A cohort study of treatment-experienced HIV-1-infected patients treated with raltegravir: factors associated with virological response and mutations selected at failure

• Published in: International journal of antimicrobial agents 2013-07, Vol.42 (1), p.42-47
• Main Authors: Marcelin, Anne-Geneviève, Delaugerre, Constance, Beaudoux, Céline, Descamps, Diane, Morand-Joubert, Laurence, Amiel, Corinne, Schneider, Veronique, Ferre, Virginie, Izopet, Jacques, Si-Mohamed, Ali, Maillard, Anne, Henquell, Cécile, Desbois, Delphine, Lazrek, Mouna, Signori-Schmuck, Anne, Rogez, Sylvie, Yerly, Sabine, Trabaud, Mary-Anne, Plantier, Jean-Christophe, Fourati, Slim, Houssaini, Allal, Masquelier, Bernard, Calvez, Vincent, Flandre, Philippe
• Format: Article
• Language: English
• Subjects: Anti-HIV Agents - therapeutic use; Antiretroviral Therapy, Highly Active - methods; CD4 Lymphocyte Count; Cohort Studies; Drug Resistance, Viral; Efficacy; Female; HIV Infections - drug therapy; HIV Infections - virology; HIV-1; HIV-1 - genetics; HIV-1 - isolation & purification; Humans; Infectious Disease; Inhibitor; Integrase; Life Sciences; Male; Microbiology and Parasitology; Mutation, Missense; Mutations; Pyrrolidinones - therapeutic use; Raltegravir; Raltegravir Potassium; Response; RNA, Viral - blood; Treatment Failure; Viral Load
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2013.02.016

Abstract This study aimed to identify factors associated with virological response (VR) to raltegravir (RAL)-containing regimens in 468 treatment-experienced but integrase inhibitor-naive HIV-1 patients receiving a RAL-containing regimen. VR was defined at Month 6 (M6) as HIV-1 RNA viral load (VL) 50 copies/mL at M6, integrase mutations selected were characterised. Median baseline VL was 4.2 log10 copies/mL (IQR 3.3–4.9 log10 copies/mL) and CD4 count was 219 cells/mm3 (IQR 96–368 cells/mm3 ). At M6, 71% of patients were responders. In multivariate analysis, baseline VL and CD4 count and ≥2 new antiretrovirals among darunavir, etravirine, maraviroc and enfuvirtide were associated with VR to RAL. Neither HIV-1 subtype nor baseline integrase polymorphisms were associated with VR to RAL. Among 63 failing patients at M6, selection of ≥1 change in the integrase gene was observed in 49 (77.8%), and 27/63 (42.9%) were considered as RAL-associated resistance mutations. Factors independently associated with the occurrence of ≥1 RAL-associated resistance mutation were VL at failure >3 log10 and having no new drugs associated with RAL. RAL showed great potency in treatment-experienced patients. The number of new drugs associated with RAL was an important factor associated with VR. HIV-1 subtype and baseline integrase polymorphisms do not influence the RAL VR.