CD4+/CD8+ ratio restoration in long-term treated HIV-1-infected individuals.

Objectives: A persistently low CD4(+)/CD8(+) ratio despite virological control reflects a higher risk of morbidity in HIV-infected individuals. The objective of the study was to assess the probability and determinants of ratio restoration (>= 1) during long-term combined antiretroviral therapy (cART). Design: Study cohort based on the French Hospital Database on HIV (ANRS CO4). Methods: Antiretroviral-naive HIV-1-infected individuals were included if they achieved virological control (plasma HIV RNA <= 500 copies/ml) within 9 months following cART, started between 2000 and 2010. Cumulative incidence of ratio restoration after virological control and predictive factors of such a favorable outcome were studied taking into account 'virological failure', 'loss to follow-up', and 'death' as competing risks for ratio restoration. Results: Among the 10012 individuals included, the probability of CD4(+)/CD8(+) ratio restoration was 30% (95% confidence interval, 29-31) at 8 years, ranging from 17% (15 to 19) among individuals with AIDS, to 45% (41 to 50) in people with CD4(+) at least 500 cells/ml at cART introduction. The main factors associated with ratio restoration were cART started during primary HIV infection whatever the CD4(+) cell count, or starting at CD4(+) at least 500 cells/ml while not in primary HIV infection [subdistribution hazard ratio = 1.67 (95% confidence interval, 1.13-2.47) and 2.26 (1.92-2.66) respectively, compared with starting cART at 200-349 CD4(+) cells/ml], and starting cART in recent years [subdistribution hazard ratio = 2.38 (2.01-2.83) in 2009-2010, compared with 2000-2002]. Higher baseline CD8(+) cell count was negatively associated with ratio restoration. Conclusion: At 8 years, only one-third of individuals achieved CD4(+)/CD8(+) ratio restoration with sustained virological control. Treatment at the earliest stage, and starting cART in recent years appeared to be key determinants. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.