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Changing mortality risk associated with CD4 cell response to antiretroviral therapy in South Africa

Lawn, Stephen Da,b; Little, Francescac; Bekker, Linda-Gaila; Kaplan, Richarda; Campbel, Elizabetha; Orrell, Catherinea; Wood, Robina

doi: 10.1097/QAD.0b013e328321823f
Clinical Science

Objective: To determine the relationship between mortality risk and the CD4 cell response to antiretroviral therapy (ART).

Design: Observational community-based ART cohort in South Africa.

Methods: CD4 cell counts were measured 4 monthly, and deaths were prospectively ascertained. Cumulative person-time accrued within a range of updated CD4 cell count strata (CD4 cell-strata) was calculated and used to derive CD4 cell-stratified mortality rates.

Results: Patients (2423) (median baseline CD4 cell count of 105 cells/μl) were observed for up to 5 years of ART. One hundred and ninety-seven patients died during 3155 person-years of observation. In multivariate analysis, mortality rate ratios associated with 0–49, 50–99, 100–199, 200–299, 300–399, 400–499 and at least 500 cells/μl updated CD4 cell-strata were 11.6, 4.9, 2.6, 1.7, 1.5, 1.4 and 1.0, respectively. Analysis of CD4 cell count recovery permitted calculations of person-time accrued within these CD4 cell-strata. Despite rapid immune recovery, high mortality in the first year of ART was related to the large proportion of person-time accrued within CD4 cell-strata less than 200 cells/μl. Moreover, patients with baseline CD4 cell counts less than 100 cells/μl had much higher cumulative mortality estimates at 1 and 4 years (11.6 and 16.7%) compared with those of patients with baseline counts of at least 100 cells/μl (5.2 and 9.5%) largely because of greater cumulative person-time at CD4 cell counts less than 200 cells/μl.

Conclusion: Updated CD4 cell counts are the variable most strongly associated with mortality risk during ART. High cumulative mortality risk is associated with person-time accrued at low CD4 cell counts. National HIV programmes in resource-limited settings should be designed to minimize the time patients spend with CD4 cell counts less than 200 cells/μl both before and during ART.

aThe Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

bClinical Research Unit, Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK

cFaculty of Science, Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa.

Received 30 September, 2008

Revised 5 November, 2008

Accepted 8 November, 2008

Correspondence to Dr Stephen D. Lawn, Faculty of Health Sciences, Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa. Tel: +27 21 650 6957; fax: +27 21 650 6963; e-mail:

© 2009 Lippincott Williams & Wilkins, Inc.