Predictive value of CD4 cell count nadir on long-term mortality in HIV-positive patients in Uganda

OBJECTIVE Although international guidelines recommend initiating antiretroviral therapy (ART) when a patient's CD4 cell count is ≤350 cells/μL, most patients in resource-limited settings present with much lower CD4 cell counts. The lowest level that their CD4 cell count reaches, the nadir, may have long-term consequences in terms of mortality. We examined this health state in a large cohort of HIV+ patients in Uganda. DESIGN This was an observational study of HIV patients in Uganda aged 14 years or older, who were enrolled in 10 major clinics across Uganda. METHODS We assessed the CD4 nadir of patients, using their CD4 cell count at initiation of ART, stratified into categories (,50, 50-99, 100-149, 150-249, 250+ cells/μL). We constructed Kaplan-Meier curves to assess the differences in survivorship for patients left-censored at 1 year and 2 years after treatment initiation. We used Cox proportional hazards regression to model the associations between CD4 nadir and mortality. We adjusted mortality for loss-to-follow-up. RESULTS Of 22,315 patients, 20,129 patients had greater than 1 year of treatment follow-up. Among these patients, 327 (1.6%) died and 444 (2.2%) were lost to follow-up. After left-censoring at one year, relative to lowest CD4 strata, patients with higher CD4 counts had significantly lower rates of mortality (CD4 150-249, hazard ratio [HR] 0.60, 95% confidence interval [CI]: 0.45-0.82, P = 0.001; 250+, HR 0.66, 95% CI, 0.44-1.00, P = -0.05). Male sex, older age, and duration of time on ART were independently associated with mortality. When left-censoring at 2 years, CD4 nadir was no longer statistically significantly associated with mortality. CONCLUSION After surviving for 1 year on ART, a CD4 nadir was strongly predictive of longer-term mortality among patients in Uganda. This should argue for efforts to increase engagement with patients to ensure a higher CD4 nadir at initiation of treatment.