The relationship between
ritonavir plasma concentration, efficacy, and tolerance was evaluated in 31 children with advanced
HIV infection who were receiving a triple
therapy with
ritonavir as
protease inhibitor. Median CD4+ lymphocyte count and median viral load before the initiation of
ritonavir-containing combination
therapy were 1320 cells/mL and 5 log10 copies/mL, respectively.
Ritonavir was given at a dose ranging from 300 to 450 mg/m2 twice daily. The median follow-up of triple
therapy was 19 months. Response was defined as a drop of
viremia of more than 1 log. Plasma
drug levels were determined twice during the observation period: after at least 4 weeks and after 3 months of combined treatment. Samples were collected before (residual) and 2 hours (T2) after
drug intake.
Cholesterol,
triglycerides,
alanine transaminase,
aspartate transaminase, and
gamma-glutamyl transpeptidase were assessed at the same time. The median values of
ritonavir residual and T2 levels were 1.64 mg/L and 5.9 mg/L at observation 1 and 3.35 mg/L and 6.29 mg/L at observation 2, respectively. According to virologic response, median residual concentrations of
ritonavir were 3.17, 2.52, and 1.04 mg/L for the complete, the partial, and the no-response groups. The authors observed a wide intersubject variability of
ritonavir concentrations with an increase in residual levels between the two observation periods. Residual levels were correlated with virologic response whereas there was no direct association between T2 levels and long-term response. Patients with complete or partial response displayed statistically significantly higher residual concentrations than the no-response group. No correlation could be demonstrated between elevated plasma
drug concentrations and abnormal
cholesterol or
triglycerides values. These results emphasize the importance of a sustained high
ritonavir concentration to achieve optimal treatment efficacy. Furthermore, these results prove the clinical benefit of therapeutic
drug monitoring and could potentially improve patient evaluation in terms of treatment efficacy, compliance, and viral resistance.