Charlotte Charpentier1,2, Gilles Peytavin1,3, François Raffi4, Charles Burdet1,5, Roland Landman1,6, Minh P Lê1,3, Christine Katlama7, Gilles Collin1,2, Aida Benalycherif8, André Cabie9, France Mentré1,5, Yazdan Yazdanpanah1,6, Diane Descamps1,2, Véronique Joly1,6. 1. Université de Paris, INSERM UMR 1137 IAME, F-75018 Paris, France. 2. Laboratoire de Virologie, AP-HP, Hôpital Bichat-Claude Bernard, F-75018 Paris, France. 3. Laboratoire de Pharmacologie-Toxicologie, Hôpital Bichat-Claude Bernard, F-75018 Paris, France. 4. Infectious Diseases Department, CHU Hôtel Dieu and INSERM UIC 1413 Nantes University, Nantes, France. 5. Département d'épidémiologie, Biostatistique et Recherche Clinique, Hôpital Bichat-Claude Bernard, F-75018 Paris, France. 6. Service de Maladies Infectieuses et Tropicales, Hôpital Bichat-Claude Bernard, F-75018 Paris, France. 7. Service de Maladies Infectieuses et Tropicales, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France. 8. IMEA, Fondation Léon M'ba, Paris, France. 9. Université des Antilles and Service de Maladies Infectieuses et Tropicales, CHU de Martinique, Fort de France, France.
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-MS/MS. 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%). 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.
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-MS/MS. 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%). 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.
Authors: Josep M Llibre; Pedro E Cahn; Janet Lo; Tristan J Barber; Cristina Mussini; Berend J van Welzen; Beatriz Hernandez; Cynthia Donovan; Michelle Kisare; Myooran Sithamparanathan; Jean van Wyk Journal: Open Forum Infect Dis Date: 2022-02-10 Impact factor: 3.835