Cause-specific mortality among HIV-infected individuals, by CD4(+) cell count at HAART initiation, compared with HIV-uninfected individuals

Abstract

Objectives: To compare the proportion, timing and hazards of non-AIDS death and AIDS death among men and women who initiated HAART at different CD4 cell counts to mortality risks of HIV-uninfected persons with similar risk factors.

Design: Prospective cohort studies.

Methods: We used parametric mixture models to compare proportions of AIDS and non-AIDS mortality and ages at death, and multivariable Cox models to compare cause-specific hazards of mortality, across levels of CD4 cell count at HAART initiation (≤200 cells/μl: 'late', 201-350 cells/μl: 'intermediate', >350 cells/μl: 'early') and with HIV-uninfected individuals from the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study. We used multiple imputation methods to address lead-time bias in sensitivity analysis.

Results: Earlier initiators were more likely to die of non-AIDS causes (early: 78%, intermediate: 74%, late: 49%), and at older ages (median years 72, 69, 66), relative to later initiators. Estimated median ages at non-AIDS death for each CD4 cell count category were lower than that estimated for the HIV-uninfected group (75 years). In multivariable analysis, non-AIDS death hazard ratios relative to early initiators were 2.15 for late initiators (P < 0.01) and 1.66 for intermediate initiators (P = 0.01); AIDS death hazard ratios were 3.26 for late initiators (P < 0.01) and 1.20 for intermediate initiators (P = 0.28). Strikingly, the adjusted hazards for non-AIDS death among HIV-uninfected individuals and early initiators were nearly identical (hazard ratio 1.01). Inferences were unchanged after adjustment for lead-time bias.

Conclusion: Results suggest the possibility of reducing the risk of non-AIDS mortality among HIV-infected individuals to approximate that faced by comparable HIV-uninfected individuals.

Fig. 1

Cause-specific mortality by CD4⁺cell count at HAART initiation, compared to HIV-negative individuals (a,b) Probability density functions for non-AIDS death (a) and AIDS death (b), stratified by CD4⁺ cell count at HAART initiation. Percentages represent proportion of all-cause mortality. (c,d) Differences in age at non-AIDS death (c) and AIDS death (d) by percentile, stratified by CD4⁺cell count at HAART initiation. Reference category for (c) is HIV-negative. Reference category for (d) is CD4⁺ cell count >350 cells/μl at HAART initiation. For example, at 50% decreased in Fig. 1c, the value of the blue dashed line (−3.0) represents the median age at non-AIDS death for the early initiators (72.0) minus the median age at death for the HIV-negative reference (75.0). 95% confidence intervals at 25th, 50th and 75th percentiles calculated using the delta method. Numbers on x-axis are deciles (years of age at death) for the reference group.