Normalisation of CD4 counts in patients with HIV-1 infection and maximum virological suppression who are taking combination antiretroviral therapy: an observational cohort study

BACKGROUND Combination antiretroviral therapy (cART) has been shown to reduce mortality and morbidity in patients with HIV. As viral replication falls, the CD4 count increases, but whether the CD4 count returns to the level seen in HIV-negative people is unknown. We aimed to assess whether the CD4 count for patients with maximum virological suppression (viral load <50 copies per mL) continues to increase with long-term cART to reach levels seen in HIV-negative populations. METHODS We compared increases in CD4 counts in 1835 antiretroviral-naive patients who started cART from EuroSIDA, a pan-European observational cohort study. Rate of increase in CD4 count (per year) occurring between pairs of consecutive viral loads below 50 copies per mL was estimated using generalised linear models, accounting for multiple measurements for individual patients. FINDINGS The median CD4 count at starting cART was 204 cells per microL (IQR 85-330). The greatest mean yearly increase in CD4 count of 100 cells per microL was seen in the year after starting cART. Significant, but lower, yearly increases in CD4 count, around 50 cells per microL, were seen even at 5 years after starting cART in patients whose current CD4 count was less than 500 cells per microL. The only groups without significant increases in CD4 count were those where cART had been taken for more than 5 years with a current CD4 count of more than 500 cells per microL, (current mean CD4 count 774 cells per microL; 95% CI 764-783). Patients starting cART with low CD4 counts (<200 cells per microL) had significant rises in CD4 counts even after 5 years of cART. INTERPRETATION Normalisation of CD4 counts in HIV-infected patients for all infected individuals might be achievable if viral suppression with cART can be maintained for a sufficiently long period of time.