Preliminary experiences with ritonavir in children with advanced HIV infection.

Abstract

The aim of this study was to obtain information on the feasibility (tolerance, safety) of antiretroviral combination therapy, including ritonavir, in children. In eight children (median age 8.9 years; range 3 to 13 years) with advanced HIV disease (median CD4+ lymphocyte count at baseline, 80 cells/microliter; range 0 to 280 cells/ microliter), drug combinations including ritonavir (approximately 300 mg/m2 b.i.d.) were administered. In seven children, previous therapy using a combination of at least two nucleoside reverse transcriptase inhibitors (NRTI) had failed. Four patients had ritonavir added to an already existing regimen of two NRTI; two patients had one NRTI replaced by 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 of CD4 cells increased in five of six patients. The median number of CD4 cells increased from 66 +/- 110 cells/microliter at baseline to 92 +/- 99 cells/microliter, 161 +/- 88 cells/microliter, and 252 +/- 25 cells/microliter after 1, 3 and 6 months of therapy, respectively. The plasma HIV RNA concentration decreased below the detection limit of 500 copies/ml in three children. In the remaining children a maximum reduction of 0.8, 1.0 and 1.8 log10 was observed. In one child the HIV RNA concentration reincreased after 6 months by 0.7 log10 above the nadir. Antiretroviral combinations including ritonavir were tolerated by six of eight children and produced substantial benefits with respect to increased numbers of CD4 cells and a decline in plasma viral RNA concentration. It can be concluded that the administration of ritonavir is possible in a significant proportion of HIV-infected children, and leads to improvement of the CD4 cell count and viral load.