HIV
Conditions
Keywords
Treatment experienced
Brief summary
The purpose of this study is to provide atazanavir or tenofovir-emtricitabine to HIV-infected subjects who have completed atazanavir or tenofovir-emtricitabine therapy on a previous BMS sponsored clinical trial and to collect long-term safety information on the treated population.
Detailed description
Provide study drug for patients rolling off BMS ATV clinical trials in countries where these medications are not commercially available.
Interventions
DRUGAtazanavir
Tablets, Oral, 400 mg, once daily, indefinitely
Tablets, Oral, 300/100 mg, once daily, indefinitely
Tablets, Oral, 300/200 mg, once daily, indefinitely
DRUGLopinavir/ritonavir
Tablets, Oral, 400/100 mg, twice daily, indefinitely
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must provide written informed consent * Currently receiving atazanavir (unboosted or boosted with 100 mg ritonavir QD)and/or tenofovir-emtricitabine at time of screening and viral load is ≤ 10,000 copies/mL while on therapy * Subjects who are receiving investigational antiretroviral agents through Expanded Access Programs will be allowed to participate following discussion and approval by the BMS Medical Monitor * ≥ 16 years of age (or minimum age as determined by local regulatory or as legal requirements dictate) * Both females of child-bearing potential and males must utilize effective barrier contraception to reduce transmission of sexually transmitted diseases, including HIV. Other contraception in addition to barrier methods are permitted, however interactions between atazanavir and oral contraceptives have not been studied
Exclusion criteria
* WOCBP 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 study * WOCBP using a prohibited contraceptive method (no contraceptive methods prohibited in this study. However, caution is warranted with coadministration of oral contraceptives) * Women who are pregnant or breastfeeding * Women with a positive pregnancy test on enrollment or prior to study drug administration, with the exception of women rolling over from AI424182, who may still have a positive β-HCG test at the time of enrollment * All subjects previously discontinued from an atazanavir study for any reason * Active alcohol or substance abuse sufficient, in the Investigator's opinion, to prevent adequate compliance with study therapy or to increase the risk of developing pancreatitis or chemical hepatitis * Any other clinical conditions or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for study, or unable to comply with the dosing requirements * Any of the following laboratory values: * a) Serum creatinine ≥ 1.5 times the upper limit of normal, * b) Liver enzymes (AST, ALT) ≥ 5 times the upper limit of normal, * Hypersensitivity to any component of the formulation of study drug * Refer to Section 6.4.1 which details all prohibited therapies * Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | Date of First Dose to 30 days post the last dose; approximately 405 weeks) | 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. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. AIDS Defining Diagnosis ( CDC Class C AIDS Events) are identified from HIV Related Diagnosis. |
Countries
Argentina, Brazil, Canada, Chile, Colombia, Costa Rica, Dominican Republic, France, Guatemala, Hungary, Indonesia, Italy, Malaysia, Mexico, Panama, Peru, Portugal, Puerto Rico, Russia, Singapore, South Africa, Spain, Taiwan, Thailand, United States
Participant flow
Recruitment details
710 participants were enrolled, 709 were treated. The participant who did not receive treatment was enrolled in error having been assigned to efavirenz in the parent study AI424034 (only subjects assigned to ATV rolled over into AI424077).
Participants by arm
| Arm | Count |
|---|---|
| Atazanavir (ATV) Atazanavir: Tablets, Oral, 400 mg (2 x 200 mg capsules), once daily with food, indefinitely | 459 |
| Atazanavir/Ritonavir (ATV/RTV) Ritonavir-boosted Atazanavir (ATV/RTV 300/100 mg). Tablets administered orally once daily (QD) with food, indefinitely.
Ritonavir: 100 mg QD Atazanavir: 300 mg QD (3 x 100 mg capsules, or 2 x 150 mg capsules) | 154 |
| Lopinavir/Ritonavir (LPV/RTV) Ritonavir-boosted Lopinavir (LPV/RTV 400/100 mg) administered twice a day (BID) with Tenofovir/ Emtricitabine (TDF/FTC).
Lopinavir: 400 mg BID Ritonavir: 100 mg BID Tenofovir/Emtricitabine: Tablets, Oral, 300/200 mg, once daily (QD) with food, indefinitely (one tablet with 300 mg - 200 mg QD) | 96 |
| Total | 709 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 8 | 5 | 11 |
| Overall Study | Death | 0 | 8 | 1 |
| Overall Study | Lack of Efficacy | 10 | 2 | 3 |
| Overall Study | Lost to Follow-up | 30 | 12 | 7 |
| Overall Study | No Longer Met Study Criteria | 4 | 1 | 0 |
| Overall Study | Poor/Non-compliance | 4 | 3 | 2 |
| Overall Study | Pregnancy | 10 | 2 | 4 |
| Overall Study | Reasons Not Identified | 14 | 13 | 8 |
| Overall Study | Subject Withdrew Consent | 12 | 5 | 7 |
Baseline characteristics
| Characteristic | Total | Atazanavir (ATV) | Atazanavir/Ritonavir (ATV/RTV) | Lopinavir/Ritonavir (LPV/RTV) |
|---|---|---|---|---|
| Age, Continuous | 36.6 years STANDARD_DEVIATION 9.12 | 36.6 years STANDARD_DEVIATION 9 | 35.9 years STANDARD_DEVIATION 8.81 | 37.6 years STANDARD_DEVIATION 10.16 |
| Race/Ethnicity, Customized American Indian/Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 84 Participants | 53 Participants | 13 Participants | 18 Participants |
| Race/Ethnicity, Customized Black or African American | 139 Participants | 112 Participants | 25 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 275 Participants | 135 Participants | 82 Participants | 58 Participants |
| Race/Ethnicity, Customized White | 210 Participants | 158 Participants | 34 Participants | 18 Participants |
| Sex: Female, Male Female | 256 Participants | 172 Participants | 54 Participants | 30 Participants |
| Sex: Female, Male Male | 453 Participants | 287 Participants | 100 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 459 | 7 / 154 | 1 / 96 |
| other Total, other adverse events | 284 / 459 | 92 / 154 | 57 / 96 |
| serious Total, serious adverse events | 35 / 459 | 19 / 154 | 12 / 96 |
Outcome results
Primary
Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death
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. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. AIDS Defining Diagnosis ( CDC Class C AIDS Events) are identified from HIV Related Diagnosis.
Time frame: Date of First Dose to 30 days post the last dose; approximately 405 weeks)
Population: All Treated Participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Atazanavir (ATV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | SAEs | 35 Participants |
| Atazanavir (ATV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | Treatment Related SAEs | 4 Participants |
| Atazanavir (ATV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | Treatment Related AEs of Any Grade | 180 Participants |
| Atazanavir (ATV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | Grade 3 to Grade 4 AEs | 72 Participants |
| Atazanavir (ATV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | CDC Class C AIDS Events | 2 Participants |
| Atazanavir (ATV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | Deaths | 2 Participants |
| Atazanavir (ATV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | AEs Leading to Discontinuation of Study Therapy | 8 Participants |
| Atazanavir (ATV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | Grade 2 to Grade 4 AEs | 102 Participants |
| Atazanavir/Ritonavir (ATV/RTV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | Treatment Related SAEs | 1 Participants |
| Atazanavir/Ritonavir (ATV/RTV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | SAEs | 19 Participants |
| Atazanavir/Ritonavir (ATV/RTV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | Deaths | 7 Participants |
| Atazanavir/Ritonavir (ATV/RTV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | AEs Leading to Discontinuation of Study Therapy | 5 Participants |
| Atazanavir/Ritonavir (ATV/RTV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | Treatment Related AEs of Any Grade | 49 Participants |
| Atazanavir/Ritonavir (ATV/RTV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | CDC Class C AIDS Events | 0 Participants |
| Atazanavir/Ritonavir (ATV/RTV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | Grade 3 to Grade 4 AEs | 27 Participants |
| Atazanavir/Ritonavir (ATV/RTV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | Grade 2 to Grade 4 AEs | 28 Participants |
| Lopinavir/Ritonavir (LPV/RTV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | Grade 3 to Grade 4 AEs | 15 Participants |
| Lopinavir/Ritonavir (LPV/RTV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | Grade 2 to Grade 4 AEs | 19 Participants |
| Lopinavir/Ritonavir (LPV/RTV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | Deaths | 1 Participants |
| Lopinavir/Ritonavir (LPV/RTV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | CDC Class C AIDS Events | 0 Participants |
| Lopinavir/Ritonavir (LPV/RTV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | SAEs | 12 Participants |
| Lopinavir/Ritonavir (LPV/RTV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | Treatment Related SAEs | 0 Participants |
| Lopinavir/Ritonavir (LPV/RTV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | Treatment Related AEs of Any Grade | 34 Participants |
| Lopinavir/Ritonavir (LPV/RTV) | Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death | AEs Leading to Discontinuation of Study Therapy | 11 Participants |