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

作者：Marcelin Anne Genevieve^*; Delaugerre Constance; Beaudoux Celine; Descamps Diane; Morand Joubert Laurence; Amiel Corinne; Schneider Veronique; Ferre Virginie; Izopet Jacques; Si Mohamed Ali; Maillard Anne; Henquell Cecile; De**ois 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

来源：International Journal of Antimicrobial Agents, 2013, 42(1): 42-47.

DOI：10.1016/j.ijantimicag.2013.02.016

• Integrase
• Inhibitor
• Raltegravir
• Mutations
• Efficacy
• HIV-1
• Response

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) %26lt;50 copies/mL. The impacts on VR of baseline integrase mutations, VL, CD4 count, genotypic sensitivity score for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors, and the number of new antiretrovirals used for the first time associated with RAL were investigated. For patients with VL %26gt;50 copies/mL at M6, integrase mutations selected were characterised. Median baseline VL was 4.2 log(10) copies/mL (IQR 3.3-4.9 log(10) copies/mL) and CD4 count was 219 cells/mm(3) (IQR 96-368 cells/mm(3)). At M6, 71% of patients were responders. In multivariate analysis, baseline VL and CD4 count and %26gt;= 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 %26gt;= 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 %26gt;= 1 RAL-associated resistance mutation were VL at failure %26gt;3 log(10) 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.

• 出版日期2013-7