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Changing Mortality Risk Associated with CD4 Cell Response to Long-term ART: Sub-Saharan Africa
Stephen Lawn*1,2, F Little1, L-G Bekker1, R Kaplan1, E Campbel1, C Orrell1, and R Wood1
1Univ of Cape Town, South Africa and 2London Sch of Hygiene and Tropical Med, UK
Background: Patients enrolling in ART programs in Sub-Saharan
Africa have high risk of early mortality. Little is known, however, about
long-term mortality risk and how this changes over time during response to ART.
We aimed to define the relationship between ART-induced changes in CD4
counts and mortality.
Methods: In this observational study, patients
enrolled in a community-based ART cohort in South Africa were studied for as
long as 5 years of ART. CD4 counts were measured at baseline and 4-monthly during
follow-up (updated CD4 counts). Deaths were prospectively ascertained. Cumulative
person-time accrued within a range of updated CD4 count strata (CD4-strata) was
calculated and used to derive CD4-stratified mortality rates.
Results: Among 2423 patients (median baseline
CD4 count, 105 cells/μL), 197 deaths occurred during 3155 person-years of
observation. In multivariate analysis, mortality rate ratios associated with 0
to 49, 50 to 99, 100 to 199, 200 to 299, 300 to 399, 400 to 499 and ≥500
cells/μL updated CD4-strata were 11.6, 4.9, 2.6, 1.7, 1.5, 1.4, and 1.0, respectively.
Analysis of CD4 count recovery over time permitted calculation of person-time
within these updated CD4-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-strata <200 cells/μL. Moreover, patients with
baseline CD4 counts <100 cells/μL had higher cumulative mortality
estimates at 1 and 4 years (11.6% and 16.7%) compared to those of patients with
baseline counts ≥100 cells/μL (5.2% and 9.5%) largely because of
greater cumulative person-time at CD4 counts <200 cells/μL. Cumulative
mortality estimates after 4 years of ART were approximately 3-fold higher than
corresponding estimates from high-income countries.
Conclusions: Updated CD4 counts are the variable
most strongly associated with mortality risk during ART. High mortality risk is
associated with person-time accrued at low CD4 counts. National HIV programmes
in resource-limited settings should be designed to minimise the time that
patients spend with CD4 counts <200 cells/μL both before and during
ART.
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