HIV
Conditions
Brief summary
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
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.
Interventions
OTHERSeminal plasma pharmacokinetics
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.
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seminal Concentrations of Raltegravir. | 6 months | Determine if concentrations of raltegravir in semen exceed the 50% and 95% inhibitory concentrations of HIV during the dosing interval. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Semen to Plasma Raltegravir Concentrations | 6 months | Determine the extent of raltegravir penetration into semen by obtaining semen to plasma ratios across the dosing interval. |
| Seminal Distribution of Raltegravir | 6 months | Determine the area under the concentration time curve of raltegravir in semen. |
| Semen to Plasma Distribution of Raltegravir | 6 months | Determine the variability in the penetration of raltegravir into the seminal compartment over the raltegravir dosing period. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Men on Raltegravir Measuring semen samples: 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. | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Men on Raltegravir |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 48 years |
| CD4 Count | 450 cells/mm^3 |
| Region of Enrollment Canada | 16 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
Seminal Concentrations of Raltegravir.
Determine if concentrations of raltegravir in semen exceed the 50% and 95% inhibitory concentrations of HIV during the dosing interval.
Time frame: 6 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 16 Male HIV-positive Patients | Seminal Concentrations of Raltegravir. | C-min | 0.18 mg/l |
| 16 Male HIV-positive Patients | Seminal Concentrations of Raltegravir. | C-max | 1.91 mg/l |
Secondary
Semen to Plasma Distribution of Raltegravir
Determine the variability in the penetration of raltegravir into the seminal compartment over the raltegravir dosing period.
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 16 Male HIV-positive Patients | Semen to Plasma Distribution of Raltegravir | 2.26 ratio |
Secondary
Semen to Plasma Raltegravir Concentrations
Determine the extent of raltegravir penetration into semen by obtaining semen to plasma ratios across the dosing interval.
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 16 Male HIV-positive Patients | Semen to Plasma Raltegravir Concentrations | 3.25 ratio |
Secondary
Seminal Distribution of Raltegravir
Determine the area under the concentration time curve of raltegravir in semen.
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 16 Male HIV-positive Patients | Seminal Distribution of Raltegravir | 6.83 h mg/l |