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

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.