Kinetics of HIV-RNA Decay in Seminal Plasma of Men Treated by Dolutegravir at the Time of Primary HIV Infection

Study Overview
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Brief Summary
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Sponsor: IMEA - Fondation Internationale Léon Mba C.H.U. Bichat - Claude Bernard 46, Rue Henri Huchard - 75018 PARIS Tél. : 01.40. 25. 63. 65 - Fax : 01.40.25.63.56 Coordinating investigator: Dr Caroline Lascoux Combe Hôpital Saint Louis Service Maladies Infectieuses 1 avenue Claude Vellefaux - 75010 PARIS Tél. : 01 42 49 49 73 - Fax : 01 42 49 47 43 E-mail : caroline.lascoux-combe@aphp.fr Participating country : FRANCE Primary objective : Comparing the kinetic of HIV-RNA decay in blood plasma and in seminal plasma in patients starting a triple combination regimen with dolutegravir + tenofovir DF (TDF) + emtricitabine (FTC) at the time of PHI. Secondary objectives : Comparison of HIV-1 RNA level in plasma (threshold 20 and 1 copies/ml) and in seminal plasma (threshold 60 copies/ml) at each visit D0, W2, W4, W8, W12, W24, W36, W48 To assess the frequency of intermittent shedding in seminal plasma once virological suppression has been achieved and until W48 Evolution of cellular HIV-1 DNA level in PBMC and in non-sperm cells between D0 and W48 Comparison of dolutegravir concentration in blood plasma and seminal plasma Study of risk factors associated with viral persistence of HIV-RNA in the seminal plasma Analysis by deep sequencing of the viral population (quasi-species) in both compartments (blood plasma and seminal plasma) before virological suppression has been achieved (i.e. at D0 and W12) Inclusion criteria : Patients diagnosed at the time of primary HIV infection (PHI) (i) a negative or indeterminate HIV ELISA associated with a positive antigenemia or plasma HIV RNA, (ii) a western blot profile compatible with ongoing seroconversion (incomplete western blot with absence of antibodies to pol proteins (p34, p68)) or (iii) an initially negative test for HIV antibodies followed within 3 months by a positive HIV serology Treatment including dolutegravir (DTG 50mg) + tenofovir/emtricitabine (TDF/FTC 245 mg/200 mg) initiated by the referee physician within a maximum of 15 days after diagnosis of PHI Genotypic sensitivity to TDF, FTC and DTG Patient with medical care insurance Exclusion criteria : Chronic infection Infection or co-infection with HIV-2 Study treatment : Dolutegravir and tenofovir/emtricitabine Number of subjets : 20 patients (exploratory study)

Detailed Description
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Secondary objectives : Comparison of HIV-1 RNA level in plasma (threshold 20 and 1 copies/ml) and in seminal plasma (threshold 60 copies/ml) at each visit D0, W2, W4, W8, W12, W24, W36, W48 To assess the frequency of intermittent shedding in seminal plasma once virological suppression has been achieved and until W48 Evolution of cellular HIV-1 DNA level in PBMC and in non-sperm cells between D0 and W48 Comparison of dolutegravir concentration in blood plasma and seminal plasma Study of risk factors associated with viral persistence of HIV-RNA in the seminal plasma Analysis by deep sequencing of the viral population (quasi-species) in both compartments (blood plasma and seminal plasma) before virological suppression has been achieved (i.e. at D0 and W12) Inclusion criteria : Patients diagnosed at the time of primary HIV infection (PHI) (i) a negative or indeterminate HIV ELISA associated with a positive antigenemia or plasma HIV RNA, (ii) a western blot profile compatible with ongoing seroconversion (incomplete western blot with absence of antibodies to pol proteins (p34, p68)) or (iii) an initially negative test for HIV antibodies followed within 3 months by a positive HIV serology Treatment including dolutegravir (DTG 50mg) + tenofovir/emtricitabine (TDF/FTC 245 mg/200 mg) initiated by the referee physician within a maximum of 15 days after diagnosis of PHI Genotypic sensitivity to TDF, FTC and DTG Patient with medical care insurance Exclusion criteria : Chronic infection Infection or co-infection with HIV-2 Study treatment : Dolutegravir and tenofovir/emtricitabine Number of subjets : 20 patients (exploratory study)

Official Title
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Kinetics of HIV-RNA Decay in Seminal Plasma of Men Receiving a Dolutegravir-based Regimen at the Time of Primary HIV Infection (IMEA 051-DOLUPRIM Study)

Conditions
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HIV Infection Primary

Intervention / Treatment
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* Drug: Dolutegravir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed at the time of primary HIV infection (PHI) (i) a negative or indeterminate HIV ELISA associated with a positive antigenemia or plasma HIV RNA, (ii) a western blot profile compatible with ongoing seroconversion (incomplete western blot with absence of antibodies to pol proteins (p34, p68)) or (iii) an initially negative test for HIV antibodies followed within 3 months by a positive HIV serology Treatment including dolutegravir (DTG 50mg) + tenofovir/emtricitabine (TDF/FTC 245 mg/200 mg) initiated by the referee physician within a maximum of 15 days after diagnosis of PHI Genotypic sensitivity to TDF, FTC and DTG Patient with medical care insurance Exclusion Criteria: Chronic infection Infection or co-infection with HIV-2

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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patient HIV primary infection<br>HIV primary infection Patient male receiving Dolutegravir | Drug: Dolutegravir<br>* All patients included must have treated by dolutegravir. They will have some exams (plasma samples, sperm samples)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparing the kinetic of HIV-RNA decay in blood plasma and in seminal fluid | Measure of HIV-RNA level in blood plasma and seminal fluid at each point and comparaison about the decay between both | 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The evolution of HIV proviral DNA in the peripheral blood mononuclear cells (PBMC) and in seminal fluid |  | Day 0 and 48 weeks | 
| Comparison of dolutegravir concentration in blood plasma and seminal fluid | Measure of doltegravir concentration in blood and seminal fluid at each points and comparaison of the value between the 2 compartments | 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks | 
| Analysis by deep sequencing of the viral population (quasi-species) in both compartments (blood plasma and seminal plasma) before virological suppression has been achieved |  | Day 0 and 12 weeks |