Article Figures & Data
Figures
- FIG 1
Kaplan-Meier curves of AIDS-free time. Three stratifications were explored (fast and slow progressors were defined by having values above or below the mean values from all participants for each stratification). (A) CD4% decline rate. (B) CD4% level at the midpoint in time between the first and last recorded CD4% values. (C) Combined effect of CD4% decline rate and CD4% level. Tick marks indicate participants with censored data. Asterisks indicate the time points in each group when five participants were still at mortality risk and at risk of developing AIDS. The numbers of individuals at risk are given below the figure panels at 5-year intervals. Data from faster progressors are shown in vermillion, and data from slower progressors are shown in blue.
- FIG 2
Synonymous and nonsynonymous divergence over time. Data represent accumulated synonymous and nonsynonymous divergences over time in the V1-C3 env region of HIV-2 for each study participant. The divergence from the level seen with the first analyzed sample from each study participant is shown. Data from faster progressors are shown in vermillion, and data from slower progressors are shown in blue.
- FIG 3
Codon-specific selective pressure. The selective pressures at each codon site of the sequence alignment of the env V1-C3 region of HIV-2 for faster and slower disease progressors are indicated. The proportions (y axis) with positive selection (vermillion or blue) or negative selection (gray) at codon sites of the sequence alignment (x axis) are shown for faster progressors (upper graph) and slower progressors (lower graph). Filled black circles indicate codons conserved between HIV-2/SIVsm strains associated with positive selection. Vertical lines divide the fragment into env regions V1V2, C2, V3, and C3.
Tables
- TABLE 1
Disease progression classifications of all individuals, based on three different stratifications for CD4% (n = 16)
Individual CD4% decline rate/year CD4% level Combined coefficient Valuea Progressorb Valuea Progressorb Valuea,c Progressorb DL3405 −1.46 Slow 33.95 Slow 1.00 Slow DL3542 0.69 Fast 32.73 Slow 0.74 Slow DL2051 1.61 Fast 31.11 Slow 0.62 Slow DL2876 0.55 Fast 28.91 Slow 0.67 Slow DL3654 −0.15 Slow 27.74 Slow 0.70 Slow DL2533 −1.10 Slow 23.96 Slow 0.68 Slow DL2316 1.10 Fast 23.45 Fast 0.50 Fast DL2794 −0.11 Slow 20.99 Fast 0.53 Fast DL3941 3.40 Fast 20.65 Fast 0.29 Fast DL2381 1.17 Fast 20.62 Fast 0.44 Fast DL2335 0.58 Fast 20.41 Fast 0.47 Fast DL3647 0.73 Fast 19.63 Fast 0.44 Fast DL3646 0.33 Slow 19.32 Fast 0.46 Fast DL3222 −0.88 Slow 19.25 Fast 0.53 Fast DL3740 −0.69 Slow 17.57 Fast 0.48 Fast DL2386 1.61 Fast 16.29 Fast 0.32 Fast ↵a Data represent individual values for the three different stratifications.
↵b Individuals with values above or below the mean values determined for all individuals were grouped as faster or slower progressors, respectively.
↵c The combined coefficient values represent a combination of CD4% decline rate and CD4% level. The combined coefficient values were obtained by transforming the CD4% decline rate values and CD4% level values, setting them to comparable scales, and subsequently multiplying them.
- TABLE 2
Evolutionary rates (10−3 codon substitutions/site/year) in the V1-C3 env regions determined using a strict clock hierarchical phylogenetic modela
Genetic
regionAll
individualscCD4% stratification CD4% decline rate CD4% level and the combined coefficientb Fast
progressorscSlow
progressorscBayes factord Fast
progressorscSlow
progressorscBayes factord V1-C3 23.5 (20.3-26.6) 24.7 (20.1-29.6) 21.9 (19.1-24.9) 0.3 28.6 (24.2-33.5) 14.9 (12.2-17.6) 20.3 V1V2 29.5 (25.1-34.2)a 30.1 (24.6-36.0) 28.8 (23.7-34.0) 0.3 35.4 (28.9-42.2) 19.6 (14.8-24.7) 11.8 C2 18.0 (15.2-20.7)a 18.6 (15.3-21.9) 16.7 (13.9-19.5) 0.3 21.5 (17.6-25.7) 12.0 (9.2-15.2) 28.4 V3 21.2 (17.0-25.7)a 21.6 (16.5-26.8) 20.8 (15.7-25.9) 0.3 24.1 (18.0-30.6) 16.5 (11.0-22.2) 2.4 C3 26.6 (22.6-31.1)a 27.0 (22.0-32.4) 26.0 (21.6-30.6) 0.2 30.4 (24.3-27.0) 20.2 (15.2-25.8) 6.1 ↵a P values for Wilcoxon signed rank tests for comparisons of rates between regions were as follows: for V1V2 versus C2, <0.001; for V1V2 versus V3, 0.002; for V1V2 versus C3, 1; for C2 versus V3, 0.005; for C2 versus C3, <0.001; for V3 versus C3, <0.001.
↵b The combined coefficient values represent a combination of CD4% decline rate and CD4% level.
↵c Data correspond to 10−3 codon substitutions per site per year (95% highest posterior density interval).
↵d Bayes factor (BF) support for association between codon substitution rate and disease progression (faster versus slower progressors). BF >3 was considered evidence of a significant association.
