RESUMO
BACKGROUND: Previous in vitro studies indicated that Atazanavir (ATV) has a distinct resistance profile than other protease inhibitors (PIs). In treatment-experienced patients ATV resistance is characterised by the accumulation of at least four mutations among those that confer cross-resistance to the PIs. OBJECTIVE: We studied the evolution of PIs resistance mutations in 10 HAART-failed patients undergoing ATV enrolled in an early access program. STUDY DESIGN: Virus genotypic resistance was determined from plasma collected at baseline and during treatment. HIV-RNA was extracted and the pol region amplified and sequenced. Genotypic data were used to determine drug susceptibility. Phylogenetic analysis was performed. RESULTS: At baseline, genotypic data showed cross-resistance patterns to approved PIs in 6 patients. In two of these subjects new mutations (I54V and A71V) conferring cross-resistance emerged after 3 months of therapy. The I50L mutation was evidenced in one subject after 12 months of treatment. The "virtual" phenotype analysis mirrored the resistance profiles to ATV and other PIs and evidenced differences with tipranavir and darunavir. CONCLUSION: Genotype evolution within the protease region did not emerge at significant levels during salvage therapy of multidrug-experienced patients. ATV exhibited certain/same virologic effect on the majority of our patients.
Assuntos
Farmacorresistência Viral/genética , Evolução Molecular , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Protease de HIV/genética , HIV-1/efeitos dos fármacos , Oligopeptídeos/uso terapêutico , Piridinas/uso terapêutico , Adulto , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Sulfato de Atazanavir , Feminino , Genótipo , Infecções por HIV/virologia , Inibidores da Protease de HIV/farmacologia , HIV-1/classificação , HIV-1/enzimologia , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação , Fenótipo , Filogenia , Análise de Sequência de DNARESUMO
OBJECTIVES: To characterize the efficacy and tolerability of multiple drug therapy (MDT) among heavily pre-treated HIV-infected children. METHODS: An observational study of seven children treated with 4-7 antiretroviral agents. MDT regimens were chosen with regard to past antiretroviral exposure and genotypic resistance data. Five children received MDT once, one child twice and one child four times. All patients had AIDS and severe CD4+ depletion and failed >2 PI-based HAART regimens. RESULTS: Virologic response, defined as a > or =log10 decrease in plasma HIV-1 RNA at week 24, was achieved in 7/11 MDT. Successful MDT kept a sustained viral suppression (<50 copies/ml) at longest follow-up (72-96 weeks). Successful MDT obtained a great immune recovery: the median rise in absolute and percentage of CD4+ cells was 261 and 4 at week 24 and it reached 480 and 16 at 72-96 weeks. Adverse events were common but generally manageable. Mild/moderate gastrointestinal complaints and laboratory abnormalities were detected in 5/11 and 8/11 MDT. Grade 2 severity pancreatitis occurred in one case with chronic active hepatitis C. Pancreatitis resolved within 30 days of MDT interruption. CONCLUSIONS: MDT may be a therapeutic option in children who failed to respond to most standard HAART regimens.