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Atazanavir/Ritonavir, Once Daily + Raltegravir, Twice Daily, Switch Study in HIV-1-Infected Patients

Phase 4
Completed
Conditions
HIV, Combination Therapy
Interventions
Registration Number
NCT01332227
Lead Sponsor
Bristol-Myers Squibb
Brief Summary

The purpose of this study is to determine whether HIV-1-infected patients, who are virologically suppressed on a regimen of 2 nucleoside reverse transcriptase inhibitors plus any third agent but are experiencing safety and/or tolerability issues, will maintain virologic suppression after switching to a regimen of heat-stable ritonavir boosted atazanavir, 300/100 mg, once daily plus raltegravir, 400 mg, twice daily.

Detailed Description

Allocation: Randomized nonstratified

Intervention model: Parallel versus comparator

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
132
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Atazanavir/Ritonavir + Tenofovir/EmtricitabineRitonavir (heat-stable)Reference Atazanavir + Ritonavir (heat-stable) + Tenofovir/Emtricitabine
Atazanavir/Ritonavir + RaltegravirAtazanavirAtazanavir + Ritonavir (heat-stable) + Raltegravir
Atazanavir/Ritonavir + Tenofovir/EmtricitabineAtazanavirReference Atazanavir + Ritonavir (heat-stable) + Tenofovir/Emtricitabine
Atazanavir/Ritonavir + RaltegravirRitonavir (heat-stable)Atazanavir + Ritonavir (heat-stable) + Raltegravir
Atazanavir/Ritonavir + Tenofovir/EmtricitabineTenofovir/EmtricitabineReference Atazanavir + Ritonavir (heat-stable) + Tenofovir/Emtricitabine
Atazanavir/Ritonavir + RaltegravirRaltegravirAtazanavir + Ritonavir (heat-stable) + Raltegravir
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With HIV-1 RNA Level <40 c/mL at Week 24From Day 1 to Week 24

HIV-1 RNA level was measured with the Abbott m2000rt® polymerase chain reaction assay. Response rates were assessed using an intent-to-treat algorithm, with numerator representing patients meeting the response criteria, and denominator representing all randomized patients. Randomized patients not meeting the criteria for treatment failure (eg, discontinuation of study therapy or virologic rebound at or before Week 24) were considered responders. Virologic rebound was defined as 2 consecutive on-treatment HIV-1 RNA levels ≥40 c/mL or the last on-treatment HIV-1 RNA level ≥40 c/mL followed by discontinuation. Patients who experienced treatment failure or had missing Week 24 HIV-1 RNA levels were considered failures. RNA=ribonucleic acid; HIV=human immunodeficiency virus.

Secondary Outcome Measures
NameTimeMethod
Number of Participants With Genotypable/Phenotypable Isolates, Emergent Genotypic Substitutions in Patients With Genotypable Isolates, and Phenotypic Resistance in Patients With Phenotypable Isolates at Week 24Day 1 to Week 24

Viral genotypic and phenotypic resistance profiles were assessed for virologic rebound (HIV-1 RNA level ≥40 c/mL). Only patients with HIV-1 RNA levels ≥500 c/mL met the criteria for resistance testing. Genotypic substitutions at baseline were summarized for virologic rebound. The genotypic resistance profile presented patients with genotypable isolates, those with protease inhibitor substitutions from genotypable isolates, those with integrase substitutions from genotypable isolates, and those with selected reverse transcriptase substitutions from genotypable isolates using the most current version of the International AIDS Society-USA list and Stanford HIV Drug Resistance Database. Newly emergent genotypic substitutions were summarized analogously for virologic rebound without baseline phenotypic resistance to atazanavir, ritonavir, or raltegravir, using all on-treatment isolates. pts=patients

Number of Patients With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Treatment-emergent Adverse Events (AEs) Leading to Discontinuation, and Treatment-emergent AEsDay 1 to Week 48

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or unknown relationship to study drug.

Mean Changes in Fasting Lipid Levels From Baseline to Week 48From Baseline to Week 48

LD=low-density lipoprotein; HDL=high-density lipoprotein.

Percentage of Participants With HIV-1 RNA Level <40 c/mL at Week 48From Day 1 to Week 48

Percentages of patients with HIV-1 RNA levels \<40 c/mL were summarized at each scheduled visit. Longitudinal plots were created to display proportion versus visit week through Weeks 24 and 48 with error bars representing 95% confidence intervals.

Number of Participants With Virologic Rebound at Weeks 24 and 48Day 1 to Weeks 28 and 48

Viral genotypic and phenotypic resistance profiles were assessed for virologic rebound (HIV-1 RNA level ≥40 c/mL). Only patients with HIV-1 RNA levels ≥500 c/mL met the criteria for resistance testing. Genotypic substitutions at baseline were summarized for virologic rebound. The genotypic resistance profile presented patients with genotypable isolates, those with protease inhibitor substitutions from genotypable isolates, those with integrase substitutions from genotypable isolates, and those with selected reverse transcriptase substitutions from genotypable isolates using the most current version of the International AIDS Society-USA list and Stanford HIV Drug Resistance Database. Newly emergent genotypic substitutions were summarized analogously for virologic rebound without baseline phenotypic resistance to atazanavir, ritonavir, or raltegravir, using all on-treatment isolates.

Number of Participants With Genotypable/Phenotypable Isolates, Emergent Genotypic Substitutions in Patients With Genotypable Isolates, and Phenotypic Resistance in Patients With Phenotypable Isolates at Week 48Day 1 to Week 48

Viral genotypic and phenotypic resistance profiles were assessed for virologic rebound (HIV-1 RNA level ≥40 c/mL). Only patients with HIV-1 RNA levels ≥500 c/mL met the criteria for resistance testing. Genotypic substitutions at baseline were summarized for virologic rebound. The genotypic resistance profile presented patients with genotypable isolates, those with protease inhibitor substitutions from genotypable isolates, those with integrase substitutions from genotypable isolates, and those with selected reverse transcriptase substitutions from genotypable isolates using the most current version of the International AIDS Society-USA list and Stanford HIV Drug Resistance Database. Newly emergent genotypic substitutions were summarized analogously for virologic rebound without baseline phenotypic resistance to atazanavir, ritonavir, or raltegravir, using all on-treatment isolates. pts=patients

Trial Locations

Locations (9)

Health For Life Clinic Pllc

🇺🇸

Little Rock, Arkansas, United States

Eisenhower Medical Center

🇺🇸

Palm Springs, California, United States

Consultive Medicine

🇺🇸

Daytona Beach, Florida, United States

Orange County Health Dept.

🇺🇸

Orlando, Florida, United States

The Research Institute

🇺🇸

Springfield, Massachusetts, United States

Aids Care

🇺🇸

Rochester, New York, United States

Local Institution

🇬🇧

Sheffield, United Kingdom

Metropolis Medical Pc

🇺🇸

San Francisco, California, United States

Triple O Medical Services, P.A.

🇺🇸

West Palm Beach, Florida, United States

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