CD4+ response and subsequent risk of death among patients on antiretroviral therapy in Lusaka, Zambia.
BACKGROUND
Where virologic monitoring is not routinely available, immunologic criteria are commonly used to determine treatment failure while on antiretroviral therapy (ART). However, few have studied CD4+ response and its relationship to subsequent clinical outcomes in a programmatic setting.


METHODS
We analyzed cohort data from Zambia to investigate whether 6- and 12-month CD4+ response after ART initiation was associated with later mortality. We used Cox proportional hazards models that accounted for different strata of baseline CD4 counts and adjusted for age, sex, clinical stage, tuberculosis coinfection, baseline hemoglobin, initial ART regimen, and adherence behavior.


RESULTS
We analyzed data from 2 cohorts, from 6 months onward (n = 24,366; median follow-up = 467 days, interquartile range 222-791) and from 12 months onward (n = 17,920; median follow-up = 423 days, interquartile range 191-689). In the post-6-month analysis, hazard for death was significantly higher when absolute CD4+ response was <100 cells per microliter [adjusted hazard ratio (AHR) = 2.25, 95% confidence interval (CI): 1.91 to 2.64], relative response was <10% above baseline (AHR = 2.60, 95% CI: 2.12 to 3.19), and absolute CD4+ count was <100 per microliter (AHR = 2.79, 95% CI: 2.26 to 3.45). In the post-12 month analysis, mortality was associated with rise in absolute CD4+ cell count <200 per microliter (AHR = 2.41, 95% CI: 1.83 to 3.17), relative rise in CD4+ cell count of <10% above baseline (AHR = 3.41, 95% CI: 2.51 to 4.64), and absolute CD4+ count at 12 months <100 per microliter (AHR = 4.11, 95% CI: 2.96 to 5.68).


CONCLUSIONS
Commonly used definitions for immunologic treatment failure are associated with elevated mortality risk among patients on ART.
Chi
Benjamin H
BH
Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu
Giganti
Mark
M
Mulenga
Priscilla L
PL
Limbada
Mohammed
M
Reid
Stewart E
SE
Mutale
Wilbroad
W
Stringer
Jeffrey S A
JS
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality; D015497:HIV-1; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D015024:Zambia / Q000453:epidemiology
D019380:Anti-HIV Agents