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

Wada, Nikolasa; Jacobson, Lisa P.a; Cohen, Mardgeb; French, Audreyb; Phair, Johnc; Muñoz, Alvaroa

doi: 10.1097/QAD.0000000000000078
Epidemiology and Social

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.

aDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

bDepartment of Medicine, Stroger Hospital of Cook County and Rush University

cFeinberg School of Medicine, Division of Infectious Diseases, Northwestern University, Chicago, Illinois, USA.

Correspondence to Nikolas Wada, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Room E7648, Baltimore, MD 21205, USA. Tel: +1 202 669 7739; fax: +1 410 955 7587; e-mail:

Received 20 June, 2013

Revised 12 September, 2013

Accepted 12 September, 2013

© 2014 Lippincott Williams & Wilkins, Inc.