You are here
EARLY MORTALITY IN HIV-INFECTED PATIENTS INITIATING ART WITHOUT A PRETHERAPY CD4
Kombatende Sikombe1, Ingrid Eshun-Wilson2, Aybuke Koyuncu1, Sandra Simbeza1, Aaloke Mody2, Nancy Czaicki2, Laura K. Beres3, Carolyn Bolton Moore4, Nancy Padian5, Izukanji Sikazwe1, Charles B. Holmes6, Elvin Geng2
1Centre for Infectious Disease Research in Zambia, Lusaka, Zambia,2University of California San Francisco, San Francisco, CA, USA,3Johns Hopkins University, Baltimore, MD, USA,4University of Alabama at Birmingham, Birmingham, AL, USA,5University of California Berkeley, Berkeley, CA, USA,6Georgetown University, Washington, DC, USA
In the treat-all era, CD4 levels are no longer required to determine treatment eligibility, resulting in some programs phasing out CD4 tests altogether. Pre-therapy CD4, however, can play a crucial role in informing screening and prophylaxis for opportunistic infections, which are contributors to HIV-related mortality. We assessed the association between presence of a pre-therapy CD4 and early mortality among patients in Zambia starting ART.
We evaluated patients starting ART between August 1, 2013 and July 31, 2015 in Zambia. We obtained pre-therapy CD4 (most recent determination within 6 months of treatment initiation), socio-demographic and clinical data from the electronic medical record. We identified a probability sample of patients lost to follow-up for intensive tracing to determine vital status. Findings from tracing were incorporated into Kaplan-Meier estimates and multivariate proportional hazards regression through inverse probability-weights. Estimates were adjusted for potential common causes of CD4 determination and survival (e.g. WHO stage, calendar time, facility type, etc.).
Of 39,556 patients starting ART (63% women, median age 35.64 (IQR 29.88 – 42.41)), 31,895 (76%) had a pre-therapy CD4 on record (median CD4 270 cells/μl (IQR 145-396)). The cumulative incidence of mortality after ART initiation in the study population was 5.12% (95% CI 4.32, 6.10). The cumulative incidence of mortality with and without pre-therapy CD4 at 1 year was 4.54% (95% CI 3.73, 5.60) and 7.06% (95% CI 5.14, 9.98), respectively (Cox test for equality p=0.03). After adjustment for pre-therapy WHO stage, sex, age, facility type, ART initiation date, patients without a pre-therapy CD4 had 1.48 times the hazard of mortality in the first year compared to those with a pre-therapy CD4 determination (95% CI 1.00, 2.17, p=0.046). Advanced WHO stage and male sex were associated with higher probability of early mortality (WHO stage IV, HR, 7.69 (95% CI, 4.19, 14.13 p< 0.001) male sex, HR, 1.62 (95% CI, 1.13, 2.32 p< 0.008)).
Despite the possibility of unmeasured confounding, these results suggest that patients initiating ART without pre-therapy CD4 experience a higher risk of early mortality even after adjustment for demographic characteristics and disease stage. Even though pre-therapy CD4 are no longer required to determine eligibility, further research to evaluate the safety of discontinuing pre-therapy CD4 is needed before widespread discontinuation.