Changing mortality risk associated with CD4 cell response to antiretroviral therapy in South Africa.
OBJECTIVE
To determine the relationship between mortality risk and the CD4 cell response to antiretroviral therapy (ART).


METHODS
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/microl) were observed for up to 5 years of ART. One hundred and ninety-seven patients died during 3155 person-years of observation. In microltivariate analysis, mortality rate ratios associated with 0-49, 50-99, 100-199, 200-299, 300-399, 400-499 and at least 500 cells/microl 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/microl. Moreover, patients with baseline CD4 cell counts less than 100 cells/microl 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/microl (5.2 and 9.5%) largely because of greater cumulative person-time at CD4 cell counts less than 200 cells/microl.


CONCLUSIONS
Updated CD4 cell counts are the variable most strongly associated with mortality risk during ART. High cumicrolative 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/microl both before and during ART.
Lawn
Stephen D
SD
The Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, University of Cape Town, South Africa. stevelawn@yahoo.co.uk
Little
Francesca
F
Bekker
Linda-Gail
LG
Kaplan
Richard
R
Campbel
Elizabeth
E
Orrell
Catherine
C
Wood
Robin
R
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D004812:Epidemiologic Methods; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality / Q000821:virology; D006801:Humans; D008297:Male; D013019:South Africa / Q000453:epidemiology; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents