HIV Infections
Conditions
Keywords
Sex differences, Pharmacokinetic, Lopinavir/ritonavir, Treatment Experienced, HIV-infection
Brief summary
The levels of lopinavir achieved in the blood following oral ingestion of standard doses of Kaletra (lopinavir/ritonavir) in HIV-infected men was compared with those achieved in HIV-infected women receiving the same dose of the drug.
Detailed description
The association between patient sex and the tolerability of antiretroviral drugs (ARVs) is increasingly being recognized. Several lines of evidence suggest that women are more likely than men to develop side effects to ARVs. On the other hand, it has been generally accepted that the efficacies of the ARVs are similar in both sexes. However, recent studies suggest that this may not always be the case. In addition to these observed sex-related differences in the effects of ARVs, there is growing evidence that the pharmacokinetic profile of some of these drugs may be different among male and female HIV infected patients. The fact that female sex is a risk factor for enhanced antiretroviral effects (including toxicities) has an important implication, particularly from a global health perspective as women now represent the fastest growing segment of the HIV/AIDS epidemic. Therefore, an understanding of the magnitude, clinical significance, and the mechanisms underlying this phenomenon deserves further study. Knowledge acquired from such studies will likely contribute to improved survival among female HIV-infected patients, through optimization of antiretroviral therapeutic regimens in manners that minimize serious adverse effects and improve adherence. Similarly, the influence of race on the pharmacological effects of ARVs deserves further investigation. Although, there is no reason to believe based on available evidence that racial differences exist in the pharmacological effects of ARVs, the need however exists to explore the influence of race on ARVs pharmacokinetics and treatment outcomes. This is so because data on race related differences on ARV effects is limited, and in addition, people of ethnic minority have been disproportionately under represented in clinical trials involving these drugs in spite of the fact that they bear a larger burden of the HIV epidemic. Our study will examine the influence of race and sex on the 24-hr pharmacokinetics of lopinavir/ritonavir (an antiretroviral agent commonly used in naïve patients) following a switch from LPV/r 400/100 mg twice daily to 800/200 mg once daily dosing. Tolerability (measured by toxicity grade of diarrhea) and change in quality of life following switch from twice daily to once daily dosing will also be assessed using appropriate validated measurement tools.
Interventions
DRUGLPV/r
LPV/r 800/200 mg once daily
Sponsors
Abbott
Emory University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age greater or equal to 18 years * Diagnosis of HIV infection as previously established by HIV Enzyme-Linked Immunosorbent Assay (ELISA) test and confirmed by Western blot analysis. * Must have been taking LPV/r as part of an antiretroviral regimen at a dose of 400/100 mg orally twice per day for at least 3 months. * Recent (within last 90 days) HIV-RNA copies must be less than 400 copies/ml
Exclusion criteria
* Hepatic abnormality: alanine-aminotransferase (ALT), aspartate-aminotransferase (AST) or total bilirubin (TBR) ≥ 3 x upper limit of normal * Renal insufficiency: serum creatinine ≥ 2 mg/dl * Co-infection with hepatitis B and/or C viruses * Pregnant or breastfeeding * Use of concurrent medications known to affect lopinavir or ritonavir concentrations significantly.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24-hr LPV AUC | 24 hours | Steady state(2 weeks after therapy change) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 24-hr LPV Cmax | 24 hours | LPV Cmax at Steady State |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the Grady Infectious Diseases Clinic in Atlanta, Georgia between June 2005 and January 2007. All subjects provided written informed consent before undergoing any study procedures.
Pre-assignment details
Of the 23 subjects enrolled, 20 completed the study including the PK sampling. Three subjects (2 males and 1 female) dropped out. Two subjects were unavailable for the 24-hour PK sampling because of changes in their work schedules, and the third subject was lost to follow-up after the initial study visit.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Male subjects | 11 |
| Group 2 Female subjects | 12 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Group 2 | Group 1 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 11 Participants | 23 Participants |
| Age Continuous | 39 years STANDARD_DEVIATION 18 | 37 years STANDARD_DEVIATION 16 | 38 years STANDARD_DEVIATION 16 |
| Region of Enrollment United States | 12 participants | 11 participants | 23 participants |
| Sex: Female, Male Female | 12 Participants | 0 Participants | 12 Participants |
| Sex: Female, Male Male | 0 Participants | 11 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 11 | 0 / 12 |
| serious Total, serious adverse events | 0 / 11 | 0 / 12 |
Outcome results
Primary
24-hr LPV AUC
Steady state(2 weeks after therapy change)
Time frame: 24 hours
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group 1 | 24-hr LPV AUC | 142,160 ng*hr/mL |
| Group 2 | 24-hr LPV AUC | 152140 ng*hr/mL |
Secondary
24-hr LPV Cmax
LPV Cmax at Steady State
Time frame: 24 hours
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group 1 | 24-hr LPV Cmax | 12417 ng/mL |
| Group 2 | 24-hr LPV Cmax | 12271 ng/mL |