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3, as described in earlier work related to the same cohort (Prentice et al., 2013, 2014b). The overall performance of multivariable logistic regression models was also assessed using the area under the curve (AUC) estimates (C-statistics). Refinement of Host Genetic Factors Based on Linkage Disequilibrium (LD) and Biological Relevance PLX4032 solubility dmso Wherever possible, HLA factors showing putative associations with CD4:CD8 ratio were refined by analyses of LD profiles and HLA haplotypes in subjects before and after stratification by geography (eastern versus southern Africa), with further reference to fully resolved haplotypes seen in other populations (Cao et al., 2001). Alternative analyses of 2- and 3-locus HLA haplotypes were deemed informative if the adjusted effect sizes improved over those for the component alleles. The likelihood of biological relevance was evaluated in the context of (i) HIV-1-specific CTL epitopes and escape mutations documented for individual HLA allelic products1,2 (Carlson et al., 2014), (ii) relationships to single nucleotide polymorphisms (SNPs) that have biological and/or epidemiological importance (Horton et al., 2004; Fellay et al., 2009; Prentice et al., 2014a), and (iii) other evidence as reported in the literature, especially the Finemapping Data Portal3 (Farh et al., 2015) and the HaploReg database4 (last accessed in April 2015). Results The Dynamics of CD4:CD8 Ratio in Primary HIV-1 Infection Among native African subjects enrolled between February 2006 and December 2011, 196 Zambians, 125 Ugandans, 102 Kenyans, and 76 Rwandans had at least three measurements of CD4:CD8 ratio and other outcomes (VL and CD4 slope) within the 3- to 24-month intervals after EDI. Overall, CD4:CD8 ratio was steady during this early period of infection (Figure ?Figure11), with a heavy bias toward the ��1.0 (abnormal) group (P = 2.2 �� 10-16 in normality tests). For seven consecutive sliding time windows (3 months each), the pairwise Spearman rho values for comparing cross-sectional CD4:CD8 ratio ranged from 0.71 to 0.88 (P