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

Brittany L Shepherd, Rashida Ferrand, Shungu Munyati, Samuel Folkard, Kathryn Boyd, Tsitsi Bandason, Sabelle Jallow, Sarah L Rowland-Jones, Louis-Marie Yindom, Brittany L Shepherd, Rashida Ferrand, Shungu Munyati, Samuel Folkard, Kathryn Boyd, Tsitsi Bandason, Sabelle Jallow, Sarah L Rowland-Jones, Louis-Marie Yindom

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.

Figures

FIG. 1.
FIG. 1.
Distribution of HLA class I alleles between infected and uninfected groups. Only alleles with an overall frequency >3% of the study population are represented. *Differences remained significant after Bonferroni correction for multiple comparisons. p-values estimated using Chi-squared or Fisher's exact test as appropriate.

References

    1. UNAIDS: Global Report: UNAIDS Report on the global AIDS epidemic 2013. 2013
    1. Group TWB: World development indicators: prevalence of HIV, total (% of population ages 15–49). 2013
    1. The Working Group on Mother-to-Child Transmission of HIV: Rates of mother-to-child transmission of HIV-1 in Africa, America, and Europe: Results from 13 perinatal studies. J Acquir Immune Defic Syndr Hum Retrovirol 1995;8(5):506–510
    1. Morgan D, Mahe C, Mayanja B, et al. : HIV-1 infection in rural Africa: Is there a difference in median time to AIDS and survival compared with that in industrialized countries? AIDS 2002;16(4):597–603
    1. Morgan D. and Whitworth J: The natural history of HIV-1 infection in Africa. Nat Med 2001;7(2):143–145
    1. Newell ML, Coovadia H, Cortina-Borja M, et al. : Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: A pooled analysis. Lancet 2004;364(9441):1236–1243
    1. Marston M, Zaba B, Salomon JA, et al. : Estimating the net effect of HIV on child mortality in African populations affected by generalized HIV epidemics. J Acquir Immune Defic Syndr 2005;38(2):219–227
    1. Stover J: Projecting the demographic consequences of adult HIV prevalence trends: The Spectrum Projection Package. Sex Transm Infect 2004;80(Suppl 1):i14–18
    1. Botswana S: Botswana Aids Impact Survey IV (BAIS IV). 2013
    1. Morgan DR, Mashange W, Mutsvangwa J, et al. : Household survey of HIV-prevalence and behaviour in Chimanimani District, Zimbabwe. Human Social Research Council, 2005
    1. Ferrand RA, Corbett EL, Wood R, et al. : AIDS among older children and adolescents in Southern Africa: Projecting the time course and magnitude of the epidemic. AIDS 2009;23(15):2039–2046
    1. Ferrand RA, Bandason T, Musvaire P, et al. : Causes of acute hospitalization in adolescence: Burden and spectrum of HIV-related morbidity in a country with an early-onset and severe HIV epidemic: A prospective survey. PLoS Med 2010;7(2):e1000178.
    1. Martin MP. and Carrington M: Immunogenetics of HIV disease. Immunol Rev 2013;254(1):245–264
    1. Pereyra F, Jia X, McLaren PJ, et al. : The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 2010;330(6010):1551–1557
    1. Blattner WA, Oursler KA, Cleghorn F, et al. : Rapid clearance of virus after acute HIV-1 infection: Correlates of risk of AIDS. J Infect Dis 2004;189(10):1793–1801
    1. Shearer WT, Quinn TC, LaRussa P, et al. : Viral load and disease progression in infants infected with human immunodeficiency virus type 1. Women and Infants Transmission Study Group. N Engl J Med 1997;336(19):1337–1342
    1. Thobakgale CF, Prendergast A, Crawford H, et al. : Impact of HLA in mother and child on disease progression of pediatric human immunodeficiency virus type 1 infection. J Virol 2009;83(19):10234–10244
    1. Ferrand RA, Munaiwa L, Matsekete J, et al. : Undiagnosed HIV infection among adolescents seeking primary health care in Zimbabwe. Clin Infect Dis 2010;51(7):844–851
    1. Rai MA, Zhang Y, Yindom LM, et al. : HLA correlates in a cohort of slow progressors from China: Effects on HIV-1 disease progression. AIDS 2013;27(17):2822–2824
    1. Yindom LM, Leligdowicz A, Martin MP, et al. : Influence of HLA class I and HLA-KIR compound genotypes on HIV-2 infection and markers of disease progression in a Manjako community in West Africa. J Virol 2010;84(16):8202–8208
    1. Lazaryan A, Lobashevsky E, Mulenga J, et al. : Human leukocyte antigen B58 supertype and human immunodeficiency virus type 1 infection in native Africans. J Virol 2006;80(12):6056–6060
    1. Costello C, Tang J, Rivers C, et al. : HLA-B*5703 independently associated with slower HIV-1 disease progression in Rwandan women. AIDS 1999;13(14):1990–1991
    1. Apps R, Qi Y, Carlson JM, et al. : Influence of HLA-C expression level on HIV control. Science 2013;340(6128):87–91
    1. Moore CB, John M, James IR, et al. : Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level. Science 2002;296(5572):1439–1443
    1. Matt C. and Roger M: Genetic determinants of pediatric HIV-1 infection: Vertical transmission and disease progression among children. Mol Med 2001;7(9):583–589

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren