Doravirine Concentrations and Antiviral Activity in Genital Fluids in HIV-1 Infected Individuals

Study Overview
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Brief Summary
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This study aims to evaluate the ability of Doravirine to penetrate the genital tract and suppress viral replication and provide evidence for the use of Doravirine as part of treatment strategies as prevention.

Detailed Description
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Objectives: To determine Doravirine concentrations in seminal plasma and cervicovaginal fluid in HIV-1 infected male and female individuals receiving antiretroviral therapy (ATR) with Doravirine plus Descovy®. To evaluate HIV-1 viral load in seminal plasma and cervicovaginal fluid in HIV-1 infected male and female individuals receiving ART with Doravirine plus Descovy®. Study Phase: Phase II Study Design: Open label, single arm, single center, prospective study. Study Disease: HIV-1 infection Study Endpoints: Concentration of Doravirine in seminal plasma and cervicovaginal fluid in HIV-1 infected male and female individuals, respectively, 8 weeks after switching to Doravirine plus Descovy®. HIV-1 RNA in seminal plasma and cervicovaginal fluid in HIV-1 infected male and female individuals, respectively, 8 weeks after switching to Doravirine plus Descovy®. Target Population: Male and female adult HIV-1 infected patients receiving standard ART with tenofovir alafenamide/emtricitabine (TAF/FTC), tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine , plus an non-nucleoside reverse transcriptase inhibitor, a boosted protease inhibitor or an integrase inhibitor during at least 3 months, with plasma HIV-1 RNA suppression (<40 copies/mL) during at least 6 months. Number of Subjects Planned: 15 male and 15 female individuals. Study duration: 16 weeks

Official Title
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Doravirine Concentrations and Antiviral Activity in Genital Fluids in HIV-1 Infected Individuals

Conditions
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HIV-1-infection

Intervention / Treatment
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* Drug: Doravirine
* Drug: Descovy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Asymptomatic, HIV-1 infected individuals ≥ 18 years of age. Be on a stable ART consisting of TAF/FTC, tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine, plus an non-nucleoside reverse transcriptase inhibitor, a boosted protease inhibitor or an integrase inhibitor, continuously for at least 3 consecutive months preceding the screening visit. Plasma HIV-1 RNA <40 copies/mL for at least 6 months at the Screening visit. Signed and dated written informed consent prior to inclusion. Female Subjects of Childbearing Potential must agree to utilize a highly effective method of contraception during heterosexual intercourse from the screening visit throughout the duration of the study. Exclusion Criteria: Severe hepatic impairment (Child-Pugh Class C) Ongoing malignancy Active opportunistic infection Resistance to any of the antiretroviral (ARV) included in the study or history of virologic failure with risk of resistance selection to any of the study drugs. Any verified Grade 4 laboratory abnormality ALT or AST ≥ 3xULN and/or bilirubin ≥ 1.5xULN Severe renal impairment (Estimated creatinine filtration rate <50mL/min). Females who are pregnant (as confirmed by positive serum pregnancy test) or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Patients with Doravirine administered orally once daily in combination with Tenofovir alafenamide (TAF) and emtricitabine (FTC) co-formulated as single tablet (Descovy® TAF/FTC) and administered orally once daily.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Doravirine + Descovy® TAF/FTC<br>Doravirine (MK-1439) 100 mg administered orally once daily in combination with Tenofovir alafenamide (TAF) and emtricitabine (FTC) co-formulated as single tablet (Descovy® TAF/FTC 25/200 mg) and administered orally once daily during 16 weeks | Drug: Doravirine<br>* Doravirine 100 mg tablet<br>* Other names: MK-1439;Drug: Descovy<br>* Tenofovir alafenamide 25 mg / emtricitabine 200 mg tablet<br>* Other names: TAF/FTC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of Doravirine in Seminal Plasma Fluid | Concentration of Doravirine in seminal plasma fluid in HIV-1 infected male individuals | 8 weeks after switching (from baseline visit) to Doravirine plus TAF/FTC | 
| Concentration of Doravirine in Cervicovaginal Fluid | Concentration of Doravirine in cervicovaginal fluid in HIV-1 infected female individuals | 8 weeks after switching to Doravirine plus TAF/FTC | 
| Number of Participants With HIV-1 RNA Seminal Plasma <40 Copies/mL | Number of participants with HIV-1 RNA seminal plasma <40 Copies / mL of HIV measured by real-Time Reverse Transcriptase Polymerase Chain Reaction Amplification | 8 weeks after switching (from baseline visit) to Doravirine plus TAF/FTC | 
| Quantification of Participants With HIV-1 RNA <40 Copies / mL in Cervicovaginal Fluid | Number of participants with HIV-1 RNA cervicovaginal fluid<40 Copies / mL of HIV measured by real-Time Reverse Transcriptase Polymerase Chain Reaction Amplification | 8 weeks after switching (from baseline visit) to Doravirine plus TAF/FTC | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Doravirine