Analysis of CCR5, CCR2, CX₃CR1, and SDF1 Polymorphisms in HIV-Positive Treated Patients: Impact on Response to HAART and on Peripheral T Lymphocyte Counts

Abstract

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).

Immune reconstitution under antiretroviral therapy: the new challenge in HIV-1 infection

“…78 Other genes. Genetic polymorphisms in the genes coding for the CXCR4-binding chemokine CXCL12 or SDF-1, 79 for the chemokine receptor CX3CR1, 79 and in genes located in the major histocompatibility complex 75,80 have also been linked to treatmentinduced CD4 ϩ T-cell restoration.…”

The role of SNPs in the α-chain of the IL-7R gene in CD4+ T-cell recovery in HIV-infected African patients receiving suppressive cART

“…[21][22][23][24] Multiple host genetic factors have also been found to influence CD4 T-cell recovery. [25][26][27][28][29][30][31] We recently demonstrated by using a multivariable model that IL-7Ra haplotype-2 was a significant predictor of more rapid CD4 T-cell recovery following suppressive cART in an Australian-based largely Caucasian HIVinfected cohort. 22 Consistent with observations in haplotype-2 carriers in HIV-uninfected cohorts, 9,11,32,33 we found that HIV-infected patients who were homozygous for haplotype-2 had significantly lower concentrations of sIL-7Ra compared with non-haplotype-2 carriers.…”

The Role of Host Genetics in the Susceptibility for HIV-associated Neurocognitive Disorders

“…This protective effect of the GP was even more pronounced in individuals with longer durations of HIV infection. SDF1-3′-A was also recently reported to be more common in a cohort of HIV+ individuals who responded well to HAART compared to those whose viral loads remained elevated after one year (Puissant et al 2006). However, others have found contrasting results.…”