Optimizing Treatment for Treatment-Experienced, HIV-Infected People

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	HIV Infections
Interventions	Drug: Enfuvirtide; Drug: Raltegravir; Drug: Darunavir; Drug: Tipranavir; Drug: Etravirine; Drug: Maraviroc
Enrollment	517

Participant Flow

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

Arm/Group Title	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2)	Non-randomized Group: Add NRTIs to Individual Regimen cPSS <=2
Arm/Group Description	[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.	[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 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.
Period Title: First Year of Follow-up
Started	181	179	53
Completed	169 [1]	168 [1]	50
Not Completed	12	11	3
Reason Not Completed
Death	7	0	0
Severe debilitation	1	0	1
Withdrawal by Subject	3	6	1
Lost to Follow-up	1	5	1
[1] Completed refers to completing first 48 weeks of follow-up.
Period Title: 2nd Year of Follow-up
Started	169	168	50
Completed	158	159	44
Not Completed	11	9	6
Reason Not Completed
Death	4	1	2
Withdrawal by Subject	0	1	2
Lost to Follow-up	6	7	2
Clinic site closure	1	0	0

Baseline Characteristics

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Arm/Group Title		Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2)	Non-randomized Group: Add NRTIs to Individual Regimen cPSS <=2	Total
Arm/Group Description		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.	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.	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 of all reporting groups
Overall Number of Baseline Participants		181	179	53	413
Baseline Analysis Population Description		Everyone randomized (ITT study sample), plus non-randomized group.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	181 participants	179 participants	53 participants	413 participants
	<=18 years	6 3.3%	8 4.5%	3 5.7%	17 4.1%
	Between 18 and 65 years	173 95.6%	168 93.9%	50 94.3%	391 94.7%
	>=65 years	2 1.1%	3 1.7%	0 0.0%	5 1.2%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	181 participants	179 participants	53 participants	413 participants
		44.7 (10.8)	44.1 (11.7)	43.1 (10.7)	44.3 (11.2)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	181 participants	179 participants	53 participants	413 participants
	Female	46 25.4%	47 26.3%	6 11.3%	99 24.0%
	Male	135 74.6%	132 73.7%	47 88.7%	314 76.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	181 participants	179 participants	53 participants	413 participants
	Hispanic or Latino	37 20.4%	46 25.7%	14 26.4%	97 23.5%
	Not Hispanic or Latino	141 77.9%	132 73.7%	38 71.7%	311 75.3%
	Unknown or Not Reported	3 1.7%	1 0.6%	1 1.9%	5 1.2%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	181 participants	179 participants	53 participants	413 participants
	American Indian or Alaska Native	3 1.7%	2 1.1%	1 1.9%	6 1.5%
	Asian	0 0.0%	4 2.2%	1 1.9%	5 1.2%
	Native Hawaiian or Other Pacific Islander	0 0.0%	1 0.6%	0 0.0%	1 0.2%
	Black or African American	81 44.8%	72 40.2%	20 37.7%	173 41.9%
	White	88 48.6%	87 48.6%	29 54.7%	204 49.4%
	More than one race	1 0.6%	2 1.1%	0 0.0%	3 0.7%
	Unknown or Not Reported	8 4.4%	11 6.1%	2 3.8%	21 5.1%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	181 participants	179 participants	53 participants	413 participants
		181	179	53	413
CD4 count, continuous; Mean (Standard Deviation); Unit of measure: Cells/mm^3
	Number Analyzed	181 participants	179 participants	53 participants	413 participants
		252.3 (194.9)	245.6 (195.1)	154.8 (170.1)	236.9 (194.2)
Plasma HIV-1 RNA, continuous; Median (Inter-Quartile Range); Unit of measure: Log10 copies/mL
	Number Analyzed	181 participants	179 participants	53 participants	413 participants
		4.2; (3.6 to 4.7)	4.2; (3.6 to 4.6)	4.4; (4.1 to 4.8)	4.2; (3.6 to 4.6)

Outcome Measures

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1. Primary Outcome

Title	Percent of Participants With Regimen Failure, Defined as a Confirmed Virologic Failure or Discontinuation of Randomized NRTI Component of Study Treatment
Description	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.
Time Frame	From study entry to end of Week 48 evaluation window

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2)
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	181	179
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	26.0; (19.6 to 32.3)	29.8; (23.1 to 36.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0), Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2)
	Comments	Null Hypothesis was that omitting NRTIs is inferior to adding NRTIs for the outcome of regimen failure through 48 weeks.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority margin defined as 15 percentage points. If the confidence interval for the difference in regimen failure between omitting versus adding NRTIs was fully below 15 percentage points, then omitting NRTIs would be concluded to be not inferior to adding NRTIs for this outcome.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	3.2
	Confidence Interval	(2-Sided) 95%; -6.1 to 12.5
	Estimation Comments	Endpoint rates with standard errors calculated from Kaplan-Meier curves for each treatment group and stratum. Differences in week 48 failure proportions by treatment calculated weighted by the inverse of the variance in each stratum.

2. Secondary Outcome

Title	Time From Treatment Dispensation to First Grade 3 or Higher (and at Least One Grade Higher Than Baseline) Signs/Symptom or Laboratory Abnormality
Description	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).
Time Frame	From treatment dispensation to week 96 study visit

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2)
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	180	177
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: weeks
5th percentile	3.1; (1.9 to 4.6)	3.9; (0.9 to 4.6)
25th percentile	24.7; (12.0 to 47.0)	25.3; (24.0 to 35.9)
50th percentile	NA [1]; (72.1 to NA)	97.7 [2]; (63.0 to NA)

[1]

Not estimable as the estimate and upper limit for survival function at all weeks is above 50%

[2]

Not estimable as the upper limit for survival function at all weeks is above 50%

3. Secondary Outcome

Title	Time From Treatment Dispensation to First Study ARV Modification (Excluding NRTIs, if Applicable)
Description	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.
Time Frame	From treatment dispensation to week 96 study visit

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2)
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	180	177
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: weeks
5th percentile	9.0; (1.1 to 29.7)	24.0; (4.0 to 35.6)
10th percentile	31.1; (14.7 to 51.1)	38.0; (24.4 to 67.7)
25th percentile	98.0 [1]; (82.7 to NA)	NA [2]; (84.4 to NA)

[1]

Not estimable as the upper limit for survival function at all weeks is above 75%.

[2]

Not estimable as the estimate for survival function at all weeks is above 75%.

4. Secondary Outcome

Title	Time From Randomization to Discontinuation of Randomized NRTI Component of Study Treatment
Description	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.
Time Frame	From randomization to week 96 study visit

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2)
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	181	179
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: weeks
1st percentile	0; (0 to 1)	0; (0 to 12)
5th percentile	36 [1]; (1 to NA)	36; (4 to 36)
10th percentile	NA [2]; (36 to NA)	48; (36 to 84)

[1]

Not estimable as the upper limit for survival function at all weeks is above 95%.

[2]

Not estimable as the estimate for survival function at all weeks is above 90%.

5. Secondary Outcome

Title	Time From Randomization to Confirmed Virological Failure
Description	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.
Time Frame	From randomization to week 96 study visit

Outcome Measure Data

Analysis Population Description

ITT (all randomized participants) included.

Arm/Group Title	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2)
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	181	179
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: weeks
5th percentile	12; (8 to 12)	12; (8 to 12)
10th percentile	12; (12 to 16)	12; (12 to 16)
25th percentile	48 [1]; (24 to NA)	48 [1]; (36 to NA)

[1]

Not estimable as the upper limit for survival function at all weeks is above 75%.

6. Secondary Outcome

Title	Number of Participants With Plasma HIV-1 Viral Load < 50 Copies/ml
Description	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.
Time Frame	At Weeks 24, 48, 96

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2)
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	181	179
Measure Type: Number; Unit of Measure: participants
Week 24: Number with RNA < 50 c/mL (N=170; N=171)	122	117
Week 48: Number with RNA < 50 c/mL (N=169; N=165)	112	106
Week 96: Number with RNA < 50 c/mL (N=158; N=158)	107	109

7. Secondary Outcome

Title	Change in Plasma HIV-1 Viral Load From Baseline to Week 1
Description	Method of Kaplan and Meier used to accommodate left-censoring for those whose week 1 levels < 50 copies/mL.
Time Frame	From baseline to Week 1 evaluation

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2)
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	172	173
Median (Inter-Quartile Range); Unit of Measure: log10 copies/mL
	1.3; (0.9 to 1.6)	1.4; (0.9 to 1.6)

8. Secondary Outcome

Title	Change in Summarized Quality of Life Score
Description	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).
Time Frame	At study entry and Weeks 24, 48, 96

Outcome Measure Data

Analysis Population Description

Two randomized arms only.

Arm/Group Title	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2)
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	181	179
Median (Inter-Quartile Range); Unit of Measure: units on a scale
Change from baseline to week 24 (N=165; N=165)	0; (-5 to 15)	5; (0 to 15)
Change from baseline to week 48 (N=161; N=158)	0; (-10 to 15)	0; (-5 to 10)
Change from baseline to week 96 (N=155; N=154)	0; (-5 to 15)	0.5; (-3 to 19)

9. Secondary Outcome

Title	Number of Participants Self-reporting Non-adherence to Assigned Study ARVS (Excluding NRTIs, if Applicable)
Description	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.
Time Frame	At Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2)
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	180	177
Measure Type: Number; Unit of Measure: participants
Week 24 (N=170; N=172)	25	26
Week 48 (N=167; N=163)	30	26

10. Secondary Outcome

Title	Change in Cardiovascular Risk Score From Baseline
Description	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.
Time Frame	At Weeks 24, 48, and 96

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2)
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	162	165
Mean (Standard Deviation); Unit of Measure: units on a scale
Week 24 (N= 150; N=147)	-0.7 (4.4)	0.3 (4.9)
Week 48 (N=143; N=144)	0.1 (4.3)	0.8 (4.9)
Week 96 (N=129; N=132)	0.5 (5.2)	1.1 (5.0)

11. Secondary Outcome

Title	Change in CD4 Count From Baseline
Description	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.
Time Frame	From study entry to Weeks 48 and 96

Outcome Measure Data

Analysis Population Description

All subjects in the two randomized arms were assessed.

Arm/Group Title	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2)
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	181	179
Median (Inter-Quartile Range); Unit of Measure: cells/mm^3
Change from entry to week 48 (N=166; N=163)	105.5; (46.0 to 214.0)	89.5; (33.0 to 166.5)
Change from entry to week 96 (N= 154; N=157)	140.8; (39.0 to 244.5)	115.5; (31.5 to 229.5)

12. Secondary Outcome

Title	Time From Treatment Dispensation to Serious Non-AIDS-defining Events
Description	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.
Time Frame	From treatment initiation to week 96 study visit

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2)
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	180	177
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: weeks
1st percentile	4.9; (1.9 to 26.0)	29.3; (23.1 to 41.3)
5th percentile	60.0 [1]; (13.0 to NA)	NA [2]; (31.7 to NA)

[1]

Not estimable as the upper limit for survival function at all weeks are above 95%.

[2]

Not estimable as the estimates and upper limit for survival function at all weeks are above 95%.

13. Secondary Outcome

Title	Number of Participants With Change in Virus Co-receptor Tropism Among Those With R5-only Tropic Virus at Study Entry
Description	HIV Co-receptor tropism test result of either dual/mixed or evidence of X4 using virus from sample collected at confirmed virologic failure.
Time Frame	From study entry to time of confirmed virological failure (up to 96 weeks)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2)
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	26	19
Measure Type: Number; Unit of Measure: participants
	3	2

14. Secondary Outcome

Title	Change in Fasting Non-HDL Cholesterol From Baseline
Description	Fasting non-HDL cholesterol calculated from difference between fasting total cholesterol and fasting HDL level. Missing values and non-fasting values excluded.
Time Frame	From study entry to Weeks 24, 48

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2)
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	180	177
Mean (Standard Deviation); Unit of Measure: mg/dL
Change from baseline to week 24 (N=131; N=121)	4.1 (35.8)	20.8 (39.8)
Change from baseline to week 48 (N=125 ; N=117)	7.6 (35.5)	19.8 (34.1)

15. Secondary Outcome

Title	Participants With Newly Acquired HIV Drug Resistance Between Study Entry and Confirmed Virologic Failure
Description	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.
Time Frame	Between baseline and confirmed virologic failure (up to 96 weeks)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	Omit NRTIs (Randomized) From Individualized Regimen(cPSS > 2)
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	52	46
Measure Type: Number; Unit of Measure: participants
	18	13

Adverse Events

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Time Frame	AE data collected between date of first dose of study Rx, and end of week 96 study visit window (up to 110 weeks post entry), which may include follow-up/events after PCD . Those who never started study Rx are excluded from AE evaluation and analysis.
Adverse Event Reporting Description	Randomized arms only. All SAEs (per ICH, regardless of relationship to treatment), all cancers, MIs and hepatic failures; grade>2 signs/symptoms per ACTG criteria; all AST, ALT, creatinine, creatinine clearance, urinalysis, fasting lipid & glucose, and other Grade>2 labs, and all S/Sx or labs that lead to a change in study treatment were requested.
Arm/Group Title	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	Omit NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)
Arm/Group Description	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.	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.
All-Cause Mortality
	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	Omit NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	Omit NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	58/180 (32.22%)	49/177 (27.68%)
Blood and lymphatic system disorders
Anaemia † 1	2/180 (1.11%)	0/177 (0.00%)
Febrile neutropenia † 1	0/180 (0.00%)	1/177 (0.56%)
Neutropenia † 1	1/180 (0.56%)	2/177 (1.13%)
Pancytopenia † 1	1/180 (0.56%)	0/177 (0.00%)
Thrombocytopenia † 1	1/180 (0.56%)	1/177 (0.56%)
Thrombocytosis † 1	0/180 (0.00%)	1/177 (0.56%)
Cardiac disorders
Angina pectoris † 1	0/180 (0.00%)	1/177 (0.56%)
Angina unstable † 1	0/180 (0.00%)	1/177 (0.56%)
Cardiac arrest † 1	1/180 (0.56%)	0/177 (0.00%)
Cardiac failure † 1	1/180 (0.56%)	0/177 (0.00%)
Myocardial infarction † 1	1/180 (0.56%)	2/177 (1.13%)
Endocrine disorders
Hyperthyroidism † 1	1/180 (0.56%)	0/177 (0.00%)
Inappropriate antidiuretic hormone secretion † 1	0/180 (0.00%)	1/177 (0.56%)
Gastrointestinal disorders
Abdominal pain † 1	2/180 (1.11%)	0/177 (0.00%)
Ascites † 1	1/180 (0.56%)	0/177 (0.00%)
Diarrhoea † 1	3/180 (1.67%)	0/177 (0.00%)
Dysphagia † 1	1/180 (0.56%)	0/177 (0.00%)
Intestinal fistula † 1	0/180 (0.00%)	1/177 (0.56%)
Intra-abdominal haemorrhage † 1	1/180 (0.56%)	0/177 (0.00%)
Nausea † 1	1/180 (0.56%)	0/177 (0.00%)
Pancreatitis † 1	1/180 (0.56%)	0/177 (0.00%)
Small intestinal obstruction † 1	1/180 (0.56%)	0/177 (0.00%)
Vomiting † 1	0/180 (0.00%)	1/177 (0.56%)
General disorders
Chest pain † 1	6/180 (3.33%)	6/177 (3.39%)
Death † 1	0/180 (0.00%)	1/177 (0.56%)
Device dislocation † 1	1/180 (0.56%)	0/177 (0.00%)
Pyrexia † 1	0/180 (0.00%)	2/177 (1.13%)
Hepatobiliary disorders
Hepatic failure † 1	1/180 (0.56%)	0/177 (0.00%)
Hepatotoxicity † 1	1/180 (0.56%)	0/177 (0.00%)
Immune system disorders
Autoimmune disorder † 1	1/180 (0.56%)	0/177 (0.00%)
Hypersensitivity † 1	0/180 (0.00%)	2/177 (1.13%)
Immune reconstitution inflammatory syndrome † 1	1/180 (0.56%)	0/177 (0.00%)
Infections and infestations
AIDS dementia complex † 1	1/180 (0.56%)	0/177 (0.00%)
Abdominal wall infection † 1	0/180 (0.00%)	1/177 (0.56%)
Abscess of salivary gland † 1	0/180 (0.00%)	1/177 (0.56%)
Acute hepatitis B † 1	0/180 (0.00%)	1/177 (0.56%)
Arthritis bacterial † 1	1/180 (0.56%)	0/177 (0.00%)
Bronchitis † 1	0/180 (0.00%)	1/177 (0.56%)
Bronchopneumonia † 1	1/180 (0.56%)	0/177 (0.00%)
Cellulitis † 1	0/180 (0.00%)	4/177 (2.26%)
Diverticulitis † 1	0/180 (0.00%)	1/177 (0.56%)
Endometritis † 1	1/180 (0.56%)	0/177 (0.00%)
Gastroenteritis † 1	1/180 (0.56%)	3/177 (1.69%)
Gastroenteritis viral † 1	0/180 (0.00%)	1/177 (0.56%)
Genital herpes † 1	1/180 (0.56%)	0/177 (0.00%)
HIV wasting syndrome † 1	1/180 (0.56%)	0/177 (0.00%)
Herpes oesophagitis † 1	1/180 (0.56%)	0/177 (0.00%)
Herpes zoster † 1	0/180 (0.00%)	2/177 (1.13%)
Influenza † 1	0/180 (0.00%)	1/177 (0.56%)
Laryngitis † 1	1/180 (0.56%)	0/177 (0.00%)
Liver abscess † 1	0/180 (0.00%)	1/177 (0.56%)
Lobar pneumonia † 1	1/180 (0.56%)	1/177 (0.56%)
Meningitis listeria † 1	1/180 (0.56%)	0/177 (0.00%)
Mycobacterium avium complex infection † 1	0/180 (0.00%)	1/177 (0.56%)
Parvovirus infection † 1	1/180 (0.56%)	0/177 (0.00%)
Pneumocystis jirovecii pneumonia † 1	0/180 (0.00%)	1/177 (0.56%)
Pneumonia † 1	7/180 (3.89%)	6/177 (3.39%)
Pneumonia bacterial † 1	2/180 (1.11%)	2/177 (1.13%)
Pneumonia viral † 1	1/180 (0.56%)	0/177 (0.00%)
Post procedural infection † 1	1/180 (0.56%)	0/177 (0.00%)
Postoperative wound infection † 1	0/180 (0.00%)	1/177 (0.56%)
Progressive multifocal leukoencephalopathy † 1	1/180 (0.56%)	0/177 (0.00%)
Sepsis † 1	0/180 (0.00%)	3/177 (1.69%)
Urinary tract infection † 1	0/180 (0.00%)	1/177 (0.56%)
Urosepsis † 1	1/180 (0.56%)	0/177 (0.00%)
Viral infection † 1	0/180 (0.00%)	1/177 (0.56%)
Viral upper respiratory tract infection † 1	1/180 (0.56%)	0/177 (0.00%)
Injury, poisoning and procedural complications
Ankle fracture † 1	2/180 (1.11%)	1/177 (0.56%)
Gun shot wound † 1	0/180 (0.00%)	1/177 (0.56%)
Joint dislocation † 1	1/180 (0.56%)	0/177 (0.00%)
Lower limb fracture † 1	0/180 (0.00%)	1/177 (0.56%)
Multiple fractures † 1	0/180 (0.00%)	1/177 (0.56%)
Overdose † 1	1/180 (0.56%)	0/177 (0.00%)
Post procedural haematoma † 1	1/180 (0.56%)	0/177 (0.00%)
Investigations
Hepatic enzyme increased † 1	0/180 (0.00%)	1/177 (0.56%)
Transaminases increased † 1	0/180 (0.00%)	1/177 (0.56%)
Metabolism and nutrition disorders
Dehydration † 1	0/180 (0.00%)	1/177 (0.56%)
Gout † 1	1/180 (0.56%)	0/177 (0.00%)
Hyperglycaemia † 1	0/180 (0.00%)	1/177 (0.56%)
Hypokalaemia † 1	0/180 (0.00%)	1/177 (0.56%)
Hyponatraemia † 1	1/180 (0.56%)	0/177 (0.00%)
Musculoskeletal and connective tissue disorders
Muscular weakness † 1	1/180 (0.56%)	0/177 (0.00%)
Osteonecrosis † 1	0/180 (0.00%)	1/177 (0.56%)
Pain in extremity † 1	1/180 (0.56%)	0/177 (0.00%)
Rhabdomyolysis † 1	1/180 (0.56%)	0/177 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenosquamous cell lung cancer † 1	1/180 (0.56%)	0/177 (0.00%)
Basal cell carcinoma † 1	1/180 (0.56%)	1/177 (0.56%)
Breast cancer † 1	1/180 (0.56%)	0/177 (0.00%)
Colon cancer metastatic † 1	1/180 (0.56%)	0/177 (0.00%)
Diffuse large B-cell lymphoma † 1	1/180 (0.56%)	0/177 (0.00%)
Hodgkin's disease † 1	1/180 (0.56%)	0/177 (0.00%)
Meningioma † 1	1/180 (0.56%)	0/177 (0.00%)
Plasmacytoma † 1	1/180 (0.56%)	0/177 (0.00%)
Squamous cell carcinoma † 1	1/180 (0.56%)	1/177 (0.56%)
Nervous system disorders
Cerebrovascular accident † 1	0/180 (0.00%)	2/177 (1.13%)
Convulsion † 1	1/180 (0.56%)	0/177 (0.00%)
Headache † 1	1/180 (0.56%)	0/177 (0.00%)
Neurological symptom † 1	0/180 (0.00%)	1/177 (0.56%)
Radiculopathy † 1	0/180 (0.00%)	1/177 (0.56%)
Syncope † 1	1/180 (0.56%)	1/177 (0.56%)
VIIth nerve paralysis † 1	1/180 (0.56%)	1/177 (0.56%)
Psychiatric disorders
Bipolar I disorder † 1	0/180 (0.00%)	1/177 (0.56%)
Mental status changes † 1	0/180 (0.00%)	1/177 (0.56%)
Mood altered † 1	0/180 (0.00%)	1/177 (0.56%)
Substance abuse † 1	0/180 (0.00%)	1/177 (0.56%)
Suicidal ideation † 1	1/180 (0.56%)	2/177 (1.13%)
Suicide attempt † 1	1/180 (0.56%)	2/177 (1.13%)
Renal and urinary disorders
Nephrolithiasis † 1	1/180 (0.56%)	0/177 (0.00%)
Renal failure † 1	1/180 (0.56%)	0/177 (0.00%)
Renal failure acute † 1	1/180 (0.56%)	1/177 (0.56%)
Urinary incontinence † 1	0/180 (0.00%)	1/177 (0.56%)
Reproductive system and breast disorders
Ovarian cyst † 1	0/180 (0.00%)	1/177 (0.56%)
Testicular torsion † 1	0/180 (0.00%)	1/177 (0.56%)
Respiratory, thoracic and mediastinal disorders
Asthma † 1	1/180 (0.56%)	0/177 (0.00%)
Cough † 1	1/180 (0.56%)	0/177 (0.00%)
Epistaxis † 1	0/180 (0.00%)	1/177 (0.56%)
Hiccups † 1	0/180 (0.00%)	1/177 (0.56%)
Pneumonia aspiration † 1	1/180 (0.56%)	0/177 (0.00%)
Skin and subcutaneous tissue disorders
Rash † 1	1/180 (0.56%)	0/177 (0.00%)
Social circumstances
Physical assault † 1	0/180 (0.00%)	1/177 (0.56%)
Surgical and medical procedures
Bartholin's cyst removal † 1	0/180 (0.00%)	1/177 (0.56%)
Colostomy † 1	0/180 (0.00%)	1/177 (0.56%)
Finger amputation † 1	1/180 (0.56%)	0/177 (0.00%)
Inguinal hernia repair † 1	1/180 (0.56%)	0/177 (0.00%)
Intervertebral disc operation † 1	0/180 (0.00%)	1/177 (0.56%)
Vascular disorders
Peripheral arterial occlusive disease † 1	0/180 (0.00%)	1/177 (0.56%)
Venous thrombosis † 1	1/180 (0.56%)	0/177 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 17.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	Omit NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	169/180 (93.89%)	165/177 (93.22%)
Gastrointestinal disorders
Diarrhoea † 1	8/180 (4.44%)	9/177 (5.08%)
Nausea † 1	12/180 (6.67%)	6/177 (3.39%)
General disorders
Fatigue † 1	9/180 (5.00%)	8/177 (4.52%)
Pyrexia † 1	7/180 (3.89%)	11/177 (6.21%)
Infections and infestations
Bronchitis † 1	12/180 (6.67%)	12/177 (6.78%)
Herpes simplex † 1	6/180 (3.33%)	9/177 (5.08%)
Herpes zoster † 1	5/180 (2.78%)	10/177 (5.65%)
Oral candidiasis † 1	10/180 (5.56%)	6/177 (3.39%)
Pneumonia bacterial † 1	12/180 (6.67%)	11/177 (6.21%)
Upper respiratory tract infection † 1	16/180 (8.89%)	14/177 (7.91%)
Urinary tract infection † 1	4/180 (2.22%)	9/177 (5.08%)
Investigations
Alanine aminotransferase increased † 1	38/180 (21.11%)	41/177 (23.16%)
Aspartate aminotransferase increased † 1	50/180 (27.78%)	47/177 (26.55%)
Blood alkaline phosphatase increased † 1	11/180 (6.11%)	4/177 (2.26%)
Blood bilirubin increased † 1	9/180 (5.00%)	6/177 (3.39%)
Blood cholesterol † 1	8/180 (4.44%)	11/177 (6.21%)
Blood cholesterol abnormal † 1	70/180 (38.89%)	82/177 (46.33%)
Blood cholesterol increased † 1	11/180 (6.11%)	22/177 (12.43%)
Blood creatinine increased † 1	26/180 (14.44%)	30/177 (16.95%)
Blood glucose abnormal † 1	54/180 (30.00%)	62/177 (35.03%)
Blood glucose decreased † 1	19/180 (10.56%)	15/177 (8.47%)
Blood glucose increased † 1	30/180 (16.67%)	37/177 (20.90%)
Blood potassium decreased † 1	3/180 (1.67%)	9/177 (5.08%)
Blood triglycerides † 1	12/180 (6.67%)	12/177 (6.78%)
Low density lipoprotein † 1	17/180 (9.44%)	22/177 (12.43%)
Low density lipoprotein abnormal † 1	48/180 (26.67%)	47/177 (26.55%)
Low density lipoprotein increased † 1	9/180 (5.00%)	13/177 (7.34%)
Neutrophil count decreased † 1	21/180 (11.67%)	9/177 (5.08%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	10/180 (5.56%)	6/177 (3.39%)
Nervous system disorders
Headache † 1	14/180 (7.78%)	13/177 (7.34%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	12/180 (6.67%)	3/177 (1.69%)
Vascular disorders
Hypertension † 1	6/180 (3.33%)	10/177 (5.65%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 17.0

Limitations and Caveats

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[Not Specified]

More Information

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

Name/Title: ACTG Clinicaltrials.gov Coordinator

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

Phone: (301)628-3313

EMail: ACTGCT.Gov@s-3.com

Publications:

Altmann A, Beerenwinkel N, Sing T, Savenkov I, Doumer M, Kaiser R, Rhee SY, Fessel WJ, Shafer RW, Lengauer T. Improved prediction of response to antiretroviral combination therapy using the genetic barrier to drug resistance. Antivir Ther. 2007;12(2):169-78.

Eshleman SH, Husnik M, Hudelson S, Donnell D, Huang Y, Huang W, Hart S, Jackson B, Coates T, Chesney M, Koblin B. Antiretroviral drug resistance, HIV-1 tropism, and HIV-1 subtype among men who have sex with men with recent HIV-1 infection. AIDS. 2007 May 31;21(9):1165-74.

Geretti AM. Clinical implications of HIV drug resistance to nucleoside and nucleotide reverse transcriptase inhibitors. AIDS Rev. 2006 Oct-Dec;8(4):210-20. Review.

Mallolas J, Blanco J, Labarga P, Vergara A, Ocampo A, Sarasa M, Arnedo M, López-Púa Y, García J, Juega J, Guelar A, Terrón A, Dalmau D, García I, Zárraga M, Martínez E, Carné X, Pumarola T, Escayola R, Gatell J. Inhibitory quotient as a prognostic factor of response to a salvage antiretroviral therapy containing ritonavir-boosted saquinavir. The CIVSA Study. HIV Med. 2007 May;8(4):226-33.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Tashima KT, Smeaton LM, Fichtenbaum CJ, Andrade A, Eron JJ, Gandhi RT, Johnson VA, Klingman KL, Ritz J, Hodder S, Santana JL, Wilkin T, Haubrich RH; A5241 Study Team. HIV Salvage Therapy Does Not Require Nucleoside Reverse Transcriptase Inhibitors: A Randomized, Controlled Trial. Ann Intern Med. 2015 Dec 15;163(12):908-17. doi: 10.7326/M15-0949. Epub 2015 Nov 24.

Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00537394 History of Changes
Other Study ID Numbers:	A5241; 10395 ( Registry Identifier: DAIDS ES ); ACTG A5241; OPTIONS
First Submitted:	September 27, 2007
First Posted:	October 1, 2007
Results First Submitted:	June 14, 2013
Results First Posted:	August 7, 2014
Last Update Posted:	May 26, 2016