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

Objective: To assess CD4(+) recovery after combined antiretroviral therapy (cART) initiation with sustained virologic control. Design: Cohort study based on the French Hospital Database on HIV (FHDH-ANRS CO4). Methods: We selected naive HIV-1-infected individuals initiating cART between 2006 and 2014 with CD4(+) cell counts less than 500 cells/mu l 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/mu l and identified associated factors, considering 'virologic failure,' 'loss to follow-up' and 'death' as competing events. Results: 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/mu l compared with CD4(+) cell counts <100 cells/mu l). 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. Conclusion: 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. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.