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Pharmacovirological analyses of blood and male genital compartment in patients receiving dolutegravir + lamivudine dual therapy as a switch strategy (ANRS 167 LAMIDOL trial).
- Source :
-
The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2020 Jun 01; Vol. 75 (6), pp. 1611-1617. - Publication Year :
- 2020
-
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.<br />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-MS/MS.<br />Results: Median HIV-DNA was 2.5 log10 copies/106 PBMC (IQR = 2.2-3.0, n = 100) at W-8 and 2.4 log10 copies/106 PBMC (IQR = 2.1-2.9, 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%).<br />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.<br /> (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Chromatography, Liquid
Genitalia, Male
Heterocyclic Compounds, 3-Ring therapeutic use
Humans
Lamivudine therapeutic use
Leukocytes, Mononuclear
Male
Oxazines
Piperazines therapeutic use
Pyridones
Tandem Mass Spectrometry
Viral Load
Anti-HIV Agents therapeutic use
HIV Infections drug therapy
HIV-1
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2091
- Volume :
- 75
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of antimicrobial chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 32091102
- Full Text :
- https://doi.org/10.1093/jac/dkaa035