Pierre Frange1, Lambert Assoumou2, Diane Descamps3, Antoine Chéret4, Cécile Goujard5, Laurent Tran6, Marine Gousset7, Veronique Avettand-Fenoël8, Laurence Bocket9, Samira Fafi-Kremer10, Jerome Guinard11, Laurence Morand-Joubert12, Florence Nicot13, Jean-Christophe Plantier14, Sylvie Rogez15, Marc Wirden16, Christine Rouzioux8, Laurence Meyer6, Marie-Laure Chaix17. 1. Laboratoire de Microbiologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker-Enfants Malades, Paris, France EA7327, Université Paris Descartes, Sorbonne Paris Cité, Paris, France pierre.frange@nck.aphp.fr. 2. Sorbonne Universités, UPMC Université Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France. 3. Laboratoire de Virologie, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France INSERM UMR1137 IAME, Université Paris Diderot, F-75018 Paris, France. 4. EA7327, Université Paris Descartes, Sorbonne Paris Cité, Paris, France Service de médecine interne, AP-HP, Hôpital Bicêtre, Le Kremlin Bicêtre, France. 5. Service de médecine interne, AP-HP, Hôpital Bicêtre, Le Kremlin Bicêtre, France INSERM CESP, U1018, Université Paris Sud, Faculté de Médecine Paris Sud, Le Kremlin Bicêtre, France. 6. INSERM CESP, U1018, Université Paris Sud, Faculté de Médecine Paris Sud, Le Kremlin Bicêtre, France Département d'Epidémiologie, AP-HP, Hôpital Bicêtre, Le Kremlin Bicêtre, France. 7. Laboratoire de Microbiologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker-Enfants Malades, Paris, France. 8. Laboratoire de Microbiologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker-Enfants Malades, Paris, France EA7327, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 9. Laboratoire de Virologie, Centre hospitalo-universitaire de Lille, Lille, France. 10. Laboratoire de Virologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France INSERM, U1109, LabEx TRANSPLANTEX Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg, France. 11. Laboratoire de Microbiologie, Centre hospitalier régional d'Orléans, Orléans, France. 12. Laboratoire de Virologie, AP-HP, Hôpital Saint Antoine, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France. 13. Laboratoire de Virologie, Institut fédératif de biologie de Purpan, CHU de Toulouse, Hôpital Purpan, F-31300 Toulouse, France. 14. Laboratoire de Virologie et COREVIH Haute Normandie, Centre hospitalo-universitaire Charles Nicolle, Rouen, France. 15. Laboratoire de Virologie, Centre hospitalo-universitaire de Limoges, Limoges, France. 16. Laboratoire de Virologie, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France. 17. Laboratoire de Virologie, AP-HP, Hôpital Saint Louis, INSERM U941, Université Paris Diderot, Laboratoire associé au Centre national de Référence du VIH, Paris, France.
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.
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.
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