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Clinical Trials
NCT00537394

Optimizing Treatment for Treatment-Experienced, HIV-Infected People

Last Updated: 2021-11-04

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

517 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-01-31

Study Completion Date

2013-04-30

Brief Summary

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The goal of anti-HIV therapy is to prevent HIV from replicating. Long-term control of HIV requires at least two anti-HIV drugs that are active against the virus. Drug resistance is a problem for many treatment-experienced, HIV-infected people. The purpose of this study was to determine the benefit of adding a nucleoside reverse transcriptase inhibitor (NRTI) to a new anti-HIV drug regimen for the suppression of HIV.

Detailed Description

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Two or more fully active antiretrovirals (ARVs) are recommended for successful suppression of HIV. In people infected with resistant HIV virus, finding two drugs that are fully active against HIV can be a challenge. However, the new generation of anti-HIV drugs has been designed to suppress drug-resistant HIV. These drugs include the FDA-approved protease inhibitors (PIs) darunavir and tipranavir, the investigational non-nucleoside transcriptase inhibitor (nNRTI) etravirine, the FDA-approved fusion inhibitor enfuvirtide, the recently FDA-approved CCR5 inhibitor maraviroc, and the investigational integrase inhibitor raltegravir. Also, it is not yet known whether multiple, partially-active drugs have the same rate of success in suppressing HIV. The purpose of this study was to use HIV resistance testing to predict the potency of a suggested ARV regimen using second generation ARVs and determine if the benefits of adding NRTIs to this new drug regimen outweigh the risks of drug toxicity and pill burden. All participants had treatment experience or resistance to NRTIs, nNRTIs, and PIs, and received novel agents.

An active screening period (after enrollment but before randomization or treatment dispensation), occurred for up to 75 days for all participants, and study participation lasted an additional 96 weeks for those who qualified for either randomization or assignment (i.e. not randomized), to the study intervention. During active screening, all participants remained on their current drug regimen. During screening, phenotypic and genotypic HIV resistance tests were performed on participants' blood samples, as well as a coreceptor tropism assay. Using this information and medication history, the study team determined the best new regimen options for each participant. Each clinician, along with the study participant, then chose a new regimen based on the recommendations of the study team and the participant's preference.

Evaluation for study outcomes began when participants started their new regimen as assigned by either randomization or determined assignment. Stratification between Arms A (Add NRTIs) and B (Omit NRTIs) or Arm C (Non-randomized to Add NRTIs) was based on predicted activity of the new regimen. Those assigned to a regimen with higher predicted activity were randomly assigned to Arm A (Add NRTIs) or B (Omit NRTIs); those assigned a regimen predicted to have lower activity were not randomized, but were assigned to Arm C (Add NRTIs).

Participants in Arms A and C were instructed to take their newly assigned study regimen plus at least 2 NRTIs (personalized from expert recommendation and choice by local provider and participant) for 96 weeks. Participants in Arm B were instructed to take their newly assigned study regimen with no NRTIs for 96 weeks. Participants in all arms who met the primary efficacy outcome of regimen failure remained in the study in order to be followed for important secondary outcomes.

All participants were scheduled to have 13 clinical visits, which included blood collection. At some visits, urine collection and quality of life and adherence questionnaires occurred. A neurocognitive assessment was performed for all participants at time of starting the new study regimen. Participants may also have consented to have cerebrospinal fluid collected via lumbar puncture following study treatment assignment and/or at Week 24. Those participants who consented to cerebrospinal fluid collection also had neurocognitive assessments at the times of collections. Participants were responsible for obtaining certain ARVs not provided by the study, including the ARVs they during the active screening period.

The primary and secondary study objectives and comparisons relate to the randomized arms, and therefore, results are not provided for the non-randomized arm (C). The purpose of the non-randomized arm (C) was to include persons higher baseline resistance (and thus, lower activity scores) in order to address an exploratory objective related to the predictive power of these activity scores (and thus a larger range of scores by inclusion of arm C), on certain, virologic outcomes.

Conditions

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HIV Infections

Keywords

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Treatment Experienced

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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A

Regimen with higher predicted activity assigned by the study plus at least 2 NRTIs (personalized choice from expert recommendation) for 96 weeks. A 3-4 drug regimen was selected from the drugs listed to the right.

Group Type EXPERIMENTAL

Enfuvirtide

Intervention Type DRUG

90mg subcutaneously twice daily

Raltegravir

Intervention Type DRUG

400 mg twice daily

Darunavir

Intervention Type DRUG

Two 300-mg tablets twice daily, given with ritonavir 100mg twice daily (ritonavir not provided by the study)

Tipranavir

Intervention Type DRUG

Two 250-mg capsules twice daily, given with ritonavir 100mg twice daily (ritonavir not provided by the study)

Etravirine

Intervention Type DRUG

Two 100-mg tablets twice daily

Maraviroc

Intervention Type DRUG

Dosage dependent on regimen in which maraviroc is included

B

Regimen with higher predicted activity assigned by the study without NRTIs for 96 weeks. A 3-4 drug regimen was selected from the drugs listed to the right.

Group Type EXPERIMENTAL

Enfuvirtide

Intervention Type DRUG

90mg subcutaneously twice daily

Raltegravir

Intervention Type DRUG

400 mg twice daily

Darunavir

Intervention Type DRUG

Two 300-mg tablets twice daily, given with ritonavir 100mg twice daily (ritonavir not provided by the study)

Tipranavir

Intervention Type DRUG

Two 250-mg capsules twice daily, given with ritonavir 100mg twice daily (ritonavir not provided by the study)

Etravirine

Intervention Type DRUG

Two 100-mg tablets twice daily

Maraviroc

Intervention Type DRUG

Dosage dependent on regimen in which maraviroc is included

C

Regimen with lower predicted activity assigned plus at least 2 NRTIs (personalized choice from expert recommendation) for 96 weeks. A 3-4 drug regimen was selected from the drugs listed to the right.

Group Type OTHER

Enfuvirtide

Intervention Type DRUG

90mg subcutaneously twice daily

Raltegravir

Intervention Type DRUG

400 mg twice daily

Darunavir

Intervention Type DRUG

Two 300-mg tablets twice daily, given with ritonavir 100mg twice daily (ritonavir not provided by the study)

Tipranavir

Intervention Type DRUG

Two 250-mg capsules twice daily, given with ritonavir 100mg twice daily (ritonavir not provided by the study)

Etravirine

Intervention Type DRUG

Two 100-mg tablets twice daily

Maraviroc

Intervention Type DRUG

Dosage dependent on regimen in which maraviroc is included

Interventions

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Enfuvirtide

90mg subcutaneously twice daily

Intervention Type DRUG

Raltegravir

400 mg twice daily

Intervention Type DRUG

Darunavir

Two 300-mg tablets twice daily, given with ritonavir 100mg twice daily (ritonavir not provided by the study)

Intervention Type DRUG

Tipranavir

Two 250-mg capsules twice daily, given with ritonavir 100mg twice daily (ritonavir not provided by the study)

Intervention Type DRUG

Etravirine

Two 100-mg tablets twice daily

Intervention Type DRUG

Maraviroc

Dosage dependent on regimen in which maraviroc is included

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* HIV-1 infection
* Triple-class drug experience or resistance. More information on this criterion can be found in the protocol.
* Currently on a failing PI-containing regimen that includes 2 other ARVs with no regimen change for 8 weeks prior to study screening
* HIV viral load of 1000 copies/ml or more
* Hepatitis B surface antigen negative within 90 days of study entry
* Able to obtain NRTIs and ritonavir and have required ARVs at time of starting study intervention
* Willing to use acceptable forms of contraception
* Parent or legal guardian willing to provide consent, if applicable
* CD4 count result from a specimen drawn within 120 days prior to study entry
* If any previous HIV-1 viral co-receptor tropism result is available, then most recent specimen date and the tropism result of that specimen AND specimen date and tropism result of any test with either X4 or D/M result, if different from the first specimen, must be available

* Receipt of successful phenotype/genotype resistance results within 105 days prior to study treatment intervention assignment
* Study team identification of a study regimen and at least 2 NRTIs for participant to take
* Certain abnormal laboratory values. More information on this criterion can be found in the protocol.

Exclusion Criteria

* Chronic, active hepatitis B virus infection (hepatitis B surface antigen positive or HBV DNA positive)
* Taking certain medications. More information on this criterion can be found in the protocol.
* Known allergy/sensitivity to components of two or more of the study-provided drugs or their formulations. For maraviroc, this includes hypersensitivity or history of allergy to soy lecithin or peanuts.
* Active drug or alcohol use that, in the opinion of the investigator, may interfere with the study
* Pregnancy or breastfeeding
* Use of any immunomodulator (interferons, interleukins, systemic corticosteroids, or cyclosporine), vaccine, or investigational therapy within 30 days prior to study treatment allocation/assignment
* Require certain medications prohibited with study treatment
* Serious illness requiring systemic treatment or hospitalization. Participants who complete therapy or are clinically stable on therapy for at least 14 days prior to study treatment allocation are not excluded.

Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Karen T. Tashima, MD

Role: STUDY_CHAIR

Brown University

Richard H. Haubrich, MD

Role: STUDY_CHAIR

Division of Infectious Diseases, UCSD Antiviral Research Center

Locations

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Alabama Therapeutics CRS

Birmingham, Alabama, United States

Site Status

Miller Children's Hosp. Long Beach CA NICHD CRS

Long Beach, California, United States

Site Status

University of Southern California CRS

Los Angeles, California, United States

Site Status

Usc La Nichd Crs

Los Angeles, California, United States

Site Status

UCLA CARE Center CRS

Los Angeles, California, United States

Site Status

UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS

Los Angeles, California, United States

Site Status

Stanford AIDS Clinical Trials Unit CRS

Palo Alto, California, United States

Site Status

UCSD Antiviral Research Center CRS

San Diego, California, United States

Site Status

Ucsf Hiv/Aids Crs

San Francisco, California, United States

Site Status

Univ. of California San Francisco NICHD CRS

San Francisco, California, United States

Site Status

University of Colorado Hospital CRS

Aurora, Colorado, United States

Site Status

Denver Public Health CRS

Denver, Colorado, United States

Site Status

Georgetown University CRS (GU CRS)

Washington D.C., District of Columbia, United States

Site Status

Children's National Med. Ctr. ATN CRS

Washington D.C., District of Columbia, United States

Site Status

Howard Univ. Washington DC NICHD CRS

Washington D.C., District of Columbia, United States

Site Status

Pediatric Perinatal HIV Clinical Trials Unit CRS

Miami, Florida, United States

Site Status

The Ponce de Leon Center CRS

Atlanta, Georgia, United States

Site Status

Northwestern University CRS

Chicago, Illinois, United States

Site Status

Rush University CRS

Chicago, Illinois, United States

Site Status

Tulane Univ. New Orleans NICHD CRS

New Orleans, Louisiana, United States

Site Status

IHV Baltimore Treatment CRS

Baltimore, Maryland, United States

Site Status

Johns Hopkins University CRS

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS

Boston, Massachusetts, United States

Site Status

Bmc Actg Crs

Boston, Massachusetts, United States

Site Status

Boston Medical Center Ped. HIV Program NICHD CRS

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Med. Ctr., ACTG CRS

Boston, Massachusetts, United States

Site Status

Wayne State Univ. CRS

Detroit, Michigan, United States

Site Status

Henry Ford Hosp. CRS

Detroit, Michigan, United States

Site Status

Washington University Therapeutics (WT) CRS

St Louis, Missouri, United States

Site Status

Cooper Univ. Hosp. CRS

Camden, New Jersey, United States

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New Jersey Medical School Clinical Research Center CRS

Newark, New Jersey, United States

Site Status