Risk Factors for Low CD4⁺ Count Recovery Despite Viral Suppression among Participants Initiating Antiretroviral Treatment with CD4⁺ Counts > 500 Cells/mm³: Findings from the Strategic Timing of AntiRetroviral Therapy (START) Trial

Background:Low CD4⁺ recovery among HIV-positive individuals who achieve virologic suppression is common but has not been studied among individuals initiating treatment at CD4⁺ counts of >500 cells/mm³.Setting:United States, Africa, Asia, Europe and Israel, Australia, Latin America.Methods:Among participants randomized to immediate antiretroviral therapy (ART) in the Strategic Timing of AntiRetroviral Therapy trial, low CD4⁺ recovery was defined as a CD4⁺ increase of <50 cells/mm³ from baseline after 8 months despite viral load of ≤200 copies/mL. Risk factors for low recovery were investigated with logistic regression.Results:Low CD4⁺ recovery was observed in 39.7% of participants. Male sex [odds ratio (OR), 1.53; P = 0.007], lower screening CD4⁺ cell counts (OR, 1.09 per 100 fewer cells/mm³; P = 0.004), higher baseline CD8⁺ cell counts (OR, 1.05 per 100 more cells/mm³; P < 0.001), and lower HIV RNA levels (OR, 1.93 per log¹⁰ decrease; P < 0.001) were associated with low CD4⁺ recovery. D-dimer had a quadratic association with low CD4⁺ recovery, with lowest odds occurring at 0.32 g/mL. At lower HIV RNA levels, the odds of low CD4⁺ recovery were elevated across the levels of screening CD4⁺ count; but at higher HIV RNA levels, the odds of low CD4⁺ recovery were higher among those with lower vs. higher screening CD4⁺.Conclusions:Low CD4⁺ recovery is frequent among participants starting ART at high CD4⁺ counts. Risk factors include male sex, lower screening CD4⁺ cell counts, higher CD8⁺ cell counts, and lower HIV RNA levels. More follow-up is required to determine the impact of low CD4⁺ recovery on clinical outcomes.