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

Abstract

BackgroundThere 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 ResultsHIV controllers were defined as asymptomatic, antiretroviral-naïve 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 underrepresented (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√CD4 and −0.28√CD4/mm3/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.ConclusionsViral 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.

Long-Term Spontaneous Control of HIV-1 Is Related to Low Frequency of Infected Cells and Inefficient Viral Reactivation

“…This response, in turn, readily controls the infection, maintaining a steady state between infected cells and the immune system (Fig. 5A), which may result in residual systemic activation and mild progression in the absence of therapy (45)(46)(47). The virtuous circle between the virus and the host response would be interrupted when the frequency of latently infected CD4 ϩ T cells falls to a very low level, hindering the stochastic reactivation of fit viruses (18) and leading to fewer viral amplification events.…”

Elite Controllers and Long-term Nonprogressors: Models for HIV Vaccine Development?

“…It is unclear whether a proportion of elite controllers are persistently <1 copy/mL or if all elite controllers have detectable virus by single-copy assay at some point during the course of untreated HIV infection. Interestingly, a French study showed that elite controllers with transient low-level viremia, termed "blips", do not experience CD4 declines compared to those who do not have detectable viremia [21]. In contrast to elite controllers, LTNP are typically viremic by standard clinical viral load assays.…”

HIV Controllers Maintain a Population of Highly Efficient Th1 Effector Cells in Contrast to Patients Treated in the Long Term

“…They can maintain a viral load below the detection threshold of standard assays (Ͻ50 copies HIV RNA/ml plasma) for decades and show a very low risk of progression to AIDS (4,23). Converging evidence indicates that HIV controllers have developed particularly efficient cellular antiviral responses, which can maintain an active control of the infected target cell population in the long term.…”