First Study to Evaluate the Capacity of Maraviroc Drug to Protect Against HIV Infection in Samples of Rectal Mucosa From Healthy Volunteers

Study Overview
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Brief Summary
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Pre-exposure prophylaxis (PrEP) is a method of preventing HIV infection through the use of antiretroviral (ARV) medications before exposure to HIV. This study will assess the potential of MVC as a on demand pre-exposure prophylaxis, within a strategy for the prevention of HIV infection in men who have sex with men (MSM).

Detailed Description
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Several clinical trials are currently under way evaluating the safety and effectiveness of ARV-based PrEP for preventing HIV infection. The results of the first efficacy trials of ARV-based PrEP showed fewer HIV infections among study participants receiving the study drugs compared to those receiving placebo. Although the results are promising, concerns about adherence, pharmacokinetics, and toxicity still needs further exploration so new and more effective preventive pharmacological approaches should be evaluated. This trial will evaluate the safety, pharmacokinetics and efficacy of ex vivo HIV infection of rectal mucosa by the CCR5 antagonist drug maraviroc (Selzentry) administered to healthy volunteers. This trial will last approximately one year. Twenty-one volunteers will receive MVC 300 mg orally in a single dose. Study visits will occur at enrollment and at days 0, 7, 9, 14 and 16. All study visits will include a physical examination, blood collection and storage and in the basal visit and a day 7 or 9 the participants will undergo a colonoscopy. Ex vivo HIV infectivity in rectal mucosa biopsies and plasma/mucosa MVC levels will be evaluated.

Official Title
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PILOT STUDY OF PROTECTION AGAINST ex Vivo HIV INFECTION IN RECTAL MUCOSA IN HEALTHY VOLUNTEERS AFTER ADMINISTRATION OF MARAVIROC

Conditions
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HIV

Intervention / Treatment
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* Drug: Maraviroc
* Drug: TVD 300/200 QD
* Drug: Maraviroc


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men who have sex with men (MSM) Age 18 years or above HIV negative at the time of inclusion 4. Signed informed consent Exclusion Criteria: Existence of sexually transmitted infection (STI) or active systemic infection Submit a contraindication to rectal biopsy Take any drugs concomitantly with interactions with the MVC Subject unable to follow protocol

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MVC 300 mg<br>MVC 300 mg in unique dose | Drug: Maraviroc<br>* Unique dose of Maraviroc 300mg<br>|
| Active Comparator: TVD 300/200 QD<br>TVD 300/200 QD during 7 days. | Drug: TVD 300/200 QD<br>* TVD 300/200 QD during 7 days<br>|
| Experimental: Maraviroc 600mg<br>MVC 600mg in unique dose | Drug: Maraviroc<br>* Unique dose of Maraviroc 600mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infectivity of HIV: p24 production | HIV replication will be measured by the determination of HIV p24 production in culture supernatant after 12 days of culture. The HIV production in ex vivo cultures from the basal and after drug administration will be compared and the results will be expressed as a measure of Maraviroc efficacy. | Baseline | 
| Infectivity of HIV: p24 production | HIV replication will be measured by the determination of HIV p24 production in culture supernatant after 12 days of culture. The HIV production in ex vivo cultures from the basal and after drug administration will be compared and the results will be expressed as a measure of Maraviroc efficacy. | Visit 1 (Group 1: day 8, Group 2: day 7, Grop 3: day 9) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maraviroc plasmatic levels |  | Visit 1 (Group 1: day 8, Group 2: day 7, Grop 3: day 9) | 
| Maraviroc levels in rectal mucosa |  | Visit 1 (Group 1: day 8, Group 2: day 7, Grop 3: day 9) | 
| Truvada plasmatic levels |  | Visit 1 (day 7) | 
| Truvada levels in rectal mucosa |  | Visit 1 (day 7) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Maraviroc, PrEP, Ex vivo infection, rectal mucosa.