Very high pre-therapy viral load is a predictor of virological rebound in HIV-1-infected patients starting a modern first-line regimen

Background: Pre-cART (combined antiretroviral therapy) plasma viral load >500,000 copies/mL has been associated with a lower probability of achieving virological suppression, while few data about its role on maintenance of virological suppression are available. In this study we aimed to clarify whether high levels of pre-cART viremia are associated with virological rebound (VR) after virological suppression. Methods: HIV-infected individuals who achieved virological suppression after first-line cART were included. VR was defined as the first of two consecutive viremia >50 copies/mL (VR50) or, in an alternative analysis, >200 copies/mL (VR200). The impact of pre-cART viremia on the risk of VR was evaluated by survival analyses. Results: Among 5,766 patients included, 59.2%, 31.4%, 5.2% and 4.2% had precART viremia d100,000, 100,001-500,000, 500,001-1,000,000, and >1,000,000 copies/mL, respectively. Patients with pre-cART viremia levels >1,000,000 copies/mL had the highest probability of VR (>1,000,000; 500,000-1,000,000; 100,000-500,000; <100,000 copies/mL; VR50: 28.4%; 24.3%; 17.6%; 13.8%, p<0.0001; VR200: 14.4%; 11.1%; 7.2%; 7.6%; p=0.009). By Cox multivariable analyses, patients with pre-cART viremia >500,000 and >1,000,000 copies/mL showed a significantly higher risk of VR regardless of the VR endpoint used. No difference in the risk of VR was found between patients with pre-cART viremia ranging 500,000-1,000,000 copies/mL and those with pre-cART viremia >1,000,000 copies/mL, regardless of the VR endpoint used. Conclusions: Pre-cART plasma viral load levels >500,000 copies/mL can identify fragile patients with poorer chance of maintaining virological control after an initial response. An effort in defining effective treatment strategies is mandatory for these patients that remain difficult to treat.