Concentrations of Raltegravir in the Semen of HIV-Infected Men

Study Overview
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Brief Summary
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The objective of this study is to determine if concentrations of raltegravir in semen exceed the 50% and 95% inhibitory concentrations of HIV during the dose interval. The secondary objective is to determine the extend of raltegravir penetration into semen by obtaining semen to plasma ratios across the dosing interval, to determine the area under the concentration time curve of raltegravir in semen, and to determine the variability in the penetration of raltegravir into the seminal compartment over the dosing period.

Detailed Description
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The patient population will consist of 12 male HIV-positive patients who have been receiving stable antiretroviral therapy that includes raltegravir 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.

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

Conditions
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HIV

Intervention / Treatment
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* Other: Seminal plasma pharmacokinetics


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV infected male 18 years old or older on raltegravir 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/ microleter (uL) aspartate aminotransferase (AST), alanine transaminase (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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Raltegravir treated men<br>Single group study of seminal plasma pharmacokinetics of raltegravir in men receiving chronic raltegravir therapy | Other: Seminal plasma pharmacokinetics<br>* Measure semen sample concentrations, obtain semen to plasma ratios across the dosing interval, the area under the concentration time curve of raltegravir in semen, the variability in penetration of raltegravir into the seminal compartment over the dosing period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seminal Concentrations of Raltegravir. | Determine if concentrations of raltegravir in semen exceed the 50% and 95% inhibitory concentrations of HIV during the dosing interval. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Semen to Plasma Raltegravir Concentrations | Determine the extent of raltegravir penetration into semen by obtaining semen to plasma ratios across the dosing interval. | 6 months | 
| Seminal Distribution of Raltegravir | Determine the area under the concentration time curve of raltegravir in semen. | 6 months | 
| Semen to Plasma Distribution of Raltegravir | Determine the variability in the penetration of raltegravir into the seminal compartment over the raltegravir dosing period. | 6 months |