JAC Advance Access originally published online on May 2, 2009
Journal of Antimicrobial Chemotherapy 2009 64(1):135-141; doi:10.1093/jac/dkp151
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Original research |
High frequency of X4/DM-tropic viruses in PBMC samples from patients with primary HIV-1 subtype-B infection in 1996–2007: the French ANRS CO06 PRIMO Cohort Study
1 Université Paris Descartes, EA 3620, AP-HP, Laboratoire de Virologie, Hôpital Necker—Enfants Malades, Paris, France 2 Unité d’Immunologie, Hématologie et Rhumatologie pédiatriques, Hôpital Necker—Enfants Malades, AP-HP, Paris, France 3 Service de Médecine Interne et Maladies Infectieuses, Hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, France 4 Inserm, U822, Université Paris-Sud, Faculté de Médecine Paris-Sud, AP-HP, Hopital Bicêtre, Service d’épidémiologie et de santé publique, 94276 Le Kremlin-Bicêtre, France
Received 4 February 2009; returned 1 March 2009; revised 30 March 2009; accepted 2 April 2009
* Corresponding author. EA 3620, Université Paris Descartes, Laboratoire de Virologie, Hôpital Necker, 149 rue de Sèvres, 75015 Paris, France. Tel: +33-1-44-49-49-61; Fax: +33-1-44-49-49-60; E-mail: marie-laure.chaix{at}nck.aphp.fr
Objectives: To estimate the frequency of viruses with X4 or dual-X4/DM tropism from peripheral blood mononuclear cells (PBMCs) of 390 human immunodeficiency virus type 1 (HIV-1) subtype-B patients diagnosed at the time of primary HIV-1 infection (PHI) between 1996 and 2007 and enrolled in the PRIMO Cohort.
Methods: V3 loop sequences were amplified from HIV-1-DNA and analysed with a combination of five genotypic rules to predict tropism: (i) the ‘11/25 rule’; (ii) the net charge rule; (iii) the PSSMX4/DM algorithm; (iv) the PSSMSI/NSI algorithm; and (v) the SVMGeno2pheno algorithm.
Results: A high proportion (62/390, 15.9%) of patients harboured X4/DM-tropic viruses. This prevalence was stable over time: 18.1% before 2003 versus 14.8% since 2003. No difference according to HIV tropism was noted in HIV-RNA levels, CD4 cell count, time between infection and enrolment, and HIV infection risk factor. The frequency of X4/DM-tropic virus was similar among patients infected with a resistant virus (12/62, 19.4%) compared with patients harbouring wild-type strains (50/328, 15.2%).
Conclusions: This large French epidemiological study evidenced a high proportion of patients (15.9%) harbouring X4/DM-tropic viruses in PBMCs at the time of PHI, suggesting the existence of a cellular X4/DM viral reservoir that could persist for lengthy period of time. Several reports identified that HIV-1 CXCR4 usage was more frequent among patients who developed AIDS and was a powerful predictor of the response to antiretrovirals. Further studies are needed to evaluate the impact of such strains on the outcome of HIV disease, when they are detected at the time of primary infection.
Keywords: CXCR4 virus , co-receptors , primary infection , genotypic algorithm
These two authors contributed equally to the work.