A total of 21 children were enrolled in the study of which 16 completed the 48 weeks study period. The baseline characteristics of all patients are summarized in table . Four children were naive to antiretroviral therapy (Group A). Seventeen children had received prior indinavir-containing HAART for a median period of 18 months (range, 2-50 months). Of these, nine had baseline HIV-1 RNA levels below 500 copies/ml (Group B1) and eight had HIV-1 RNA levels above 500 copies/ml (Group B2). Indinavir was started at a median dosage of 400 mg/m2 (range 300–600) and ritonavir was started at a median dosage of 125 mg/m2 (range 100–125).
Baseline characteristics of the 21 children.
The clinical condition of the patients during the study period was good. None of the patients showed signs and symptoms of AIDS and no progression in their CDC-classification stage was observed. The course of the surrogate markers viral load and CD4 + T-cell counts during the follow- up are depicted in table . Overall after 48 weeks of treatment 13 out of the 16 children still on treatment had HIV-1 RNA levels < 500 copies/ml and 11 < 50 copies/ml. In Group A, three out of four patients had HIV-1 RNA levels < 50 copies after 48 weeks of treatment. In Group B1, seven out of eight patients had HIV-1 RNA levels < 50 copies. In Group B2, three of four children had HIV-1 RNA levels < 500 copies/ml, but only 1 had HIV-1 RNA levels < 50 copies/ml. Over time an increase in CD4 + T-cells was observed, albeit not significant for any treatment group. (p-value baseline vs week 48 for the total group CD4% total T-cells 0.234 and for CD4% normal 0.14).
Clinical en immunological parameters during 1-year follow-up of 21 children treated with indinavir/ritonavir.
Most children (n = 19) reported side effects related to the medication. The adverse events occurred throughout the entire study period. These side effects were often mild and of gastrointestinal origin. However, serious adverse were reported in seven children. These included nephrolithiasis (n = 2), silent nephrolithiasis found upon ultrasound research (n = 2), jaundice (n = 1), impaired liver functions, vomiting and malaise (n = 1) and dehydration due to vomiting (n = 1). Serious side effects were observed in all study groups (Group A: 1, Group B1: 3 and B2: 3) (Table ).
No significant difference in the occurrence of SAE’s between the three treatment groups: NPar tests occurrence of SAE’s χ2-test frequencies.
Five patients stopped therapy during the follow-up period. In one additional patient medication was discontinued on the last study day. Discontinuation happened four times because of drug toxicity (1 nephrolithiasis, 1 silent nephrolithiasis, 1 rash, 1 hepatitis) and twice on patient request. All children that stopped medication were pretreated and most (n = 4) had detectable viral loads at the start of the study. These patients had suffered from indinavir related toxicity in the past. However, none of the adverse events that had occurred before the start of the study were serious (Table ).
Study termination and viral load at start of the study: NPar tests χ2-test frequencies.
No significant differences were found between the PK parameters of children with or without side effects (data not shown). However, in two children renal side effects resolved after a decrease of the indinavir or ritonavir dosage. In the four children who discontinued medication because of side effects dosage adjustments were not performed. This was because of the seriousness of the side effects and hesitation in the patients and their parents to restart indinavir.