RESUMO
Objectives: To assess the safety and efficacy of a dolutegravir-based regimen in perinatally HIV-1-infected adolescents. Patients and methods: We conducted a retrospective multicentre study of 50 adolescents beginning dolutegravir-based treatment regimens between January 2014 and December 2015. Clinical and biological data collected before and after dolutegravir initiation were analysed. The primary endpoint was the proportion of patients achieving a plasma viral load (PVL) <50 copies/mL within 3 months of dolutegravir initiation (for patients with detectable viraemia at baseline) and maintaining virological suppression (PVL <50 copies/mL) until the last follow-up visit (for all patients). Results: Virological suppression was noted for 17/50 adolescents at baseline. Dolutegravir-based regimens maintained virological success in 14/17 patients (82%). The other three patients experienced a transient viral rebound, before PVL fell to < 50 copies/mL again, with no need to change the antiretroviral regimen. Thirty-three viraemic adolescents were enrolled. All but one had already received antiretroviral drugs. Virological success was achieved and maintained in 19/33 subjects (58%). Another three adolescents with initial virological failure had an undetectable PVL at the end of follow-up, with reinforced measures to improve compliance. Overall, sustained virological success was observed in 66% of patients and 78% of patients had an undetectable PVL at the last visit. Dolutegravir was well tolerated. Only one patient stopped treatment for severe drug-related adverse effects (dizziness and sleep disturbance). No emergence of resistance mutations was observed in patients with virological failure. Conclusions: Dolutegravir was safe and virologically effective in these patients, for whom multiple interventions were required to improve compliance.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Adolescente , Farmacorresistência Viral , Feminino , França , Infecções por HIV/virologia , Inibidores de Integrase de HIV/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Humanos , Transmissão Vertical de Doenças Infecciosas , Masculino , Oxazinas , Piperazinas , Plasma/virologia , Piridonas , Estudos Retrospectivos , Carga Viral/efeitos dos fármacosRESUMO
The size of the antiretroviral capsules which children infected with HIV have to take is a major problem. It often requires an assessment of the feasibility of taking this medication through a specialist nursing consultation. It is above all through adopting a suitable technique as well as the motivation of the children that this objective can be achieved.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Tratamento Farmacológico/enfermagem , Soropositividade para HIV/enfermagem , Adesão à Medicação/psicologia , Educação de Pacientes como Assunto/organização & administração , Administração Oral , Adolescente , Fármacos Anti-HIV/química , Contagem de Linfócito CD4 , Química Farmacêutica , Criança , Tratamento Farmacológico/psicologia , Tratamento Farmacológico/estatística & dados numéricos , Feminino , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/imunologia , Soropositividade para HIV/psicologia , Hospitais Pediátricos , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pesquisa em Avaliação de Enfermagem , Pais/educação , Pais/psicologia , Paris , Enfermagem Pediátrica/organização & administraçãoRESUMO
Newborns from human immunodeficiency virus-infected mothers are given antiretroviral prophylaxis against mother-to-child transmission, including predominantly nucleoside reverse transcriptase inhibitors. Pharmacological monitoring of these drugs in newborns has so far been limited to plasma and cord blood. In this study, samples from newborns (up to 45 days old) treated with zidovudine (AZT) alone (n = 29) or in combination with lamivudine (3TC) (n = 20) were analyzed for both intracellular concentrations of phosphate metabolites in peripheral blood mononuclear cells and levels of parent drugs in plasma. Plasma AZT and intracellular AZT-monophosphate and AZT-triphosphate (TP) concentrations were significantly higher during the first 15 days of life (199 versus 52.7 ng/ml [P < 0.0001], 732 versus 282 fmol/10(6) cells [P < 0.0001], and 170 versus 65.1 fmol/10(6) cells [P < 0.0001], respectively) and then became comparable to those of adults. No difference in intracellular AZT metabolite concentrations was found when AZT- and AZT-3TC-treated groups were compared. Plasma 3TC levels (lower limit of quantification [LLOQ], 1,157 ng/ml; median, 412.5 ng/ml) were not associated with the newborn's age, gender, or weight. Intracellular 3TC-TP concentrations (LLOQ, 40.4 pmol/10(6) cells; median, 18.9 pmol/10(6) cells) determined for newborns receiving the AZT-3TC combination were associated with neither the age nor weight of the newborns. Concentrations in females were significantly higher (1.8-fold [P = 0.0415]) than those in males. Unexpectedly, newborns on AZT monotherapy whose mothers' treatment included 3TC displayed residual plasma 3TC and intracellular 3TC-TP levels up to 1 week after birth.