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

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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/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.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/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.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.

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