Genotypic resistance profiles of HIV-2-treated patients in West Africa

Charpentier, Charlottea; Eholié, Sergeb,c,d; Anglaret, Xavierd,e,f; Bertine, Mélaniea; Rouzioux, Christineg; Avettand-Fenoël, Véroniqueg; Messou, Eugènec,d; Minga, Albertd; Damond, Florencea; Plantier, Jean-Christopheh; Dabis, Françoise,f; Peytavin, Gillesi; Brun-Vézinet, Françoisea; Ekouevi, Didier K.d,e,f,j; the IeDEA West Africa Collaboration

doi: 10.1097/QAD.0000000000000244
Clinical Science

Objective: To assess the virological response, genotypic resistance profiles, and antiretroviral plasma concentrations in HIV-2 antiretroviral-treated (antiretroviral therapy, ART) patients in Côte d‘Ivoire.

Methods: A cross-sectional survey was conducted among HIV-2 patients receiving ART. Plasma HIV-2 viral load was performed using the Agence Nationale de Recherche sur le SIDA et les hépatites virales (ANRS) assay. Protease and reverse transcriptase sequencing was performed using in-house methods and antiretroviral plasma concentrations were assessed using ultra performance liquid chromatography combined with tandem mass spectrometry.

Results: One hundred and forty-five HIV-2-treated patients were enrolled with a median CD4+ cell count of 360 cells/μl (interquartile range, IQR = 215–528). Median duration of ART was 4 years (IQR = 2–7) and 74% of patients displayed viral load less than 50 copies/ml. Median plasma HIV-2 RNA among patients with viral load more than 50 copies/ml was 3016 copies/ml (IQR = 436–5156). Most patients (84%) received a lopinavir/ritonavir-based regimen. HIV-2 resistance mutations to nucleoside reverse transcriptase inhibitors and protease inhibitors were detected in 21 of 25 (84%) and 20 of 29 (69%) samples, respectively. The most prevalent nucleoside reverse transcriptase inhibitor resistance mutations were M184I/V (90%), Q151M (24%), and S215F/Y (24%). The most prevalent protease inhibitor resistance mutations were V47A (60%) and I54M (30%). Median CD4+ cell counts were 434 cells/μl (292–573) and 204 cells/μl (122–281) in patients with viral load less than 50 copies/ml and those exhibiting virological failure (P < 0.0001), respectively. The proportions of patients with adequate antiretroviral plasma concentrations were 81 and 93% in patients displaying virological failure and in those with viral load less than 50 copies/ml, respectively (P = 0.046), suggesting good treatment adherence.

Conclusion: We observed adequate drug plasma concentrations and virological suppression in a high proportion of HIV-2-infected patients. However, in cases of virological failure, the limited HIV-2 therapeutic arsenal and cross-resistance dramatically reduced treatment options.

aLaboratoire de Virologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Bichat-Claude Bernard, HUPNVS, Université Paris Diderot, Sorbonne Paris Cité, Paris, France

bDepartment of Infectious and Tropical Diseases, Treichville University Teaching Hospital

cDepartment of Dermatology-Infectiology, Medical School, University Felix Houphouët-Boigny

dProgramme PACCI, Site ANRS, Abidjan, Côte d’Ivoire

eUniversité Bordeaux, INSERM, IPSED, Centre INSERM U897-Epidémiologie et Biostatistique

fINSERM, IPSED, Centre INSERM U897-Epidémiologie et Biostatistique, Bordeaux

gLaboratoire de Virologie, Faculté de Médecine, AP-HP, Hôpital Necker, Université René Descartes, Sorbonne Paris Cité, Paris

hLaboratoire de Virologie, Pôle de Biologie Clinique, Hôpital Charles Nicolle, CHU de Rouen and EA2656, IRIB, Université de Rouen, Rouen

iLaboratoire de Pharmaco-Toxicologie, AP-HP, Groupe Hospitalier Bichat-Claude Bernard, HUPNVS, Université Paris Diderot, Sorbonne Paris Cité, Paris, France

jFaculté des Sciences de la Santé, Département de Santé Publique, Université de Lomé, Lomé, Togo.

Correspondence to Dr Charlotte Charpentier, Laboratoire de Virologie, Hôpital Bichat-Claude Bernard, 46 Rue Henri Huchard, 75018 Paris, France. Tel: +33 1 40 25 61 50; fax: +33 1 40 25 67 69; e-mail: charlotte.charpentier@bch.aphp.fr

Received 14 December, 2013

Revised 31 January, 2014

Accepted 31 January, 2014

This study is presented in part at the International Workshop on HIV & Hepatitis Virus Drug Resistance and Curative Strategies, Toronto, Canada, June 2013 [abstract 58].

© 2014 Lippincott Williams & Wilkins, Inc.