CD4+ cell count recovery after combined antiretroviral therapy in the modern combined antiretroviral therapy era

To assess CD4 recovery after combined antiretroviral therapy (cART) initiation with sustained virologic control.Cohort study based on the French Hospital Database on HIV (FHDH-ANRS CO4).We selected naive HIV-1-infected individuals initiating cART between 2006 and 2014 with CD4 cell counts less than 500 cells/μl who achieved virologic control, defined as two consecutive viral loads less than 50 copies/ml. We estimated the cumulative incidence of CD4 recovery at least 500 cells/μl and identified associated factors, considering 'virologic failure,' 'loss to follow-up' and 'death' as competing events.We analyzed 6050 individuals with a median follow-up of 14.2 months since virologic control. The cumulative incidence for CD4 recovery after 6 years of virologic control reached 69.7%. The main factor associated with CD4 recovery was the CD4 count at treatment initiation [subdistribution hazard ratio (sHR) 9.64, 95% confidence interval (95% CI) 8.12-11.43 for CD4 cell counts between 350 and 500 cells/μl compared with CD4 cell counts <100 cells/μl). A higher CD4/CD8 ratio at initiation was also independently associated with a higher probability of CD4 recovery [sHR 1.67; 95% CI 1.34-2.09] for a CD4/CD8 ratio ≥1.00 vs. < 0.30). Higher viral load at initiation was also associated with a higher probability of CD4 recovery, whereas time to viral suppression was not.After 6 years of sustained virologic control, a large majority of the population achieved CD4 recovery. A higher CD4 cell count at initiation was a strong predictor of CD4 recovery and, to a lesser extent, a higher CD4/CD8 ratio at initiation. These results confirm the necessity of early treatment.