We constructed CD4+ cell count gain percentile distributions standardized by baseline CD4+ cell count and assessed the association between poor CD4+ cell count gain and subsequent death and virological failure on antiretroviral therapy (ART).Design:
Secondary analysis of 10 years of clinical data from a cohort of adults initiated on ART at the Themba Lethu clinic in Johannesburg, South Africa.Methods:
The generalized additive model for location, scale and shape was used to construct percentile curves for CD4+ cell count gain standardized by baseline CD4+ cell count in the first 28 months of ART. Cox proportional models were used to assess the association between lower percentiles (<50th) of CD4+ cell count gain, and subsequent death and virological failure.Results:
Among 9640 nonpregnant adults 7406, with available CD4+ cell count results for CD4+ gain calculation at 4 months of ART, 843 (8.7%) died subsequently and 1101 (11.4%) experienced virologic failure, respectively. For CD4+ gains below the third percentile, the adjusted hazard ratios at different time points ranged between 2.72 and 5.73 for death, and between 1.48 and 6.93 for virologic failure. The CD4+ percentile curves revealed a gradient of increasing risk of subsequent death and virological failure, with lower CD4+ gain percentiles and increasing time on ART, and were more informative than the WHO criteria for immunological failure or current CD4+ cell count.Conclusion:
Percentile curves of CD4+ cell count gain provide a simple tool for healthcare workers in low-resource settings to monitor response to ART with improved information regarding risk of death and virological failure compared to current WHO criteria for immunological failure.