Concentrations of Maraviroc in the Semen of HIV-Infected Men (NCT01009034)

Study to Determine the Concentrations of Maraviroc in Semen, the Seminal to Plasma Ratio of Maraviroc and the Variability in Seminal to Plasma Ratios Over the Maraviroc Dosing Period.

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.

Study Overview

• Status: Completed
• Conditions: Maraviroc Concentrations in Semen
• Intervention / Treatment: Other: Measuring semen samples

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.

• Study Type: Observational
• Enrollment (Actual): 14

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital
    • Toronto, Ontario, Canada, M5B1L6
      • Canadian Immunodeficiency Research Collaborative

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

12 HIV-positive males

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
12 male HIV-positive patients; Male HIV-positive patients who have been receiving stable antiretroviral therapy that includes maraviroc for a minimum of three months.	Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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
Determine the Area Under the Concentration Time Curve of Maraviroc in Semen.		6 months

Collaborators and Investigators

• Sponsor: Canadian Immunodeficiency Research Collaborative

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: November 5, 2009
• First Submitted That Met QC Criteria: November 5, 2009
• First Posted (Estimate): November 6, 2009

Study Record Updates

• Last Update Posted (Estimate): September 9, 2014
• Last Update Submitted That Met QC Criteria: September 8, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Other Study ID Numbers: WS 353380