CD4 Dynamics over a 15 Year-Period among HIV Controllers Enrolled in the ANRS French Observatory

Background: There are few large published studies of HIV controllers with long-term undetectable viral load (VL). We describe the characteristics and outcomes of 81 French HIV controllers. Methods and Results: HIV controllers were defined as asymptomatic, antiretroviral-naive persons infected >= 10 years previously, with HIV-RNA < 400 copies/mL in > 90% of plasma samples. All available CD4 and VL values were collected at enrolment. Mixed-effect linear models were used to analyze CD4 cell count slopes since diagnosis. HIV controllers represented 0.31% of all patients managed in French hospitals. Patients infected through intravenous drug use were overrepresented (31%) and homosexual men were under represented (26% of men) relative to the ANRS SEROCO cohort of subjects diagnosed during the same period. HIV controllers whose VL values were always below the detection limit of the assays were compared with those who had rare "blips" (< 50% of VL values above the detection limit) or frequent blips (< 50% of VL values above the detection limit). Estimated CD4 cell counts at HIV diagnosis were similar in the three groups. CD4 cell counts remained stable after HIV diagnosis in the "no blip" group, while they fell significantly in the two other groups (-0.26 root CD4 and -0.28 root CD4/mm(3)/year in the rare and frequent blip groups, respectively). No clinical, immunological or virological progression was observed in the no blip group, while 3 immunological and/or virological events and 4 cancers were observed in the blip subgroups. Conclusions: Viral blips in HIV controllers are associated with a significant decline in CD4 T cells and may be associated with an increased risk of pathological events, possibly owing to chronic inflammation/immune activation.