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Int J Antimicrob Agents ; 54(5): 592-600, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31394172

RESUMO

Antiretroviral therapy (ART) is typically composed of a combination of three antiretroviral drugs and is the treatment of choice for people with human immunodeficiency virus type 1/acquired immune deficiency syndrome (HIV-1/AIDS). However, it is unable to impact on viral reservoirs, which harbour latent HIV-1 genomes that are able to reignite the infection upon treatment suspension. The aim of this study was to provide an estimate of the safety of the disease-modifying antirheumatic agent auranofin and its impact on the HIV-1 reservoir in humans under intensified ART. For this purpose, an interim analysis was conducted of three of the six arms of the NCT02961829 clinical trial (five patients each) with: no intervention, i.e. continuation of first-line ART; intensified ART (ART + dolutegravir and maraviroc); and intensified ART plus auranofin. Auranofin treatment was found to be well tolerated. No major adverse events were detected apart from a transient decrease in CD4+ T-cell counts at Weeks 8 and 12. Auranofin decreased total viral DNA in peripheral blood mononuclear cells compared with ART-only regimens at Week 20 (P = 0.036) and induced a decrease in integrated viral DNA as quantified by Alu PCR. Despite the limited number of patient-derived sequences available in this study, phylogenetic analyses of nef sequences support the idea that auranofin may impact on the viral reservoir. [ClinicalTrials.gov ID: NCT02961829].


Assuntos
Antirreumáticos/uso terapêutico , Auranofina/uso terapêutico , HIV-1/genética , Provírus/efeitos dos fármacos , Provírus/genética , Latência Viral/efeitos dos fármacos , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , DNA Viral/efeitos dos fármacos , DNA Viral/genética , Inibidores da Fusão de HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Maraviroc/uso terapêutico , Oxazinas , Piperazinas , Piridonas
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