Distribution of human leucocyte antigen-C in HIV-1-infected patients in Mumbai, India.

HIV pathogenesis is known to be highly influenced by host genetic factors, such as human leucocyte antigens (HLAs) HLA-A and HLA-B. However, the role of HLA-C remains largely unexplored. We evaluated HLA-C distribution in 186 HIV-1-infected individuals and compared them to ethnically matched data derived from the Allele Frequency Net Database using Chi-square test with Fisher's exact two-tailed test. The frequency of HLA-C*05 and HLA-C*15 was higher in infected group, whereas the frequency of HLA-C*04 and HLA-C*14 was higher in control group. HLA-C*17, a rare allele, was significantly higher in infected group. These data could be useful in designing and testing vaccines in Indian population.

Distribution of killer immunoglobulin-like receptor genes in HIV infected long-term non-progressors from Mumbai, India.

BACKGROUND: Few reports suggest the association of killer immunoglobulin-like receptors of natural killer cells with human immunodeficiency virus infection. India with world's third largest population of human immunodeficiency virus / acquired immunodeficiency syndrome, offers scope to study such association. OBJECTIVE: Current study (2010-2015) was designed to evaluate if killer immunoglobulin-like receptors gene polymorphisms are associated with HIV infection outcomes specifically, with long term non progressors. METHODS: Killer immunoglobulin-like receptors genotyping was done using polymerase chain reaction - sequence-specific primer method. Viral load was measured by Cobas Taqman HIV-1 test. Estimation of CD4 counts was done using BD FACS CD4 count reagent. RESULTS: The activating gene frequencies identified were 3DS1 (53.8%), 2DS3 (69.2%), 2DS4 (76.9%), 2DS5 (69.2%), 2DS1 (76.9%) and 2DS2 (92.3%). The inhibitory gene frequencies were 2DL2 (92.3%), 2DL5 (76.9%), 2DL3 (69.5%), 3DL1 (84.6%), 3DL2 (92.3%) and 2DL1 (100%). The results highlight high frequency of 3DS1/3DL1 heterozygote and killer immunoglobulin-like receptor 2DS1, among these long term non progressors indicating their possible association with slow progression. Genotype analysis shows total 13 genotypes, of which 8 genotypes were identified for the first time from India. Two genotypes were unique/novel, which were unreported. All genotypes observed in this study were considered to be Bx genotype (100 %). LIMITATIONS: A small sample size (n=13, due to a rare cohort) and the absence of control group were the limitations of this study. CONCLUSIONS: The present study highlights the distribution of killer immunoglobulin-like receptor genes in a very rare group of human immunodeficiency virus -1 infected individuals - long term non progressors. All the long term non progressors tested show the presence of Bx haplotype and each long term non progressors has a different killer immunoglobulin-like receptor genotype.

Diversity in KIR gene repertoire in HIV-1 exposed infected and uninfected infants: A study from India.

Natural killer (NK) cells have antiviral activity mediated through killer immunoglobulin receptors (KIRs). Studies have shown the importance of KIR receptors in HIV infection. However reports on association of KIR genes in HIV infection from Indian population are limited, not a single study is reported in HIV exposed uninfected (EU) and infected infants. This study compared the KIR gene repertoire of HIV-1 positive (n = 29) with EU (n = 76) infants to elucidate its association with transmission. KIR genotyping was analysed using the PCR-SSP method. Viral load of mothers, CD4 count of both mothers and infected infants were done using commercial kits. The data was analysed using SPSS software. Results revealed presence of significantly high frequencies of activating gene KIR 2DS5 (P = 0.040) and inhibitory gene KIR 2DL3 (P = 0.013) in EU infants as compared to HIV-1 positive infants, confirmed with multivariable linear regression modelling. Fifty-nine KIR genotypes were identified in these 105 infants. Nine genotypes were unique, reported for the first time. Twenty six genotypes were shared with the World populations. Twenty four genotypes were reported for the first time from India. Specific KIR genotype combinations (GIDs) were exclusively present either in HIV-1 positive (n = 19) or in EU infants (n = 30). The Linkage disequilibrium (LD) analysis shows a strong linkage between four pairs of genes in HIV-1 positive and three pairs of genes in EU infants. In conclusion, this study revealed that, besides maternal confounding factors such as ART and viral load, specific KIR genes are associated independently with perinatal HIV infection.

Variations in KIR genes: a study in HIV-1 serodiscordant couples.

BACKGROUND: NK cells have anti-HIV activity mediated through killer cell immunoglobulin-like receptors (KIRs). The current prospective cohort study evaluated whether variation in KIR genes is associated with HIV infection in discordant couples (DCs), where one spouse remains seronegative (HSN) despite repeated exposure to the HIV. METHODS: KIR was genotyped using PCR SSP. Viral load and CD4 counts were estimated using commercially available reagents. Data were analyzed using SPSS software. RESULTS: Among the 47 DCs, HSN spouses had significantly (P = 0.006) higher frequencies of KIR3DS1. Regression analysis revealed significant (P = 0.009) association of KIR2DS1 with low viral load. KIR2DS4 variant was associated (P = 0.032) with high viral load. Three pairs of KIR genes were in strong LD in HSNs and two pairs in HSPs. There were 60 KIR genotypes, and 16 are reported the first time in the Indian population. Exclusive genotypes were present either in HSPs (N = 22, 11 unique genotypes) or in HSNs (n = 27, 9 unique genotypes). CONCLUSIONS: This study highlights for the first time in the Indian population an association of KIR genes in HIV infection where presence of exclusive and unique genotypes indicates possible association with either HIV infection or with protection.

Human leukocyte antigen B distribution in HIV discordant cohort from India.

Limited reports are available on association of HLA-B with HIV infection from India, a home to the third largest population of HIV infected people in the world. This emphasizes the need to have more information specifically the genetic constitution of HIV serodiscordant couples (DCs), where one spouse is seropositive (HSP) while the other remains seronegative (HSN) even after repeated exposure. Hence, aim of this study was to document association of HLA-B with HIV infection in DCs living in Mumbai, India. A cohort was designed to enroll DCs attending the ICTC/Shakti Clinic of KEM Hospital, Mumbai. A group of unexposed volunteers were also enrolled as healthy controls (HC). HLA-B alleles were typed using sequence-specific oligonucleotide probes. Allele frequency comparison was done using 2×2 contingency tables. Results were considered significant, when p<0.05 with two-tailed Fisher's exact test. At HLA-B locus, the frequencies of HLA-B*40;-B*35;-B*07;-B*15;-B*51;-B*44;-B*52;-B*37 and -B*57 were found in decreasing order in the population. Frequency of HLA-B*35 allele was significantly higher (HSP vs HSN; p<0.02 and HSP vs HC; p<0.04) in HSP. HLA-B*40 (HSN vs HSP; p<0.01 and HC vs HSP; p<0.01) and HLA-B*18 (HSN vs HSP; p<0.02) were significantly associated with HSN. Both HSN and HC had similar HLA-B*35 and -B*40 allele frequency. HLA-B*57 allele was observed in 15 individuals (3.69%). However, HLA-B*57:01 which is known to be associated with adverse reactions against Abacavir was observed in 7 of them. HLA-B*39 was observed exclusively in HSP. Our observation in DCs confirmed the association of HLA-B*35 with susceptibility while HLA-B*40 (specifically *B40:06), -B*18 with protection. These identified alleles can be used as possible marker associated with HIV transmission. In India, HLA screening is not carried out before initiation of HIV treatment. However, the presence of HLA-B*57:01 in the population emphasizes the importance of such screening to predict/avoid Abacavir hypersensitivity.