Low pre-ART CD4 count is associated with increased risk of clinical progression or death even after reaching 500 CD4 cells/μL on ART

INTRODUCTION: Clinical disadvantages of initiating ART at low CD4 counts have been clearly demonstrated but whether any excess risk remains even after reaching relatively high/safe CD4 levels remains unclear. We explore whether individuals starting ART with <500 CD4 cells/μL who increased their CD4 count above this level, have, from this point onwards, similar risk of clinical progression to serious AIDS/non-AIDS events or death with individuals starting ART with ≥500 CD4 cells/μL. METHODS: Data were derived from a multicenter cohort (AMACS). Adults, starting PI, NNRTI or INSTI based ART, in or after 2000 were eligible, provided they started ART with ≥500 (“High CD4”) or started with CD4 <500 cells/μL but surpassed this threshold while on ART (“Low CD4”). Baseline was the date of ART initiation (“High CD4”) or of first reaching 500 CD4 cells/μL (“Low CD4”). Survival analysis, allowing for competing risks, was used to explore the risk of progression to study’s endpoints. RESULTS: The study included 694 persons in the “High CD4” and 3,306 in the “Low CD4” group. Median (IQR) follow-up was 66 (36, 106) months. In total, 257 events (40 AIDS related, 217 SNAEs) were observed. Rates of progression did not differ significantly between the two groups but the subgroup of those initiating ART with <200 CD4 cells/μL had significantly higher risk of progression after baseline, compared to those in the “High CD4” group. CONCLUSIONS: Individuals starting ART with <200 cells/μL remain on increased risk even after reaching 500 CD4 cells/μL. These patients should be closely followed.