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/μl 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/μl 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/μl], 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.