Pharmacovirological Analyses of Blood and Male Genital Compartment in Patients Receiving Dolutegravir + Lamivudine Dual Therapy as a Switch Strategy (ANRS 167 LAMIDOL Trial) - Sorbonne Université Access content directly
Journal Articles Journal of Antimicrobial Chemotherapy Year : 2020

Pharmacovirological Analyses of Blood and Male Genital Compartment in Patients Receiving Dolutegravir + Lamivudine Dual Therapy as a Switch Strategy (ANRS 167 LAMIDOL Trial)

André Cabié

Abstract

Abstract Objectives To describe plasma residual HIV viraemia, cellular HIV reservoir size, blood plasma drug concentrations and their male genital tract penetration during the maintenance dual therapy dolutegravir\,+\,lamivudine. Patients and methods ANRS167 LAMIDOL enrolled 104 virologically suppressed patients to switch to dolutegravir\,+\,lamivudine. In this pharmacovirological substudy, ultrasensitive plasma viral load (USpVL) and plasma drug concentrations were measured at Day 0 (D0), Week 24 (W24) and W48 of dolutegravir\,+\,lamivudine, and HIV-DNA was measured at W-8 and W48. Semen samples were collected at D0 and W24 from 18 participants. Total and unbound blood and seminal plasma drug concentrations were measured using UPLC\textendash MS/MS. Results Median HIV-DNA was 2.5\,log10\,copies/106 PBMC (IQR\,=\,2.2\textendash 3.0, n\,=\,100) at W-8 and 2.4\,log10\,copies/106 PBMC (IQR\,=\,2.1\textendash 2.9, n\,=\,100) at W48 (P\,=\,0.17). The proportion of patients with undetected USpVL was 38% (n\,=\,98), 43% (n\,=\,98) and 49% (n\,=\,97) at D0, W24 and W48, respectively (P\,=\,0.08). Total and unbound plasma dolutegravir concentrations were stable between timepoints (P\,=\,0.13) and all total plasma dolutegravir concentrations except one were adequate. Median free fraction of dolutegravir in plasma was 0.21%. Median blood plasma and seminal plasma concentrations of total dolutegravir at 24\,h were 1812\,ng/mL and 206\,ng/mL, respectively. Median seminal plasma/blood plasma total concentration ratios were 11.6% and 2478% for dolutegravir and lamivudine, respectively. HIV-RNA (365 to 475\,copies/mL) was detected in seminal plasma of one patient at D0 (5.9%) and of two patients at W24 (11.8%). Conclusions These findings add further important information regarding the effectiveness of dolutegravir\,+\,lamivudine maintenance dual therapy in terms of plasma residual viraemia, cellular reservoir size and drug penetration in the male genital tract.

Dates and versions

hal-03793443 , version 1 (01-10-2022)

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Charles Burdet, Roland Landman, Minh P Lê, Christine Katlama, Gilles Collin, et al.. Pharmacovirological Analyses of Blood and Male Genital Compartment in Patients Receiving Dolutegravir + Lamivudine Dual Therapy as a Switch Strategy (ANRS 167 LAMIDOL Trial). Journal of Antimicrobial Chemotherapy, 2020, 75 (6), pp.1611--1617. ⟨10.1093/jac/dkaa035⟩. ⟨hal-03793443⟩
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