HIV-1 subtype B-infected MSM may have driven the spread of transmitted resistant strains in France in 2007–12: impact on susceptibility to first-line strategies
Authors: Frange Pierre , Assoumou Lambert , Descamps Diane , Chéret Antoine , Goujard Cécile , Tran Laurent , Gousset Marine , Avettand-Fenoël Veronique , Bocket Laurence , Fafi-Kremer Samira , Guinard Jerome , Morand-Joubert Laurence , Nicot Florence , Plantier Jean-Christophe , Rogez Sylvie , Wirden Marc , Rouzioux Christine , Meyer Laurence , Chaix Marie-Laure ,   on behalf of the French ANRS CO 6 PRIMO Cohort, the ANRS 147 OPTIPRIM Clinical Trial and the AC11 Resistance Study Groups, Abel S. , Abraham B. , Allegre T. , Antoniotti A. , Armero R. , Audhuy B. , Aumaitre H. , Beaucaire G. , Beck-Wirth G. , Berger J.L. , Bernard L. , Beuscart C. , Bodard L. , Bouchaud O. , Boué F. , Cabane J.-P. , Cabie A. , Champagne H. , Cheneau C. , Chennebault J.-M. , Cheret A. , Christian B. , Compagnucci A. , Daneluzzi V. , Debab Y. , Dellamonica P. , Delfraissy J.-F. , Devidas A. , Diab G. , Doll J. , Drobacheff-Thebaut M.C. , Durel A. , Duvivier C. , Esnault J.-L. , Faba L. , Froguel E. , Garipuy D. , Garrait V. , Geffray L. , Genet C. , Genet P. , Gerard L. , Ghosn J. , Girard J-.J. , Girard P.-M. , Godin-Collet C. , Hochedez P. , Hoen B. , Houlbert D. , Jacomet C. , Jeantils V. , Jidar K. , Katlama C. , Klement E. , Lafeuillade A. , Lascoux C. , Launay V. , Lepretre A. , Levy Y. , Makhloufi D. , Malbec D. , Martha B. , May T. , Merrien D. , Miailhes P. , Miodovski C. , Molina J.-M. , Morlat P. , Mortier E. , Neau D. , Obadia M. , Patey O. , Pellegrin J.-L. , Perronne V. , Philibert P. , Pialoux G. , Pichancourt G. , Piroth L. , Poinsignon Y. , Poizot-Martin I. , Prazuck T. , Prendki V. , du Clary F. Preveteau , Quinsat D. , Raffi F. , Regnier A. , Reynes J. , Rosenthal E. , Rouveix E. , Salmon D. , Salanville F. , Schmitt J.-L. , Simon-Coutellier A. , Sotto A. , Souala F. , Stein A. , Timsit F. , de Truchis P. , Uludag A. , Vaillant O. , Verdon R. , Verlesch-Langlin A. , Viard J.-P. , Vittecoq D. , Weiss L. , Yéni P. , Zucman D. , Allavena C. , Allegre T. , Amri I. , Autran B. , Bacchus C. , Blanc C. , Bonne S. , Bonnet B. , Bouchez S. , Charlier C. , Consigny P.-H. , Duvivier C. , Fourn E. , Guiroy F. , Huleux T. , Katlama C. , Lascoux-Combe C. , Leplatois A. , Lyavanc T. , Molina J.-M. , Naqvi A. , Nembot G. , Quertainmont Y. , Raffi F. , Samri A. , Schneider L. , Seang S. , Seksik B.C.P. , Shoai-Tehrani M. , Slama L. , Valentin M.-A. , Yazdanpanah Y. , Alloui C. , Amiel C. , André P. , André-Garnier E. , Anies G. , Barin F. , Bellecave P. , Bettinger D. , Bouvier-Alias M. , Brun-Vézinet F. , Calmy A. , Calvez V. , Caveng W. , Chaillon A. , Chapalay S. , Charpentier C. , Costagliola D. , Cottalorda J. , Delamare C. , Delaugerre C. , Dina J. , Santos G. Dos , Férré V. , Flandre P. , Fleury H. , Fourati S. , Gaille C. , Giraudeau G. , Guigon A. , Haim-Boukobza S. , Lagier E. , Le Guillou-Guillemette H. , Henquell C. , Izopet J. , Lambert-Niclot S. , Leroux M. , Maillard A. , Malet I. , Marcelin A.-G. , Marque-Juillet S. , Masquelier B. , Mirand A. , Morand P. , Montes B. , Mouna L. , Noel C. , Pallier C. , Peytavin G. , Pinson-Recordon P. , Poveda J.D. , Raymond S. , Reigadas S. , Roques A.-M. , de Rougemont A. , Roussel C. , Schmitt M.-P. , Schneider V. , Schvoerer E. , Signori-Schmuck A. , Soulié C. , Tamalet C. , Tardy J.C. , Trabaud M.-A. , Vabret A. , Vallet S. , Yerly S. 
Published: February 2017

Abstract

Background
Our study describes the prevalence of transmitted drug resistance (TDR) among 1318 French patients diagnosed at the time of primary HIV-1 infection (PHI) in 2007–12.

Methods
HIV-1 resistance-associated mutations (RAMs) were characterized using both the 2009 WHO list of mutations and the French ANRS algorithm. A genotypic susceptibility score was estimated for each first-line recommended ART combination.

Results
Patients were mainly MSM (72.6%). Non-B variants were identified in 33.7% of patients. The proportion of TDR was estimated as 11.7% (95% CI 10.0–13.5). The prevalences of PI-, NRTI-, first-generation NNRTI and etravirine/rilpivirine-associated RAMs were 2.5%, 5.2%, 3.9% and 3.2%, respectively. Single, dual and triple class resistance was found in 9.6%, 1.0% and 1.1% of cases, respectively. Additionally, 5/331 strains isolated in 2010–12 had integrase inhibitor (II)-related RAMs (isolated E157Q mutation in all cases). TDR was more common among MSM than in other groups (12.9% versus 8.6%, P = 0.034), and in case of B versus non-B subtype infections (13.6% versus 7.9%, P = 0.002). The proportions of fully active combinations were ≥99.2%, ≥97.3% and ≥95.3% in cases of PI-, II- and NNRTI-based regimens, respectively. In 2010–12, the proportion of fully active efavirenz-based ART was lower in cases of subtype B versus non-B infection (P = 0.021).

Conclusions
Compared with our previous studies, the proportion of NRTI- and first-generation NNRTI-related TDR has continued to decline in French seroconverters. However, subtype B-infected MSM could drive the spread of resistant HIV strains. Finally, we suggest preferring PI- or II- to NNRTI-based combinations to treat PHI patients.