The role of a 32 base pair deletion in the CCR5 gene (CCR5Δ32) in HIV-disease progression and response to combined antiretroviral therapy (cART) is well established.
As a switch from chemokine (C-C motif) receptor 5 [CCR5 (R5)] to chemokine (C-X-C motif) receptor 4 [CXCR4 (X4)] HIV-1 tropism is associated with symptomatic and AIDS stages of infection, while chemokine receptor gene variants modify the tempo of HIV disease progression, we aimed to analyse the association between pretreatment HIV-1 tropism and chemokine polymorphisms known to restrict disease progression.
There was high concordance between CCR5 polymorphisms and haplotype pairs that influenced delayed-type hypersensitivity responses in healthy persons and HIV disease progression.
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.
A 32-bp deletion of the CCR5 gene, leading to complete absence of functional CCR5 expression, has been associated with resistance to human immunodeficiency virus (HIV) infection in homozygotes and slower HIV disease progression in heterozygotes.
Effects of plasma HIV RNA, CD4+ T lymphocytes, and the chemokine receptors CCR5 and CCR2b on HIV disease progression in hemophiliacs. Hemophilia Growth and Development Study.
A mutant allele of CCR5 confers a high degree of resistance to HIV-1 infection in homozygous individuals and partial protection against HIV disease progression in heterozygotes.
These studies demonstrate that HLA-B*27:02 mediates protection against HIV disease progression that is at least as strong as or stronger than that mediated by HLA-B*27:05.
Furthermore, the HLA-B*14-associated protection against HIV disease progression is significantly greater for HLA-B*14:02 than for HLA-B*14:01, consistent with the superior antiviral efficacy of the HLA-B*14-EL9 response.
The precise immune responses mediated by HLA class I molecules such as HLA-B*27:05 and HLA-B*57:01 that protect against HIV disease progression remain unclear.
HLA-B*57:01 and HLA-B*57:03, the most prevalent HLA-B*57 subtypes in Caucasian and African populations, respectively, are the HLA alleles most protective against HIV disease progression.
The analysis revealed complete linkage disequilibrium between HCP5 and HLA-B*5701/HLA-Cw*06, a modest effect of 5' HLA-C on viral set point in the absence of HLA-B*5701, and no influence of the RNF39 /ZNRD1 extended haplotype on HIV disease progression.