Impact of pre-therapy viral load on virological response to modern first-line HAART

BACKGROUND: We tested whether pre-HAART (Highly Active Antiretroviral Therapy) viremia affects the achievement and maintenance of virological-success in HIV-1 infected patients starting modern first-line therapies. METHODS: 1430 patients starting their first HAART (genotype-tailored) in median in 2008 (IQR: 2006-2009) were grouped according to levels of pre-HAART viremia (<30K, 30-100K, 100-300K, 300-500K, >500K copies/mL). The impact of pre-therapy viremia on the time to virological-success (viremia ≤50 copies/mL) and on the time to virological-rebound (first of two consecutive viremia-values >50 copies/mL after virological-success) were evaluated by Kaplan-Meier curves and Cox regression analyses. RESULTS: Median pre-HAART-viremia was 5.1(IQR:4.5-5.5) log(10) copies/mL, and 53% of patients had viremia >100K copies/mL. By week 48, the prevalence of patients reaching the virological-success was >90% in all pre-HAART viremia ranges, with the only exception of range >500K copies/mL (virological-success = 83%) (p<0.001). Higher pre-HAART-viremia tightly correlated with longer median time to achieve virological-success. Cox multivariable estimates confirmed this result: patients with pre-HAART viremia>500K copies/mL showed the lowest hazard of virological undetectability after adjusting for age, gender, pre-HAART CD4 cell-count, transmitted drug-resistance, calendar year, third drug-administered (adjusted RH[95%CI]: 0.27[0.21-0.35], p<0.001). Pre-HAART viremia >500K copies/mL was also associated with higher probability of virological-rebound compared to patients belonging to lower viremia strata at weeks 4/12/24 (p=0.050). CONCLUSIONS: At the time of modern HAART, and beside an average >90% of virological-success, high pre-HAART viremia remains an independent factor associated with delayed and decreased virological-success. Patients starting HAART with >500K copies/mL represent a significant population that may deserve special attention.