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.
OBJECTIVE
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 PSSM(X4/DM) algorithm; (iv) the PSSM(SI/NSI) algorithm; and (v) the SVM(Geno2pheno) 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.
Frange
Pierre
P
EA 3620, AP-HP, Laboratoire de Virologie, Hôpital Necker-Enfants Malades, Université Paris Descartes, Paris, France.
Galimand
Julie
J
Goujard
Cécile
C
Deveau
Christiane
C
Ghosn
Jade
J
Rouzioux
Christine
C
Meyer
Laurence
L
Chaix
Marie-Laure
ML
D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification* / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008297:Male; D012367:RNA, Viral / Q000235:genetics; D015728:Receptors, HIV / Q000032:analysis*; D017422:Sequence Analysis, DNA; D053585:Virus Attachment; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics
D012367:RNA, Viral; D015728:Receptors, HIV; D054299:env Gene Products, Human Immunodeficiency Virus