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doi: 10.1097/QAD.0b013e328321823f
Clinical Science

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

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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.

© 2009 Lippincott Williams & Wilkins, Inc.


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