CD4+ gain percentile curves for monitoring response to antiretroviral therapy in HIV-infected adults

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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).


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.


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.


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.


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.

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