Trial Outcomes & Findings for Atazanavir/Ritonavir, Once Daily + Raltegravir, Twice Daily, Switch Study in HIV-1-Infected Patients (NCT NCT01332227)

NCT ID: NCT01332227

Last Updated: 2015-02-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

132 participants

Primary outcome timeframe

From Day 1 to Week 24

Results posted on

2015-02-19

Participant Flow

Of 132 patients enrolled, 109 were randomized to receive treatment, and 23 patients were not randomized for the following reasons: 10 did not meet study criteria; 5 withdrew consent; 3 were lost to follow-up, and 5 withdrew for other reasons.

Participant milestones

Participant milestones
Measure
Atazanavir/Ritonavir + Raltegravir
Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks.
Atazanavir/Ritonavir + Tenofovir/Emtricitabine
Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks.
Overall Study
STARTED
72
37
Overall Study
COMPLETED
56
32
Overall Study
NOT COMPLETED
16
5

Reasons for withdrawal

Reasons for withdrawal
Measure
Atazanavir/Ritonavir + Raltegravir
Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks.
Atazanavir/Ritonavir + Tenofovir/Emtricitabine
Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks.
Overall Study
Adverse Event
4
1
Overall Study
Withdrawal by Subject
5
1
Overall Study
Lost to Follow-up
2
0
Overall Study
Lack of Efficacy
3
1
Overall Study
Poor compliance/noncompliance
1
1
Overall Study
Patient moved from area
1
0
Overall Study
Patient began prohibited medication
0
1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Atazanavir/Ritonavir + Raltegravir
n=72 Participants
Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks.
Atazanavir/Ritonavir + Tenofovir/Emtricitabine
n=37 Participants
Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks.
Total
n=109 Participants
Total of all reporting groups
Age, Continuous
44.0 Years
n=5 Participants
44.0 Years
n=7 Participants
44.0 Years
n=5 Participants
Age, Customized
< 65 years
69 Participants
n=5 Participants
36 Participants
n=7 Participants
105 Participants
n=5 Participants
Age, Customized
65-85 years
3 Participants
n=5 Participants
1 Participants
n=7 Participants
4 Participants
n=5 Participants
Sex: Female, Male
Female
14 Participants
n=5 Participants
6 Participants
n=7 Participants
20 Participants
n=5 Participants
Sex: Female, Male
Male
58 Participants
n=5 Participants
31 Participants
n=7 Participants
89 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
5 Participants
n=5 Participants
1 Participants
n=7 Participants
6 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
29 Participants
n=5 Participants
13 Participants
n=7 Participants
42 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
38 Participants
n=5 Participants
23 Participants
n=7 Participants
61 Participants
n=5 Participants
Race/Ethnicity, Customized
White
54 Participants
n=5 Participants
24 Participants
n=7 Participants
78 Participants
n=5 Participants
Race/Ethnicity, Customized
Black or African American
8 Participants
n=5 Participants
6 Participants
n=7 Participants
14 Participants
n=5 Participants
Race/Ethnicity, Customized
Hispanic
2 Participants
n=5 Participants
0 Participants
n=7 Participants
2 Participants
n=5 Participants
Race/Ethnicity, Customized
Unknown
8 Participants
n=5 Participants
7 Participants
n=7 Participants
15 Participants
n=5 Participants
Mean CD4 count
587.7 Cells/mm^3
STANDARD_DEVIATION 252.09 • n=5 Participants
630.9 Cells/mm^3
STANDARD_DEVIATION 270.02 • n=7 Participants
601.5 Cells/mm^3
STANDARD_DEVIATION 257.48 • n=5 Participants
Median CD4 count
588.5 Cells/mm^3
n=5 Participants
639.5 Cells/mm^3
n=7 Participants
593.0 Cells/mm^3
n=5 Participants
Cardiovascular disease risk factors
Hypertension
5 Participants
n=5 Participants
6 Participants
n=7 Participants
11 Participants
n=5 Participants
Cardiovascular disease risk factors
Diabetes mellitus
3 Participants
n=5 Participants
1 Participants
n=7 Participants
4 Participants
n=5 Participants
Cardiovascular disease risk factors
Current smoker
27 Participants
n=5 Participants
11 Participants
n=7 Participants
38 Participants
n=5 Participants
Cardiovascular disease risk factors
Previous smoker
7 Participants
n=5 Participants
8 Participants
n=7 Participants
15 Participants
n=5 Participants
Cardiovascular disease risk factors
Family history of premature coronary heart disease
4 Participants
n=5 Participants
0 Participants
n=7 Participants
4 Participants
n=5 Participants

PRIMARY outcome

Timeframe: From Day 1 to Week 24

Population: All patients who received study drug and who had an HIV-1 RNA measurement at the analysis week.

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.

Outcome measures

Outcome measures
Measure
Atazanavir/Ritonavir + Raltegravir
n=72 Participants
Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks.
Atazanavir/Ritonavir + Tenofovir/Emtricitabine
n=37 Participants
Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks.
Percentage of Participants With HIV-1 RNA Level <40 c/mL at Week 24
80.6 Percentage of participants
Interval 69.5 to 88.9
94.6 Percentage of participants
Interval 81.8 to 99.3

SECONDARY outcome

Timeframe: From Day 1 to Week 48

Population: All patients who received study drug and who had an HIV-1 RNA measurement at the analysis week.

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.

Outcome measures

Outcome measures
Measure
Atazanavir/Ritonavir + Raltegravir
n=72 Participants
Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks.
Atazanavir/Ritonavir + Tenofovir/Emtricitabine
n=37 Participants
Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks.
Percentage of Participants With HIV-1 RNA Level <40 c/mL at Week 48
69.4 Percentage of participants
Interval 57.5 to 79.8
86.5 Percentage of participants
Interval 71.2 to 95.5

SECONDARY outcome

Timeframe: Day 1 to Weeks 28 and 48

Population: All patients who received study drug and who had an HIV-1 RNA measurement at the analysis week.

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.

Outcome measures

Outcome measures
Measure
Atazanavir/Ritonavir + Raltegravir
n=72 Participants
Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks.
Atazanavir/Ritonavir + Tenofovir/Emtricitabine
n=37 Participants
Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks.
Number of Participants With Virologic Rebound at Weeks 24 and 48
Week 24: Virologic rebound
7 Participants
1 Participants
Number of Participants With Virologic Rebound at Weeks 24 and 48
Week 48: Virologic rebound
9 Participants
1 Participants

SECONDARY outcome

Timeframe: Day 1 to Week 24

Population: Patients who received study drug, who had an HIV-1 RNA measurement at the analysis week and who experienced virologic rebound.

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

Outcome measures

Outcome measures
Measure
Atazanavir/Ritonavir + Raltegravir
n=7 Participants
Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks.
Atazanavir/Ritonavir + Tenofovir/Emtricitabine
n=1 Participants
Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks.
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 24
Genotypable (GI)/phenotypable isolates (PI)
4 Participants
0 Participants
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 24
Emergent genotypic substitutions in GI pts (n=4,0)
4 Participants
0 Participants
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 24
Phenotypic resistance in PI pts (n=4,0)
1 Participants
0 Participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: Participants with virologic rebound

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

Outcome measures

Outcome measures
Measure
Atazanavir/Ritonavir + Raltegravir
n=9 Participants
Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks.
Atazanavir/Ritonavir + Tenofovir/Emtricitabine
n=1 Participants
Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks.
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 48
Emergent genotypic substitutions in GI pts (n=5,0)
5 Participants
0 Participants
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 48
Genotypable (GI)/phenotypable isolates (PI)
5 Participants
0 Participants
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 48
Phenotypic resistance in PI pts (n=5,0)
1 Participants
0 Participants

SECONDARY outcome

Timeframe: Day 1 to Week 48

Population: All participants who received study drug

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.

Outcome measures

Outcome measures
Measure
Atazanavir/Ritonavir + Raltegravir
n=72 Participants
Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks.
Atazanavir/Ritonavir + Tenofovir/Emtricitabine
n=37 Participants
Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks.
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 AEs
Deaths
0 Particpants
0 Particpants
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 AEs
SAEs
4 Particpants
1 Particpants
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 AEs
Related SAEs
1 Particpants
0 Particpants
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 AEs
Treatment-emergent AEs leading to discontinuation
3 Particpants
1 Particpants
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 AEs
Treatment-emergent AEs
51 Particpants
28 Particpants

SECONDARY outcome

Timeframe: From Baseline to Week 48

Population: All participants who received study drug

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

Outcome measures

Outcome measures
Measure
Atazanavir/Ritonavir + Raltegravir
n=72 Participants
Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks.
Atazanavir/Ritonavir + Tenofovir/Emtricitabine
n=37 Participants
Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks.
Mean Changes in Fasting Lipid Levels From Baseline to Week 48
Fasting total cholesterol
11.7 mg/dL
Standard Error 5.239
-10.2 mg/dL
Standard Error 4.769
Mean Changes in Fasting Lipid Levels From Baseline to Week 48
Fasting LDL cholesterol
7.7 mg/dL
Standard Error 3.986
-5.4 mg/dL
Standard Error 4.691
Mean Changes in Fasting Lipid Levels From Baseline to Week 48
Fasting HDL cholesterol
2.7 mg/dL
Standard Error 2.055
-0.3 mg/dL
Standard Error 1.915
Mean Changes in Fasting Lipid Levels From Baseline to Week 48
Fasting non-HDL cholesterol
9.0 mg/dL
Standard Error 4.983
-9.8 mg/dL
Standard Error 4.430
Mean Changes in Fasting Lipid Levels From Baseline to Week 48
Fasting triglycerides
14.7 mg/dL
Standard Error 16.667
-17.6 mg/dL
Standard Error 16.994

Adverse Events

Atazanavir/Ritonavir + Raltegravir

Serious events: 4 serious events
Other events: 27 other events
Deaths: 0 deaths

Atazanavir/Ritonavir + Tenofovir/Emtricitabine

Serious events: 1 serious events
Other events: 23 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Atazanavir/Ritonavir + Raltegravir
n=72 participants at risk
Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks.
Atazanavir/Ritonavir + Tenofovir/Emtricitabine
n=37 participants at risk
Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks.
Metabolism and nutrition disorders
Cachexia
1.4%
1/72
0.00%
0/37
Infections and infestations
Device related infection
1.4%
1/72
0.00%
0/37
Gastrointestinal disorders
Gastrooesophageal reflux disease
1.4%
1/72
0.00%
0/37
Renal and urinary disorders
Calculus urinary
1.4%
1/72
0.00%
0/37
General disorders
Non-cardiac chest pain
1.4%
1/72
0.00%
0/37
Injury, poisoning and procedural complications
Accidental overdose
0.00%
0/72
2.7%
1/37
Infections and infestations
Pneumonia legionella
1.4%
1/72
0.00%
0/37

Other adverse events

Other adverse events
Measure
Atazanavir/Ritonavir + Raltegravir
n=72 participants at risk
Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks.
Atazanavir/Ritonavir + Tenofovir/Emtricitabine
n=37 participants at risk
Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks.
Metabolism and nutrition disorders
Hyperlactacidaemia
0.00%
0/72
5.4%
2/37
Hepatobiliary disorders
Jaundice
5.6%
4/72
10.8%
4/37
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
0.00%
0/72
5.4%
2/37
Eye disorders
Ocular icterus
8.3%
6/72
8.1%
3/37
Infections and infestations
Gonorrhoea
1.4%
1/72
5.4%
2/37
Gastrointestinal disorders
Abdominal distension
1.4%
1/72
5.4%
2/37
Infections and infestations
Nasopharyngitis
5.6%
4/72
5.4%
2/37
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
0.00%
0/72
5.4%
2/37
Hepatobiliary disorders
Hyperbilirubinaemia
8.3%
6/72
10.8%
4/37
Nervous system disorders
Headache
5.6%
4/72
5.4%
2/37
Skin and subcutaneous tissue disorders
Dry skin
1.4%
1/72
5.4%
2/37
Renal and urinary disorders
Proteinuria
1.4%
1/72
8.1%
3/37
Skin and subcutaneous tissue disorders
Rash
0.00%
0/72
5.4%
2/37
Infections and infestations
Bronchitis
5.6%
4/72
2.7%
1/37
Gastrointestinal disorders
Diarrhoea
4.2%
3/72
10.8%
4/37
Psychiatric disorders
Insomnia
5.6%
4/72
0.00%
0/37

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Results disclosure agreements

  • Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
  • Publication restrictions are in place

Restriction type: OTHER