Maintenance darunavir/ritonavir monotherapy to prevent perinatal HIV transmission, ANRS-MIE 168 MONOGEST study
Authors: Mandelbrot Laurent , Tubiana Roland , Frange Pierre , Peytavin Gilles , Le Chenadec Jerome , Canestri Ana , Morlat Philippe , Brunet-Cartier Cécile , Sibiude Jeanne , Peretti Delphine , Chambrin Véronique , Chabrol Amélie , Bui Eida , Simon-Toulza Caroline , Marchand Lucie , Paul Christelle , Delmas Sandrine , Avettand-Fenoel Véronique , Warszawski Josiane ,   the Monogest study group, Delmas Sandrine , Capitant Catherine , Fournier Isabelle , Saillard Juliette , Marchand Lucie , Meyer Elie Azria Laurence , Rouveix Elisabeth , Goetghebuer Tessa , Barin Francis , Leroy Valériane , Arvieux Cédric , Blanche Stéphane , Dommergues Marc , Frange Pierre , Guerin Corinne , Marchand Lucie , Peytavin Gilles , Pollard Hélène , Plantier Jean-Christophe , Avettand Fenoel Véronique , Tubiana Roland , Diallo Alpha , Paul Christelle , Mandelbrot Laurent , Sibiude Jeanne , Meier Françoise , Floch Corinne , Tubiana Roland , Dommergues Marc , Blanc Christine , Canestri Ana , Selleret Lise , Morlat Philippe , Hessamfar Mojgan , Caldato Sabrina , Peretti Delphine , Houllier Marie , Fourcade Corinne , Chambrin Véronique , Letourneau Alexandra , Clech Laure , Chabrol Amélie , Canon Bérengère , Granier Michèle , Bui Eida , Dollfus Catherine , Simon-Toulza Caroline , Brazet Edith , Abbal Julie , Matheron Sophie , Bourgeois Moine Agnès , Arvieux Cédric , Pannier Emmanuelle , Marcou Valérie , Medus Marie , Wajszczak Ilona , Genet Philippe , Tordjeman Nathalie , Brault Dominique , Genet Philippe , Rami Agathe , Maraux Barbara , Bottero Julie , Benbara Amélie , Lachassine Eric , Rosenthal Eric , Naqvi Alissa , Bongain André , Monpoux Fabrice , Cotte Laurent , Huissoud Cyril , Labaune Jean-Marc , Dupon Michel , Roux Denis , Elleau Christophe , Duvivier Claudine , Driessen Marine , Frange Pierre , Avettand-Fenoel Véronique , Gardiennet Elise , Karmochkine Marina , Zucman David , Laperrelle Juliette , Brunet-Cartier Cécile , Winer Norbert , Reliquet Véronique , Mambert Marina , Levier Axel , Ladjal Hayette , Houel Cleìa , Lebas Barbara , Rahmoun Manal , Eliette Véronique , Resch Martine , Gardiennet Elise , Le Chenadec Jérôme , Arezes Elisa 
Published: May 2023

Abstract

Objectives
Because NRTIs can have fetal toxicities, we evaluated a perinatal NRTI-sparing strategy to prevent perinatal HIV transmission. Our primary objective was to determine the proportion maintaining a viral load (VL) of &lt;50 copies/mL up to delivery on darunavir/ritonavir monotherapy, without requiring treatment intensification.

Methods
In a one-arm, multicentre Phase 2 clinical trial, eligible patients in the first trimester of pregnancy on ART with plasma VL &lt; 50 copies/mL received maintenance monotherapy with darunavir/ritonavir, 600/100 mg twice daily. VL was monitored monthly. ART was intensified in the case of VL &gt; 50 copies/mL. Neonates received nevirapine prophylaxis for 14 days.

Results
Of 89 patients switching to darunavir/ritonavir monotherapy, 4 miscarried before 22 weeks’ gestation, 2 changed treatment for elevated liver enzymes without virological failure, and 83 were evaluable for the main outcome. Six had virological failure confirmed on a repeat sample (median VL = 193 copies/mL; range 78–644), including two before switching to monotherapy. In these six cases, ART was intensified with tenofovir disoproxil fumarate/emtricitabine. The success rate was 75/83, 90.4% (95% CI, 81.9%–95.7%) considering two patients with VL missing at delivery as failures, and 77/83, 92.8% (95% CI, 84.9%–97.3%) when considering them as successes since both had undetectable VL on darunavir/ritonavir throughout pregnancy. In ITT, the last available VL before delivery was &lt;50 copies/mL in all of the patients. There was no case of perinatal HIV transmission.

Conclusions
Darunavir/ritonavir maintenance monotherapy required intensification in nearly 10% of cases. This limits its widespread use, thus other regimens should be evaluated in order to limit exposure to antiretrovirals, particularly NRTIs, during pregnancy.