HLA Correlates of Long-Term Survival in Vertically Infected HIV-1-Positive Adolescents in Harare, Zimbabwe

Abstract

African infants with vertically acquired HIV infection progress rapidly, with only 50% surviving beyond 2 years in the absence of treatment. Despite this high initial mortality, recent reports describe a substantial burden of older children living with untreated vertically acquired HIV infection in Southern Africa. The immunological and genetic factors associated with long-term survival following vertical infection are poorly understood. We performed medium-to-high resolution HLA typing on DNA samples obtained from a cohort of presumed vertically HIV-1-infected children and age-matched uninfected controls in Harare, Zimbabwe. Overall, 93 HLA class I alleles were detected in the study population with a significant enrichment of HLA-C*08:02 and -C*08:04 in the HIV-1-infected long-term survivor group. Conversely, HLA-A*02:01, A*34:02, and -B*58:02 were overrepresented in the uninfected control group. Our data indicate that HLA alleles may have differential effects against HIV acquisition and disease progression in vertical HIV-1 infection.

Human leucocyte antigen but not KIR alleles and haplotypes associated with chronic HCV infection in a Chinese Han population

“…this finding suggests that HLA-C*08:04 has a role in the protection that HLA-C*08:02 and C*08:04 were associated with HIV-1-infected long-time survivors (Shepherd et al, 2015). The HLA allele polymorphisms determine a unique peptide binding mode, contributing to high peptide specificity (Simpson et al, 2011).…”

“…Shepherd BL. et al performed an association study between HLA and HIV infection progress and suggested that HLA‐C*08:02 and C*08:04 were associated with HIV‐1‐infected long‐time survivors (Shepherd et al, ). The HLA allele polymorphisms determine a unique peptide binding mode, contributing to high peptide specificity (Simpson et al, ).…”

HLA-C*18:01 and KIR2DL2+C1 genetic variants are associated with low viral load in cART naïve HIV-infected adult Zimbabweans

“…Instead, carriage of the C*08:02 allele was associated with higher CD4+ T lymphocyte count when compared to non-carriage of the allele suggesting a favourable role. Interestingly, a study among Zimbabwean adolescents reported a significant enrichment of the C*08:02 allele among the long term survivor group compared to an HIV-uninfected control group [31]. Thus carriage of the C*08:02 allele was associated with longevity in the HIV infected adolescents perhaps due to the allele conferring a favourable immunological profile.…”

Study of Human Leukocyte Antigen (HLA) in 13 cases of familial frontal fibrosing alopecia: CYP21A2 gene p.V281L mutation from congenital adrenal hyperplasia linked to HLA class I haplotype HLA‐A*33:01; B*14:02; C*08:02 as a genetic marker

“…HLA‐B14 is found in severe aplastic anaemia and associated negatively with progression to autoantibodies generation in patients with diabetes type I . Finally, HLA‐C*08:02 is associated with the HIV‐1‐infected long‐term survivor group in Zimbabwe population and with low cytotoxic T lymphocytes immune response in Iranian patients having Human T‐cell lymphotropic virus type I‐associated myelopathy/tropical spastic paraparesis . There are no data about HLA‐C*08:02 association with autoimmune diseases.…”