Phase IIIb Study to Evaluate the Effectiveness and Safety of Atazanavir/Ritonavir as Single Enhanced Protease Inhibitor Therapy in Human Immunodeficiency Virus (HIV)-Infected Subjects Evidencing Virologic Suppression

Phase 3

Completed

Conditions: Human Immunodeficiency Virus (HIV) Infections

Interventions: Drug: Atazanavir + Ritonavir

Registration Number: NCT00337467

Lead Sponsor: Bristol-Myers Squibb

Brief Summary: The main purpose is to explore whether atazanavir/ritonavir (ATV/RTV) single enhanced protease inhibitor therapy can maintain virologic suppression without a marked increase in virologic failure.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 61

Inclusion Criteria

On continued antiretroviral (ARV) treatment, with no discontinuation periods, for the previous 6 months (24 weeks).
Absence of evidence or suspected virologic failure on antiretroviral therapy
Absence of known primary mutations in the protease gene
Only 1 highly active antiretroviral therapy (HAART) prior to current one
HIV RNA < 50 copies/mL in the last 6 months (single blip below 200 c/mL allowed)
On ATV/RTV +2 nucleoside reverse transcriptase inhibitors (NRTIs) (or 1 NRTI + tenofovir [TDF]) for at least 8 weeks before study entry, without treatment-limiting adverse effects

Exclusion Criteria

Presence of a newly diagnosed HIV-related opportunistic infection or any medical condition requiring acute therapy at the time of enrollment.
Active disease condition (e.g. moderate to severe hepatic impairment/active renal disease/history of clinically significant heart conduction disease)
Patients with chronic hepatitis B receiving lamivudine (3TC), Tenofovir Disoproxil Fumarate (TDF) or emtricitabine (FTC).
CD4 < 100 cells/mm3
Grade IV laboratory values: Hemoglobin < 6.5 g/dL or white blood cells (WBC) <800/mmm3 or absolute neutrophil count < 500/mm3, or platelets < 20,000/mm3 or diffuse petechiae.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
A1	Atazanavir + Ritonavir	-

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Treatment Failure Through Week 48	Week 48	Treatment Failure through Week 48 defined as virologic rebound (HIV RNA \>=400 c/mL) on or before Week 48 or study discontinuation before Week 48. Virological rebound is defined as confirmed on-treatment HIV ribonucleic acid (RNA) \>= 400 c/mL at 2 consecutive visits or last on-treatment HIV RNA \>=400 c/mL followed by discontinuation of study therapy.

Secondary Outcome Measures

Name	Time	Method
Cumulative Proportion of Participants Without Treatment Failure Through Week 100	Through Week 100	This Kaplan-Meier life table reports the cumulative proportion of participants without treatment failure up to the end of the respective time interval. Failure time is measured from the start of study therapy, and is based on the earliest event defining failure (virologic rebound at or before Week 96, or discontinuation prior to Week 96).
Proportion of Participants With Virologic Rebound Through Week 96	Through Week 96	Virologic rebound is defined as confirmed on-study HIV RNA ≥ 400 c/mL or last on-study HIV RNA ≥ 400 c/mL followed by treatment discontinuation.
Percentage of Participants With Virological Rebound Through Week 96	Week 96	Virological rebound is defined as confirmed on-treatment HIV RNA \>= 400 c/mL at 2 consecutive visits or last on-treatment HIV RNA \>=400 c/mL followed by discontinuation of study therapy. In addition, virologic rebound defined based on HIV RNA \>=50 c/m, latter analysis performed on subjects with baseline HIV RNA \< 50 c/mL.
Mean Percent Changes From Baseline in Fasting Total Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Non-HDL Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, and Triglycerides at Week 48	Baseline, Week 48	Lipid values after starting lipid-reducing agents are excluded from analyses. Baseline values are provided in Baseline Characteristics.
Number of Participants With Genotype Substitutions for Virologic Rebounds (HIV-RNA ≥ 400 c/mL) Through Week 96	Week 96	International Aids Society of the United States (IAS-USA)-defined major protease inhibitor (PI) substitutions are V32I, L33F, M46I/L, I47V, G48V, I50L/V, I54M/L, I76V, I82A/F/T/S, I84V, N88S, and L90M. Reverse Transcriptase (RT) are TAMS and M184V.
Number of Participants With Genotype Substitutions for Virologic Rebounds (HIV-RNA ≥ 400 c/mL) Through Week 48	Week 48	International Aids Society of the United States (IAS-USA)-defined major protease inhibitor (PI) substitutions are V32I, L33F, M46I/L, I47V, G48V, I50L/V, I54M/L, I76V, I82A/F/T/S, I84V, N88S, and L90M. Reverse Transcriptase (RT) are TAMS and M184V.
Percentage of Participants With Treatment Failure Through Week 96	Week 96	Treatment Failure through Week 96 defined as virologic rebound (HIV RNA \>=400 c/mL) on or before Week 96 or study discontinuation before Week 96. In addition, treatment failure defined based on HIV RNA \>= 50 c/mL, latter analysis performed on treated subjects with baseline HIV RNA \< 50 c/mL.
Mean Change From Baseline in CD4 Cell Count at Week 48	Baseline, Week 48
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs	From Baseline through Week 96	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition that does not necessarily have a causal relationship to treatment. SAE=any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. AE grades are: mild (1), moderate (2), severe (3), life-threatening (4), and death (5).
Percentage of Participants With Virological Rebound Through Week 48	Week 48	Virological rebound is defined as confirmed on-treatment HIV RNA \>= 400 c/mL at 2 consecutive visits or last on-treatment HIV RNA \>=400 c/mL followed by discontinuation of study therapy. In addition, virologic rebound defined based on HIV RNA \>=50 c/m, latter analysis performed on subjects with baseline HIV RNA \< 50 c/mL.
Mean Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 24	Baseline, Week 24
Mean Change From Baseline in CD4 Cell Count at Week 96	Baseline, Week 96
Mean Percent Changes From Baseline in Fasting Total Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Non-HDL Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, and Triglycerides at Week 96	Baseline, Week 96	Lipid values after starting lipid-reducing agents are excluded from analyses. Baseline values are provided in Baseline Characteristics.