Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study
Authors: Gagliardini Roberta , Ciccullo Arturo , Borghetti Alberto , Maggiolo Franco , Bartolozzi Dario , Borghi Vanni , Pecorari Monica , Di Biagio Antonio , Callegaro Anna Paola , Bruzzone Bianca , Saladini Francesco , Paolucci Stefania , Maserati Renato , Zazzi Maurizio , Di Giambenedetto Simona , De Luca Andrea ,   ARCA Study Group, Mellace Vincenzo , Capetti Amedeo , Rita Gismondo Maria , Luisa Biondi Maria , Mussini Cristina , Pecorari Monica , Gianotti Nicola , Sacchini Daria , Parruti Giustino , Polilli Ennio , Baldelli Franco , Zanussi Stefania , Nerli Alessandro , Lenzi Lucia , Calzetti Carlo , Vivarelli Angela , Maserati Renato , Baldanti Fausto , Poletti Federica , Mondino Vincenzo , Malena Marina , Cascio Antonio , Filice Gaetano , Magnani Giacomo , Zerbini Alessandro , Lombardi Francesca , Di Giambenedetto Simona , Andreoni Massimo , Montano Marco , Vullo Vincenzo , Turriziani Ombretta , Zazzi Maurizio , Gonnelli Angela , De Luca Andrea , Boeri Enzo , Bonora Stefano , Ghisetti Valeria , Francisci Daniela , Grossi Paolo , Bagnarelli Patrizia , Butini Luca , del Gobbo Romana , Giacometti Andrea , Tacconi Danilo , Monno Laura , Punzi Grazia , Callegaro Annapaola , Maggiolo Franco , Zoncada Alessia , Paolini Elisabetta , Sighinolfi Laura , Colao Grazia , Corsi Paola , Blanc Pierluigi , Galli Luisa , Meraviglia Paola , Tosti Andrea , Bruzzone Bianca , Setti Maurizio , Penco Giovanni , Di Biagio Antonio , Nencioni Cesira , Pardelli Riccardo , Arcidiacono Irene , Degiuli Alberto , De Gennaro Michele , Soria Alessandro , Focà Alfredo , Surace Latella , Cosco Lucio , Malandrin Sergio , Milini Paola , Cicconi Paola , Rusconi Stefano , Micheli Valeria 
Published: May 2018

Abstract

Background
Dual therapy (DT) with boosted protease inhibitors (bPIs) plus lamivudine has been shown to be superior to bPI monotherapy in virologically suppressed patients despite previous selection of the lamivudine resistance M184V mutation. We compared the virological efficacy of lamivudine-based DT in patients with and without a history of M184V detection.

Methods
We retrospectively analyzed patients with HIV-RNA ≤50 copies/mL switching to DT with at least 1 previous resistance genotype in the ARCA database. Time to virological failure (VF; HIV-RNA ≥200 copies/mL or 2 consecutive HIV-RNA &gt;50 copies/mL) and to treatment discontinuation (TD) was analyzed by survival analysis.

Results
Four hundred thirty-six patients switching to lamivudine plus bPIs (70%) or integrase inhibitors (30%) were included. Patients with M184V (n = 87) were older, had lower nadir CD4+ cell count, longer duration of antiretroviral therapy and of virologic suppression, and higher rate of hepatitis C virus infection compared with patients without M184V. The 3-year probability of remaining free from VF was 91.9% (95% confidence interval [CI], 86.6–97.2) without M184V and 87.8% (95% CI, 78.4–97.2) with M184V (P = .323). The time to TD did not differ between groups. Multivariate analysis adjusting for baseline variables differing between groups also did not detect M184V as being associated with VF or TD; however, the 3-year probability of remaining free of viral blips (isolated HIV-RNA 51–199 copies/mL) was 79.8% (95% CI, 67.8%–91.8%) with M184V vs 90.1% (95% CI, 84.0%–96.2%) without M184V (P = .016).

Conclusions
Previous selection of M184V did not increase the risk of VF or TD with lamivudine-based DT but was associated with a higher probability of viral blips.