HIV Infection
Conditions
Keywords
antiretroviral therapy, protease inhibitors, drug interactions, HIV infection, acquired immunodeficiency syndrome, Treatment Experienced
Brief summary
The objective of this study is to determine the pharmacokinetics of lopinavir, ritonavir, and atazanavir when lopinavir/ritonavir and atazanavir are used in combination.
Detailed description
Thirty patients with HIV infection will be enrolled in this open-label, parallel arm pharmacokinetic study. Subjects receiving either lopinavir/ritonavir or atazanavir/ritonavir as part of their antiretroviral therapy will have a pharmacokinetic study performed over 12-20 days to examine whether coadministration of lopinavir and atazanavir alters the pharmacokinetics of either agent. The safety of these agents in combination will also be explored.
Interventions
DRUGatazanavir
Atazanavir 300 mg daily on Days 6-12.
DRUGlopinavir/ritonavir
Lopinavir/ritonavir 400 mg/100 mg twice daily on Days 6-16, then 800 mg/200 mg daily on Days 17-21.
Sponsors
Abbott
University of Oklahoma
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* HIV-seropositive * Currently receiving atazanavir/ritonavir or lopinavir/ritonavir in combination with 2-3 nucleoside RT inhibitors or are antiretroviral treatment-naïve * If female, is not of childbearing potential or is of childbearing potential and agrees to use a barrier method of contraception throughout the study
Exclusion criteria
* HIV-1 RNA \> 400 copies/mL if currently receiving antiretroviral therapy * Concurrent use of CYP450 inhibitors or inducers * Concurrent use of P-glycoprotein substrates, inhibitors, or inducers * Concurrent use of medications known to interact with ritonavir or atazanavir * Presence of a chronic health condition deemed by the investigators to potentially impair lopinavir, ritonavir, or atazanavir pharmacokinetics * Presence of conduction abnormalities on electrocardiogram * Women who are pregnant or breastfeeding * Laboratory Abnormalities at baseline: * Aminotransferases \> 3x ULN * Serum bilirubin \> 5x ULN * Serum creatinine \> 1.5x ULN * Hemoglobin concentration \< 8.0 g/dL * Absolute neutrophil count \< 800 cells/μL * Platelet count \< 50,000 cells/μL
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean pharmacokinetic parameters (Cmax, Cmin, AUC) for lopinavir, ritonavir, atazanavir | Day 6, Day 12 or 16, Day 20 |
Secondary
| Measure | Time frame |
|---|---|
| Safety (e.g., GI tolerance, lab abnormalities, ECG changes) | Day 6, Day 12 or Day 16, Day 20 |
Countries
United States
Outcome results
None listed