24 and Week 48 | Virologic responses were assessed at weeks 24 and 48 as percentages of participants and exact 95% Confidence Interval (CI), The virologic response or virologic failure was defined and calculated according to FDA's Snapshot algorithm. |
| PK Parameter: Plasma Concentration Observed at End of 24 Hour Dosing Interval (C24h) | One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing | Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). C24h was taken directly from the observed concentration-time data or estimated using the elimination rate constant. |
| PK Parameter: Plasma Concentration Observed Immediately to Dosing of 24 Hour Dosing Interval (C0h) | One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing | Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). C0h was taken directly from the observed concentration-time data. |
| PK Parameter: Minimum Plasma Concentration (Cmin) | One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing | Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ) and were performed in real-time. Cmin was taken directly from the observed concentration-time data. |
| PK Parameter: Maximum Plasma Concentration (Cmax) | One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing | Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). Cmax was taken directly from the observed concentration-time data. |
| PK Parameter: Apparent Clearance (CL/F) | One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing | Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). CL/F was calculated as Dose/AUC. |
| PK Parameter: Apparent Volume of Distribution (Vz/F) | One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing | Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). Vz/F was calculated as Dose/(ke x AUC). |
| PK Parameter: Terminal Half-life (t1/2) | One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing | Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). t1/2 was calculated as ln(2)/ke. |
| Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | From treatment initiation through Week 192. AEs after that time were censored. | Percentage and exact 95% Confidence Interval (CI) of participants with Grade 3 or higher AEs. AEs were graded based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004, Clarification August 2009 (see References). All grade 3 or higher signs, symptoms, and laboratory toxicities were included. |
| Summary of Changes in CD4 Percent From Baseline | Measured at Day 0, Week 24, and Week 48 | The median differences between CD4 percent at Week 24 and 48 minus at the Day 0 (baseline), and Interquartile Ranges (IQRs) are presented. |
| Summary of Changes in CD8 Count From Baseline | Measured at Day 0, Week 24, and Week 48 | The median differences between CD8 count at Week 24 and 48 minus at the Day 0 (baseline), and Interquartile Ranges (IQRs) are presented. |
| Summary of Changes in CD8 Percent From Baseline | Measured at Day 0, Week 24, and Week 48 | The median differences between CD8 percent at Week 24 and 48 minus at the Day 0 (baseline), and Interquartile Ranges (IQRs) are presented. |
| Genotypic Measures of Resistance to Integrase | At baseline | Genes were sequenced and compared to a reference sequence to identify mutations |
| Genotypic Measures of Resistance to Protease | at baseline | Genes were sequenced and compared to a reference sequence to identify mutations |
| Genotypic Measures of Resistance to Reverse Transcriptase | at baseline | Genes were sequenced and compared to a reference sequence to identify mutations |
| Phenotypic Measures of Resistance | Whenever virological failures took place from baseline to week 192 | The participant viral culture is considered to be reduced susceptibility if more DTG is needed to inactivate 50% of the participant viral culture compared to the control viral specimen |
| Worst Case CDC HIV Classification Status | From baseline through Week 192 | Disease progression as measured by change from baseline to the worst case CDC HIV classification status |
| Summary of Changes in CD4 Count From Baseline | Measured at Day 0, Week 24, and Week 48 | The median differences between CD4 count at Week 24 and 48 minus at the Day 0 (baseline), and Interquartile Ranges (IQRs) are presented. |
| Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | From treatment initiation through Week 192. AEs after that time were censored. | Percentage and exact 95% Confidence Interval (CI) of participants with Grade 3 or higher AEs assessed by the site investigator as related to the study drug. |
| Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | From treatment initiation through Week 192. AEs after that time were censored. | Number of participants with permanent discontinuation of study drug due to AEs assessed by the site investigator as related to the study drug. |
| Number of Participants Who Died | From treatment initiation through Week 192. AEs after that time were censored. | Number of participants who died were summarized. |
| Percentage of Participants With Plasma HIV-1 RNA Less Than 400 Copies/ml | Week 24 and Week 48 | Virologic responses were assessed at weeks 24 and 48 as percentages of participants and exact 95% Confidence Interval (CI). The virologic response or virologic failure was defined and calculated according to FDA's Snapshot algorithm. |
Countries
Botswana, Brazil, Kenya, South Africa, Tanzania, Thailand, United States, Zimbabwe
Participant flow
Recruitment details
Participants were enrolled from April 20, 2011 to February 19, 2020. Participants were recruited from 9 countries in North America, South America, Africa, and Asia.
Pre-assignment details
There was no study randomization. A participant was enrolled to a cohort based on their age at study entry.
Participants by arm
| Arm | Count |
|---|---|
| Cohort I Adolescents 12 to younger than 18 years of age who received DTG film-coated tablets.
DTG film-coated tablets initial starting dose at \
1 mg/kg with a maximum dose of 50 mg; orally once daily. | 23 |
| Cohort IIA Children 6 to younger than 12 years of age who received DTG film-coated tablets.
DTG film-coated tablets initial starting dose at \
1 mg/kg with a maximum dose of 50 mg; orally once daily. | 23 |
| Cohort IIB Children 6 to younger than 12 years of age who received DTG granules for suspension.
DTG granules for suspension initial starting dose at \
0.64 mg/kg with a maximum dose of 32 mg; orally once daily. | 15 |
| Cohort III Children 2 to younger than 6 years of age who received DTG granules for suspension.
DTG granules for suspension initial starting dose at \
0.64 mg/kg with a maximum dose of 32 mg; orally once daily. | 17 |
| Cohort IV Children 6 months to younger than 2 years of age who received DTG granules for suspension.
DTG granules for suspension initial starting dose at \
0.64 mg/kg with a maximum dose of 32 mg; orally once daily. | 7 |
| Cohort III-DT Children 2 to younger than 6 years of age who received DTG dispersible tablets.
DTG dispersible tablets initial starting dose of \
0.8 mg/kg with a maximum dose of 30 mg; orally once daily. | 36 |
| Cohort IV-DT Children 6 months to younger than 2 years of age who received DTG dispersible tablets.
DTG dispersible tablets initial starting dose of \
1.25 mg/kg with a maximum dose of 30 mg; orally once daily. | 35 |
| Cohort V-DT Infants 4 weeks to younger than 6 months of age who received DTG dispersible tablets.
DTG dispersible tablets initial starting dose of \
1.25 mg/kg with a maximum dose of 30 mg; orally once daily. | 25 |
| Total | 181 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Not able to get to clinic | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Not willing to adhere to requirements | 5 | 0 | 1 | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Pregnancy | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Severe debilitation, unable to continue | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Site closing | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Site unable to contact participant | 2 | 1 | 0 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Virologic failure | 0 | 2 | 0 | 2 | 1 | 3 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort IIA | Total | Cohort V-DT | Cohort IV-DT | Cohort III-DT | Cohort IV | Cohort III | Cohort IIB | Cohort I |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 8.96 years STANDARD_DEVIATION 1.99 | 4.84 years STANDARD_DEVIATION 4.78 | 0.03 years STANDARD_DEVIATION 0.01 | 1.13 years STANDARD_DEVIATION 0.44 | 3.25 years STANDARD_DEVIATION 1.18 | 1.14 years STANDARD_DEVIATION 0.41 | 3.59 years STANDARD_DEVIATION 1 | 7.73 years STANDARD_DEVIATION 1.79 | 14.26 years STANDARD_DEVIATION 1.79 |
| Baseline Plasma HIV-1 RNA (copies/mL) >=100,000 | 11 Participants | 62 Participants | 11 Participants | 14 Participants | 12 Participants | 3 Participants | 7 Participants | 2 Participants | 2 Participants |
| Baseline Plasma HIV-1 RNA (copies/mL) 10,000 - <25,000 | 0 Participants | 21 Participants | 2 Participants | 4 Participants | 4 Participants | 0 Participants | 0 Participants | 3 Participants | 8 Participants |
| Baseline Plasma HIV-1 RNA (copies/mL) 1,000 - <5,000 | 3 Participants | 27 Participants | 7 Participants | 7 Participants | 5 Participants | 0 Participants | 2 Participants | 1 Participants | 2 Participants |
| Baseline Plasma HIV-1 RNA (copies/mL) 25,000 - <50,000 | 4 Participants | 22 Participants | 1 Participants | 3 Participants | 5 Participants | 1 Participants | 2 Participants | 1 Participants | 5 Participants |
| Baseline Plasma HIV-1 RNA (copies/mL) <400 | 0 Participants | 6 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Baseline Plasma HIV-1 RNA (copies/mL) 400 - <1,000 | 1 Participants | 6 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Baseline Plasma HIV-1 RNA (copies/mL) 50,000 - <100,000 | 3 Participants | 22 Participants | 0 Participants | 1 Participants | 4 Participants | 1 Participants | 5 Participants | 6 Participants | 2 Participants |
| Baseline Plasma HIV-1 RNA (copies/mL) 5,000 - <10,000 | 1 Participants | 15 Participants | 3 Participants | 4 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants |
| CD4 Cell Count | 645.0 cells/mm^3 | 1053.0 cells/mm^3 | 1916.0 cells/mm^3 | 2121.0 cells/mm^3 | 1049.5 cells/mm^3 | 1482.5 cells/mm^3 | 900.0 cells/mm^3 | 749.0 cells/mm^3 | 466.0 cells/mm^3 |
| CD4 Percent | 24.0 Percentage of total lymphocytes | 24.0 Percentage of total lymphocytes | 22.7 Percentage of total lymphocytes | 24.2 Percentage of total lymphocytes | 24.0 Percentage of total lymphocytes | 20.7 Percentage of total lymphocytes | 25.0 Percentage of total lymphocytes | 25.3 Percentage of total lymphocytes | 22.0 Percentage of total lymphocytes |
| CD8 Cell Count | 1089.0 cells/mm^3 | 1679.0 cells/mm^3 | 2435.0 cells/mm^3 | 2922.0 cells/mm^3 | 1725.0 cells/mm^3 | 1888.5 cells/mm^3 | 1730.0 cells/mm^3 | 1103.0 cells/mm^3 | 1009.0 cells/mm^3 |
| CD8 Percent | 53.0 Percentage of total lymphocytes | 43.0 Percentage of total lymphocytes | 31.6 Percentage of total lymphocytes | 39.4 Percentage of total lymphocytes | 42.2 Percentage of total lymphocytes | 28.5 Percentage of total lymphocytes | 39.7 Percentage of total lymphocytes | 48.0 Percentage of total lymphocytes | 49.5 Percentage of total lymphocytes |
| Class of Prior Antiretroviral Therapy (ART) Fusion inhibitor (FI) | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Class of Prior Antiretroviral Therapy (ART) Non-nucleoside reverse transcriptase inhibitor (NNRTI) | 13 Participants | 92 Participants | 15 Participants | 18 Participants | 14 Participants | 5 Participants | 5 Participants | 10 Participants | 12 Participants |
| Class of Prior Antiretroviral Therapy (ART) Nucleoside reverse transcriptase inhibitor (NRTI) | 23 Participants | 165 Participants | 23 Participants | 29 Participants | 30 Participants | 6 Participants | 17 Participants | 14 Participants | 23 Participants |
| Class of Prior Antiretroviral Therapy (ART) Protease inhibitor (PI) | 17 Participants | 138 Participants | 20 Participants | 28 Participants | 25 Participants | 5 Participants | 15 Participants | 10 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 37 Participants | 2 Participants | 4 Participants | 6 Participants | 1 Participants | 8 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 129 Participants | 23 Participants | 31 Participants | 28 Participants | 6 Participants | 6 Participants | 6 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 15 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants | 5 Participants | 1 Participants |
| Height | 131.1 cm STANDARD_DEVIATION 14 | 98.9 cm STANDARD_DEVIATION 32.4 | 59.2 cm STANDARD_DEVIATION 3.7 | 71.9 cm STANDARD_DEVIATION 5.7 | 93.4 cm STANDARD_DEVIATION 8.9 | 71.0 cm STANDARD_DEVIATION 6 | 95.9 cm STANDARD_DEVIATION 8.7 | 121.2 cm STANDARD_DEVIATION 9.6 | 155.4 cm STANDARD_DEVIATION 8.9 |
| HIV-1 log10 RNA | 4.9 log10 copies/mL STANDARD_DEVIATION 1 | 4.6 log10 copies/mL STANDARD_DEVIATION 1.1 | 4.6 log10 copies/mL STANDARD_DEVIATION 1.4 | 4.6 log10 copies/mL STANDARD_DEVIATION 1.1 | 4.5 log10 copies/mL STANDARD_DEVIATION 1.2 | 4.5 log10 copies/mL STANDARD_DEVIATION 1.4 | 4.9 log10 copies/mL STANDARD_DEVIATION 0.9 | 4.4 log10 copies/mL STANDARD_DEVIATION 0.8 | 4.3 log10 copies/mL STANDARD_DEVIATION 0.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 25 Participants | 3 Participants | 1 Participants | 7 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 123 Participants | 20 Participants | 30 Participants | 25 Participants | 3 Participants | 11 Participants | 10 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 9 Participants | 2 Participants | 2 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 8 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 15 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 7 Participants |
| Region of Enrollment Botswana | 0 Participants | 5 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Brazil | 0 Participants | 19 Participants | 3 Participants | 2 Participants | 6 Participants | 1 Participants | 5 Participants | 2 Participants | 0 Participants |
| Region of Enrollment Kenya | 0 Participants | 14 Participants | 1 Participants | 5 Participants | 8 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment South Africa | 4 Participants | 28 Participants | 2 Participants | 4 Participants | 6 Participants | 2 Participants | 4 Participants | 6 Participants | 0 Participants |
| Region of Enrollment Tanzania | 0 Participants | 10 Participants | 3 Participants | 3 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Thailand | 3 Participants | 23 Participants | 3 Participants | 1 Participants | 6 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants |
| Region of Enrollment Uganda | 0 Participants | 3 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 16 Participants | 51 Participants | 0 Participants | 2 Participants | 3 Participants | 0 Participants | 5 Participants | 5 Participants | 20 Participants |
| Region of Enrollment Zimbabwe | 0 Participants | 28 Participants | 10 Participants | 15 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 7 Participants | 86 Participants | 12 Participants | 20 Participants | 13 Participants | 5 Participants | 8 Participants | 3 Participants | 18 Participants |
| Sex: Female, Male Male | 16 Participants | 95 Participants | 13 Participants | 15 Participants | 23 Participants | 2 Participants | 9 Participants | 12 Participants | 5 Participants |
| Weight | 30.1 kg STANDARD_DEVIATION 10.4 | 19.6 kg STANDARD_DEVIATION 17 | 5.7 kg STANDARD_DEVIATION 1.1 | 8.5 kg STANDARD_DEVIATION 1.8 | 13.7 kg STANDARD_DEVIATION 2.6 | 8.4 kg STANDARD_DEVIATION 2 | 14.4 kg STANDARD_DEVIATION 2.9 | 23.0 kg STANDARD_DEVIATION 4.6 | 55.1 kg STANDARD_DEVIATION 15.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 1 / 23 | 0 / 15 | 0 / 17 | 0 / 7 | 1 / 36 | 1 / 35 | 0 / 25 |
| other Total, other adverse events | 23 / 23 | 23 / 23 | 15 / 15 | 17 / 17 | 7 / 7 | 36 / 36 | 35 / 35 | 25 / 25 |
| serious Total, serious adverse events | 8 / 23 | 5 / 23 | 1 / 15 | 8 / 17 | 2 / 7 | 12 / 36 | 8 / 35 | 2 / 25 |
Outcome results
Primary
Number of Participants Who Died
Number of participants who died were summarized
Time frame: From treatment initiation through Weeks 24 and 48
Population: Participants who received at least one dose of DTG and were deemed safety evaluable by the protocol team.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort I | Number of Participants Who Died | Through Week 48 | 0 Participants |
| Cohort I | Number of Participants Who Died | Through Week 24 | 0 Participants |
| Cohort IIA | Number of Participants Who Died | Through Week 48 | 0 Participants |
| Cohort IIA | Number of Participants Who Died | Through Week 24 | 0 Participants |
| Cohort IIB | Number of Participants Who Died | Through Week 48 | 0 Participants |
| Cohort IIB | Number of Participants Who Died | Through Week 24 | 0 Participants |
| Cohort III | Number of Participants Who Died | Through Week 24 | 0 Participants |
| Cohort III | Number of Participants Who Died | Through Week 48 | 0 Participants |
| Cohort IV | Number of Participants Who Died | Through Week 24 | 0 Participants |
| Cohort IV | Number of Participants Who Died | Through Week 48 | 0 Participants |
| Cohort III-DT | Number of Participants Who Died | Through Week 24 | 1 Participants |
| Cohort III-DT | Number of Participants Who Died | Through Week 48 | 1 Participants |
| Cohort IV-DT | Number of Participants Who Died | Through Week 24 | 1 Participants |
| Cohort IV-DT | Number of Participants Who Died | Through Week 48 | 1 Participants |
| Cohort V-DT | Number of Participants Who Died | Through Week 24 | 0 Participants |
| Cohort V-DT | Number of Participants Who Died | Through Week 48 | 0 Participants |
Primary
Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug
Number of participants with permanent discontinuation of study drug due to AEs assessed by the site investigator as related to the study drug.
Time frame: From treatment initiation through Weeks 24 and 48
Population: Participants who received at least one dose of DTG and were deemed safety evaluable by the protocol team.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort I | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 24 | 0 Participants |
| Cohort I | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 48 | 0 Participants |
| Cohort IIA | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 24 | 0 Participants |
| Cohort IIA | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 48 | 0 Participants |
| Cohort IIB | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 24 | 0 Participants |
| Cohort IIB | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 48 | 0 Participants |
| Cohort III | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 24 | 0 Participants |
| Cohort III | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 48 | 0 Participants |
| Cohort IV | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 24 | 0 Participants |
| Cohort IV | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 48 | 0 Participants |
| Cohort III-DT | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 24 | 0 Participants |
| Cohort III-DT | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 48 | 0 Participants |
| Cohort IV-DT | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 48 | 0 Participants |
| Cohort IV-DT | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 24 | 0 Participants |
| Cohort V-DT | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 24 | 0 Participants |
| Cohort V-DT | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 48 | 0 Participants |
Primary
Percentage of Participants With Grade 3 or Higher Adverse Events (AEs)
All grade 3 or higher signs/symptoms, diagnoses, and laboratory AEs were included. AE grading was based on DAIDS AE Grading Table, Version 1.0, December 2004 (Clarification, August 2009). A 2-sided 95% Confidence Interval (CI) was calculated for the percentage using the binominal exact method.
Time frame: From treatment initiation through Weeks 24 and 48
Population: Participants who received at least one dose of DTG and were deemed safety evaluable by the protocol team.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort I | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | Through Week 24 | 4.3 percentage of participants |
| Cohort I | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | Through Week 48 | 8.7 percentage of participants |
| Cohort IIA | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | Through Week 24 | 8.7 percentage of participants |
| Cohort IIA | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | Through Week 48 | 17.4 percentage of participants |
| Cohort IIB | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | Through Week 24 | 6.7 percentage of participants |
| Cohort IIB | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | Through Week 48 | 13.3 percentage of participants |
| Cohort III | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | Through Week 24 | 29.4 percentage of participants |
| Cohort III | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | Through Week 48 | 35.3 percentage of participants |
| Cohort IV | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | Through Week 24 | 57.1 percentage of participants |
| Cohort IV | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | Through Week 48 | 57.1 percentage of participants |
| Cohort III-DT | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | Through Week 24 | 38.9 percentage of participants |
| Cohort III-DT | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | Through Week 48 | 41.7 percentage of participants |
| Cohort IV-DT | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | Through Week 48 | 51.4 percentage of participants |
| Cohort IV-DT | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | Through Week 24 | 42.9 percentage of participants |
| Cohort V-DT | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | Through Week 24 | 60 percentage of participants |
| Cohort V-DT | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | Through Week 48 | 64 percentage of participants |
Primary
Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug
All grade 3 or higher signs/symptoms, diagnoses, and laboratory AEs were included. AE grading was based on DAIDS AE Grading Table, Version 1.0, December 2004 (Clarification, August 2009). A 2-sided 95% Confidence Interval (CI) was calculated for the percentage using the binominal exact method.
Time frame: From treatment initiation through Weeks 24 and 48
Population: Participants who received at least one dose of DTG and were deemed safety evaluable by the protocol team.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort I | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 24 | 0 percentage of participants |
| Cohort I | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 48 | 0 percentage of participants |
| Cohort IIA | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 24 | 0 percentage of participants |
| Cohort IIA | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 48 | 0 percentage of participants |
| Cohort IIB | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 24 | 0 percentage of participants |
| Cohort IIB | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 48 | 0 percentage of participants |
| Cohort III | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 24 | 0 percentage of participants |
| Cohort III | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 48 | 0 percentage of participants |
| Cohort IV | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 24 | 14.3 percentage of participants |
| Cohort IV | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 48 | 14.3 percentage of participants |
| Cohort III-DT | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 24 | 0 percentage of participants |
| Cohort III-DT | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 48 | 0 percentage of participants |
| Cohort IV-DT | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 48 | 0 percentage of participants |
| Cohort IV-DT | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 24 | 0 percentage of participants |
| Cohort V-DT | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 24 | 0 percentage of participants |
| Cohort V-DT | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | Through Week 48 | 0 percentage of participants |
Primary
PK Parameter: Area-under-the-curve From 0 to 24 Hours (AUC0-24)
Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). AUC0-24 was determined using linear up-log down estimation in WinNonlin.
Time frame: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
Population: Participants with intensive pharmacokinetic (PK) data at the proposed dose for Cohorts I, IIA, III-DT, IV-DT, and V-DT.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort I | PK Parameter: Area-under-the-curve From 0 to 24 Hours (AUC0-24) | 52.98 hr*mg/L | Standard Deviation 23.11 |
| Cohort IIA | PK Parameter: Area-under-the-curve From 0 to 24 Hours (AUC0-24) | 68.33 hr*mg/L | Standard Deviation 43.33 |
| Cohort IIB | PK Parameter: Area-under-the-curve From 0 to 24 Hours (AUC0-24) | 63.16 hr*mg/L | Standard Deviation 37.77 |
| Cohort III | PK Parameter: Area-under-the-curve From 0 to 24 Hours (AUC0-24) | 82.67 hr*mg/L | Standard Deviation 47.05 |
| Cohort IV | PK Parameter: Area-under-the-curve From 0 to 24 Hours (AUC0-24) | 71.45 hr*mg/L | Standard Deviation 28.21 |
Secondary
Genotypic Measures of Resistance to Integrase
Genes were sequenced and compared to a reference sequence to identify mutations
Time frame: At baseline
Population: All participants with a confirmed decrease in HIV RNA of \< 1.0 log10 at or after week 12 unless the HIV RNA is \< 400 copies/mL, or a confirmed HIV RNA \> 400 copies/mL starting at Week 24 or beyond on 2 consecutive measurements at least 1 week and within 4 weeks apart
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort I | Genotypic Measures of Resistance to Integrase | A128T | 2 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | Gene not found | 3 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | L74I | 7 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | L74I,S230N | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | S230N | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | T97A | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | V151I | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | None | 40 Participants |
Secondary
Genotypic Measures of Resistance to Integrase
Genes were sequenced and compared to a reference sequence to identify mutations
Time frame: at virological failure visit at or prior to Week 192
Population: All participants with a confirmed decrease in HIV RNA of \< 1.0 log10 at or after week 12 unless the HIV RNA is \< 400 copies/mL, or a confirmed HIV RNA \> 400 copies/mL starting at Week 24 or beyond on 2 consecutive measurements at least 1 week and within 4 weeks apart
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort I | Genotypic Measures of Resistance to Integrase | A128T | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | A128T,S153AFSV | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | E138AEKT,E138T,S147G,S147GS,R263K,R263KR | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | E138K,Q148K | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | E157Q | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | E92EG,T97A,N155H,N155HN | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | E92EQ,G118GR | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | H51HY | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | L74I | 4 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | L74I,G118R | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | L74I,S230N | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | L74M,G118R | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | R263K | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | S230N | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | T66I,G118R,E138A | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | T66I,L74I,G118R | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | T97A,G118R,E138EK,S147G,V151I,N155H | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | missing | 11 Participants |
| Cohort I | Genotypic Measures of Resistance to Integrase | None | 25 Participants |
Secondary
Genotypic Measures of Resistance to Protease
Genes were sequenced and compared to a reference sequence to identify mutations
Time frame: at baseline
Population: all participants with a confirmed decrease in HIV RNA of \< 1.0 log10 at or after week 12 unless the HIV RNA is \< 400 copies/mL, or a confirmed HIV RNA \> 400 copies/mL starting at Week 24 or beyond on 2 consecutive measurements at least 1 week and within 4 weeks apart
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort I | Genotypic Measures of Resistance to Protease | A71T | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | D30N,A71T,N88D | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | D30N,M46I,Q58EQ,A71T,N88D | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | I84V | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | K20I | 2 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | K20I,V82I | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | K20R | 8 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | K20R,A71T | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | K20R,L33F,M46I,I50V,I54V,T74P,V82A | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | K20R,T74S | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | K20R,T74S,V82A | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | K20T,V82I | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | K43T,A71T,V82A | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | L10I,K20KR,M46LM,I54IL,A71AV,V82AFSV | 3 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | L10I | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | L10V | 2 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | T74S | 3 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | None | 26 Participants |
Secondary
Genotypic Measures of Resistance to Protease
Genes were sequenced and compared to a reference sequence to identify mutations
Time frame: at virological failures at or prior to Week 192
Population: all participants with a confirmed decrease in HIV RNA of \< 1.0 log10 at or after week 12 unless the HIV RNA is \< 400 copies/mL, or a confirmed HIV RNA \> 400 copies/mL starting at Week 24 or beyond on 2 consecutive measurements at least 1 week and within 4 weeks apart
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort I | Genotypic Measures of Resistance to Protease | A71T | 2 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | D30N,A71T,N88D | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | D30N,M46I,Q58E,Q58EQ,A71T,N88D | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | I84V | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | K20I | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | K20R | 7 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | K20R,T74S | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | K20R,T74S,V82A | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | K20T,V82I | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | L10I | 6 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | L10I,K20R | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | L10I,K43T,I54V,A71T,V82A | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | L10I,L10IV | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | L10IL,K20KR,L33FL,M46IM,I50IV,I54IV,T74PT,V82AV | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | L10V | 2 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | L10V,K20IV,K20V | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | T74S | 3 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | V11IV,K20I,V82I | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | missing | 8 Participants |
| Cohort I | Genotypic Measures of Resistance to Protease | None | 15 Participants |
Secondary
Genotypic Measures of Resistance to Reverse Transcriptase
Genes were sequenced and compared to a reference sequence to identify mutations
Time frame: at virologic failure at or prior to Week 192
Population: all participants with a confirmed decrease in HIV RNA of \< 1.0 log10 at or after week 12 unless the HIV RNA is \< 400 copies/mL, or a confirmed HIV RNA \> 400 copies/mL starting at Week 24 or beyond on 2 consecutive measurements at least 1 week and within 4 weeks apart
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | M41L,T215FL | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | 101i,V179I,M184V | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | A62V,K65R,S68G,K70R,V75I,F77L,K101Q,K103N,F116Y,Q151M,P225H | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | D67N,K219Q,N348I | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | E138A | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | E44D,E44DE,K103N,M184V | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | E44DE | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | K103KN,K103N,M184V | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | K103N | 4 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | K103N,M184V | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | K103N,V179I | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V179E,P225H | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | K103N,V179I,M184V | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | K103S,M184V,G190A,Y318F | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | K238R | 2 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | K238R,M41LM,D67DN,T69NT,K70KR,L74IL,A98AG,M184MV,T215FIST,K219Q,M230IM | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | L74IL,L74V,K103N,E138G,M184V,M230L | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | M184V | 3 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | M184V,H221Y | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | M184V,K238R | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V179D,V179DV,G190A,G190AG | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | M41LM,M184V,S68G,S68GS,Y181CY,M184MV | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | S68G,V106I,K238R | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | S68G,V90I,K103N,V179I,M184V | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | S68GS,K103KN,K238KR,K238R | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | T69NT,K103N,P225H | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V106M,Y181C,P236LP | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V179I | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V179I,M184V | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V179I,M184V,G190A,K219R | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V179I,M184V,K238R | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V179I,M184V,Y188L | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V179S,M184V | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V75M,K103N | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V90I | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | missing | 6 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | None | 9 Participants |
Secondary
Genotypic Measures of Resistance to Reverse Transcriptase
Genes were sequenced and compared to a reference sequence to identify mutations
Time frame: at baseline
Population: all participants with a confirmed decrease in HIV RNA of \< 1.0 log10 at or after week 12 unless the HIV RNA is \< 400 copies/mL, or a confirmed HIV RNA \> 400 copies/mL starting at Week 24 or beyond on 2 consecutive measurements at least 1 week and within 4 weeks apart
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V179I | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | A62V,K65R,S68G,K70R,V75I,F77L,K101Q,K103N,F116Y,Q151M,P225H | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | D67DN,K238R | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | D67DN,V179I,V179IV,M184V,K219Q,N348I | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | E138A | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | E44D,K103N,M184V | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | K103N | 4 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | K103N,M184V | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | K103N,M184V,M184MV | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | K103N,P225H | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | K103N,V179I | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | K103N,V179I,M184V | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | K103N,Y181C | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | K103S,V179I,G190A,Y318F | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | K65R,V106M,G190A | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | K70KR,T215F,T215FIST,K238R | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | L74LV,Y181CY,M184V | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | L74V,K103N,E138G,M184V,M230L | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | L74V,V106M,Y181C | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | M184V | 2 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | M184V,H221Y | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | M184V,K238R | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | M41L,D67N,T69N,K70R,L74I,A98G,M184V,T215F,K219Q,K238R | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | M41L,K101E,V179I,M184V,G190A,T215F | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | M41L,T215L | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | S68G,K103N,E138Q,M184V,Y318F | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | S68G,V106I,K238R | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | S68G,V90I,K103N,V179I | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | T69D | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V118I,E138A | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V118IV,V179I,M184V | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V179E,P225H | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V179I,M184V | 2 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V179I,M184V,G190A,K219R | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V179I,M184V,K238R | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V179I,M184V,Y188L | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V179S | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V75M,K103N | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | V90I | 2 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | Y181C | 1 Participants |
| Cohort I | Genotypic Measures of Resistance to Reverse Transcriptase | None | 10 Participants |
Secondary
Number of Participants Who Died
Number of participants who died were summarized.
Time frame: From treatment initiation through Week 192. AEs after that time were censored.
Population: All participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort I | Number of Participants Who Died | 0 Participants |
| Cohort IIA | Number of Participants Who Died | 1 Participants |
| Cohort IIB | Number of Participants Who Died | 0 Participants |
| Cohort III | Number of Participants Who Died | 0 Participants |
| Cohort IV | Number of Participants Who Died | 0 Participants |
| Cohort III-DT | Number of Participants Who Died | 1 Participants |
| Cohort IV-DT | Number of Participants Who Died | 1 Participants |
| Cohort V-DT | Number of Participants Who Died | 0 Participants |
Secondary
Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug
Number of participants with permanent discontinuation of study drug due to AEs assessed by the site investigator as related to the study drug.
Time frame: From treatment initiation through Week 192. AEs after that time were censored.
Population: All participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort I | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | 0 Participants |
| Cohort IIA | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | 0 Participants |
| Cohort IIB | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | 0 Participants |
| Cohort III | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | 0 Participants |
| Cohort IV | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | 0 Participants |
| Cohort III-DT | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | 0 Participants |
| Cohort IV-DT | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | 0 Participants |
| Cohort V-DT | Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug | 0 Participants |
Secondary
Percentage of Participants With Grade 3 or Higher Adverse Events (AEs)
Percentage and exact 95% Confidence Interval (CI) of participants with Grade 3 or higher AEs. AEs were graded based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004, Clarification August 2009 (see References). All grade 3 or higher signs, symptoms, and laboratory toxicities were included.
Time frame: From treatment initiation through Week 192. AEs after that time were censored.
Population: All participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort I | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | 34.8 percentage of participants |
| Cohort IIA | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | 30.4 percentage of participants |
| Cohort IIB | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | 20 percentage of participants |
| Cohort III | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | 52.9 percentage of participants |
| Cohort IV | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | 57.1 percentage of participants |
| Cohort III-DT | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | 58.3 percentage of participants |
| Cohort IV-DT | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | 51.4 percentage of participants |
| Cohort V-DT | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) | 64 percentage of participants |
Secondary
Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug
Percentage and exact 95% Confidence Interval (CI) of participants with Grade 3 or higher AEs assessed by the site investigator as related to the study drug.
Time frame: From treatment initiation through Week 192. AEs after that time were censored.
Population: All participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort I | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | 0 percentage of participants |
| Cohort IIA | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | 0 percentage of participants |
| Cohort IIB | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | 0 percentage of participants |
| Cohort III | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | 0 percentage of participants |
| Cohort IV | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | 14.3 percentage of participants |
| Cohort III-DT | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | 0 percentage of participants |
| Cohort IV-DT | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | 0 percentage of participants |
| Cohort V-DT | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug | 0 percentage of participants |
Secondary
Percentage of Participants With Plasma HIV-1 RNA Less Than 400 Copies/ml
Virologic responses were assessed at weeks 24 and 48 as percentages of participants and exact 95% Confidence Interval (CI). The virologic response or virologic failure was defined and calculated according to FDA's Snapshot algorithm.
Time frame: Week 24 and Week 48
Population: Participants who received at least one dose of DTG.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort I | Percentage of Participants With Plasma HIV-1 RNA Less Than 400 Copies/ml | Week 24 | 82.6 percentage of participants |
| Cohort I | Percentage of Participants With Plasma HIV-1 RNA Less Than 400 Copies/ml | Week 48 | 73.9 percentage of participants |
| Cohort IIA | Percentage of Participants With Plasma HIV-1 RNA Less Than 400 Copies/ml | Week 24 | 78.3 percentage of participants |
| Cohort IIA | Percentage of Participants With Plasma HIV-1 RNA Less Than 400 Copies/ml | Week 48 | 78.3 percentage of participants |
| Cohort IIB | Percentage of Participants With Plasma HIV-1 RNA Less Than 400 Copies/ml | Week 24 | 100 percentage of participants |
| Cohort IIB | Percentage of Participants With Plasma HIV-1 RNA Less Than 400 Copies/ml | Week 48 | 93.3 percentage of participants |
| Cohort III | Percentage of Participants With Plasma HIV-1 RNA Less Than 400 Copies/ml | Week 24 | 88.2 percentage of participants |
| Cohort III | Percentage of Participants With Plasma HIV-1 RNA Less Than 400 Copies/ml | Week 48 | 94.1 percentage of participants |
| Cohort IV | Percentage of Participants With Plasma HIV-1 RNA Less Than 400 Copies/ml | Week 24 | 71.4 percentage of participants |
| Cohort IV | Percentage of Participants With Plasma HIV-1 RNA Less Than 400 Copies/ml | Week 48 | 71.4 percentage of participants |
| Cohort III-DT | Percentage of Participants With Plasma HIV-1 RNA Less Than 400 Copies/ml | Week 24 | 86.1 percentage of participants |
| Cohort III-DT | Percentage of Participants With Plasma HIV-1 RNA Less Than 400 Copies/ml | Week 48 | 86.1 percentage of participants |
| Cohort IV-DT | Percentage of Participants With Plasma HIV-1 RNA Less Than 400 Copies/ml | Week 48 | 85.7 percentage of participants |
| Cohort IV-DT | Percentage of Participants With Plasma HIV-1 RNA Less Than 400 Copies/ml | Week 24 | 88.6 percentage of participants |
| Cohort V-DT | Percentage of Participants With Plasma HIV-1 RNA Less Than 400 Copies/ml | Week 24 | 68 percentage of participants |
| Cohort V-DT | Percentage of Participants With Plasma HIV-1 RNA Less Than 400 Copies/ml | Week 48 | 72 percentage of participants |
Secondary
Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/ml
Virologic responses were assessed at weeks 24 and 48 as percentages of participants and exact 95% Confidence Interval (CI), The virologic response or virologic failure was defined and calculated according to FDA's Snapshot algorithm.
Time frame: Week 24 and Week 48
Population: Participants who received at least one dose of DTG.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort I | Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/ml | Week 24 | 69.6 percentage of participants |
| Cohort I | Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/ml | Week 48 | 60.9 percentage of participants |
| Cohort IIA | Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/ml | Week 24 | 60.9 percentage of participants |
| Cohort IIA | Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/ml | Week 48 | 69.6 percentage of participants |
| Cohort IIB | Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/ml | Week 24 | 93.3 percentage of participants |
| Cohort IIB | Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/ml | Week 48 | 93.3 percentage of participants |
| Cohort III | Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/ml | Week 24 | 58.8 percentage of participants |
| Cohort III | Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/ml | Week 48 | 64.7 percentage of participants |
| Cohort IV | Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/ml | Week 24 | 42.9 percentage of participants |
| Cohort IV | Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/ml | Week 48 | 42.9 percentage of participants |
| Cohort III-DT | Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/ml | Week 24 | 61.1 percentage of participants |
| Cohort III-DT | Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/ml | Week 48 | 69.4 percentage of participants |
| Cohort IV-DT | Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/ml | Week 48 | 65.7 percentage of participants |
| Cohort IV-DT | Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/ml | Week 24 | 51.4 percentage of participants |
| Cohort V-DT | Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/ml | Week 24 | 32 percentage of participants |
| Cohort V-DT | Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/ml | Week 48 | 36 percentage of participants |
Secondary
Phenotypic Measures of Resistance
The participant viral culture is considered to be reduced susceptibility if more DTG is needed to inactivate 50% of the participant viral culture compared to the control viral specimen
Time frame: Whenever virological failures took place from baseline to week 192
Population: Protocol defined virological failure population for which drug susceptibility was measured
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort I | Phenotypic Measures of Resistance | missing | 1 Participants |
| Cohort I | Phenotypic Measures of Resistance | Reduced susceptibility to DTG | 2 Participants |
| Cohort I | Phenotypic Measures of Resistance | Sensitive to DTG | 8 Participants |
| Cohort IIA | Phenotypic Measures of Resistance | Sensitive to DTG | 4 Participants |
| Cohort IIA | Phenotypic Measures of Resistance | missing | 1 Participants |
| Cohort IIA | Phenotypic Measures of Resistance | Reduced susceptibility to DTG | 0 Participants |
| Cohort IIB | Phenotypic Measures of Resistance | missing | 0 Participants |
| Cohort IIB | Phenotypic Measures of Resistance | Reduced susceptibility to DTG | 1 Participants |
| Cohort IIB | Phenotypic Measures of Resistance | Sensitive to DTG | 0 Participants |
| Cohort III | Phenotypic Measures of Resistance | missing | 1 Participants |
| Cohort III | Phenotypic Measures of Resistance | Sensitive to DTG | 2 Participants |
| Cohort III | Phenotypic Measures of Resistance | Reduced susceptibility to DTG | 0 Participants |
| Cohort IV | Phenotypic Measures of Resistance | Sensitive to DTG | 0 Participants |
| Cohort IV | Phenotypic Measures of Resistance | missing | 2 Participants |
| Cohort IV | Phenotypic Measures of Resistance | Reduced susceptibility to DTG | 1 Participants |
| Cohort III-DT | Phenotypic Measures of Resistance | Reduced susceptibility to DTG | 1 Participants |
| Cohort III-DT | Phenotypic Measures of Resistance | Sensitive to DTG | 5 Participants |
| Cohort III-DT | Phenotypic Measures of Resistance | missing | 4 Participants |
| Cohort IV-DT | Phenotypic Measures of Resistance | Sensitive to DTG | 4 Participants |
| Cohort IV-DT | Phenotypic Measures of Resistance | Reduced susceptibility to DTG | 0 Participants |
| Cohort IV-DT | Phenotypic Measures of Resistance | missing | 7 Participants |
| Cohort V-DT | Phenotypic Measures of Resistance | Sensitive to DTG | 9 Participants |
| Cohort V-DT | Phenotypic Measures of Resistance | missing | 3 Participants |
| Cohort V-DT | Phenotypic Measures of Resistance | Reduced susceptibility to DTG | 0 Participants |
Secondary
PK Parameter: Apparent Clearance (CL/F)
Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). CL/F was calculated as Dose/AUC.
Time frame: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
Population: Participants with intensive pharmacokinetic (PK) data at the proposed dose for Cohorts I, IIA, III-DT, IV-DT, and V-DT.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort I | PK Parameter: Apparent Clearance (CL/F) | 1.29 L/h | Standard Deviation 1.03 |
| Cohort IIA | PK Parameter: Apparent Clearance (CL/F) | 1.11 L/h | Standard Deviation 0.92 |
| Cohort IIB | PK Parameter: Apparent Clearance (CL/F) | 0.49 L/h | Standard Deviation 0.31 |
| Cohort III | PK Parameter: Apparent Clearance (CL/F) | 0.23 L/h | Standard Deviation 0.11 |
| Cohort IV | PK Parameter: Apparent Clearance (CL/F) | 0.11 L/h | Standard Deviation 0.05 |
Secondary
PK Parameter: Apparent Volume of Distribution (Vz/F)
Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). Vz/F was calculated as Dose/(ke x AUC).
Time frame: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
Population: Participants with intensive pharmacokinetic (PK) data at the proposed dose for Cohorts I, IIA, III-DT, IV-DT, and V-DT.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort I | PK Parameter: Apparent Volume of Distribution (Vz/F) | 21.95 L | Standard Deviation 13.71 |
| Cohort IIA | PK Parameter: Apparent Volume of Distribution (Vz/F) | 19.11 L | Standard Deviation 16.51 |
| Cohort IIB | PK Parameter: Apparent Volume of Distribution (Vz/F) | 5.75 L | Standard Deviation 3.66 |
| Cohort III | PK Parameter: Apparent Volume of Distribution (Vz/F) | 3.19 L | Standard Deviation 1.5 |
| Cohort IV | PK Parameter: Apparent Volume of Distribution (Vz/F) | 2.37 L | Standard Deviation 1.04 |
Secondary
PK Parameter: Maximum Plasma Concentration (Cmax)
Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). Cmax was taken directly from the observed concentration-time data.
Time frame: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
Population: Participants with intensive pharmacokinetic (PK) data at the proposed dose for Cohorts I, IIA, III-DT, IV-DT, and V-DT.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort I | PK Parameter: Maximum Plasma Concentration (Cmax) | 3945.97 ng/mL | Standard Deviation 1499.34 |
| Cohort IIA | PK Parameter: Maximum Plasma Concentration (Cmax) | 5111.10 ng/mL | Standard Deviation 2459.92 |
| Cohort IIB | PK Parameter: Maximum Plasma Concentration (Cmax) | 5530.16 ng/mL | Standard Deviation 2466.62 |
| Cohort III | PK Parameter: Maximum Plasma Concentration (Cmax) | 6256.67 ng/mL | Standard Deviation 2508.57 |
| Cohort IV | PK Parameter: Maximum Plasma Concentration (Cmax) | 4832.58 ng/mL | Standard Deviation 1679.69 |
Secondary
PK Parameter: Minimum Plasma Concentration (Cmin)
Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ) and were performed in real-time. Cmin was taken directly from the observed concentration-time data.
Time frame: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
Population: Participants with intensive pharmacokinetic (PK) data at the proposed dose for Cohorts I, IIA, III-DT, IV-DT, and V-DT.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort I | PK Parameter: Minimum Plasma Concentration (Cmin) | 1193.94 ng/mL | Standard Deviation 668.76 |
| Cohort IIA | PK Parameter: Minimum Plasma Concentration (Cmin) | 1155.52 ng/mL | Standard Deviation 1152.98 |
| Cohort IIB | PK Parameter: Minimum Plasma Concentration (Cmin) | 757.92 ng/mL | Standard Deviation 439.83 |
| Cohort III | PK Parameter: Minimum Plasma Concentration (Cmin) | 1343.74 ng/mL | Standard Deviation 1370.79 |
| Cohort IV | PK Parameter: Minimum Plasma Concentration (Cmin) | 1213.68 ng/mL | Standard Deviation 886.21 |
Secondary
PK Parameter: Plasma Concentration Observed at End of 24 Hour Dosing Interval (C24h)
Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). C24h was taken directly from the observed concentration-time data or estimated using the elimination rate constant.
Time frame: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
Population: Participants with intensive pharmacokinetic (PK) data at the proposed dose for Cohorts I, IIA, III-DT, IV-DT, and V-DT.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort I | PK Parameter: Plasma Concentration Observed at End of 24 Hour Dosing Interval (C24h) | 1145.36 ng/mL | Standard Deviation 659.65 |
| Cohort IIA | PK Parameter: Plasma Concentration Observed at End of 24 Hour Dosing Interval (C24h) | 1475.46 ng/mL | Standard Deviation 1139.52 |
| Cohort IIB | PK Parameter: Plasma Concentration Observed at End of 24 Hour Dosing Interval (C24h) | 1065.12 ng/mL | Standard Deviation 1112.46 |
| Cohort III | PK Parameter: Plasma Concentration Observed at End of 24 Hour Dosing Interval (C24h) | 1488.24 ng/mL | Standard Deviation 1175.44 |
| Cohort IV | PK Parameter: Plasma Concentration Observed at End of 24 Hour Dosing Interval (C24h) | 1765.19 ng/mL | Standard Deviation 929.97 |
Secondary
PK Parameter: Plasma Concentration Observed Immediately to Dosing of 24 Hour Dosing Interval (C0h)
Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). C0h was taken directly from the observed concentration-time data.
Time frame: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
Population: Participants with intensive pharmacokinetic (PK) data at the proposed dose for Cohorts I, IIA, III-DT, IV-DT, and V-DT.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort I | PK Parameter: Plasma Concentration Observed Immediately to Dosing of 24 Hour Dosing Interval (C0h) | 1429.09 ng/mL | Standard Deviation 738.69 |
| Cohort IIA | PK Parameter: Plasma Concentration Observed Immediately to Dosing of 24 Hour Dosing Interval (C0h) | 1508.44 ng/mL | Standard Deviation 1271.93 |
| Cohort IIB | PK Parameter: Plasma Concentration Observed Immediately to Dosing of 24 Hour Dosing Interval (C0h) | 944.22 ng/mL | Standard Deviation 549.36 |
| Cohort III | PK Parameter: Plasma Concentration Observed Immediately to Dosing of 24 Hour Dosing Interval (C0h) | 1584.29 ng/mL | Standard Deviation 1388.27 |
| Cohort IV | PK Parameter: Plasma Concentration Observed Immediately to Dosing of 24 Hour Dosing Interval (C0h) | 1376.15 ng/mL | Standard Deviation 1132.28 |
Secondary
PK Parameter: Terminal Half-life (t1/2)
Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). t1/2 was calculated as ln(2)/ke.
Time frame: One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing
Population: Participants with intensive pharmacokinetic (PK) data at the proposed dose for Cohorts I, IIA, III-DT, IV-DT, and V-DT.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort I | PK Parameter: Terminal Half-life (t1/2) | 13.21 h | Standard Deviation 5.51 |
| Cohort IIA | PK Parameter: Terminal Half-life (t1/2) | 12.22 h | Standard Deviation 2.63 |
| Cohort IIB | PK Parameter: Terminal Half-life (t1/2) | 9.10 h | Standard Deviation 3.4 |
| Cohort III | PK Parameter: Terminal Half-life (t1/2) | 9.93 h | Standard Deviation 2.58 |
| Cohort IV | PK Parameter: Terminal Half-life (t1/2) | 16.85 h | Standard Deviation 8.22 |
Secondary
Summary of Changes in CD4 Count From Baseline
The median differences between CD4 count at Week 24 and 48 minus at the Day 0 (baseline), and Interquartile Ranges (IQRs) are presented.
Time frame: Measured at Day 0, Week 24, and Week 48
Population: Participants who received at least one dose of DTG. Study participants who had non-missing values were summarized.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort I | Summary of Changes in CD4 Count From Baseline | From baseline to Week 24 | 63 cells/mm^3 |
| Cohort I | Summary of Changes in CD4 Count From Baseline | From baseline to Week 48 | 84 cells/mm^3 |
| Cohort IIA | Summary of Changes in CD4 Count From Baseline | From baseline to Week 24 | 209 cells/mm^3 |
| Cohort IIA | Summary of Changes in CD4 Count From Baseline | From baseline to Week 48 | 387 cells/mm^3 |
| Cohort IIB | Summary of Changes in CD4 Count From Baseline | From baseline to Week 24 | 268 cells/mm^3 |
| Cohort IIB | Summary of Changes in CD4 Count From Baseline | From baseline to Week 48 | 246 cells/mm^3 |
| Cohort III | Summary of Changes in CD4 Count From Baseline | From baseline to Week 24 | 199 cells/mm^3 |
| Cohort III | Summary of Changes in CD4 Count From Baseline | From baseline to Week 48 | 134.5 cells/mm^3 |
| Cohort IV | Summary of Changes in CD4 Count From Baseline | From baseline to Week 24 | 472 cells/mm^3 |
| Cohort IV | Summary of Changes in CD4 Count From Baseline | From baseline to Week 48 | 577 cells/mm^3 |
| Cohort III-DT | Summary of Changes in CD4 Count From Baseline | From baseline to Week 24 | 249 cells/mm^3 |
| Cohort III-DT | Summary of Changes in CD4 Count From Baseline | From baseline to Week 48 | 191 cells/mm^3 |
| Cohort IV-DT | Summary of Changes in CD4 Count From Baseline | From baseline to Week 48 | -1 cells/mm^3 |
| Cohort IV-DT | Summary of Changes in CD4 Count From Baseline | From baseline to Week 24 | 110 cells/mm^3 |
| Cohort V-DT | Summary of Changes in CD4 Count From Baseline | From baseline to Week 24 | 441 cells/mm^3 |
| Cohort V-DT | Summary of Changes in CD4 Count From Baseline | From baseline to Week 48 | 721 cells/mm^3 |
Secondary
Summary of Changes in CD4 Percent From Baseline
The median differences between CD4 percent at Week 24 and 48 minus at the Day 0 (baseline), and Interquartile Ranges (IQRs) are presented.
Time frame: Measured at Day 0, Week 24, and Week 48
Population: Participants who received at least one dose of DTG. Study participants who had non-missing values were summarized.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort I | Summary of Changes in CD4 Percent From Baseline | From baseline to Week 24 | 4.9 Percentage of total lymphocytes |
| Cohort I | Summary of Changes in CD4 Percent From Baseline | From baseline to Week 48 | 4.7 Percentage of total lymphocytes |
| Cohort IIA | Summary of Changes in CD4 Percent From Baseline | From baseline to Week 24 | 8 Percentage of total lymphocytes |
| Cohort IIA | Summary of Changes in CD4 Percent From Baseline | From baseline to Week 48 | 9 Percentage of total lymphocytes |
| Cohort IIB | Summary of Changes in CD4 Percent From Baseline | From baseline to Week 24 | 6 Percentage of total lymphocytes |
| Cohort IIB | Summary of Changes in CD4 Percent From Baseline | From baseline to Week 48 | 9.2 Percentage of total lymphocytes |
| Cohort III | Summary of Changes in CD4 Percent From Baseline | From baseline to Week 24 | 6 Percentage of total lymphocytes |
| Cohort III | Summary of Changes in CD4 Percent From Baseline | From baseline to Week 48 | 5.6 Percentage of total lymphocytes |
| Cohort IV | Summary of Changes in CD4 Percent From Baseline | From baseline to Week 24 | 5.7 Percentage of total lymphocytes |
| Cohort IV | Summary of Changes in CD4 Percent From Baseline | From baseline to Week 48 | 9.9 Percentage of total lymphocytes |
| Cohort III-DT | Summary of Changes in CD4 Percent From Baseline | From baseline to Week 24 | 6.1 Percentage of total lymphocytes |
| Cohort III-DT | Summary of Changes in CD4 Percent From Baseline | From baseline to Week 48 | 9.1 Percentage of total lymphocytes |
| Cohort IV-DT | Summary of Changes in CD4 Percent From Baseline | From baseline to Week 48 | 8.8 Percentage of total lymphocytes |
| Cohort IV-DT | Summary of Changes in CD4 Percent From Baseline | From baseline to Week 24 | 6 Percentage of total lymphocytes |
| Cohort V-DT | Summary of Changes in CD4 Percent From Baseline | From baseline to Week 24 | 5.1 Percentage of total lymphocytes |
| Cohort V-DT | Summary of Changes in CD4 Percent From Baseline | From baseline to Week 48 | 9.7 Percentage of total lymphocytes |
Secondary
Summary of Changes in CD8 Count From Baseline
The median differences between CD8 count at Week 24 and 48 minus at the Day 0 (baseline), and Interquartile Ranges (IQRs) are presented.
Time frame: Measured at Day 0, Week 24, and Week 48
Population: Participants who received at least one dose of DTG. Study participants who had non-missing values were summarized.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort I | Summary of Changes in CD8 Count From Baseline | From baseline to Week 24 | -36 cells/mm^3 |
| Cohort I | Summary of Changes in CD8 Count From Baseline | From baseline to Week 48 | -52.5 cells/mm^3 |
| Cohort IIA | Summary of Changes in CD8 Count From Baseline | From baseline to Week 24 | -147 cells/mm^3 |
| Cohort IIA | Summary of Changes in CD8 Count From Baseline | From baseline to Week 48 | -117 cells/mm^3 |
| Cohort IIB | Summary of Changes in CD8 Count From Baseline | From baseline to Week 24 | -43 cells/mm^3 |
| Cohort IIB | Summary of Changes in CD8 Count From Baseline | From baseline to Week 48 | -126 cells/mm^3 |
| Cohort III | Summary of Changes in CD8 Count From Baseline | From baseline to Week 24 | -282 cells/mm^3 |
| Cohort III | Summary of Changes in CD8 Count From Baseline | From baseline to Week 48 | -431.5 cells/mm^3 |
| Cohort IV | Summary of Changes in CD8 Count From Baseline | From baseline to Week 24 | 223 cells/mm^3 |
| Cohort IV | Summary of Changes in CD8 Count From Baseline | From baseline to Week 48 | -376 cells/mm^3 |
| Cohort III-DT | Summary of Changes in CD8 Count From Baseline | From baseline to Week 24 | -395 cells/mm^3 |
| Cohort III-DT | Summary of Changes in CD8 Count From Baseline | From baseline to Week 48 | -464 cells/mm^3 |
| Cohort IV-DT | Summary of Changes in CD8 Count From Baseline | From baseline to Week 48 | -1242 cells/mm^3 |
| Cohort IV-DT | Summary of Changes in CD8 Count From Baseline | From baseline to Week 24 | -813 cells/mm^3 |
| Cohort V-DT | Summary of Changes in CD8 Count From Baseline | From baseline to Week 24 | -210 cells/mm^3 |
| Cohort V-DT | Summary of Changes in CD8 Count From Baseline | From baseline to Week 48 | -442 cells/mm^3 |
Secondary
Summary of Changes in CD8 Percent From Baseline
The median differences between CD8 percent at Week 24 and 48 minus at the Day 0 (baseline), and Interquartile Ranges (IQRs) are presented.
Time frame: Measured at Day 0, Week 24, and Week 48
Population: Participants who received at least one dose of DTG. Study participants who had non-missing values were summarized.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort I | Summary of Changes in CD8 Percent From Baseline | From baseline to Week 24 | -5 Percentage of total lymphocytes |
| Cohort I | Summary of Changes in CD8 Percent From Baseline | From baseline to Week 48 | -6 Percentage of total lymphocytes |
| Cohort IIA | Summary of Changes in CD8 Percent From Baseline | From baseline to Week 24 | -10 Percentage of total lymphocytes |
| Cohort IIA | Summary of Changes in CD8 Percent From Baseline | From baseline to Week 48 | -11.4 Percentage of total lymphocytes |
| Cohort IIB | Summary of Changes in CD8 Percent From Baseline | From baseline to Week 24 | -7 Percentage of total lymphocytes |
| Cohort IIB | Summary of Changes in CD8 Percent From Baseline | From baseline to Week 48 | -8 Percentage of total lymphocytes |
| Cohort III | Summary of Changes in CD8 Percent From Baseline | From baseline to Week 24 | -6.8 Percentage of total lymphocytes |
| Cohort III | Summary of Changes in CD8 Percent From Baseline | From baseline to Week 48 | -6.5 Percentage of total lymphocytes |
| Cohort IV | Summary of Changes in CD8 Percent From Baseline | From baseline to Week 24 | -2 Percentage of total lymphocytes |
| Cohort IV | Summary of Changes in CD8 Percent From Baseline | From baseline to Week 48 | -1.8 Percentage of total lymphocytes |
| Cohort III-DT | Summary of Changes in CD8 Percent From Baseline | From baseline to Week 24 | -3 Percentage of total lymphocytes |
| Cohort III-DT | Summary of Changes in CD8 Percent From Baseline | From baseline to Week 48 | -6.5 Percentage of total lymphocytes |
| Cohort IV-DT | Summary of Changes in CD8 Percent From Baseline | From baseline to Week 48 | -9 Percentage of total lymphocytes |
| Cohort IV-DT | Summary of Changes in CD8 Percent From Baseline | From baseline to Week 24 | -4.2 Percentage of total lymphocytes |
| Cohort V-DT | Summary of Changes in CD8 Percent From Baseline | From baseline to Week 24 | -4 Percentage of total lymphocytes |
| Cohort V-DT | Summary of Changes in CD8 Percent From Baseline | From baseline to Week 48 | -3.5 Percentage of total lymphocytes |
Secondary
Worst Case CDC HIV Classification Status
Disease progression as measured by change from baseline to the worst case CDC HIV classification status
Time frame: From baseline through Week 192
Population: All participants enrolled into the study
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort I | Worst Case CDC HIV Classification Status | Mildly symptomatic at entry | 0 Participants |
| Cohort I | Worst Case CDC HIV Classification Status | Stage I or II at entry | 0 Participants |
| Cohort I | Worst Case CDC HIV Classification Status | Moderately symptomatic at entry | 0 Participants |
| Cohort I | Worst Case CDC HIV Classification Status | Stage III at entry | 0 Participants |
| Cohort I | Worst Case CDC HIV Classification Status | Severely symptomatic at entry | 0 Participants |
| Cohort I | Worst Case CDC HIV Classification Status | Not symptomatic at entry | 74 Participants |
| Cohort IIA | Worst Case CDC HIV Classification Status | Not symptomatic at entry | 0 Participants |
| Cohort IIA | Worst Case CDC HIV Classification Status | Stage I or II at entry | 0 Participants |
| Cohort IIA | Worst Case CDC HIV Classification Status | Mildly symptomatic at entry | 37 Participants |
| Cohort IIA | Worst Case CDC HIV Classification Status | Moderately symptomatic at entry | 0 Participants |
| Cohort IIA | Worst Case CDC HIV Classification Status | Severely symptomatic at entry | 0 Participants |
| Cohort IIA | Worst Case CDC HIV Classification Status | Stage III at entry | 0 Participants |
| Cohort IIB | Worst Case CDC HIV Classification Status | Not symptomatic at entry | 1 Participants |
| Cohort IIB | Worst Case CDC HIV Classification Status | Moderately symptomatic at entry | 20 Participants |
| Cohort IIB | Worst Case CDC HIV Classification Status | Severely symptomatic at entry | 0 Participants |
| Cohort IIB | Worst Case CDC HIV Classification Status | Stage I or II at entry | 0 Participants |
| Cohort IIB | Worst Case CDC HIV Classification Status | Stage III at entry | 0 Participants |
| Cohort IIB | Worst Case CDC HIV Classification Status | Mildly symptomatic at entry | 0 Participants |
| Cohort III | Worst Case CDC HIV Classification Status | Not symptomatic at entry | 0 Participants |
| Cohort III | Worst Case CDC HIV Classification Status | Stage I or II at entry | 0 Participants |
| Cohort III | Worst Case CDC HIV Classification Status | Stage III at entry | 0 Participants |
| Cohort III | Worst Case CDC HIV Classification Status | Severely symptomatic at entry | 31 Participants |
| Cohort III | Worst Case CDC HIV Classification Status | Mildly symptomatic at entry | 0 Participants |
| Cohort III | Worst Case CDC HIV Classification Status | Moderately symptomatic at entry | 1 Participants |
| Cohort IV | Worst Case CDC HIV Classification Status | Moderately symptomatic at entry | 0 Participants |
| Cohort IV | Worst Case CDC HIV Classification Status | Stage I or II at entry | 0 Participants |
| Cohort IV | Worst Case CDC HIV Classification Status | Stage III at entry | 7 Participants |
| Cohort IV | Worst Case CDC HIV Classification Status | Mildly symptomatic at entry | 0 Participants |
| Cohort IV | Worst Case CDC HIV Classification Status | Severely symptomatic at entry | 0 Participants |
| Cohort IV | Worst Case CDC HIV Classification Status | Not symptomatic at entry | 0 Participants |
| Cohort III-DT | Worst Case CDC HIV Classification Status | Stage I or II at entry | 10 Participants |
| Cohort III-DT | Worst Case CDC HIV Classification Status | Not symptomatic at entry | 0 Participants |
| Cohort III-DT | Worst Case CDC HIV Classification Status | Mildly symptomatic at entry | 0 Participants |
| Cohort III-DT | Worst Case CDC HIV Classification Status | Moderately symptomatic at entry | 0 Participants |
| Cohort III-DT | Worst Case CDC HIV Classification Status | Severely symptomatic at entry | 0 Participants |
| Cohort III-DT | Worst Case CDC HIV Classification Status | Stage III at entry | 0 Participants |