Maraviroc Concentrations in Semen
Conditions
Brief summary
The objective of this study is to determine if concentrations of maraviroc in semen exceed the 50% and 95% inhibitory concentrations of HIV during the dose interval. The secondary objective is to determine the extent of maraviroc penetration into semen by obtaining semen to plasma ratios across the dosing interval, to determine the area under the concentration time curve of maraviroc in semen, and to determine the variability in the penetration of maraviroc into the seminal compartment over the maraviroc dosing period.
Detailed description
The patient population will consist of 12 male HIV-positive patients who have been receiving stable antiretroviral therapy that includes maraviroc for a minimum of three months. Patients will be enrolled from one clinic in downtown Toronto and a hospital affiliated HIV specialty clinic in Ottawa, Ontario. Eligible patients will have evidence of full virologic suppression (HIV viral load \< 50 copies/mL) at least one month prior to enrollment in the study. No changes will be made to the patients antiretroviral therapy during the course of the study.
Interventions
OTHERMeasuring semen samples
Measure semen sample concentrations, obtain semen to plasma ratios across the dosing interval, the area under the concentration time curve of maraviroc in semen, the variability in the penetration of maraviroc into the seminal compartment over the raltegravir dosing period.
Sponsors
Canadian Immunodeficiency Research Collaborative
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* HIV infected male * 18 years old or older * on maraviroc twice daily as part of their antiretroviral regimen for at least 3 months prior to screening * viral load \< 50 copies/mL at least one month prior to enrolling * able to read, understand and sign a written informed consent prior to initiation of the study * medically stable at the time of the study, with no evidence of acute illness
Exclusion criteria
* having difficulty adhering to current antiretroviral therapy * patient is expected to have difficulties adhering with study protocol * patients with malignancy, or acute renal or liver disease * patient with active AIDS-defining illness * patient with any medical, psychiatric or other circumstance that may impede the provision of informed consent * patient with any of the following abnormalities at the time of screening: * hemoglobin \< 85 g/L * absolute neutrophil count \< 1000 cells/uL * platelet count \< 50,000 cells/uL * AST, ALT or total bilirubin \> 3 times the upper limit of normal * serum creatinine \> 1.5 times upper limit of normal * patient receiving concomitant therapy with rifampin or St. John's wort
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Semen to Plasma Ratio of HIV Concentration During the Dosing Interval for Dar, Evr, Mar & Ral. | Semen samples were collected 30 minutes to 1 hour before the morning dose of medication (day 1), and then at hours 1, 2, 4, 8, and 12 postdrug ingestion on days 2-6. Blood samples were collected within 1 hour of the semen sample. | We used a staggered sampling approach in which semen samples were produced by participants over several days at different sampling times relative to the morning dose of antiretrovirals. Specifi- cally, semen samples were collected 30 minutes to 1 hour before the morning dose of medication (day 1), and then at hours 1, 2, 4, 8, and 12 postdrug ingestion on days 2-6. We collected corresponding blood samples within 1 hour of the semen sample. For each participant a single value (the HIV concentration ratio) was calculated as the minimum HIV concentration in the semen over the minimum HIV concentration in the blood throughout the dosing interval. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine the Extent of Maraviroc Penetration Into Semen by Obtaining Semen to Plasma Ratios Across the Dosing Interval | Semen samples were collected 30 minutes to 1 hour before the morning dose of medication (day 1), and then at hours 1, 2, 4, 8, and 12 postdrug ingestion on days 2-6. Blood samples were collected within 1 hour of the semen sample | For each participant, the Maraviroc penetration ratio was calculated as the maximum Maraviroc concentration in the semen over the maximum Maraviroc concentration in the blood throughout the dosing interval. |
| Determine the Area Under the Concentration Time Curve of Maraviroc in Semen. | 6 months | — |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 10 Male HIV-positive Patients Male HIV-positive patients who have been receiving stable antiretroviral therapy that includes maraviroc for a minimum of three months.
Measuring semen samples: Measure semen sample concentrations, obtain semen to plasma ratios across the dosing interval, the area under the concentration time curve of maraviroc in semen, the variability in the penetration of maraviroc into the seminal compartment over the raltegravir dosing period. | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | 10 Male HIV-positive Patients |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Age, Continuous | 51 years |
| Region of Enrollment Canada | 14 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Semen to Plasma Ratio of HIV Concentration During the Dosing Interval for Dar, Evr, Mar & Ral.
We used a staggered sampling approach in which semen samples were produced by participants over several days at different sampling times relative to the morning dose of antiretrovirals. Specifi- cally, semen samples were collected 30 minutes to 1 hour before the morning dose of medication (day 1), and then at hours 1, 2, 4, 8, and 12 postdrug ingestion on days 2-6. We collected corresponding blood samples within 1 hour of the semen sample. For each participant a single value (the HIV concentration ratio) was calculated as the minimum HIV concentration in the semen over the minimum HIV concentration in the blood throughout the dosing interval.
Time frame: Semen samples were collected 30 minutes to 1 hour before the morning dose of medication (day 1), and then at hours 1, 2, 4, 8, and 12 postdrug ingestion on days 2-6. Blood samples were collected within 1 hour of the semen sample.
Population: We used a staggered sampling approach in which semen samples were produced by participants over several days at different sampling times relative to the morning dose of antiretrovirals.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 10 Male HIV-positive Patients | Semen to Plasma Ratio of HIV Concentration During the Dosing Interval for Dar, Evr, Mar & Ral. | dar | 0.20 Inhibitory concentration ratio |
| 10 Male HIV-positive Patients | Semen to Plasma Ratio of HIV Concentration During the Dosing Interval for Dar, Evr, Mar & Ral. | evr | 0.16 Inhibitory concentration ratio |
| 10 Male HIV-positive Patients | Semen to Plasma Ratio of HIV Concentration During the Dosing Interval for Dar, Evr, Mar & Ral. | mar | 0.92 Inhibitory concentration ratio |
| 10 Male HIV-positive Patients | Semen to Plasma Ratio of HIV Concentration During the Dosing Interval for Dar, Evr, Mar & Ral. | ral | 4.32 Inhibitory concentration ratio |
Secondary
Determine the Area Under the Concentration Time Curve of Maraviroc in Semen.
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 10 Male HIV-positive Patients | Determine the Area Under the Concentration Time Curve of Maraviroc in Semen. | 3.43 h*mg/L |
Secondary
Determine the Extent of Maraviroc Penetration Into Semen by Obtaining Semen to Plasma Ratios Across the Dosing Interval
For each participant, the Maraviroc penetration ratio was calculated as the maximum Maraviroc concentration in the semen over the maximum Maraviroc concentration in the blood throughout the dosing interval.
Time frame: Semen samples were collected 30 minutes to 1 hour before the morning dose of medication (day 1), and then at hours 1, 2, 4, 8, and 12 postdrug ingestion on days 2-6. Blood samples were collected within 1 hour of the semen sample
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 10 Male HIV-positive Patients | Determine the Extent of Maraviroc Penetration Into Semen by Obtaining Semen to Plasma Ratios Across the Dosing Interval | 0.62 ratio |