Conduction disturbances and arrhythmias are common in cancer children at the beginning of the therapy, but no acute or long-term adverse consequences are related to their appearance.

Each of the 17 vertically infected infants born to HIV-1-infected mothers in Belgian HIV reference centers since 1996 was treated with a combination of 3 reverse transcription inhibitors as soon as the diagnosis was established. Treatment was initiated in all patients before 66 days of life. Twelve patients, including 11/13 infants treated with the combination of zidovudine, lamivudine and nevirapine, experienced a complete viral suppression (<50 copies/mL) with their first drug regimen. At last follow-up, 12 patients were asymptomatic, 2 were CDC stage A and 3 were stage B; 15 had HIV-1 RNA levels of <50 copies/mL and 14 had >or=25% CD4 lymphocytes. These results suggest that early initiation of treatment with 3 reverse transcription inhibitors is highly effective to inhibit viral replication and to prevent clinical and immunologic progression of HIV infection in vertically infected infants.

Objective. To assess genotypic and phenotypic resistance testing in HIV-1-infected children failing a first protease inhibitor (PI) therapy.Methods. In a multicenter observational study 21 children, ages 3 to 16 years, were given two reverse transcriptase inhibitors and one PI (mainly ritonavir, n = 18). They were subsequently treated with single or dual Pi-based therapy (predominantly nelfinavir, n = 10, or ritonavir-saquinavir, n = 7). Resistance testing was performed at the time of therapy switch via direct sequencing and a recombinant virus susceptibility assay.Results. A total of 21 genotypic and 15 phenotypic resistance profiles were obtained. Most viruses displayed several reverse transcriptase mutations; however, 7 isolates maintained a wild-type protease. Ritonavir targeted the well-known pathway containing 82, 54, 46 and other secondary (nonactive site) mutations including T74A. No in vitro cross-resistance, i.e. ≥8-fold resistance to saquinavir or amprenavir, was encountered. Secondary mutations enhanced the prediction of ritonavir resistance (i.e. L10I) and in vitro nelfinavir cross-resistance (i.e. K20R/I) conferred by primary (active site) resistance mutations. Either the 82, 54, 46 mutational genotype or the phenotype showing ≥8-fold nelfinavir cross-resistance predicted a poorer virologic response to nelfinavir salvage therapy. Conclusion.In a small cohort of heavily pre-treated pediatric patients, resistance testing appears to predict the response to nelfinavir as salvage for a ritonavir-based therapy. This is further supported by the correlation between ritonavir-selected mutations and in vitro nelfinavir cross-resistance. Prospective studies should assess clinical outcome in children undergoing regimen changes based on resistance testing.

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