Analysis of CCR5, CCR2, CX3CR1, and SDF1 polymorphisms in HIV-positive treated patients: impact on response to HAART and on peripheral T lymphocyte counts.
Although polymorphisms of chemokine genes (SDF1, stromal cell-derived factor-1 and RANTES, regulated on activation, normal T cell expressed and secreted) and chemokine-receptor genes (CCR5, CCR2, CX(3)CR1) were shown to be associated with sensitivity to HIV infection and untreated HIV disease progression, their association with the response to highly active antiretroviral therapy (HAART) remains unclear. To explore the possible influence of such polymorphisms on the evolution of AIDS in treated patients, we have studied SDF1-3'A, CCR5Delta32, CCR2-64I, CX(3)CR1-249I, and CX(3)CR1-280M polymorphisms in HIV-infected patients under HAART (n = 169). We studied the evolution of plasma virus load and peripheral T lymphocyte counts in these patients up to 3 years after the initiation of HAART. We observed that some of the genetic polymorphisms studied had an impact on the evolution of these two parameters. After 1 year of HAART, patients with a virological response (undetectable plasma HIV-1 RNA) have a higher frequency of the homozygous SDF1-3'A genotype than other patients (p = 0.005). Similarly, patients with a CD4 increase of over 200/mm(3) from baseline after 1 year of HAART display higher frequencies of homozygous SDF1-3'A (p = 0.035) and homozygous CX(3)CR1-280M genotypes (p = 0.04) than other patients. Moreover, we showed that the CX(3)CR1- 280M allele was associated with higher peripheral CD4+ T cell counts not only in HIV+ patients but also in healthy controls (p = 0.003).
Laboratoire d'Immunogénétique Moléculaire, Université Paul Sabatier, Faculté de Médecine Toulouse-Rangueil, 31062 Toulouse Cedex 04, France.
Bénédicte
B
Puissant
Francis
F
Roubinet
Patrice
P
Massip
Karine
K
Sandres-Saune
Pol-André
PA
Apoil
Michel
M
Abbal
Christophe
C
Pasquier
Jacques
J
Izopet
Antoine
A
Blancher
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001483:Base Sequence; D018791:CD4 Lymphocyte Count; D000073883:CX3C Chemokine Receptor 1; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics*; D019707:Receptors, Chemokine / Q000235:genetics*
C515334:CCR2 protein, human; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D017931:DNA Primers; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine