Induction/Simplification With Atazanavir + Ritonavir + Abacavir/Lamivudine Fixed-Dose Combination In HIV-1 Infection

Phase 3

Completed

Conditions: Infection, Human Immunodeficiency Virus I
HIV Infection

Interventions: Drug: Abacavir (ABC)/lamivudine (3TC) + atazanavir (ATV)
Drug: Abacavir (ABC)/lamivudine (3TC) + atazanavir (ATV) + ritonavir (/r)

Registration Number: NCT00440947

Lead Sponsor: ViiV Healthcare

Brief Summary: This study was designed to test the efficacy, safety, tolerability and durability of the antiviral response between atazanavir (ATV) + ritonavir (/r) + abacavir/lamivudine(ABC/3TC) Fixed dose combination (FDC) each administered once daily (QD) for 36 weeks followed by randomization to either a simplification regimen of ATV or continuation of ATV +/r for an additional 48 weeks, each in combination with ABC/3TC in antiretroviral (ART)-naive, HIV-1 infected, HLA-B\*5701 negative subjects.

All subjects who complete the 84-week study will be eligible to enter the treatment extension phase and continue for an additional 60 weeks. The purpose of this extension is to obtain longer term treatment data in subjects who have completed the 84-week study.

Detailed Description: Safety and Efficacy of an Initial Regimen of Atazanavir (ATV) + Ritonavir (/r) + the Abacavir/Lamivudine Fixed-Dose Combination Tablet (ABC/3TC FDC) for 36 weeks followed by Simplification to Atazanavir with ABC/3TC FDC or Maintenance of the Initial Regimen for an Additional 48 weeks in Antiretroviral-Naive HIV-1 Infected HLA-B\*5701 Negative Subjects followed by an Optional 60-Week Treatment Extension Phase

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 515

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Simplification	Abacavir (ABC)/lamivudine (3TC) + atazanavir (ATV)	Atazanavir (ATV) 400 mg QD + abacavir (ABC) 600 mg/lamivudine (3TC) 300 mg fixed dose combination (FDC) QD for 48 weeks followed by optional treatment extension for 60 weeks on the same regimen.
Continuation	Abacavir (ABC)/lamivudine (3TC) + atazanavir (ATV) + ritonavir (/r)	Atazanavir (ATV) 300 mg QD + ritonavir (/r) 100 mg QD + abacavir (ABC) 600mg/lamivuidine (3TC )300 mg FDC QD for 48 weeks followed by optional treatment extension for 60 weeks on the same regimen.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <50 Copies (c) /Milliliter (ml) at the Week 84 Visit	Week 84	The percentage of PAR with HIV-1 RNA virus \<50 c/ml determined from a blood sample drawn at Week 84 was tabulated by treatment arm with stratification by baseline HIV-1 RNA (\<100,000 c/ml and \>=100,000 c/ml). Per TLOVR algorithm, responders were PAR with confirmed viral load \<50 c/ml who had not met any non-responder criterion. Non-responders were PAR who never achieved confirmed HIV RNA \<50 c/ml, prematurely discontinued study or study medication for any reason, had confirmed rebound to at least 50 c/ml, or had an unconfirmed HIV RNA of at least 50 c/ml at last visit.

Secondary Outcome Measures

Name	Time	Method
Mean Age at Baseline of Participants Randomized to Treatment for the 48-Week Randomized Phase	Baseline of Randomized Phase	The mean age of participants randomized to treatment in the Randomized Phase was calculated at Baseline.
Percentage of Participants Who Achieved Plasma HIV-1 RNA <50 c/ml at the Week 36 Visit	Week 36	The percentage of PAR with HIV-1 RNA virus \<50 c/ml from a Week 36 blood sample was tabulated. Per TLOVR algorithm, responders were PAR with confirmed viral load \<50 c/ml who had not met any non-responder criterion. Non-responders were PAR who never achieved confirmed HIV RNA \<50 c/ml, prematurely discontinued (DC) study or study medication (any reason), had confirmed rebound to \>=50 c/ml, or had an unconfirmed HIV RNA \>=50 c/ml at last visit. ITT-E observed analysis (Obs): all observed data. ITT-E M/D=F analysis: PAR with missing data/data collected after study medication DC were failures.
Percentage of Participants Who Achieved Plasma HIV-1 RNA <50 c/ml at the Week 84 Visit	Week 84	A blood sample was drawn to determine the amount of HIV-1 RNA virus in c/ml at Week 84. The percentage of participants with HIV-1 RNA \<50 c/ml at Week 84 was tabulated. The secondary analysis methods were: Observed (Obs; uses all visits with data in the analysis period), and missing/discontinuation=failure (M/D=F) analyses. M/D=F: participants with missing data or data collected after study medication DC were considered failures.
Percentage of Participants Who Achieved Plasma HIV-1 RNA <50 c/ml at the Week 144 Visit	Week 144	Percentage of PAR with HIV-1 RNA \<50 c/ml at Week 144 was tabulated; stratified by baseline HIV-1 RNA (\<100,000 and \>=100,000 c/ml). Per TLOVR algorithm, responders were PAR with confirmed (CF) HIV RNA \<50 c/ml who had not met any non-responder (NR) criterion. NR were PAR who never achieved CF HIV RNA \<50 c/ml, prematurely discontinued (DC) study or study medication (Med), had CF rebound to \>=50 c/ml, or had an unconfirmed HIV RNA \>=50 c/ml at last visit. Observed analysis (Obs): all observed data. M/D=F analysis: PAR with missing data/data collected after study Med DC were failures.
Percentage of Participants Who Achieved Plasma HIV-1 RNA <400 c/ml at the Week 36 Visit	Week 36	The percentage of PAR with HIV-1 RNA virus \<400 c/ml from a Week 36 blood sample was tabulated. Per TLOVR algorithm, responders were PAR with confirmed (CF) HIV RNA \<400 c/ml who had not met any non-responder criterion. Non-responders were PAR who never achieved CF HIV RNA \<400 c/ml, prematurely discontinued (DC) study or study medication (Med; any reason), had CF rebound to \>=400 c/ml, or had an unconfirmed HIV RNA \>=400 c/ml at last visit. ITT-E observed analysis (Obs): all observed data. ITT-E M/D=F analysis: PAR with missing data/data collected after study Med DC were failures.
Percentage of Participants Who Achieved HIV-1 RNA <400 c/ml at the Week 84 Visit	Week 84	Percentage of PAR with HIV-1 RNA \<400 c/ml at Week 84 was tabulated; stratified by baseline HIV-1 RNA (\<100,000 and \>=100,000 c/ml). Per TLOVR algorithm, responders were PAR with confirmed (CF) HIV-RNA \<400 c/ml who had not met any non-responder (NR) criterion. NR were PAR who never achieved CF HIV RNA \<400 c/ml, prematurely discontinued (DC) study or study medication (Med), had CF rebound to \>=400 c/ml, or had an unconfirmed HIV RNA \>=400 c/ml at last visit. Observed analysis (Obs): all observed data. M/D=F analysis: PAR with missing data/data collected after study Med DC were failures.
Percentage of Participants Who Achieved HIV-1 RNA <400 c/ml at the Week 144 Visit	Week 144	Percentage of PAR with HIV-1 RNA \<400 c/ml at Week 144 was tabulated; stratified by baseline HIV-1 RNA (\<100,000 and \>=100,000 c/ml). Per TLOVR algorithm, responders were PAR with confirmed (CF) HIV-RNA \<400 c/ml who had not met any non-responder (NR) criterion. NR were PAR who never achieved CF HIV RNA \<400 c/ml, prematurely discontinued (DC) study or study medication (Med), had CF rebound to \>=400 c/ml, or had an unconfirmed HIV RNA \>=400 c/ml at last visit. Observed analysis (Obs): all observed data. M/D=F analysis: PAR with missing data/data collected after study Med DC were failures.
Number of Participants Who Met the Protocol-defined Virologic Failure (PDVF) Criteria at Week 36	Week 36	The number of participants that failed to respond to therapy through 36 weeks on treatment, based on the protocol definition of virologic failure (PDVF), was tabulated. PDVF was defined as (a) failure to achieve plasma HIV-1 RNA \<400 c/ml by Week 30 or (b) confirmed HIV-1 RNA rebound \>=400 c/ml after achieving HIV-1 \<400 c/ml.
Number of Participants Who Met the PDVF Criteria at Week 84	Week 84	The number of participants that failed to respond to therapy from the time of treatment randomization through Week 84, based on the protocol definition of virologic failure (PDVF), was tabulated. PDVF was defined as (a) failure to achieve plasma HIV-1 RNA \<400 c/ml by Week 30 or (b) confirmed HIV-1 RNA rebound \>=400 c/ml after achieving HIV-1 \<400 c/ml.
Number of Participants Who Met the PDVF Criteria at Week 144	Week 144	The number of participants enrolled in the extension phase that failed to respond to therapy from Week 84 through Week 144, based on the protocol definition of virologic failure (PDVF) was tabulated,. PDVF was defined as (a) failure to achieve plasma HIV-1 RNA \<400 c/ml by Week 30 or (b) confirmed HIV-1 RNA rebound \>=400 c/ml after achieving HIV-1 \<400 c/ml.
Change From Baseline in HIV-1 RNA at Week 36	Baseline and Week 36	Change from baseline was calculated as the Week 36 value minus the baseline value. Blood was drawn to analyze for plasma HIV viral load.
Change From Baseline in HIV-1 RNA at Week 84	Baseline and Week 84	Change from baseline was calculated as the Week 84 value minus the baseline value. Blood was drawn to analyze for plasma HIV viral load.
Change From Baseline in HIV-1 RNA at Week 144	Baseline and Week 144	Change from baseline was calculated as the Week 144 value minus the baseline value. Blood was drawn to analyze for plasma HIV viral load.
Change From Baseline in CD4+ Cell Count at Week 36	Baseline and Week 36	Blood was drawn to analyze for CD4+ cell count. A CD4+ cell is a T lymphocyte that carries the CD4 antigen. Immunologic response was assessed by CD4+ counts. Change from baseline was calculated as the Week 36 value minus the baseline value.
Change From Baseline in CD4+ Cell Count at Week 84	Baseline and Week 84	A CD4+ cell is a T lymphocyte that carries the CD4 antigen. Immunologic response was assessed by CD4+ counts. Change from baseline was calculated as the Week 84 value minus the baseline value. Blood was drawn to analyze for CD4+ cell count.
Change From Baseline in CD4+ Cell Count at Week 144	Baseline and Week 144	A CD4+ cell is a T lymphocyte that carries the CD4 antigen. Immunologic response was assessed by CD4+ counts. Change from baseline was calculated as the Week 144 value minus the baseline value. Blood was drawn to analyze for CD4+ cell count.
Number of Confirmed Virologic Failure Participants With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Baseline Through Week 36	Baseline through Week 36	A blood sample was drawn for participants failing to respond to therapy, and the mutations present in the virus were identified. For each participant, the mutations found at the time of failure were compared with any mutations found in the blood sample at baseline. New resistance-associated mutations (defined by the International AIDS Society-USA guidelines) that developed at the time of failure were tabulated by drug class. PAR, participants; VF, virologic failure; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.
Number of Confirmed Virologic Failure Participants With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Randomization at Week 36 Through Week 84	Randomization at Week 36 through Week 84	A blood sample was drawn for participants failing to respond to therapy, and the mutations present in the virus were identified. For each participant, the mutations found at the time of failure were compared with any mutations found in the blood sample at baseline. New International AIDs Society-USA defined resistance mutations that developed at the time of failure were tabulated by drug class. VF, virologic failure; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.
Number of Confirmed Virologic Failure Participants With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Week 84 Through Week 144	Week 84 through Week 144	A blood sample was drawn for participants failing to respond to therapy, and the mutations present in the virus were identified. For each participant, the mutations found at the time of failure were compared with any mutations found in the blood sample at baseline. New International AIDs Society-USA defined resistance mutations that developed at the time of failure were tabulated by drug class. VF, virologic failure; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.
Number of Confirmed Virologic Failure Participants From Baseline Through Week 36 With Treatment-emergent Reductions in Susceptibility to Abacavir, Lamivudine, Atazanavir, or Ritonavir	Baseline through Week 36	A blood sample was drawn for participants failing to respond to therapy, and changes in drug susceptibility for HIV isolated from the participants for each drug used in the study were assessed. For each participant, the changes in drug susceptibility detected by phenotypic assay in virus from the sample collected at the time of failure was compared with drug susceptibility in the virus from the blood sample at baseline. PAR, participant.
Number of Confirmed Virologic Failure Participants From Randomization at Week 36 Through Week 84 With Treatment-emergent Reductions in HIV Susceptibility to Abacavir, Lamivudine, Atazanavir, or Ritonavir	Randomization at Week 36 through Week 84	A blood sample was drawn for participants failing to respond to therapy, and changes in drug susceptibility for HIV isolated from the participants for each drug used in the study were assessed. For each participant, the changes in drug susceptibility detected by phenotypic assay in virus from the sample collected at the time of failure was compared with drug susceptibility in the virus from the blood sample at baseline. PAR, participant.
Number of Confirmed Virologic Failure Participants From Week 84 Through Week 144 With Treatment-emergent Reductions in HIV Susceptibility to Abacavir, Lamivudine, Atazanavir, or Ritonavir	Week 84 through Week 144	A blood sample was drawn for participants failing to respond to therapy, and changes in drug susceptibility for HIV isolated from the participants for each drug used in the study were assessed. For each participant, the changes in drug susceptibility detected by phenotypic assay in virus from the sample collected at the time of failure was compared with drug susceptibility in the virus from the blood sample at baseline. PAR, participant.
Mean Percent Compliance at Week 36	Week 36	Percent compliance is defined as the total number of pills taken divided by the total number of pills prescribed. The total number of pills taken was calculated by subtracting any returned pills from the total number of pills that were dispensed to each participant during this period. Compliance was calculated for each medication in the regimen.
Mean Percent Compliance at Week 84	Week 84	Percent compliance is defined as the total number of pills taken divided by the total number of pills prescribed. The total number of pills taken was calculated by subtracting any returned pills from the total number of pills that were dispensed to each participant during this period. Compliance was calculated for each medication in the regimen.
Mean Percent Compliance at Week 144	Week 144	Percent compliance is defined as the total number of pills taken divided by the total number of pills prescribed. The total number of pills taken was calculated by subtracting any returned pills from the total number of pills that were dispensed to each participant during this period. Compliance was calculated for each medication in the regimen.