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Protective Effect of HLA-B*5701 and HLA-C -35 Genetic Variants in HIV-Positive Caucasians from Northern Poland.

Leszczyszyn-Pynka M, Aksak-Wąs B, Urbańska A, Parczewski M - PLoS ONE (2015)

Bottom Line: Moreover, CD4+ T cell nadir among patients with C allele [median: 205 (IQR:83.5-390) cells/μl] was significantly higher compared to T/T group [median: 133 (IQR:46-328) cells/μl] (p=0.006).Among cases with HLA-B*5701 allele, significantly lower pretreatment viremia and higher baseline CD4+ T cell count were found (mean: 4.08 [SD: 1.2] vs. mean: 4.84 [SD:0.97] log HIV-RNA copies/ml, p=0.003 and 431 vs. 270 cells/μl, p=0.04, respectively) compared to HLA-B*5701 negative individuals.This protective effect is additive for the compound HLA-B*5701(+)/HLA-C -35 C/C haplotype.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious, Tropical Diseases and Acquired Immunodeficiency, Pomeranian Medical University, Szczecin, Poland.

ABSTRACT

Aim of the study: Association of two HLA class I variants with HIV-1 pretreatment viremia, CD4+ T cell count at the care-entry and CD4+ T cell nadir.

Methods: 414 HIV-positive Caucasians (30% women) aged 19-73 years were genotyped for HLA-C -35 (rs9264942) and HLA-B*5701 variants. HIV-1 viral load, as well as CD4+ T cell count at care-entry and nadir, were compared across alleles, genotypes and haplotypes.

Results: HLA-C -35 C/C genotype was found in 17.6% patients, C/T genotype in 48.1%, and T/T genotype in 34.3% patients. HLA-B*5701 variant was present in 5.8% of studied population. HIV plasma viremia in the group with C allele was significantly lower (p=0.0002) compared to T/T group [mean:4.66 log (SD:1.03) vs. 5.07 (SD:0.85) log HIV-RNA copies/ml, respectively], while CD4+ T cell count at baseline was notably higher among C allele carriers compared to T/T homozygotes [median: 318 (IQR:127-537) cells/μl vs. median: 203 (IQR:55-410) cells/μl, respectively] (p=0.0007). Moreover, CD4+ T cell nadir among patients with C allele [median: 205 (IQR:83.5-390) cells/μl] was significantly higher compared to T/T group [median: 133 (IQR:46-328) cells/μl] (p=0.006). Among cases with HLA-B*5701 allele, significantly lower pretreatment viremia and higher baseline CD4+ T cell count were found (mean: 4.08 [SD: 1.2] vs. mean: 4.84 [SD:0.97] log HIV-RNA copies/ml, p=0.003 and 431 vs. 270 cells/μl, p=0.04, respectively) compared to HLA-B*5701 negative individuals. The lowest viremia (mean: 3.85 log [SD:1.3]) HIV-RNA copies/ml and the highest baseline and nadir CD4+ T cell [median: 476 (IQR:304-682) vs. median: 361 (IQR: 205-574) cells/μl, respectively) were found in individuals with HLA-B*5701(+)/HLA-C -35 C/C haplotype.

Conclusions: HLA-C -35 C and HLA-B*5701 allele exert a favorable effect on the immunological (higher baseline and nadir CD4+ T cell count) and virologic (lower pretreatment HIV viral load) variables. This protective effect is additive for the compound HLA-B*5701(+)/HLA-C -35 C/C haplotype.

No MeSH data available.


Related in: MedlinePlus

The relationship between pretreatment HIV plasma viremia and (a) HLA-C locus -35 genotypes for T/T homozygotes vs. C allele carriers (C/T+C/C), (b) HLA B*5701(+) vs HLA B*5701(-) genotype, and (c) compound HLA-C locus -35 C/C and HLA B*5701 (+) haplotype.Raw values for each genotype are presented as triangles, means as squares. For statistics t-test was used.
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pone.0127867.g001: The relationship between pretreatment HIV plasma viremia and (a) HLA-C locus -35 genotypes for T/T homozygotes vs. C allele carriers (C/T+C/C), (b) HLA B*5701(+) vs HLA B*5701(-) genotype, and (c) compound HLA-C locus -35 C/C and HLA B*5701 (+) haplotype.Raw values for each genotype are presented as triangles, means as squares. For statistics t-test was used.

Mentions: Results of statistical relationships between HLA-B*5701 and HLA-C -35 rs9264942 genetic variants and selected virologic as well as immunologic parameters are shown in Table 2. No gender related differences in the distribution of the HLA-C alleles and genotypes were observed with genotype frequencies of 18.6% (n = 54) for C/C, 47.9% (n = 139) for C/T and 33.5% (n = 97) for T/T for male cases versus 15.3% (n = 19) for C/C, 48.4% (n = 60) for C/T and 36.35% (n = 45) for T/T among women. HLA B*5701 allele frequency was slightly higher among women (11 cases, 8.9%) compared to men (13 cases, 4.48%), p = 0.08. In the group with HLA-C -35 C allele, baseline viral load was significantly lower compared to baseline viremia for T/T homozygotes [mean: 4.66 (SD: 1.03) log HIV-RNA copies/ml vs. mean: 5.07 (SD: 0.85) log HIV-RNA copies/ml (p = 0.0002)] (Fig 1a).


Protective Effect of HLA-B*5701 and HLA-C -35 Genetic Variants in HIV-Positive Caucasians from Northern Poland.

Leszczyszyn-Pynka M, Aksak-Wąs B, Urbańska A, Parczewski M - PLoS ONE (2015)

The relationship between pretreatment HIV plasma viremia and (a) HLA-C locus -35 genotypes for T/T homozygotes vs. C allele carriers (C/T+C/C), (b) HLA B*5701(+) vs HLA B*5701(-) genotype, and (c) compound HLA-C locus -35 C/C and HLA B*5701 (+) haplotype.Raw values for each genotype are presented as triangles, means as squares. For statistics t-test was used.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4465896&req=5

pone.0127867.g001: The relationship between pretreatment HIV plasma viremia and (a) HLA-C locus -35 genotypes for T/T homozygotes vs. C allele carriers (C/T+C/C), (b) HLA B*5701(+) vs HLA B*5701(-) genotype, and (c) compound HLA-C locus -35 C/C and HLA B*5701 (+) haplotype.Raw values for each genotype are presented as triangles, means as squares. For statistics t-test was used.
Mentions: Results of statistical relationships between HLA-B*5701 and HLA-C -35 rs9264942 genetic variants and selected virologic as well as immunologic parameters are shown in Table 2. No gender related differences in the distribution of the HLA-C alleles and genotypes were observed with genotype frequencies of 18.6% (n = 54) for C/C, 47.9% (n = 139) for C/T and 33.5% (n = 97) for T/T for male cases versus 15.3% (n = 19) for C/C, 48.4% (n = 60) for C/T and 36.35% (n = 45) for T/T among women. HLA B*5701 allele frequency was slightly higher among women (11 cases, 8.9%) compared to men (13 cases, 4.48%), p = 0.08. In the group with HLA-C -35 C allele, baseline viral load was significantly lower compared to baseline viremia for T/T homozygotes [mean: 4.66 (SD: 1.03) log HIV-RNA copies/ml vs. mean: 5.07 (SD: 0.85) log HIV-RNA copies/ml (p = 0.0002)] (Fig 1a).

Bottom Line: Moreover, CD4+ T cell nadir among patients with C allele [median: 205 (IQR:83.5-390) cells/μl] was significantly higher compared to T/T group [median: 133 (IQR:46-328) cells/μl] (p=0.006).Among cases with HLA-B*5701 allele, significantly lower pretreatment viremia and higher baseline CD4+ T cell count were found (mean: 4.08 [SD: 1.2] vs. mean: 4.84 [SD:0.97] log HIV-RNA copies/ml, p=0.003 and 431 vs. 270 cells/μl, p=0.04, respectively) compared to HLA-B*5701 negative individuals.This protective effect is additive for the compound HLA-B*5701(+)/HLA-C -35 C/C haplotype.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious, Tropical Diseases and Acquired Immunodeficiency, Pomeranian Medical University, Szczecin, Poland.

ABSTRACT

Aim of the study: Association of two HLA class I variants with HIV-1 pretreatment viremia, CD4+ T cell count at the care-entry and CD4+ T cell nadir.

Methods: 414 HIV-positive Caucasians (30% women) aged 19-73 years were genotyped for HLA-C -35 (rs9264942) and HLA-B*5701 variants. HIV-1 viral load, as well as CD4+ T cell count at care-entry and nadir, were compared across alleles, genotypes and haplotypes.

Results: HLA-C -35 C/C genotype was found in 17.6% patients, C/T genotype in 48.1%, and T/T genotype in 34.3% patients. HLA-B*5701 variant was present in 5.8% of studied population. HIV plasma viremia in the group with C allele was significantly lower (p=0.0002) compared to T/T group [mean:4.66 log (SD:1.03) vs. 5.07 (SD:0.85) log HIV-RNA copies/ml, respectively], while CD4+ T cell count at baseline was notably higher among C allele carriers compared to T/T homozygotes [median: 318 (IQR:127-537) cells/μl vs. median: 203 (IQR:55-410) cells/μl, respectively] (p=0.0007). Moreover, CD4+ T cell nadir among patients with C allele [median: 205 (IQR:83.5-390) cells/μl] was significantly higher compared to T/T group [median: 133 (IQR:46-328) cells/μl] (p=0.006). Among cases with HLA-B*5701 allele, significantly lower pretreatment viremia and higher baseline CD4+ T cell count were found (mean: 4.08 [SD: 1.2] vs. mean: 4.84 [SD:0.97] log HIV-RNA copies/ml, p=0.003 and 431 vs. 270 cells/μl, p=0.04, respectively) compared to HLA-B*5701 negative individuals. The lowest viremia (mean: 3.85 log [SD:1.3]) HIV-RNA copies/ml and the highest baseline and nadir CD4+ T cell [median: 476 (IQR:304-682) vs. median: 361 (IQR: 205-574) cells/μl, respectively) were found in individuals with HLA-B*5701(+)/HLA-C -35 C/C haplotype.

Conclusions: HLA-C -35 C and HLA-B*5701 allele exert a favorable effect on the immunological (higher baseline and nadir CD4+ T cell count) and virologic (lower pretreatment HIV viral load) variables. This protective effect is additive for the compound HLA-B*5701(+)/HLA-C -35 C/C haplotype.

No MeSH data available.


Related in: MedlinePlus