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CD4+ count and risk of non-AIDS diseases following initial treatment for HIV infection

Baker, Jason Va,b; Peng, Gracea; Rapkin, Joshuaa; Abrams, Donald Ic; Silverberg, Michael Jd; MacArthur, Rodger De; Cavert, Winston Pa; Henry, W Keitha,b; Neaton, James Da; for the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA)

doi: 10.1097/QAD.0b013e3282f7cb76
Clinical Science

Background: Reductions in AIDS-related morbidity and mortality following the advent of combination antiretroviral therapy have coincided with relative increases in chronic non-AIDS end-organ diseases among HIV+ patients.

Objective: To examine the association of latest CD4+ counts with risk of non-AIDS diseases in a cohort of 1397 patients who initiate antiretroviral therapy.

Methods: CD4+ counts and HIV RNA levels along with fatal, and non-fatal, AIDS and non-AIDS diseases (liver, cardiovascular, renal, and cancer) were assessed over a median follow-up of 5 years. Cox proportional regression models were used to study risk associations.

Results: A total of 227 patients experienced an AIDS event and 80 patients developed a non-AIDS disease event. Both AIDS and non-AIDS diseases rates (events/100 person-years), respectively, declined with higher latest CD4+ counts: 13.8 and 2.1 with latest CD4+ counts less than 200 cells/μl; 2.0 and 1.7 for counts of 200–350 cells/μl; and 0.7 and 0.7 for counts greater than 350 cells/μl. After adjusting for baseline covariates and the latest HIV RNA level, risk of AIDS and non-AIDS diseases were lowered by 44% (95% confidence interval for hazard ratio 0.50–0.62, P < 0.01) and 14% (95% confidence interval for hazard ratio 0.77–0.96, P = 0.01), respectively, for each 100 cell/μl higher latest CD4+ count.

Conclusion: Higher CD4+ counts on antiretroviral therapy are associated with lower rates of non-AIDS diseases and AIDS. These findings expand our understanding of the implications of HIV-related immunodeficiency and motivate randomized studies to evaluate the effects of antiretroviral therapy on a broad set of clinical outcomes at CD4+ counts greater than 350 cells/μl.

From the aUniversity of Minnesota, Minneapolis, USA

bHennepin County Medical Center, Minneapolis, Minnesota, USA

cUniversity of California San Francisco, San Francisco, USA

dKaiser Permanente Northern California, Oakland, California, USA

eWayne State University, Detroit, Michigan, USA.

Correspondence to Dr Jason Baker, MD, MS, Hennepin County Medical Center, 701 Park Ave; Mail Code G5, Minneapolis, MN 55415, USA. Tel: +1 612 873 2705; fax: +1 612 904 4299; e-mail: baker459@umn.edu

© 2008 Lippincott Williams & Wilkins, Inc.