Natural History of HIV control since seroconversion

OBJECTIVES:: HIV-controllers spontaneously maintain HIV viraemia at an undetectable level. We aimed to describe the delay to control from seroconversion, the duration of control, and risk factors for losing control. METHODS:: HIV-controllers were identified from a pooled dataset of 24 seroconverter cohorts from Europe, Australia and Canada (CASCADE). HIV-controllers had ≥5 consecutive viral loads (VL) <400/500 copies/mL, while ART-naïve, for ≥5 years after seroconversion. End of control was defined as two consecutive VL >2000 copies/mL.Duration of control was described using Kaplan-Meier estimates; factors associated with duration of control identified using a Cox model. CD4 count evolution during control was described using a mixed model. RESULTS:: Of 9,896 eligible seroconverters, we identified 140 (1.4%) HIV-controllers, the largest database of HIV-controllers followed from seroconversion. For 64 with VL measured within 24 months from seroconversion, median delay to control was 16.7 (IQR: 7.8-37.9) months. Probability of maintaining control 20 years after seroconversion was 0.74 (95% confidence interval (CI): 0.64-0.85). Occurrence of blips followed by return to undetectability did not increase the risk of loss of control (hazard ratio: 0.81 (95% CI: 0.10-6.70). However, CD4 cell loss during control was significantly accelerated in individuals with blips. CONCLUSIONS:: In most individuals, control occurred rapidly after seroconversion; however, >3 years were required to achieve control in 25% of HIV-controllers. Control may be sustained even while CD4 levels are below 500 cells/mm, opening important new perspectives to understand the physiopathology underlying control.