HIV
Conditions
Keywords
Pharmacokinetics, antiretroviral therapy, nucleoside analogs, mitochondrial toxicity, clinical pharmacology, cellular pharmacology, pharmacogenetics
Brief summary
This study evaluated the blood and blood cell concentrations of zidovudine and lamivudine in men versus women and in those with versus without HIV infection. Additionally, markers of side effects were correlated with blood levels of the drugs. The hypothesis was that women and those with HIV would have higher drug levels, as well as markers of side effects.
Interventions
DRUGzidovudine 300mg and lamivudine 150mg as Combivir
twice daily for 12 days in the HIV-negative group and indefinitely for their care in the HIV-positive group
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
University of Hawaii
University of Colorado, Denver
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Documented physician-diagnosed HIV-infection (HIV+ antibody or plasma HIV-RNA+); HIV-negative volunteers must have a negative HIV-ELISA. * Age 18 to 55 years; * Either antiretroviral naïve, or no HIV-therapy in the preceding 6 months; * Planned antiretroviral regimen includes standard doses of ZDV plus 3TC as part of the antiretroviral regimen. Once- or twice-daily 3TC will be allowed.
Exclusion criteria
* Any medical condition that in the opinion of the investigators would jeopardize the intent of the study. * In the opinion of the investigator, any concomitant immunomodulatory medications, chemotherapeutic agents, investigational drugs, and alternative therapies, including, glucocorticoids, recombinant growth factors or cytokines (e.g. Granulocyte-macrophage colony-stimulating factor, Granulocyte colony-stimulating factor, interferon-alpha or gamma, human growth hormone, etc), ribavirin, birth-control pills, and sex hormones that could interfere with the cellular pharmacology of the study medications; * Concomitant medications that interfere with renal drug clearances including, tenofovir, adefovir, cidofovir, ganciclovir, probenecid, or any similarly problematic medication in the opinion of the investigators; * Concomitant warfarin or daily aspirin (to prevent excess bleeding from biopsy). * Pregnancy or a plan to become pregnant, or menopause; * Any \> or = grade II abnormality in hemoglobin, absolute neutrophil count, routine liver function tests, serum creatinine, or other organ function abnormalities. * Any medical or personal condition that, in the judgment of the investigators, may influence the subject's ability to comply with study conditions, such as active mental illnesses, or plans to leave the geographical area. * Inability to give informed consent. * Triple nucleoside analog reverse transcriptase regimens.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ZDV-TP Drug Levels Compared Between HIV Negative and HIV Infected Subject | Day 12 of dosing | To compare ZDV- triphosphate concentrations in HIV-negative versus HIV-infected subjects. |
| 3TC-TP Drug Levels Compared Between HIV Negative and HIV Infected Subject | Day 12 of dosing | To compare 3TC- triphosphate concentrations in HIV-negative versus HIV-infected subjects. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HIV-negative This group was used to compare intracellular ZDV- and 3TC-triphosphate concentrations to the HIV-infected group and in men versus women.
zidovudine 300mg and lamivudine 150mg as Combivir: twice daily for 12 days in the HIV-negative group | 20 |
| HIV-infected This group was started on ZDV-3TC based therapy. Intracellular ZDV- and 3TC-triphosphate concentrations were compared in men versus women and the HIV-negative group.
zidovudine 300mg and lamivudine 150mg as Combivir: indefinitely for their care in the HIV-positive group | 23 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | HIV-negative | HIV-infected | 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 | 20 Participants | 23 Participants | 43 Participants |
| Race/Ethnicity, Customized African American | 4 Participants | 7 Participants | 11 Participants |
| Race/Ethnicity, Customized Non- African-American | 16 Participants | 16 Participants | 32 Participants |
| Sex: Female, Male Female | 8 Participants | 6 Participants | 14 Participants |
| Sex: Female, Male Male | 12 Participants | 17 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 23 |
| other Total, other adverse events | 7 / 20 | 8 / 23 |
| serious Total, serious adverse events | 0 / 20 | 0 / 23 |
Outcome results
Primary
3TC-TP Drug Levels Compared Between HIV Negative and HIV Infected Subject
To compare 3TC- triphosphate concentrations in HIV-negative versus HIV-infected subjects.
Time frame: Day 12 of dosing
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HIV-negative | 3TC-TP Drug Levels Compared Between HIV Negative and HIV Infected Subject | 7.25 pmol/10^6 cells |
| HIV-infected | 3TC-TP Drug Levels Compared Between HIV Negative and HIV Infected Subject | 5.3 pmol/10^6 cells |
Primary
ZDV-TP Drug Levels Compared Between HIV Negative and HIV Infected Subject
To compare ZDV- triphosphate concentrations in HIV-negative versus HIV-infected subjects.
Time frame: Day 12 of dosing
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HIV-negative | ZDV-TP Drug Levels Compared Between HIV Negative and HIV Infected Subject | 33.89 pmol/10^6 cells |
| HIV-infected | ZDV-TP Drug Levels Compared Between HIV Negative and HIV Infected Subject | 29.7 pmol/10^6 cells |