Host HLA B*allele-associated multi-clade Gag T-cell recognition correlates with slow HIV-1 disease progression in antiretroviral therapy-naïve Ugandans.

PloS One
Jennifer SerwangaPontiano Kaleebu

Abstract

Some HIV infected individuals remain asymptomatic for protracted periods of time in the absence of antiretroviral therapy (ART). Virological control, CD4 T cell loss and HIV-specific responses are some of the key interrelated determinants of HIV-1 disease progression. In this study, possible interactions between viral load, CD4 T cell slopes, host genetics and HIV-specific IFN-gamma responses were evaluated in chronically HIV-1-infected adults. Multilevel regression modeling was used to stratify clade A or D HIV-infected individuals into disease progression groups based on CD4 T cell slopes. ELISpot assays were used to quantify the frequency and magnitude of HIV-induced IFN-gamma responses in 7 defined rapid progressors (RPs) and 14 defined slow progressors (SPs) at a single time point. HLA typing was performed using reference strand conformational analysis (RSCA). Although neither the breadth nor the magnitude of the proteome-wide HIV-specific IFN-gamma response correlated with viral load, slow disease progression was associated with over-representation of host immunogenetic protective HLA B* alleles (10 of 14 SPs compared to 0 of 7; p = 0.004, Fisher's Exact) especially B*57 and B*5801, multiclade Gag T-cell targeting (71%, 1...Continue Reading

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Citations

Jun 28, 2011·Infectious Agents and Cancer·Michael OdidaElisabete Weiderpass
Nov 10, 2010·AIDS·Patricia E Fast, Pontiano Kaleebu
Sep 1, 2015·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Anju BansalPaul A Goepfert
Jan 1, 2010·Viruses·Vlad NovitskyMax Essex

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Methods Mentioned

BETA
PCR
density gradient centrifugation

Software Mentioned

Ms Excel
Stata
Treecon
Simplot
ELISpot
Graph Pad
BioEdit

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