Trial Outcomes & Findings for Optimizing Treatment for Treatment-Experienced, HIV-Infected People (NCT NCT00537394)

Last Updated: 2021-11-04

Results Overview

Virologic failure defined as confirmed plasma HIV-1 RNA meeting 1 of the following 4 criteria: \< 1.0 log10 copies/mL reduction from baseline level and \>= 200 copies/mL at or after week 12 evaluation; \>= 200 copies/mL after 1 measurement \< 200 copies/mL; absence of any values \< 200 copies/mL by and including week 24 evaluation; \>= 200 copies/mL at week 48 evaluation. Discontinuation of Randomized NRTI component of Study Treatment is defined as permanently stopping all NRTIs among those randomized to add NRTIs, or starting any NRTI among those randomized to omit NRTIs. Subjects leaving the study for reasons other than death, relocation, incarceration, or site closure were reviewed for the discontinuation outcome by a blinded, independent panel. Additionally, any participant failing to start study treatment after randomization and prior to closure was also reviewed. Results report percent of participants reaching regimen failure outcome by week 48 evaluation using Kaplan-Meier method.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

517 participants

Primary outcome timeframe

From study entry to end of Week 48 evaluation window

Results posted on

2021-11-04

Participant Flow

Subjects recruited between February 2008 and May 2011 from participating ACTG, IMPAACT, and ATN network sites located in the continental US and Puerto Rico.

A total of 104 exclusions among 517 enrolled to active screening but prior to assignment and dispensation of study treatment were due to any of the following: no resistance/tropism test results, not willing to accept any ARV study regimens, changes to current PI based ARV regimen or non-adherence, or changes with respect to eligibility criteria.

Participant milestones

Participant milestones
Measure	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0) \[Arm A\]Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was also started.	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2) \[Arm B\] Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was omitted, and any NRTIs the participant had been taking prior to randomization were to be permanently discontinued.	Non-randomized Group: Add NRTIs to Individual Regimen cPSS <=2 \[Non-randomized Group C\] : Among persons whose ARV resistance and history profile precluded any of the 20 possible ARV regimens having high enough potential potency (cPSS \<=2), treatment was assigned rather than being a randomized. To their regimen, individualized NRTI combination of at least 2 drugs from this class were added in order to form the most potent ARV regimen possible.
First Year of Follow-up STARTED	181	179	53
First Year of Follow-up COMPLETED	169	168	50
First Year of Follow-up NOT COMPLETED	12	11	3
2nd Year of Follow-up STARTED	169	168	50
2nd Year of Follow-up COMPLETED	158	159	44
2nd Year of Follow-up NOT COMPLETED	11	9	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0) \[Arm A\]Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was also started.	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2) \[Arm B\] Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was omitted, and any NRTIs the participant had been taking prior to randomization were to be permanently discontinued.	Non-randomized Group: Add NRTIs to Individual Regimen cPSS <=2 \[Non-randomized Group C\] : Among persons whose ARV resistance and history profile precluded any of the 20 possible ARV regimens having high enough potential potency (cPSS \<=2), treatment was assigned rather than being a randomized. To their regimen, individualized NRTI combination of at least 2 drugs from this class were added in order to form the most potent ARV regimen possible.
First Year of Follow-up Death	7	0	0
First Year of Follow-up Severe debilitation	1	0	1
First Year of Follow-up Withdrawal by Subject	3	6	1
First Year of Follow-up Lost to Follow-up	1	5	1
2nd Year of Follow-up Death	4	1	2
2nd Year of Follow-up Withdrawal by Subject	0	1	2
2nd Year of Follow-up Lost to Follow-up	6	7	2
2nd Year of Follow-up Clinic site closure	1	0	0

Baseline Characteristics

Optimizing Treatment for Treatment-Experienced, HIV-Infected People

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0) n=181 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was also started.	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2) n=179 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was omitted, and any NRTIs the participant had been taking prior to randomization were to be permanently discontinued.	Non-randomized Group: Add NRTIs to Individual Regimen cPSS <=2 n=53 Participants Among persons whose ARV resistance and history profile precluded any of the 20 possible ARV regimens having high enough potential potency (cPSS \<=2), treatment was assigned rather than being a randomized. To their regimen, individualized NRTI combination of at least 2 drugs from this class were added in order to form the most potent ARV regimen possible.	Total n=413 Participants Total of all reporting groups
Age, Categorical <=18 years	6 Participants n=5 Participants	8 Participants n=7 Participants	3 Participants n=5 Participants	17 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	173 Participants n=5 Participants	168 Participants n=7 Participants	50 Participants n=5 Participants	391 Participants n=4 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants
Age, Continuous	44.7 years STANDARD_DEVIATION 10.8 • n=5 Participants	44.1 years STANDARD_DEVIATION 11.7 • n=7 Participants	43.1 years STANDARD_DEVIATION 10.7 • n=5 Participants	44.3 years STANDARD_DEVIATION 11.2 • n=4 Participants
Sex: Female, Male Female	46 Participants n=5 Participants	47 Participants n=7 Participants	6 Participants n=5 Participants	99 Participants n=4 Participants
Sex: Female, Male Male	135 Participants n=5 Participants	132 Participants n=7 Participants	47 Participants n=5 Participants	314 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	37 Participants n=5 Participants	46 Participants n=7 Participants	14 Participants n=5 Participants	97 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	141 Participants n=5 Participants	132 Participants n=7 Participants	38 Participants n=5 Participants	311 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	81 Participants n=5 Participants	72 Participants n=7 Participants	20 Participants n=5 Participants	173 Participants n=4 Participants
Race (NIH/OMB) White	88 Participants n=5 Participants	87 Participants n=7 Participants	29 Participants n=5 Participants	204 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	11 Participants n=7 Participants	2 Participants n=5 Participants	21 Participants n=4 Participants
Region of Enrollment United States	181 participants n=5 Participants	179 participants n=7 Participants	53 participants n=5 Participants	413 participants n=4 Participants
CD4 count, continuous	252.3 cells/mm^3 STANDARD_DEVIATION 194.9 • n=5 Participants	245.6 cells/mm^3 STANDARD_DEVIATION 195.1 • n=7 Participants	154.8 cells/mm^3 STANDARD_DEVIATION 170.1 • n=5 Participants	236.9 cells/mm^3 STANDARD_DEVIATION 194.2 • n=4 Participants
Plasma HIV-1 RNA, continuous	4.2 log10 copies/mL n=5 Participants	4.2 log10 copies/mL n=7 Participants	4.4 log10 copies/mL n=5 Participants	4.2 log10 copies/mL n=4 Participants

PRIMARY outcome

Timeframe: From study entry to end of Week 48 evaluation window

Population: Analysis uses intent to treat population, among the two randomized arms only.

Outcome measures

Outcome measures
Measure	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0) n=181 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was also started.	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2) n=179 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was omitted, and any NRTIs the participant had been taking prior to randomization were to be permanently discontinued.
Percent of Participants With Regimen Failure, Defined as a Confirmed Virologic Failure or Discontinuation of Randomized NRTI Component of Study Treatment	26.0 percentage of participants Interval 19.6 to 32.3	29.8 percentage of participants Interval 23.1 to 36.6

SECONDARY outcome

Timeframe: From treatment dispensation to week 96 study visit

Population: Only randomized participants included. Persons not starting study treatment excluded.

Events following permanent discontinuation of NRTI assignment are excluded (i.e. censoring at time of this event, if applicable). Week 96 study visit could occur up to 110 weeks following randomization. Censoring time was the latest study visit when participant was evaluated or when NRTI assignment was discontinued (when applicable). Event time was the exact number of weeks following treatment initiation when the qualifying sign/symptom started (for those safety events triggered by a sign/symptom), or exact number of weeks following treatment initiation when specimen from qualifying laboratory result was drawn (for those safety events triggered by a laboratory abnormality).

Outcome measures

Outcome measures
Measure	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0) n=180 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was also started.	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2) n=177 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was omitted, and any NRTIs the participant had been taking prior to randomization were to be permanently discontinued.
Time From Treatment Dispensation to First Grade 3 or Higher (and at Least One Grade Higher Than Baseline) Signs/Symptom or Laboratory Abnormality 5th percentile	3.1 weeks Interval 1.9 to 4.6	3.9 weeks Interval 0.9 to 4.6
Time From Treatment Dispensation to First Grade 3 or Higher (and at Least One Grade Higher Than Baseline) Signs/Symptom or Laboratory Abnormality 25th percentile	24.7 weeks Interval 12.0 to 47.0	25.3 weeks Interval 24.0 to 35.9
Time From Treatment Dispensation to First Grade 3 or Higher (and at Least One Grade Higher Than Baseline) Signs/Symptom or Laboratory Abnormality 50th percentile	NA weeks Interval 72.1 to Not estimable as the estimate and upper limit for survival function at all weeks is above 50%	97.7 weeks Interval 63.0 to Not estimable as the upper limit for survival function at all weeks is above 50%

SECONDARY outcome

Timeframe: From treatment dispensation to week 96 study visit

Population: Only randomized participants included, and those who never started study treatment were excluded.

First study ARV modification included any discontinuation or substitution of any chosen and initiated ARV for any reason. Events prompting study medication change could include protocol required (e.g. safety), protocol recommended but not required (e.g. virologic failure), or participant motivated (such as non-adherence, loss to follow-up or death; in other words, not protocol recommended or required). Event times were the exact weeks from treatment initiation to the time of qualifying regimen modification. Censoring times were the exact weeks from treatment initiation to the last date of study drugs. The week 96 (final study visit) could occur up through 110 weeks following randomization.

Outcome measures

Outcome measures
Measure	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0) n=180 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was also started.	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2) n=177 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was omitted, and any NRTIs the participant had been taking prior to randomization were to be permanently discontinued.
Time From Treatment Dispensation to First Study ARV Modification (Excluding NRTIs, if Applicable) 5th percentile	9.0 weeks Interval 1.1 to 29.7	24.0 weeks Interval 4.0 to 35.6
Time From Treatment Dispensation to First Study ARV Modification (Excluding NRTIs, if Applicable) 10th percentile	31.1 weeks Interval 14.7 to 51.1	38.0 weeks Interval 24.4 to 67.7
Time From Treatment Dispensation to First Study ARV Modification (Excluding NRTIs, if Applicable) 25th percentile	98.0 weeks Interval 82.7 to Not estimable as the upper limit for survival function at all weeks is above 75%.	NA weeks Interval 84.4 to Not estimable as the estimate for survival function at all weeks is above 75%.

SECONDARY outcome

Timeframe: From randomization to week 96 study visit

Population: All randomized participants included (i.e. ITT analysis).

Discontinuation of Randomized NRTI component of Study Treatment is defined as permanently stopping all NRTIs among those randomized to add NRTIs, or starting any NRTI among those randomized to omit NRTIs. Subjects leaving the study for reasons other than death, relocation, incarceration, or site closure were reviewed for meeting this outcome by a blinded, independent panel. Additionally, any participant failing to start study treatment after randomization and prior to closure was also reviewed. Event times were scheduled study weeks when discontinuation events occurred. Censoring times were latest scheduled study visit weeks with evaluation.

Outcome measures

Outcome measures
Measure	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0) n=181 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was also started.	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2) n=179 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was omitted, and any NRTIs the participant had been taking prior to randomization were to be permanently discontinued.
Time From Randomization to Discontinuation of Randomized NRTI Component of Study Treatment 1st percentile	0 weeks Interval 0.0 to 1.0	0 weeks Interval 0.0 to 12.0
Time From Randomization to Discontinuation of Randomized NRTI Component of Study Treatment 5th percentile	36 weeks Interval 1.0 to Not estimable as the upper limit for survival function at all weeks is above 95%.	36 weeks Interval 4.0 to 36.0
Time From Randomization to Discontinuation of Randomized NRTI Component of Study Treatment 10th percentile	NA weeks Interval 36.0 to Not estimable as the estimate for survival function at all weeks is above 90%.	48 weeks Interval 36.0 to 84.0

SECONDARY outcome

Timeframe: From randomization to week 96 study visit

Population: ITT (all randomized participants) included.

Virologic failure defined as confirmed (two consecutive) plasma HIV-1 RNA meeting 1 of the following 4 criteria: \< 1.0 log10 copies/mL reduction from baseline level and \>= 200 copies/mL at or after week 12 evaluation; \>= 200 copies/mL after 1 measurement \< 200 copies/mL; absence of any values \< 200 copies/mL by and including week 24 evaluation; \>= 200 copies/mL at week 48 evaluation. Event time was the scheduled study visit week when the initial plasma HIV-1 RNA specimen meeting the failure definition was collected. Censoring time was the latest scheduled study visit week when a plasma HIV-1 RNA specimen was collected and tested.

Outcome measures

Outcome measures
Measure	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0) n=181 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was also started.	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2) n=179 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was omitted, and any NRTIs the participant had been taking prior to randomization were to be permanently discontinued.
Time From Randomization to Confirmed Virological Failure 5th percentile	12 weeks Interval 8.0 to 12.0	12 weeks Interval 8.0 to 12.0
Time From Randomization to Confirmed Virological Failure 10th percentile	12 weeks Interval 12.0 to 16.0	12 weeks Interval 12.0 to 16.0
Time From Randomization to Confirmed Virological Failure 25th percentile	48 weeks Interval 24.0 to Not estimable as the upper limit for survival function at all weeks is above 75%.	48 weeks Interval 36.0 to Not estimable as the upper limit for survival function at all weeks is above 75%.

SECONDARY outcome

Timeframe: At Weeks 24, 48, 96

Population: ITT - among 2 randomized arms only; closest value to scheduled week used if multiple values available; missing values excluded. Numbers analyzed at each time point represent those with a valid RNA result.

Number of participants with plasma HIV-1 Viral load \< 50 copies/mL at study visit weeks 24, 48, and 96. Closest observed result between 20 and up to 30 weeks (for week 24), between 42 and up to 54 (for week 48), and between 90 and up to 110 (for week 96) used if multiple results available. Missing values excluded.

Outcome measures

Outcome measures
Measure	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0) n=181 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was also started.	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2) n=179 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was omitted, and any NRTIs the participant had been taking prior to randomization were to be permanently discontinued.
Number of Participants With Plasma HIV-1 Viral Load < 50 Copies/ml Week 24: Number with RNA < 50 c/mL (N=170; N=171)	122 participants	117 participants
Number of Participants With Plasma HIV-1 Viral Load < 50 Copies/ml Week 48: Number with RNA < 50 c/mL (N=169; N=165)	112 participants	106 participants
Number of Participants With Plasma HIV-1 Viral Load < 50 Copies/ml Week 96: Number with RNA < 50 c/mL (N=158; N=158)	107 participants	109 participants

SECONDARY outcome

Timeframe: From baseline to Week 1 evaluation

Population: Modified intent to treat population among two randomized arms only: 2 participants (both in Omit NRTIs arm) were excluded because their baseline and week 1 RNA levels were both \< 50 copies/mL.

Method of Kaplan and Meier used to accommodate left-censoring for those whose week 1 levels \< 50 copies/mL.

Outcome measures

Outcome measures
Measure	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0) n=172 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was also started.	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2) n=173 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was omitted, and any NRTIs the participant had been taking prior to randomization were to be permanently discontinued.
Change in Plasma HIV-1 Viral Load From Baseline to Week 1	1.3 log10 copies/mL Interval 0.9 to 1.6	1.4 log10 copies/mL Interval 0.9 to 1.6

SECONDARY outcome

Timeframe: At study entry and Weeks 24, 48, 96

Population: Two randomized arms only.

Quality-of-life score at each evaluation based upon a single question assessing participants' self-report of general health with a range of 0 (representing worst health status) to 100 (representing perfect health).

Outcome measures

Outcome measures
Measure	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0) n=181 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was also started.	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2) n=179 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was omitted, and any NRTIs the participant had been taking prior to randomization were to be permanently discontinued.
Change in Summarized Quality of Life Score Change from baseline to week 24 (N=165; N=165)	0 units on a scale Interval -5.0 to 15.0	5 units on a scale Interval 0.0 to 15.0
Change in Summarized Quality of Life Score Change from baseline to week 48 (N=161; N=158)	0 units on a scale Interval -10.0 to 15.0	0 units on a scale Interval -5.0 to 10.0
Change in Summarized Quality of Life Score Change from baseline to week 96 (N=155; N=154)	0 units on a scale Interval -5.0 to 15.0	0.5 units on a scale Interval -3.0 to 19.0

SECONDARY outcome

Timeframe: At Weeks 24 and 48

Population: Persons not starting study treatment, or not receiving assigned study treatment by randomization were excluded from all analyses. If person no longer in study follow-up before beginning of week 24 or 48 evaluation window, additionally excluded as applicable.

Results represent self-report of non-adherence during the 4-day period prior to the outcome evaluation visit. Participants in follow-up for whom these data are missing for any reason are inferred as not-adherent.

Outcome measures

Outcome measures
Measure	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0) n=180 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was also started.	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2) n=177 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was omitted, and any NRTIs the participant had been taking prior to randomization were to be permanently discontinued.
Number of Participants Self-reporting Non-adherence to Assigned Study ARVS (Excluding NRTIs, if Applicable) Week 24 (N=170; N=172)	25 participants	26 participants
Number of Participants Self-reporting Non-adherence to Assigned Study ARVS (Excluding NRTIs, if Applicable) Week 48 (N=167; N=163)	30 participants	26 participants

SECONDARY outcome

Timeframe: At Weeks 24, 48, and 96

Population: Persons not starting treatment (N=1; N=2), who had cardiovascular disease prior to study entry (N=12; N=8), or were missing input values needed to calculate a baseline Framingham score (N= 6; N=4), were excluded.

Cardiovascular risk score defined by Framingham providing an estimate of the probability of developing cardiovascular disease over the next 10-year period. Persons with a historical cardiovascular event (CAD, cerebro- or peripheral- vascular disorder, MI or stroke), were excluded, and scores were not calculated at follow-up times after individuals had a cardiovascular event. Missing values for input data (e.g. smoking status) resulted in a missing value for Framingham score.

Outcome measures

Outcome measures
Measure	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0) n=162 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was also started.	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2) n=165 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was omitted, and any NRTIs the participant had been taking prior to randomization were to be permanently discontinued.
Change in Cardiovascular Risk Score From Baseline Week 24 (N= 150; N=147)	-0.7 units on a scale Standard Deviation 4.4	0.3 units on a scale Standard Deviation 4.9
Change in Cardiovascular Risk Score From Baseline Week 48 (N=143; N=144)	0.1 units on a scale Standard Deviation 4.3	0.8 units on a scale Standard Deviation 4.9
Change in Cardiovascular Risk Score From Baseline Week 96 (N=129; N=132)	0.5 units on a scale Standard Deviation 5.2	1.1 units on a scale Standard Deviation 5.0

SECONDARY outcome

Timeframe: From study entry to Weeks 48 and 96

Population: All subjects in the two randomized arms were assessed.

Baseline CD4 calculated as average of pre-entry and entry values. Closest observed result between 42 and up to 54 weeks (for week 48) or between 90 and up to 110 weeks (for week 96), used if multiple results available. Missing values excluded.

Outcome measures

Outcome measures
Measure	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0) n=181 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was also started.	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2) n=179 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was omitted, and any NRTIs the participant had been taking prior to randomization were to be permanently discontinued.
Change in CD4 Count From Baseline Change from entry to week 48 (N=166; N=163)	105.5 cells/mm^3 Interval 46.0 to 214.0	89.5 cells/mm^3 Interval 33.0 to 166.5
Change in CD4 Count From Baseline Change from entry to week 96 (N= 154; N=157)	140.8 cells/mm^3 Interval 39.0 to 244.5	115.5 cells/mm^3 Interval 31.5 to 229.5

SECONDARY outcome

Timeframe: From treatment initiation to week 96 study visit

Population: Randomized participants were included, and those not starting study treatment were excluded.

Serious Non-AIDS defining Events were adjudicated by independent and blinded review and possible events included serious diagnoses in the following disease areas: liver, cardiovascular, end-stage renal, non-AIDS malignancy, and diabetes mellitus. Week 96 study visit could take place up to 110 weeks following randomization. Event times were the exact weeks following treatment initiation corresponding to the diagnosis dates of the qualifying serious non-AIDS defining events. Censoring times were the weeks following treatment initiation corresponding to the latest study visit.

Outcome measures

Outcome measures
Measure	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0) n=180 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was also started.	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2) n=177 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was omitted, and any NRTIs the participant had been taking prior to randomization were to be permanently discontinued.
Time From Treatment Dispensation to Serious Non-AIDS-defining Events 1st percentile	4.9 weeks Interval 1.9 to 26.0	29.3 weeks Interval 23.1 to 41.3
Time From Treatment Dispensation to Serious Non-AIDS-defining Events 5th percentile	60.0 weeks Interval 13.0 to Not estimable as the upper limit for survival function at all weeks are above 95%.	NA weeks Interval 31.7 to Not estimable as the estimates and upper limit for survival function at all weeks are above 95%.

SECONDARY outcome

Timeframe: From study entry to time of confirmed virological failure (up to 96 weeks)

Population: Only randomized participants with R5-tropic virus at study entry (N=89; N=88), and who experienced confirmed virologic failure (N=27; N=22) during follow-up, and who had a tropism test following failure are included.

HIV Co-receptor tropism test result of either dual/mixed or evidence of X4 using virus from sample collected at confirmed virologic failure.

Outcome measures

Outcome measures
Measure	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0) n=26 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was also started.	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2) n=19 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was omitted, and any NRTIs the participant had been taking prior to randomization were to be permanently discontinued.
Number of Participants With Change in Virus Co-receptor Tropism Among Those With R5-only Tropic Virus at Study Entry	3 participants	2 participants

SECONDARY outcome

Timeframe: From study entry to Weeks 24, 48

Population: All randomized participants who started study treatment. Non-fasting results and missing results excluded from analysis. Therefore, differences reported here represent a complete case analysis.

Fasting non-HDL cholesterol calculated from difference between fasting total cholesterol and fasting HDL level. Missing values and non-fasting values excluded.

Outcome measures

Outcome measures
Measure	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0) n=180 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was also started.	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2) n=177 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was omitted, and any NRTIs the participant had been taking prior to randomization were to be permanently discontinued.
Change in Fasting Non-HDL Cholesterol From Baseline Change from baseline to week 24 (N=131; N=121)	4.1 mg/dL Standard Deviation 35.8	20.8 mg/dL Standard Deviation 39.8
Change in Fasting Non-HDL Cholesterol From Baseline Change from baseline to week 48 (N=125 ; N=117)	7.6 mg/dL Standard Deviation 35.5	19.8 mg/dL Standard Deviation 34.1

SECONDARY outcome

Timeframe: Between baseline and confirmed virologic failure (up to 96 weeks)

Population: Those with confirmed virologic failure (N=54; N=50) among the randomized arms included; and those who were missing resistance information following virologic failure (N=2; N=4) are excluded.

Defined among the subgroup of participants experiencing the outcome of confirmed virologic failure. Newly acquired HIV drug resistance is defined as one or more ARVs with partial resistance or resistance when pre-entry resistance was fully sensitive or resistant when pre-entry resistance was fully sensitive or partially sensitive. The ARVs included for resistance acquisition included the following: darunavir/ritonavir; etravirine, tipranavir, tenofovir, emtracitabine, lamivudine, zidovudine, abacavir.

Outcome measures

Outcome measures
Measure	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0) n=52 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was also started.	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2) n=46 Participants Individualized ARV study regimen with antiretroviral potency defined as continuous phenotype sensitivity score (cPSS) greater than 2.0 recommended and chosen prior to randomization. To this regimen, an individualized NRTI combination of at least 2 drugs from this class, chosen prior to randomization, was omitted, and any NRTIs the participant had been taking prior to randomization were to be permanently discontinued.
Participants With Newly Acquired HIV Drug Resistance Between Study Entry and Confirmed Virologic Failure	18 participants	13 participants

Adverse Events

Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)

Serious events: 58 serious events

Other events: 169 other events

Deaths: 0 deaths

Omit NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)

Serious events: 49 serious events

Other events: 165 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

ACTG Clinicaltrials.gov Coordinator

ACTG Network Coordinating Center, Social & Scientific Systems, Inc.

Phone: (301)628-3313

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER