Table 3.
Survival analysis for progression to three AIDS outcomes among seroconverters as a function of IL10-5′A/5′A or +/5′A vs. IL10-+/+ genotype
Time* interval, years | AIDS-1993
|
AIDS-1987
|
Death
|
|||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
n/event | RHu | P value | adjRH† | P value | n/event | RHu | P value | adjRH† | P value | n/event | RHu | P value | adjRH† | P value | ||
All races | All | 766/462 | 1.28 | 0.01 | 1.37 | 0.002 | 769/332 | 1.43 | 0.002 | 1.44 | 0.002 | 769/253 | 1.32 | 0.03 | 1.32 | 0.03 |
0–5 | 1.06 | 0.66 | 1.17 | 0.26 | 1.26 | 0.24 | 1.25 | 0.27 | 1.04 | 0.86 | 1.05 | 0.82 | ||||
>5 | 1.54 | 0.002 | 1.58 | 0.0009 | 1.52 | 0.003 | 1.54 | 0.002 | 1.49 | 0.01 | 1.48 | 0.02 | ||||
Caucasians | All | 511/336 | 1.44 | 0.0009 | 1.45 | 0.0008 | 514/265 | 1.51 | 0.001 | 1.51 | 0.001 | 514/213 | 1.40 | 0.02 | 1.41 | 0.02 |
0–5 | 1.23 | 0.21 | 1.27 | 0.15 | 1.21 | 0.42 | 1.26 | 0.33 | 1.05 | 0.85 | 1.09 | 0.75 | ||||
>5 | 1.63 | 0.0009 | 1.61 | 0.001 | 1.65 | 0.0007 | 1.63 | 0.001 | 1.57 | 0.007 | 1.56 | 0.008 | ||||
Multicenter AIDS Cohort Study | All | 345/234 | 1.56 | 0.0008 | 1.57 | 0.0007 | 348/186 | 1.52 | 0.005 | 1.53 | 0.004 | 348/147 | 1.34 | 0.08 | 1.36 | 0.06 |
0–5 | 1.28 | 0.17 | 1.30 | 0.15 | 1.19 | 0.49 | 1.22 | 0.43 | 1.05 | 0.87 | 1.07 | 0.81 | ||||
>5 | 1.96 | 0.0005 | 1.96 | 0.0005 | 1.74 | 0.003 | 1.74 | 0.003 | 1.55 | 0.04 | 1.57 | 0.03 | ||||
Multicenter Hemophilia Cohort Study | All | 157/100 | 1.34 | 0.17 | 1.39 | 0.13 | 157/78 | 1.49 | 0.10 | 1.56 | 0.10 | 157/65 | 1.46 | 0.15 | 1.45 | 0.17 |
0–5 | 0.97 | 0.95 | 1.15 | 0.75 | 1.15 | 0.83 | 1.39 | 0.62 | 0.95 | 0.95 | 1.33 | 0.74 | ||||
>5 | 1.48 | 0.11 | 1.50 | 0.10 | 1.56 | 0.09 | 1.54 | 0.10 | 1.53 | 0.13 | 1.49 | 0.16 | ||||
African Americans‡ | All | 220/102 | 0.92 | 0.69 | 1.22 | 0.42 | 220/53 | 1.08 | 0.81 | 1.12 | 0.73 | 220/31 | 1.01 | 0.81 | 1.07 | 0.87 |
0–5 | 0.74 | 0.24 | 0.93 | 0.80 | 1.48 | 0.37 | 1.31 | 0.57 | 1.02 | 0.96 | 0.96 | 0.94 | ||||
>5 | 1.42 | 0.37 | 1.93 | 0.13 | 0.77 | 0.54 | 0.96 | 0.93 | 1.25 | 0.74 | 1.32 | 0.69 |
Statistical analysis. Cox models (15, 16) were used for calculating relative hazards and P values for separate and combined cohorts and racial groups, as we have previously reported (5, 6). Nonsignificant 2- and 3-year windows in the initial infection period were grouped together and later times considered separately in further Cox analyses of AIDS outcomes (14, 35). A strict and conservative Bonferroni correction of the 120 P values presented would mean that only those of P ≤ 0.00042 are significant, which is coincidentally equivalent to the smallest observed P value (P = 0.0005; Multicenter AIDS Cohort Study, AIDS-1993 >5-year portion of the analysis). Because the tests were not independent, the observed statistical associations seem robust. Eighteen of the AIDS progression P values are lower than 0.002 (some by an order of magnitude), and overall, 45 are P ≤ 0.05 and 30 are P ≤ 0.01.
Time was not taken into account in all models and was included as an interaction term by separating 0–5 and >5 years in the models (except death, where 0–6 and >6 years was used).
Relative hazards were shown as RHu from unadjusted models and as adjRH from adjusted models, in which the effects of the previously described CCR5-Δ32 and CCR2-64I genotypes were taken into account. The effects of IL10 and CCR (CCR5-Δ32 and CCR2-64I) appear additive, because, in the Cox analyses, interaction terms were not significant (P = 0.53–0.87) for the four outcomes in Caucasians.
IL10-5′A AIDS accelerating effects were most apparent in Caucasian and mixed ethnic group analyses. The less significant P values in African Americans are likely a consequence of fewer patients (n = 220 seroconverters), fewer AIDS cases after 5 years of infection (15 AIDS-1987 and 5 AIDS deaths), and the relative recency of the recruitment of the AIDS Link to the Intravenous Experience cohort, which comprises 70% of the African American seroconverters (5, 27). This interpretation is supported by high relative hazards (at >5 years); RH = 3.41 and 1.93 for CD4 < 200 and AIDS-1993, respectively, the two earliest AIDS end points.