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Toll-like receptor 2 (TLR2) plays a key role in innate immune response recognizing molecular patterns expressed by pathogens. rs111200466 is a TLR2 promoter insertion/deletion polymorphism with contradictory data about its role in human immunodeficiency virus type 1 (HIV-1) infection. We analyzed rs111200466 in HIV-1 disease progression and showed a correlation with a faster progression to the CD4+ < 200 cells/μL outcome for deletion allele carriers (Cox regression analysis: hazard ratio, 2.4 [95% confidence interval, 1.4-4]; P = .001). When naive patients with CD4+ < 200 cells/μL started antiretroviral treatment, rs111200466-deletion carriers showed a trend toward a slower, recovery rate (time required to reach CD4+ > 350 cells/μL; Cox P = .36). Our data suggest rs111200466 as a prognosis factor for HIV-1 disease progression. [ABSTRACT FROM AUTHOR]

We tested bone marrow stromal cell antigen 2 (BST-2) gene variants rs3217318, a 19-base-pair insertion/deletion polymorphism in the promoter region, and rs10415893, a tag single-nucleotide polymorphism in the 3' untranslated region, for their association with human immunodeficiency virus type 1 (HIV-1) infection and disease progression. The study included 356 subjects exposed to HIV-1 (185 with and 171 without infection) and 188 controls. The first decrease in the CD4(+) T-cell count to <200 cells/µL was used as the primary outcome, whereas the primary outcome plus initiation of any antiretroviral treatment was used as a secondary composite outcome. Association with progression was found for both rs3217318 and rs10415893, following an overdominant model. Diplotype analysis revealed faster progression to both outcomes for subjects carrying the Δ19&#95;G/i19&#95;A diplotype. Luciferase assay showed that a promoter sequence containing the i19 allele had the lowest expression levels, suggesting that i19 allele carriers could have less BST-2 expression, reducing their capability to retain viral particles. These results point to the relevance of BST-2 as a host genetic factor modifying HIV-1 disease progression.

Vitamin D receptor (VDR) participates in multiple immune functions. Here, we determined whether VDR gene-sequence variations are associated with intersubject differences in the risk of acquiring human immunodeficiency virus type 1 (HIV-1) infection. We assessed this in 460 males exposed to HIV-1 by injection drug use (335 infected and 125 uninfected) and 124 seronegative healthy subjects. Multilocus logistic regression analysis revealed haplotypes for rs11568820, rs4516035, rs10735810, rs1544410, and rs17878969 polymorphisms showing association with protection to HIV-1 infection (odds ratio, 0.4 [95% confidence interval, 0.22-0.72]; P = .0025), which remained significant after correction for multiple testing. We infer that VDR haplotypes might influence the risk of HIV-1 acquisition.

The effect of polymorphisms on genes encoding the CCR5 chemokine receptor and vitamin D receptor (VDR) in human immunodeficiency virus (HIV) type 1 disease progression was analyzed in a cohort of 185 HIV-seropositive injection drug users. Results confirmed a lack of association in patients with HIV disease between CCR5 wtDelta32 heterozygosity and a slow progression to AIDS and to a CD4 cell count <200 cells/microL. In contrast, a more rapid disease progression was associated with the VDR-BB genotype. A higher proportion of this genotype was found in patients with <200 CD4 cells/microL (P=.009; odds ratio [OR], 2.4; 95% confidence interval [CI], 1.3-4.7), as well as a faster progression both to AIDS (1993 CDC classification [CDC 1993]) and to a CD4 cell count <200 cells/microL. When the analysis was restricted to patients with a VDR-bb genetic background, patients with CCR5 wtDelta32 heterozygosity were overrepresented in CDC 1993 nonprogressors (P=.033; OR, 0.28; 95% CI, 0.08-0.92) and in those with >200 CD4 cells/microL (P=.062; OR, 0.26; 95% CI, 0.06-1.08). Also, patients with CCR5 wtDelta32 heterozygosity showed a slow progression both to AIDS CDC 1993 and to a CD4 cell count <200 cells/microL.