The relationship between ritonavir plasma trough concentration and virological and immunological response in HIV‐infected children

Publisher Website
Google Scholar
Abstract
We studied a number of factors, including ritonavir plasma levels, and their capability of predicting response to therapy with ritonavir (RTV). Eleven HIV-positive children, nucleoside reverse transcriptase inhibitor (NRTI)-experienced, protease inhibitor (PI) naive, receiving RTV in combination with two NRTIs were enrolled in the study. Demographic parameters were: median age (range) 10 (2–13) years, weight 26 (10–38) kg, body surface area (BSA) 0.93 (0.47–1.21) m2. Baseline values of CD4, percent CD4 and viral load were 137 (2–1390) cells/µL, 9.5 (0.4–32.4)%, and 5.15 (4.30–6.18) log10 copies/mL, respectively. The dose of RTV was 318 (266–409) mg/m2 twice daily. Peak (3.5 h after administration) and trough (predose) plasma concentrations of RTV were determined on one occasion at steady-state after a morning dose. Virological response to treatment was quantified as the difference between the baseline value of viral load and the value observed at 6 months of therapy (Δ6). The relationship between Δ6 and demographic parameters (age, weight, BSA, and baseline CD4, percent CD4, and viral load) and plasma concentrations of RTV was studied by linear regression. Median (range) Δ6 was 0.88 (0.77–2.62) log10 copies/mL. Peak and trough of RTV were 14.9 (3.2–31.4) and 5.0 (0.1–15.6) mg/L, respectively. Trough concentration of RTV was the best predictor of Δ6, although the relationship between these two variables was not statistically significant (r = 0.56, P= 0.075). Our observation of a trend for a greater decrease in viral load in patients with higher trough concentration of RTV warrants further pharmacodynamic studies of PI in paediatric patients.