HIV
Conditions
Keywords
AIDS, HIV, Atazanavir, Raltegravir, Tenofovir, protease inhibitors
Brief summary
The purpose of this Phase IV pilot study is to evaluate the safety, tolerability, and satisfaction of a nucleoside analog reverse-transcriptase inhibitors (NRTI)sparing regimen for participants fully suppressed on an atazanavir/ritonavir based highly active antiretroviral therapy (HAART)regimen plus emtricitabine/tenofovir (Truvada). Several pharmacologic factors support this concept including the favorable drug interaction between atazanavir and raltegravir. Participants will be randomized to either continue on their current regimen or one of two study arms (atazanavir 300mg plus ritonavir 100mg daily plus raltegravir 400mg twice daily or atazanavir 300mg twice daily plus raltegravir 400mg twice daily). Participants will be followed for 48 weeks for safety, tolerability, and satisfaction. After baseline, the participants will have six clinic visits for evaluation and labs.
Interventions
DRUGatazanavir/raltegravir
Atazanavir/r 300/100mg once daily plus raltegravir 400mg twice daily
DRUGatazanavir/tenofovir/emtricitabine
Continue baseline regimen of atazanavir/r 300/100mg once daily plus tenofovir and emtricitabine
Sponsors
Bristol-Myers Squibb
Merck Sharp & Dohme LLC
Community Research Initiative of New England
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV-1 infection * Treatment with a stable antiretroviral regiment containing boosted atazanavir, tenofovir and emtricitabine at screen and for at least 90 days prior to screening * No plan to make changes to HIV treatment regimen (other than those required by the study) in the next 48 weeks * Undetectable HIV RNA at screening AND no HIV RNA\>200 copies during the 180 day period prior to screening * CD4 count\>200 * No evidence of resistance to any of the drugs in any of the 3 arms, if prior resistance tests are available * Subjects who, in the opinion of their treating physicians, would be candidates to switch antiretroviral medications * Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of study drug * Ability and willingness to provide written informed consent and comply with protocol requirements
Exclusion criteria
* Prior exposure to raltegravir or elvitegravir * Women who are pregnant, breast-feeding, or with a positive pregnancy test * Sexually active fertile men not using effective birth control if their female partners are of child-bearing potential * Women of child-bearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of study drug * Life expectancy less than 6 months * Presence of any currently active AIDS defining conditions with the exception of stable cutaneous Kaposi's sarcoma * Treatment with proton-pump inhibitor or H2-receptor antagonist * ECG demonstrating atrioventricular block, prolonged QRS interval greater than 12 ms, or known complete bundle branch block * Acute or chronic hepatitis B infection as evidenced by presence of hepatitis B surface antigen and absence of hepatitis B surface antibody * Clinical or laboratory evidence of significantly decreased hepatic function of decompensation irrespective of liver enzyme levels * Prisoners or subjects who are involuntarily incarcerated * Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maintenance of Virologic Suppression | 48 weeks | To evaluate and compare maintenance of virologic suppression with raltegravir (RAL) 400mg 2x daily plus atazanavir (ATV) dosed either as ATV/ritonavir (RTV)300/100mg 1x daily or ATV 300mg 2x daily in subjects with virologic suppression on a standard regimen of ATV/RTV plus Truvada. Virologic suppression is defined as HIV RNA \< 40 copies/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Difference in CD4 From Baseline to Week 48 | Baseline and Week 48 | Change in mean CD4 from Baseline to Week 48. |
| The Change in Adherence to Study Treatment Arm From Baseline to Week 48 | Baseline and Week 48 | Adherence to study treatment reported as the percentage of doses of the prescribed treatment arm regimen taken, described by each subject through recall of dosing in the three days prior to the visit Baseline and Week 48 vistis. The change in adherence is reflected as the difference of the mean percentage of adherence per arm between Baseline and Week 48 visits. |
| Change in Quality of Life From Baseline to 48 Weeks of Study Treatment | baseline and 48 weeks | Quality of Life was measured by self report using a standardized scale, where 0 is death and 100 is perfect health. The baseline measure was obtained prior to initiation of study treatment arm. The week 48 measure captures Quality of Life by self report at 48 weeks of study treatment. |
Countries
United States
Participant flow
Recruitment details
Recruitment was initiated on 15 APR 2010 and enrolled subjects through 31 JAN 2011. Recruitment and screening took place at 10 participating sites (9 medical clinics and 1 clinical research organization). 43 subjects were enrolled.
Pre-assignment details
There were 7 participants that did not meet eligibility criteria (either due to disallowed concomitant medication use or safety labs outside of the required parameters). 2 of those 7 subjects re-screened at a later date and were confirmed eligible. 2 subjects withdrew consent after the screening visit but prior to starting the assigned treatment.
Participants by arm
| Arm | Count |
|---|---|
| Control Arm atazanavir/tenofovir/emtricitabine : Continue baseline regimen of atazanavir/r 300/100mg once daily plus tenofovir and emtricitabine | 14 |
| Intervention Arm No.1 atazanavir/raltegravir: switch to atazanavir/r 300/100mg once daily plus raltegravir 400mg twice daily | 15 |
| Intervention Arm No.2 atazanavir/raltegravir: switch to atazanavir 300mg twice daily plus raltegravir 400mg twice daily | 14 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Confirmed Virologic Failure | 0 | 0 | 3 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Control Arm | Intervention Arm No.1 | Intervention Arm No.2 | Total |
|---|---|---|---|---|
| Age, Continuous | 43.5 years STANDARD_DEVIATION 11.6 | 47.6 years STANDARD_DEVIATION 11.5 | 46.6 years STANDARD_DEVIATION 6.6 | 45.9 years STANDARD_DEVIATION 10.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 2 Participants | 5 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 13 Participants | 9 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Mean CD4 | 544.6 cells/mm3 STANDARD_DEVIATION 197.7 | 518.5 cells/mm3 STANDARD_DEVIATION 198.9 | 533.9 cells/mm3 STANDARD_DEVIATION 198.3 | 532.0 cells/mm3 STANDARD_DEVIATION 193.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 9 Participants | 12 Participants | 11 Participants | 32 Participants |
| Region of Enrollment United States | 14 participants | 15 participants | 14 participants | 43 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Male | 12 Participants | 13 Participants | 13 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 14 | 13 / 15 | 13 / 14 | 35 / 43 |
| serious Total, serious adverse events | 1 / 14 | 2 / 15 | 2 / 14 | 5 / 43 |
Outcome results
Primary
Maintenance of Virologic Suppression
To evaluate and compare maintenance of virologic suppression with raltegravir (RAL) 400mg 2x daily plus atazanavir (ATV) dosed either as ATV/ritonavir (RTV)300/100mg 1x daily or ATV 300mg 2x daily in subjects with virologic suppression on a standard regimen of ATV/RTV plus Truvada. Virologic suppression is defined as HIV RNA \< 40 copies/mL.
Time frame: 48 weeks
Population: All enrolled participants were included in this analysis of primary outcome measurement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control Arm | Maintenance of Virologic Suppression | Virologic Response | 13 participants |
| Control Arm | Maintenance of Virologic Suppression | Confirmed Virologic Failures | 0 participants |
| Control Arm | Maintenance of Virologic Suppression | Withdrawal Due to AE; HIV RNA < 50 copies/mL | 0 participants |
| Control Arm | Maintenance of Virologic Suppression | Other Withdrawal; HIV RNA < 50 copies/mL | 1 participants |
| Intervention Arm No.1 | Maintenance of Virologic Suppression | Other Withdrawal; HIV RNA < 50 copies/mL | 1 participants |
| Intervention Arm No.1 | Maintenance of Virologic Suppression | Virologic Response | 14 participants |
| Intervention Arm No.1 | Maintenance of Virologic Suppression | Withdrawal Due to AE; HIV RNA < 50 copies/mL | 0 participants |
| Intervention Arm No.1 | Maintenance of Virologic Suppression | Confirmed Virologic Failures | 0 participants |
| Intervention Arm No.2 | Maintenance of Virologic Suppression | Other Withdrawal; HIV RNA < 50 copies/mL | 0 participants |
| Intervention Arm No.2 | Maintenance of Virologic Suppression | Confirmed Virologic Failures | 3 participants |
| Intervention Arm No.2 | Maintenance of Virologic Suppression | Withdrawal Due to AE; HIV RNA < 50 copies/mL | 1 participants |
| Intervention Arm No.2 | Maintenance of Virologic Suppression | Virologic Response | 10 participants |
Secondary
Change in Quality of Life From Baseline to 48 Weeks of Study Treatment
Quality of Life was measured by self report using a standardized scale, where 0 is death and 100 is perfect health. The baseline measure was obtained prior to initiation of study treatment arm. The week 48 measure captures Quality of Life by self report at 48 weeks of study treatment.
Time frame: baseline and 48 weeks
Population: Data for all participants assigned to a study treatment was analyzed except data for participants that did not have both baseline and week 48 data, including early withdrawal, virologic failure, loss to follow-up or missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Arm | Change in Quality of Life From Baseline to 48 Weeks of Study Treatment | Mean Quality of Life Score at Baseline | 92.9 units on a scale | Standard Deviation 8.6 |
| Control Arm | Change in Quality of Life From Baseline to 48 Weeks of Study Treatment | Change in Quality of Life | -2.5 units on a scale | Standard Deviation 8.2 |
| Control Arm | Change in Quality of Life From Baseline to 48 Weeks of Study Treatment | Mean Quality of Life Score at Week 48 | 90.5 units on a scale | Standard Deviation 11.1 |
| Intervention Arm No.1 | Change in Quality of Life From Baseline to 48 Weeks of Study Treatment | Mean Quality of Life Score at Baseline | 77.4 units on a scale | Standard Deviation 16.1 |
| Intervention Arm No.1 | Change in Quality of Life From Baseline to 48 Weeks of Study Treatment | Change in Quality of Life | 0.8 units on a scale | Standard Deviation 20 |
| Intervention Arm No.1 | Change in Quality of Life From Baseline to 48 Weeks of Study Treatment | Mean Quality of Life Score at Week 48 | 78.2 units on a scale | Standard Deviation 22.6 |
| Intervention Arm No.2 | Change in Quality of Life From Baseline to 48 Weeks of Study Treatment | Mean Quality of Life Score at Week 48 | 81.3 units on a scale | Standard Deviation 17.5 |
| Intervention Arm No.2 | Change in Quality of Life From Baseline to 48 Weeks of Study Treatment | Mean Quality of Life Score at Baseline | 82.5 units on a scale | Standard Deviation 11.6 |
| Intervention Arm No.2 | Change in Quality of Life From Baseline to 48 Weeks of Study Treatment | Change in Quality of Life | -1.3 units on a scale | Standard Deviation 12.7 |
| Total | Change in Quality of Life From Baseline to 48 Weeks of Study Treatment | Mean Quality of Life Score at Baseline | 84.2 units on a scale | Standard Deviation 14.1 |
| Total | Change in Quality of Life From Baseline to 48 Weeks of Study Treatment | Change in Quality of Life | -0.9 units on a scale | Standard Deviation 14.4 |
| Total | Change in Quality of Life From Baseline to 48 Weeks of Study Treatment | Mean Quality of Life Score at Week 48 | 83.3 units on a scale | Standard Deviation 18.2 |
Secondary
The Change in Adherence to Study Treatment Arm From Baseline to Week 48
Adherence to study treatment reported as the percentage of doses of the prescribed treatment arm regimen taken, described by each subject through recall of dosing in the three days prior to the visit Baseline and Week 48 vistis. The change in adherence is reflected as the difference of the mean percentage of adherence per arm between Baseline and Week 48 visits.
Time frame: Baseline and Week 48
Population: Values included for all enrolled participants excluding participants with confirmed virologic failure or those missing values due to early withdrawal, loss to follow-up or other error.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Arm | The Change in Adherence to Study Treatment Arm From Baseline to Week 48 | 3 Day Adherence Recall at Baseline | 100 percentage of prescribed doses | Standard Deviation 0 |
| Control Arm | The Change in Adherence to Study Treatment Arm From Baseline to Week 48 | Change in 3 Day Adherence Recall | 0 percentage of prescribed doses | Standard Deviation 0 |
| Control Arm | The Change in Adherence to Study Treatment Arm From Baseline to Week 48 | 3 Day Adherence Recall at Week 48 | 100 percentage of prescribed doses | Standard Deviation 0 |
| Intervention Arm No.1 | The Change in Adherence to Study Treatment Arm From Baseline to Week 48 | 3 Day Adherence Recall at Baseline | 97.5 percentage of prescribed doses | Standard Deviation 9.2 |
| Intervention Arm No.1 | The Change in Adherence to Study Treatment Arm From Baseline to Week 48 | Change in 3 Day Adherence Recall | 0 percentage of prescribed doses | Standard Deviation 13.5 |
| Intervention Arm No.1 | The Change in Adherence to Study Treatment Arm From Baseline to Week 48 | 3 Day Adherence Recall at Week 48 | 97.5 percentage of prescribed doses | Standard Deviation 9.2 |
| Intervention Arm No.2 | The Change in Adherence to Study Treatment Arm From Baseline to Week 48 | 3 Day Adherence Recall at Week 48 | 95.0 percentage of prescribed doses | Standard Deviation 15.8 |
| Intervention Arm No.2 | The Change in Adherence to Study Treatment Arm From Baseline to Week 48 | 3 Day Adherence Recall at Baseline | 96.7 percentage of prescribed doses | Standard Deviation 10.4 |
| Intervention Arm No.2 | The Change in Adherence to Study Treatment Arm From Baseline to Week 48 | Change in 3 Day Adherence Recall | -1.7 percentage of prescribed doses | Standard Deviation 19.9 |
| Total | The Change in Adherence to Study Treatment Arm From Baseline to Week 48 | 3 Day Adherence Recall at Baseline | 98.1 percentage of prescribed doses | Standard Deviation 7.8 |
| Total | The Change in Adherence to Study Treatment Arm From Baseline to Week 48 | Change in 3 Day Adherence Recall | -0.5 percentage of prescribed doses | Standard Deviation 13 |
| Total | The Change in Adherence to Study Treatment Arm From Baseline to Week 48 | 3 Day Adherence Recall at Week 48 | 97.6 percentage of prescribed doses | Standard Deviation 10 |
Secondary
The Difference in CD4 From Baseline to Week 48
Change in mean CD4 from Baseline to Week 48.
Time frame: Baseline and Week 48
Population: Values included for all enrolled participants excluding participants with confirmed virologic failure or those missing values due to early withdrawal, loss to follow-up or lab error.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Arm | The Difference in CD4 From Baseline to Week 48 | CD4 at Baseline | 535.8 cells/mm3 | Standard Deviation 210.9 |
| Control Arm | The Difference in CD4 From Baseline to Week 48 | CD4 Change | 75.4 cells/mm3 | Standard Deviation 133.9 |
| Control Arm | The Difference in CD4 From Baseline to Week 48 | CD4 at Week 48 | 611.2 cells/mm3 | Standard Deviation 218.1 |
| Intervention Arm No.1 | The Difference in CD4 From Baseline to Week 48 | CD4 at Baseline | 514.1 cells/mm3 | Standard Deviation 205.7 |
| Intervention Arm No.1 | The Difference in CD4 From Baseline to Week 48 | CD4 Change | 12.1 cells/mm3 | Standard Deviation 96.4 |
| Intervention Arm No.1 | The Difference in CD4 From Baseline to Week 48 | CD4 at Week 48 | 526.3 cells/mm3 | Standard Deviation 210.5 |
| Intervention Arm No.2 | The Difference in CD4 From Baseline to Week 48 | CD4 at Week 48 | 507.2 cells/mm3 | Standard Deviation 201.7 |
| Intervention Arm No.2 | The Difference in CD4 From Baseline to Week 48 | CD4 at Baseline | 539.1 cells/mm3 | Standard Deviation 206.2 |
| Intervention Arm No.2 | The Difference in CD4 From Baseline to Week 48 | CD4 Change | -31.9 cells/mm3 | Standard Deviation 122 |
| Total | The Difference in CD4 From Baseline to Week 48 | CD4 at Baseline | 528.3 cells/mm3 | Standard Deviation 201.9 |
| Total | The Difference in CD4 From Baseline to Week 48 | CD4 Change | 21.0 cells/mm3 | Standard Deviation 121.5 |
| Total | The Difference in CD4 From Baseline to Week 48 | CD4 at Week 48 | 549.3 cells/mm3 | Standard Deviation 209.5 |