Optimizing Treatment for Treatment-Experienced, HIV-Infected People

This study has been completed.

Sponsor:

Collaborator:

AIDS Clinical Trials Group

Information provided by (Responsible Party):

National Institute of Allergy and Infectious Diseases (NIAID)

ClinicalTrials.gov Identifier:

NCT00537394

First received: September 27, 2007

Last updated: February 11, 2015

Last verified: February 2015

History of Changes

Results First Received: June 14, 2013

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	HIV Infections
Interventions:	Drug: Enfuvirtide Drug: Raltegravir Drug: Darunavir Drug: Tipranavir Drug: Etravirine Drug: Maraviroc

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups

	Description
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.

Participant Flow for 2 periods

Period 1: First Year of Follow-up

	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
STARTED	181	179	53
COMPLETED	169 ^[1]	168 ^[1]	50
NOT COMPLETED	12	11	3
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 2: 2nd Year of Follow-up

	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
STARTED	169	168	50
COMPLETED	158	159	44
NOT COMPLETED	11	9	6
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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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Everyone randomized (ITT study sample), plus non-randomized group.

Reporting Groups

	Description
Add NRTIs (Randomized) to Individualized Regimen (cPSS > 2.0)	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)	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	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	Total of all reporting groups

Baseline Measures

	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
Number of Participants [units: participants]	181	179	53	413
Age [units: participants]
<=18 years	6	8	3	17
Between 18 and 65 years	173	168	50	391
>=65 years	2	3	0	5
Age [units: years] Mean ± Standard Deviation	44.7 ± 10.8	44.1 ± 11.7	43.1 ± 10.7	44.3 ± 11.2
Gender [units: participants]
Female	46	47	6	99
Male	135	132	47	314
Ethnicity (NIH/OMB) [units: participants]
Hispanic or Latino	37	46	14	97
Not Hispanic or Latino	141	132	38	311
Unknown or Not Reported	3	1	1	5
Race (NIH/OMB) [units: participants]
American Indian or Alaska Native	3	2	1	6
Asian	0	4	1	5
Native Hawaiian or Other Pacific Islander	0	1	0	1
Black or African American	81	72	20	173
White	88	87	29	204
More than one race	1	2	0	3
Unknown or Not Reported	8	11	2	21
Region of Enrollment [units: participants]
United States	181	179	53	413
CD4 count, continuous [units: cells/mm^3] Mean ± Standard Deviation	252.3 ± 194.9	245.6 ± 195.1	154.8 ± 170.1	236.9 ± 194.2
Plasma HIV-1 RNA, continuous [units: log10 copies/mL] Median ( Inter-Quartile Range )	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:

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

Show Outcome Measure 1

2. Secondary:

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

Show Outcome Measure 2

3. Secondary:

Time From Treatment Dispensation to First Study ARV Modification (Excluding NRTIs, if Applicable) [ Time Frame: From treatment dispensation to week 96 study visit ]

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4. Secondary:

Time From Randomization to Discontinuation of Randomized NRTI Component of Study Treatment [ Time Frame: From randomization to week 96 study visit ]

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5. Secondary:

Time From Randomization to Confirmed Virological Failure [ Time Frame: From randomization to week 96 study visit ]

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6. Secondary:

Number of Participants With Plasma HIV-1 Viral Load < 50 Copies/ml [ Time Frame: At Weeks 24, 48, 96 ]

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7. Secondary:

Change in Plasma HIV-1 Viral Load From Baseline to Week 1 [ Time Frame: From baseline to Week 1 evaluation ]

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8. Secondary:

Change in Summarized Quality of Life Score [ Time Frame: At study entry and Weeks 24, 48, 96 ]

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9. Secondary:

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

Show Outcome Measure 9

10. Secondary:

Change in Cardiovascular Risk Score From Baseline [ Time Frame: At Weeks 24, 48, and 96 ]

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11. Secondary:

Change in CD4 Count From Baseline [ Time Frame: From study entry to Weeks 48 and 96 ]

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12. Secondary:

Time From Treatment Dispensation to Serious Non-AIDS-defining Events [ Time Frame: From treatment initiation to week 96 study visit ]

Show Outcome Measure 12

13. Secondary:

Number of Participants With Change in Virus Co-receptor Tropism Among Those With R5-only Tropic Virus at Study Entry [ Time Frame: From study entry to time of confirmed virological failure (up to 96 weeks) ]

Show Outcome Measure 13

14. Secondary:

Change in Fasting Non-HDL Cholesterol From Baseline [ Time Frame: From study entry to Weeks 24, 48 ]

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15. Secondary:

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

Show Outcome Measure 15

Serious Adverse Events

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Other Adverse Events

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Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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
e-mail: 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.

Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00537394 History of Changes
Other Study ID Numbers:	A5241, 10395, ACTG A5241, OPTIONS
Study First Received:	September 27, 2007
Results First Received:	June 14, 2013
Last Updated:	February 11, 2015
Health Authority:	United States: Food and Drug Administration

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