Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers. PLoS One
Chereau et al. on behalf of the HIV Controllers Project Working Group for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCOORD aimed to identify factors associated with loss of virological control among HIV controllers (HICs). HICs were defined as ≥5 consecutive viral loads (VL) ≤500 copies/mL over ≥1 year whilst ART-naive, with the last VL ≤500 copies/mL measured ≥5 years after HIV diagnosis.
Among the 111’073 eligible individuals, 1’067 HICs (0.96%) were identified; 86 lost virological control, 293 initiated ART, and 13 died during virological control. Six years after confirmation of HIC status, the probability of losing virological control, initiating ART and dying were 13%, 37%, and 2%. Current lower CD4/CD8 ratio and a history of transient viral rebounds were associated with an increased risk of losing virological control. CD4 declined and CD8 increased before loss of virological control, and before viral rebounds.
From this internationally largest series of HIV controllers, the authors conclude that expansion of CD8 and decline of CD4 during HIV control may result from repeated low-level viremia. The study-findings suggest that in addition to superinfection, other mechanisms, such as low grade viral replication, can lead to loss of virological control in HICs. From a clinical perspective, careful monitoring of untreated HICs who experience decrease of CD4 and CD4/CD8 ratio during virological control, or transient viral rebounds, is needed.