Preliminary experiences with ritonavir in children with advanced HIV infection

The aim of this study was to obtain information on the feasibility (toleran ce, safety) of antiretroviral combination therapy, including ritonavir, in children. In eight children (median age 8.9 years; range 3 to 13 years) wit h advanced HIV disease (median CD4+ lymphocyte count at baseline, 80 cells/ mu l; range 0 to 280 cells/mu l), drug combinations including ritonavir (ap proximately 300 mg/m(2) b.i.d.) were administered. In seven children, previ ous therapy using a combination of at least two nucleoside reverse transcri ptase inhibitors (NRTI) had failed. Four patients had ritonavir added to an already existing regimen of two NRTI; two patients had one NRTI replaced b y a new one; and in two patients two new NRTI were initiated. The number of CD4 T cells, plasma HIV RNA concentration, CBC and blood chemistry profile were monitored. Medication had to be discontinued in two children because of severe nausea and vomiting. In the remaining six children, ritonavir was tolerated and treatment was maintained for at least 6 months. The number o f CD4 cells increased in five of six patients. The median number of CD4 cel ls increased from 66 +/- 110 cells/mu l at baseline to 92 +/- 99 cells/mu l , 161 +/- 88 cells/mu l, and 252 +/- 25 cells/mu l after 1, 3 and 6 months of therapy respectively, The plasma HIV RNA concentration decreased below t he detection limit of 500 copies/ml in three children. In the remaining chi ldren a maximum reduction of 0.8, 1.0 and 1.8 log(10) was observed, In one child the HIV RNA concentration reincreased after 6 months by 0.7 log(10) a bove the nadir. Antiretroviral combinations including ritonavir were tolera ted by six of eight children and produced substantial benefits with respect to increased numbers of CD4 cells and a decline in plasma viral RNA concen tration. It can be concluded that the administration of ritonavir is possib le in a significant proportion of HIV-infected children, and leads to impro vement of the CD4 cell count and viral load.