A5288/MULTI-OCTAVE: Management Using Latest Technologies to Optimize Combination Therapy After Viral Failure

Phase 4

Completed

• Conditions: HIV-1 Infection
• Interventions: Drug: Second line ART regimens - based on a boosted protease inhibitor (bPI) plus two nucleoside analogues (NRTIs); Drug: Study provided drugs according to patient resistance profile (DRV, ETR, RTV, FTC/TDF) + any in country available drug as applicable & available; Drug: Darunavir; Drug: Emtricitabine/tenofovir disoproxil fumarate; Other: SOC adherence versus SOC+CPI adherence; Drug: Etravirine; Drug: Raltegravir

• Registration Number: NCT01641367
• Lead Sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

Brief Summary

The study was done to:

* test a strategy of using a resistance test to choose anti-HIV drugs

* see how well combinations of new anti-HIV drugs work to lower HIV infection

* see if taking new anti-HIV drugs together is safe and tolerable

* see if text messages improve people's anti-HIV drug-taking behavior (only at sites participating in the adherence study)

* in people taking certain combinations of anti-HIV drugs with an anti-TB drug, compare how these drugs act in the body

* to see how people do after they stop having frequent clinic visits as part of a research study

Detailed Description

A5288 was an open-label phase IV, prospective interventional, strategy study in resource-limited settings (RLS) for HIV-1 infected participants with triple-class experience or resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), and protease inhibitors (PIs) and who were failing their current regimen. The use of novel agents and contemporary clinical decision management tools that include standard genotyping and plasma HIV viral load (VL) monitoring were evaluated. The screening genotype results and antiretroviral (ARV) history were used to allocate potential participants to one of four Cohorts (A, B, C or D) and to select an associated ARV regimen based on the Cohort assignment. In brief, individuals assigned to Cohort A continued on the same PI as in their second-line regimen, with the ability to modify NRTIs. Those assigned to Cohort B who were negative for hepatitis B were randomized to receive RAL and DRV/RTV with either the best available NRTIs (Cohort B1) or ETR (Cohort B2). If they were positive for hepatitis B they were assigned to Cohort B3 and received RAL, DRV/RTV and either FTC/TDF or 3TC/TDF. Individuals assigned to Cohort C received RAL and DRV/RTV with the best available NRTIs. Those ineligible for Cohorts A, B or C were assigned to Cohort D and received the best available regimen that included study provided drugs and any locally provided drugs.

At sites where feasible and relevant, the study evaluated an adherence support intervention. This involved a randomized comparison of a cell phone-based adherence support intervention plus local standard-of-care adherence support procedures (CPI+SOC) versus the SOC adherence support procedures.

Participants enrolled to the study in Step 1. If a participant experienced a confirmed virologic failure (defined as two consecutive HIV-1 RNA measures \>= 1000 copies/mL) at/after 22 weeks on their Step 1 regimen, they had another genotype test performed and cohort/regimen selected for Step 2. With the exception of one additional visit 4 weeks after enrollment to Step 2, the visit schedule for Step 2 followed the participant's original Step 1 schedule throughout the remainder of follow up.

Participants were followed in Steps 1 and 2 until 48 weeks after the last participant was enrolled to Step 1. During the first 48 weeks after Step 1 enrollment, clinic visits occurred at weeks 4, 12, 24, 36 and 48. After week 48, visits occurred every 12 weeks for adherence, safety and efficacy measures.

Participants had a final step 1/2 visit between November 22, 2016 and February 13, 2017. At the final step 1/2 visit, participants taking RAL, ETR, or DRV who were unable to obtain these drugs locally (e.g., through local treatment programs), and were otherwise eligible, entered Step 3 and continued to receive these drugs through the study for up to 96 additional weeks. Step 3 participants were dispensed ARVs every 12 weeks and had clinical assessments every 24 weeks. The purpose of Step 3 was to assist participants with the transition back to local care.

The primary analysis specified in the protocol and in the Statistical Analysis Plan was to estimate the proportion of participants in the overall study population who were virologically suppressed (HIV-1 RNA ≤200 copies/mL) at week 48 with a 95% confidence interval.

Study Timeline

• Study First Submitted: 2012-06-28
• Study First Submitted QC: 2012-07-12
• Study First Posted: 2012-07-16
• Study Start: 2013-02-22
• Primary Completion: 2016-11-23
• Results First Submitted: 2017-11-20
• Results First Submitted QC: 2018-01-22
• Results First Posted: 2018-02-20
• Study Completion: 2018-12-31
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-14
• Last Update Posted: 2019-03-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 545

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sub-cohort B3	Emtricitabine/tenofovir disoproxil fumarate	Under Protocol version 1.0: Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and with active hepatitis B infection at screening • RAL, DRV/RTV, and FTC/TDF or TDF+3TC Changed under LOA#2 to: Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (with active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (with active hepatitis B infection at screening) • RAL, DRV/RTV, and FTC/TDF or TDF+3TC
Cohort A	SOC adherence versus SOC+CPI adherence	Under Protocol version 1.0: No resistance to NRTIs, PIs, or NNRTI • Continue current second-line regimen; NRTIs could be modified Changed under LOA#2 to: No LPV/RTV resistance and susceptible to at least one NRTI, regardless of NNRTI resistance or prior RAL exposure • Continue second-line regimen which may include LPV/RTV; NRTIs could be modified Changed under LOA#3 to: No LPV/RTV resistance and susceptible to at least one NRTI, regardless of NNRTI resistance or prior RAL exposure • Continue PI backbone; NRTIs could be modified. If on a RAL-containing regimen, RAL must be discontinued.
Cohort A	Second line ART regimens - based on a boosted protease inhibitor (bPI) plus two nucleoside analogues (NRTIs)	Under Protocol version 1.0: No resistance to NRTIs, PIs, or NNRTI • Continue current second-line regimen; NRTIs could be modified Changed under LOA#2 to: No LPV/RTV resistance and susceptible to at least one NRTI, regardless of NNRTI resistance or prior RAL exposure • Continue second-line regimen which may include LPV/RTV; NRTIs could be modified Changed under LOA#3 to: No LPV/RTV resistance and susceptible to at least one NRTI, regardless of NNRTI resistance or prior RAL exposure • Continue PI backbone; NRTIs could be modified. If on a RAL-containing regimen, RAL must be discontinued.
Sub-cohort B1	SOC adherence versus SOC+CPI adherence	Under Protocol version 1.0: Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening • Best available NRTIs, RAL, \& DRV/RTV Changed under LOA#2 to: Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening) • Best available NRTIs, RAL, \& DRV/RTV
Cohort D	Study provided drugs according to patient resistance profile (DRV, ETR, RTV, FTC/TDF) + any in country available drug as applicable & available	Under Protocol version 1.0: Multiple NRTI resistance and/or DRV/RTV resistance or prior RAL exposure: • Best available regimen, including study-provided and any locally available drugs Changed under LOA#2: Not eligible for Cohort A, B, or C: • Best available regimen, including study-provided and any locally available drugs Updated under protocol v2.0: • Best available ART regimen, including study-provided and any locally available non-experimental drugs
Sub-cohort B2	Etravirine	Under Protocol version 1.0: Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening • ETR, RAL, and DRV/RTV Changed under LOA#2 to: Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening) • ETR, RAL, and DRV/RTV
Sub-cohort B2	SOC adherence versus SOC+CPI adherence	Under Protocol version 1.0: Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening • ETR, RAL, and DRV/RTV Changed under LOA#2 to: Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening) • ETR, RAL, and DRV/RTV
Sub-cohort B3	SOC adherence versus SOC+CPI adherence	Under Protocol version 1.0: Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and with active hepatitis B infection at screening • RAL, DRV/RTV, and FTC/TDF or TDF+3TC Changed under LOA#2 to: Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (with active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (with active hepatitis B infection at screening) • RAL, DRV/RTV, and FTC/TDF or TDF+3TC
Cohort D	SOC adherence versus SOC+CPI adherence	Under Protocol version 1.0: Multiple NRTI resistance and/or DRV/RTV resistance or prior RAL exposure: • Best available regimen, including study-provided and any locally available drugs Changed under LOA#2: Not eligible for Cohort A, B, or C: • Best available regimen, including study-provided and any locally available drugs Updated under protocol v2.0: • Best available ART regimen, including study-provided and any locally available non-experimental drugs
Cohort C	SOC adherence versus SOC+CPI adherence	Under Protocol version 1.0: Resistance to NRTIs and ETR or resistance to ETR alone (and may have resistance to PIs other than DRV) • Best available NRTIs, RAL, and DRV/RTV Changed under LOA#2: Resistance to LPV/RTV and ETR but susceptible to DRV/RTV and with no prior RAL exposure and regardless of NRTI resistance OR Resistance to ETR and to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and with no prior RAL exposure • Best available NRTIs, RAL, and DRV/RTV
Sub-cohort B1	Darunavir	Under Protocol version 1.0: Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening • Best available NRTIs, RAL, \& DRV/RTV Changed under LOA#2 to: Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening) • Best available NRTIs, RAL, \& DRV/RTV
Sub-cohort B1	Raltegravir	Under Protocol version 1.0: Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening • Best available NRTIs, RAL, \& DRV/RTV Changed under LOA#2 to: Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening) • Best available NRTIs, RAL, \& DRV/RTV
Sub-cohort B2	Darunavir	Under Protocol version 1.0: Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening • ETR, RAL, and DRV/RTV Changed under LOA#2 to: Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening) • ETR, RAL, and DRV/RTV
Sub-cohort B2	Raltegravir	Under Protocol version 1.0: Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening • ETR, RAL, and DRV/RTV Changed under LOA#2 to: Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening) • ETR, RAL, and DRV/RTV
Sub-cohort B3	Darunavir	Under Protocol version 1.0: Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and with active hepatitis B infection at screening • RAL, DRV/RTV, and FTC/TDF or TDF+3TC Changed under LOA#2 to: Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (with active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (with active hepatitis B infection at screening) • RAL, DRV/RTV, and FTC/TDF or TDF+3TC
Sub-cohort B3	Raltegravir	Under Protocol version 1.0: Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and with active hepatitis B infection at screening • RAL, DRV/RTV, and FTC/TDF or TDF+3TC Changed under LOA#2 to: Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (with active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (with active hepatitis B infection at screening) • RAL, DRV/RTV, and FTC/TDF or TDF+3TC
Cohort C	Darunavir	Under Protocol version 1.0: Resistance to NRTIs and ETR or resistance to ETR alone (and may have resistance to PIs other than DRV) • Best available NRTIs, RAL, and DRV/RTV Changed under LOA#2: Resistance to LPV/RTV and ETR but susceptible to DRV/RTV and with no prior RAL exposure and regardless of NRTI resistance OR Resistance to ETR and to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and with no prior RAL exposure • Best available NRTIs, RAL, and DRV/RTV
Cohort C	Raltegravir	Under Protocol version 1.0: Resistance to NRTIs and ETR or resistance to ETR alone (and may have resistance to PIs other than DRV) • Best available NRTIs, RAL, and DRV/RTV Changed under LOA#2: Resistance to LPV/RTV and ETR but susceptible to DRV/RTV and with no prior RAL exposure and regardless of NRTI resistance OR Resistance to ETR and to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and with no prior RAL exposure • Best available NRTIs, RAL, and DRV/RTV

Primary Outcome Measures

Name	Time	Method
Proportion of Participants With Plasma HIV-1 RNA ≤200 Copies/mL at 48 Weeks	48 weeks after the date of entry	The measurement closest to exactly 48 weeks (ie, 7x48=336 days) after the date of entry, within the window of 48 weeks ± 6 weeks (specifically 295 to 378 days after randomization, inclusive).; The analysis in the protocol and in the Stat. Analysis Plan involved estimating the proportion of participants in the overall study population with HIV-1 RNA ≤200 copies/mL at week 48 with a 95% confidence interval calculated via a Wald approach. Death or lost to follow-up before week 48 was considered as HIV-1 RNA\>200 copies/mL at week 48. Missing results at week 48 were considered as HIV-1 RNA \>200 copies/mL at week 48 unless the immediately preceding and succeeding HIV-1 RNA measurements were ≤200 copies/mL. Since the primary analysis was on the total study population, overall results were also submitted. All participants in B3 had HIV-1 RNA ≤200 copies/mL at week 48. Therefore, Wald confidence interval could not be computed for B3 and Clopper-Pearson Exact confidence interval is provided.

Secondary Outcome Measures

Name	Time	Method
Proportion of Participants With Plasma HIV-1 RNA ≤200 Copies/mL at 24 Weeks	24 weeks after the date of entry	The measurement closest to exactly 24 weeks (ie, 7x24=168 days) after the date of entry, within the window of 24 weeks ± 6 weeks (specifically 127 to 210 days after randomization, inclusive).; The analysis in the protocol and in the Stat. Analysis Plan involved estimating the proportion of participants in the overall study population with HIV-1 RNA ≤200 copies/mL at week 24 with a 95% confidence interval calculated via a Wald approach. Death or lost to follow-up before week 24 was considered as HIV-1 RNA\>200 copies/mL at week 24. Missing results at week 24 were considered as HIV-1 RNA \>200 copies/mL at week 24 unless the immediately preceding and succeeding HIV-1 RNA measurements were ≤200 copies/mL. Since the primary analysis was on the total study population, overall results were also submitted. All participants in B3 had HIV-1 RNA ≤200 copies/mL at week 24. Therefore, Wald confidence interval could not be computed for B3 and Clopper-Pearson Exact confidence interval is provided.
Proportion of Participants With Plasma HIV-1 RNA ≤200 Copies/mL at 72 Weeks	72 weeks after the date of entry	The measurement closest to exactly 72 weeks (ie, 7x72=504 days) after the date of entry, within the window of 72 weeks ± 6 weeks (specifically 463 to 546 days, inclusive).; The analysis in the protocol and in the Analysis Plan involved estimating the proportion of participants in the overall study population with HIV-1 RNA ≤200 copies/mL at week 72 with a 95% confidence interval calculated via a Wald approach. Death or lost to follow-up before week 72 was considered as HIV-1 RNA\>200 copies/mL at week 72. If a result was expected, missing results at week 72 were considered as HIV-1 RNA \>200 copies/mL at week 72 unless the immediately preceding and succeeding HIV-1 RNA measurements were ≤200 copies/mL. Since the primary analysis was on the total study population, overall results were also submitted. All participants in B3 had HIV-1 RNA ≤200 copies/mL at week 72. Therefore, Wald confidence interval could not be computed for B3 and Clopper-Pearson Exact confidence interval is provided.
Percent of Participants With Confirmed Virologic Failure by Week 48	From week 24 to Week 48	Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure \[specimens on separate dates\] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7\*22=154 days after study entry(to allow for 14 day window for scheduling the visit). HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement,allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure. Event times were the scheduled week of the initial failing measurement (RNA scheduled at week 0, 12, 24, 48 and every 24 weeks after). Censoring times were the scheduled week of the last RNA result. Length of follow-up varied by Cohort.
Number of Participants With Confirmed Virologic Failure, Defined as First HIV-1 RNA ≥1000 Copies/mL at or After 24 Weeks on Study, With a New Resistance-associated Mutation Detected in Population-based Sequencing	From week 24 through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure\[specimens on separate dates\] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7\*22=154 days after study entry (to allow for 14 day window for scheduling the visit).HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement, allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure. Length of follow-up varied by Cohort. A new resistance-associated mutation is defined as one not present in the genotype prior to entry.
Percent of Participants With Confirmed Virologic Failure, Defined as First HIV-1 RNA ≥1000 Copies/mL at or After 24 Weeks on Study, With a New Resistance-associated Mutation Detected in Population-based Sequencing, by Week 48	From week 24 to Week 48	Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure\[specimens on separate dates\] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7\*22=154 days after study entry(to allow for 14 day window for scheduling the visit).HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement,allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure.Event times were the scheduled week of the initial failing measurement(RNA scheduled at week 0, 12, 24, 48 and every 24 weeks after).Censoring times were the scheduled week of the last RNA result.Length of follow-up varied by Cohort.A new resistance-associated mutation is defined as one not present in the genotype prior to entry.
Number of Weeks of Follow-up	From study entry through Step 1/2 follow-up	All participants were followed on step 1/2 until 48 weeks after the last participant was enrolled to step 1 regardless of virologic status or treatment switches. Length of follow-up varied by Cohort.
Time to Confirmed Virologic Failure, Defined as First HIV-1 RNA ≥1000 Copies/mL at or After 24 Weeks on Study	From week 24 through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure \[specimens on separate dates\] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7\*22=154 days after study entry (to allow for 14 day window for scheduling the visit). HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement, allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure. Event times were the scheduled week of the initial failing measurement (RNA scheduled at week 0, 12, 24, 48 and every 24 weeks after). Censoring times were the scheduled week of the last RNA result. Length of follow-up varied by Cohort.
Time to Confirmed Virologic Failure, Defined as First HIV-1 RNA ≥1000 Copies/mL at or After 24 Weeks on Study, With a New Resistance-associated Mutation Detected in Population-based Sequencing	From week 24 through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure \[specimens on separate dates\] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7\*22=154 days after study entry (to allow for 14 day window for scheduling the visit). HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement, allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure. Event times were the scheduled week of the initial failing measurement (RNA scheduled at week 0, 12, 24, 48 and every 24 weeks after). Censoring times were the scheduled week of the last RNA result. Length of follow-up varied by Cohort. A new resistance-associated mutation is defined as one not present in the genotype prior to entry.
Time From Study Entry/Randomization to Death	From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Event time was the exact week of death. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. Length of follow-up varied by Cohort.
Percent of Participants With Death or Hospitalization by Week 48	From study entry to Week 48	Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Event time was the exact week of death or hospitalization. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. If a participant experienced multiple events, then the time of the first event was used in the analysis.
Percent of Participants With Confirmed Virologic Failure by Week 48 [CPI+SOC v SOC]	From week 24 to Week 48	Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure \[specimens on separate dates\] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7\*22=154 days after study entry(to allow for 14 day window for scheduling the visit). HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement,allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure. Event times were the scheduled week of the initial failing measurement (RNA scheduled at week 0, 12, 24, 48 and every 24 weeks after). Censoring times were the scheduled week of the last RNA result.
Number of Participants With Confirmed Virologic Failure, Defined as First HIV-1 RNA ≥1000 Copies/mL at or After 24 Weeks on Study	From week 24 through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure \[specimens on separate dates\] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7\*22=154 days after study entry (to allow for 14 day window for scheduling the visit). HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement, allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure. Length of follow-up varied by Cohort.
Percent of Participants Experiencing Death by Week 48	From study entry to Week 48	Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Event time was the exact week of death. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit.
Percent of Participants That Developed Immune Reconstitution Inflammatory Syndrome (IRIS) by Week 48	From study entry to week 48	Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Event time was the exact week of the diagnosis. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit.
Percent of Participants With a Dose Modification Due to Grade 3 or 4 Toxicity by Week 48	From study entry to week 48	Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Event time was the exact week of the modification. Censoring time was the earliest time point between last dose week and the week of the last step 1/2 visit. DAIDS AE Grading Table, Version 1.0 was used.
Change From Baseline in CD4+ T-cell Count	Baseline, week 24, 48, and 72	Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen (this second date applies only to Cohorts B, C and D as there is no change of regimen for patients in Cohort A)
Time to Confirmed Virologic Failure, Defined as First HIV-1 RNA ≥1000 Copies/mL at or After 24 Weeks on Study [CPI+SOC v SOC]	From week 24 through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure \[specimens on separate dates\] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7\*22=154 days after study entry (to allow for 14 day window for scheduling the visit). HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement, allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure. Event times were the scheduled week of the initial failing measurement (RNA scheduled at week 0, 12, 24, 48 and every 24 weeks after). Censoring times were the scheduled week of the last RNA result.
Time From Study Entry/Randomization to the First of Death, an AIDS-defining Event or a Non-AIDS-defining Event	From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Event time was the exact week of death, AIDS-defining event or non-AIDS defining event. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. Only new events were considered, an event that was also reported at or prior to study entry was not included. If a participant experienced multiple events, then the time of the first event was used in the analysis. AIDS defining events included parasitic, fungal, bacterial, and viral infections as well as neoplastic diseases, and neurological disorders. Non-AIDS defining events included malignancies, diabetes, neuropathies, cardiac and renal events. Length of follow-up varied by Cohort.
Percent of Participants With Treatment Modification or Discontinuation by Week 48	From study entry to Week 48	Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Treatment modification is defined as the first occurrence of a substitution or subtraction of one or more drugs in the study regimen, a temporary hold lasting 7 days or longer, or the addition of a new drug to the regimen. This would not include splitting any fixed dose combination medications if the participant continues on the active drugs of the combination. Event time was the exact week of the modification or discontinuation. Censoring time was the earliest time point between last dose week and the week of the last step 1/2 visit.
Percent of Participants With Treatment Modification or Discontinuation Due to Toxicity by Week 48	From study entry to Week 48	Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Treatment modification is defined as the first occurrence of a substitution or subtraction of one or more drugs in the study regimen, a temporary hold lasting 7 days or longer, or the addition of a new drug to the regimen, due to an adverse event. This would not include splitting any fixed dose combination medications if the participant continues on the active drugs of the combination. Event time was the exact week of the modification or discontinuation. Censoring time was the earliest time point between last dose week and the week of the last step 1/2 visit. DAIDS AE Grading Table, Version 1.0 was used.
Time From Study Entry/Randomization to the Development of Immune Reconstitution Inflammatory Syndrome (IRIS)	From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Event time was the exact week of the diagnosis. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. Length of follow-up varied by Cohort.
Time to First Dose Modification Due to Grade 3 or 4 Toxicity	From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Event time was the exact week of the modification. Censoring time was the earliest time point between last dose week and the week of the last step 1/2 visit. Length of follow-up varied by Cohort. DAIDS AE Grading Table, Version 1.0 was used.
Change From Baseline in Fasting Values of Glucose	Baseline, week 24, 48 and 72	Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen (this second date applies only to Cohorts B, C and D as there is no change of regimen for patients in Cohort A)
Proportion of Participants With Plasma HIV-1 RNA ≤200 Copies/mL at 24 Weeks [CPI+SOC v SOC]	24 weeks after the date of entry	The measurement closest to exactly 24 weeks (ie, 7x24=168 days) after the date of entry, within the window of 24 weeks ± 6 weeks (specifically 127 to 210 days after randomization, inclusive).; The analysis in the protocol and in the Stat. Analysis Plan involved estimating the proportion of participants in the overall study population with HIV-1 RNA ≤200 copies/mL at week 24 with a 95% confidence interval calculated via a Wald approach. Death or lost to follow-up before week 24 was considered as HIV-1 RNA\>200 copies/mL at week 24. Missing results at week 24 were considered as HIV-1 RNA \>200 copies/mL at week 24 unless the immediately preceding and succeeding HIV-1 RNA measurements were ≤200 copies/mL.
Percent of Participants Experiencing Death, AIDS-defining Event or a Non-AIDS-defining Event by Week 48	From study entry to Week 48	Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Event time was the exact week of death, AIDS-defining event or non-AIDS defining event. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. Only new events were considered, an event that was also reported at or prior to study entry was not included. If a participant experienced multiple events, then the time of the first event was used in the analysis. AIDS defining events included parasitic, fungal, bacterial, and viral infections as well as neoplastic diseases, and neurological disorders. Non-AIDS defining events included malignancies, diabetes, neuropathies, cardiac and renal events.
Time From Study Entry/Randomization to Treatment Modification or Discontinuation.	From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Treatment modification is defined as the first occurrence of a substitution or subtraction of one or more drugs in the study regimen, a temporary hold lasting 7 days or longer, or the addition of a new drug to the regimen. This would not include splitting any fixed dose combination medications if the participant continues on the active drugs of the combination. Event time was the exact week of the modification or discontinuation. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. Length of follow-up varied by Cohort.
Time From Study Entry/Randomization to Treatment Modification or Discontinuation Due to Toxicity	From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Treatment modification is defined as the first occurrence of a substitution or subtraction of one or more drugs in the study regimen, a temporary hold lasting 7 days or longer, or the addition of a new drug to the regimen, due to an adverse event. This would not include splitting any fixed dose combination medications if the participant continues on the active drugs of the combination. Event time was the exact week of the modification or discontinuation. Censoring time was the earliest time point between last dose week and the week of the last step 1/2 visit. Length of follow-up varied by Cohort. DAIDS AE Grading Table, Version 1.0 was used.
Change From Baseline in Fasting Values of Total Cholesterol	Baseline, week 24, 48 and 72	Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen (this second date applies only to Cohorts B, C and D as there is no change of regimen for patients in Cohort A)
Change From Baseline in Fasting Values of High-density Lipoprotein Cholesterol	Baseline, week 24, 48 and 72	Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen (this second date applies only to Cohorts B, C and D as there is no change of regimen for patients in Cohort A)\]
Change From Baseline in Fasting Values of Calculated Low-density Lipoprotein Cholesterol	Baseline, week 24, 48 and 72	Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen (this second date applies only to Cohorts B, C and D as there is no change of regimen for patients in Cohort A)
Change From Baseline in Fasting Values of Triglycerides	Baseline, week 24, 48 and 72	Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen (this second date applies only to Cohorts B, C and D as there is no change of regimen for patients in Cohort A)
Proportion of Participants With Plasma HIV-1 RNA ≤200 Copies/mL at 48 Weeks [CPI+SOC v SOC]	48 weeks after the date of entry	The measurement closest to exactly 48 weeks (ie, 7x48=336 days) after the date of entry, within the window of 48 weeks ± 6 weeks (specifically 295 to 378 days after randomization, inclusive).; The analysis in the protocol and in the Stat. Analysis Plan involved estimating the proportion of participants in the overall study population with HIV-1 RNA ≤200 copies/mL at week 48 with a 95% confidence interval calculated via a Wald approach. Death or lost to follow-up before week 48 was considered as HIV-1 RNA\>200 copies/mL at week 48. Missing results at week 48 were considered as HIV-1 RNA \>200 copies/mL at week 48 unless the immediately preceding and succeeding HIV-1 RNA measurements were ≤200 copies/mL.
Number of Weeks of Follow-up [CPI+SOC v SOC]	From study entry through Step 1/2 follow-up	All participants were followed on step 1/2 until 48 weeks after the last participant was enrolled to step 1 regardless of virologic status or treatment switches.
Time From Study Entry/Randomization to the First of Death or Hospitalization.	From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Event time was the exact week of death or hospitalization. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. If a participant experienced multiple events, then the time of the first event was used in the analysis. Length of follow-up varied by Cohort.
Number of Participants With Confirmed Virologic Failure, Defined as First HIV-1 RNA ≥1000 Copies/mL at or After 24 Weeks on Study, With a New Resistance-associated Mutation Detected in Population-based Sequencing [CPI+SOC v SOC]	From week 24 through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure\[specimens on separate dates\] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7\*22=154 days after study entry (to allow for 14 day window for scheduling the visit).HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement, allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure. A new resistance-associated mutation is defined as one not present in the genotype prior to entry.
Time From Study Entry/Randomization to Death [CPI+SOC v SOC]	From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Event time was the exact week of death. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit.
Proportion of Participants With Plasma HIV-1 RNA ≤200 Copies/mL at 72 Weeks [CPI+SOC v SOC]	72 weeks after the date of entry	The measurement closest to exactly 72 weeks (ie, 7x72=504 days) after the date of entry, within the window of 72 weeks ± 6 weeks (specifically 463 to 546 days, inclusive).; The analysis in the protocol and in the Analysis Plan involved estimating the proportion of participants in the overall study population with HIV-1 RNA ≤200 copies/mL at week 72 with a 95% confidence interval calculated via a Wald approach. Death or lost to follow-up before week 72 was considered as HIV-1 RNA\>200 copies/mL at week 72. If a result was expected, missing results at week 72 were considered as HIV-1 RNA \>200 copies/mL at week 72 unless the immediately preceding and succeeding HIV-1 RNA measurements were ≤200 copies/mL.
Time to Confirmed Virologic Failure, Defined as First HIV-1 RNA ≥1000 Copies/mL at or After 24 Weeks on Study, With a New Resistance-associated Mutation Detected in Population-based Sequencing [CPI+SOC v SOC]	From week 24 through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure \[specimens on separate dates\] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7\*22=154 days after study entry (to allow for 14 day window for scheduling the visit). HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement, allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure. Event times were the scheduled week of the initial failing measurement (RNA scheduled at week 0, 12, 24, 48 and every 24 weeks after). Censoring times were the scheduled week of the last RNA result. A new resistance-associated mutation is defined as one not present in the genotype prior to entry.
Percent of Participants Experiencing Death by Week 48 [CPI+SOC v SOC]	From study entry to Week 48	Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Event time was the exact week of death. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit.
Time From Study Entry/Randomization to Treatment Modification or Discontinuation [CPI+SOC v SOC]	From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Treatment modification is defined as the first occurrence of a substitution or subtraction of one or more drugs in the study regimen, a temporary hold lasting 7 days or longer, or the addition of a new drug to the regimen. This would not include splitting any fixed dose combination medications if the participant continues on the active drugs of the combination. Event time was the exact week of the modification or discontinuation. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit.
Time From Study Entry/Randomization to the Development of Immune Reconstitution Inflammatory Syndrome (IRIS) [CPI+SOC v SOC]	From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Event time was the exact week of the diagnosis. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit.
Time to First Dose Modification Due to Grade 3 or 4 Toxicity [CPI+SOC v SOC]	From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Event time was the exact week of the modification. Censoring time was the earliest time point between last dose week and the week of the last step 1/2 visit. DAIDS AE Grading Table, Version 1.0 was used.
Percent of Participants With a Dose Modification Due to Grade 3 or 4 Toxicity by Week 48 [CPI+SOC v SOC]	From study entry to Week 48	Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Event time was the exact week of the modification. Censoring time was the earliest time point between last dose week and the week of the last step 1/2 visit. DAIDS AE Grading Table, Version 1.0 was used.
Change From Baseline in Fasting Values of High-density Lipoprotein Cholesterol [CPI+SOC v SOC]	Baseline, week 24, 48, and 72	Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen.
Number of Participants With Confirmed Virologic Failure, Defined as First HIV-1 RNA ≥1000 Copies/mL at or After 24 Weeks on Study [CPI+SOC v SOC]	From week 24 through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure \[specimens on separate dates\] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7\*22=154 days after study entry (to allow for 14 day window for scheduling the visit). HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement, allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure.
Time From Study Entry/Randomization to the First of Death, an AIDS-defining Event or a Non-AIDS-defining Event [CPI+SOC v SOC]	From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Event time was the exact week of death, AIDS-defining event or non-AIDS defining event. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. Only new events were considered, an event that was also reported at or prior to study entry was not included. If a participant experienced multiple events, then the time of the first event was used in the analysis. AIDS defining events included parasitic, fungal, bacterial, and viral infections as well as neoplastic diseases, and neurological disorders. Non-AIDS defining events included malignancies, diabetes, neuropathies, cardiac and renal events.
Time From Study Entry/Randomization to the First of Death or Hospitalization [CPI+SOC v SOC]	From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Event time was the exact week of death or hospitalization. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. If a participant experienced multiple events, then the time of the first event was used in the analysis.
Percent of Participants With Treatment Modification or Discontinuation by Week 48 [CPI+SOC v SOC]	From study entry to Week 48	Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Treatment modification is defined as the first occurrence of a substitution or subtraction of one or more drugs in the study regimen, a temporary hold lasting 7 days or longer, or the addition of a new drug to the regimen. This would not include splitting any fixed dose combination medications if the participant continues on the active drugs of the combination. Event time was the exact week of the modification or discontinuation. Censoring time was the earliest time point between last dose week and the week of the last step 1/2 visit.
Change From Baseline in Fasting Values of Total Cholesterol [CPI+SOC v SOC]	Baseline, week 24, 48, and 72	Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen.
Percent of Participants With Confirmed Virologic Failure, Defined as First HIV-1 RNA ≥1000 Copies/mL at or After 24 Weeks on Study, With a New Resistance-associated Mutation Detected in Population-based Sequencing, by Week 48 [CPI+SOC v SOC]	From week 24 to Week 48	Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure\[specimens on separate dates\] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7\*22=154 days after study entry(to allow for 14 day window for scheduling the visit).HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement,allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure.Event times were the scheduled week of the initial failing measurement(RNA scheduled at week 0, 12, 24, 48 and every 24 weeks after).Censoring times were the scheduled week of the last RNA result.A new resistance-associated mutation is defined as one not present in the genotype prior to entry.
Percent of Participants Experiencing Death, AIDS-defining Event or a Non-AIDS-defining Event by Week 48 [CPI+SOC v SOC]	From study entry to Week 48	Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Event time was the exact week of death, AIDS-defining event or non-AIDS defining event. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. Only new events were considered, an event that was also reported at or prior to study entry was not included. If a participant experienced multiple events, then the time of the first event was used in the analysis. AIDS defining events included parasitic, fungal, bacterial, and viral infections as well as neoplastic diseases, and neurological disorders. Non-AIDS defining events included malignancies, diabetes, neuropathies, cardiac and renal events.
Time From Study Entry/Randomization to Treatment Modification or Discontinuation Due to Toxicity [CPI+SOC v SOC]	From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks	Treatment modification is defined as the first occurrence of a substitution or subtraction of one or more drugs in the study regimen, a temporary hold lasting 7 days or longer, or the addition of a new drug to the regimen, due to an adverse event. This would not include splitting any fixed dose combination medications if the participant continues on the active drugs of the combination. Event time was the exact week of the modification or discontinuation. Censoring time was the earliest time point between last dose week and the week of the last step 1/2 visit. DAIDS AE Grading Table, Version 1.0 was used.
Change From Baseline in CD4+ T-cell Count [CPI+SOC v SOC]	Baseline, week 24, 48, and 72	Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen.
Change From Baseline in Fasting Values of Glucose [CPI+SOC v SOC]	Baseline, week 24, 48, and 72	Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen.
Percent of Participants With Death or Hospitalization by Week 48 [CPI+SOC v SOC]	From study entry to Week 48	Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Event time was the exact week of death or hospitalization. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. If a participant experienced multiple events, then the time of the first event was used in the analysis.
Percent of Participants With Treatment Modification or Discontinuation Due to Toxicity by Week 48 [CPI+SOC v SOC]	From study entry to Week 48	Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Treatment modification is defined as the first occurrence of a substitution or subtraction of one or more drugs in the study regimen, a temporary hold lasting 7 days or longer, or the addition of a new drug to the regimen, due to an adverse event. This would not include splitting any fixed dose combination medications if the participant continues on the active drugs of the combination. Event time was the exact week of the modification or discontinuation. Censoring time was the earliest time point between last dose week and the week of the last step 1/2 visit. DAIDS AE Grading Table, Version 1.0 was used.
Percent of Participants That Developed Immune Reconstitution Inflammatory Syndrome (IRIS) by Week 48 [CPI+SOC v SOC]	From study entry to Week 48	Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Event time was the exact week of the diagnosis. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit.
Change From Baseline in Fasting Values of Calculated Low-density Lipoprotein Cholesterol [CPI+SOC v SOC]	Baseline, week 24, 48, and 72	Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen.
Change From Baseline in Fasting Values of Triglycerides [CPI+SOC v SOC]	Baseline, week 24, 48, and 72	Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen.

Trial Locations

Locations (19)

Hospital Nossa Senhora da Conceicao CRS (12201); 🇧🇷 Porto Alegre, RS, Brazil

Instituto de Pesquisa Clinica Evandro Chagas (12101); 🇧🇷 Rio de Janeiro, Brazil

Chennai Antiviral Research and Treatment (CART) CRS (11701); 🇮🇳 Chennai, Taramani, India

GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS; 🇭🇹 Port Au Prince, Haiti

Kenya Medical Research Institute/Center for Disease Control (KEMRI/CDC) CRS (31460); 🇰🇪 Kisumu, Kenya

Barranco CRS (11301); 🇵🇪 Lima, Peru

University of the Witwatersrand Helen Joseph (WITS HJH) CRS (11101); 🇿🇦 Johannesburg, Gauteng, South Africa

Family Clinical Research Unit (FAM-CUR) CRS (8950); 🇿🇦 Cape Town, West Cape, South Africa

Durban Adult HIV CRS (11201); 🇿🇦 Durban, South Africa

Soweto ACTG CRS (12301); 🇿🇦 Johannesburg, South Africa

San Miguel CRS (11302); 🇵🇪 San Miguel, Lima, Peru

Les Centres GHESKIO CRS (30022); 🇭🇹 Port-au-Prince, Bicentaire, Haiti

BJ Medical College CRS (31441); 🇮🇳 Pune, Maharashtra, India

AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS (12601); 🇰🇪 Eldoret, Kenya

31802 Thai Red Cross AIDS Research Centre (TRC-ARC) CRS; 🇹🇭 Bangkok, Patumwan, Thailand

31784 Chiang Mai University HIV Treatment CRS; 🇹🇭 Chiang Mai, Thailand

UZ-Parirenyatwa CRS (30313); 🇿🇼 Harare, Zimbabwe

Malawi CRS (12001); 🇲🇼 Lilongwe, Malawi

JCRC CRS; 🇺🇬 Kampala, Uganda