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

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)

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)

Study Overview

• Status: Completed
• Conditions: HIV Infection Primary
• Intervention / Treatment: Drug: Dolutegravir

Detailed Description

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)

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: November 22, 2016
• First Submitted That Met QC Criteria: November 24, 2016
• First Posted (Estimate): November 29, 2016

Study Record Updates

• Last Update Posted (Actual): October 30, 2019
• Last Update Submitted That Met QC Criteria: October 28, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Slow Virus Diseases; HIV Infections; Infections; Communicable Diseases; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Dolutegravir
• Other Study ID Numbers: IMEA 051

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No