Potential impact of the antirheumatic agent auranofin on proviral HIV-1 DNA in individuals under intensified antiretroviral therapy

• Verfasst von: Diaz, Ricardo Sobhie [VerfasserIn]
• Verfasst von: Fackler, Oliver Till [VerfasserIn]
• Verfasst von: Lusic, Marina [VerfasserIn]
• Titel: Potential impact of the antirheumatic agent auranofin on proviral HIV-1 DNA in individuals under intensified antiretroviral therapy
• Titelzusatz: results from a randomised clinical trial
• Verf.angabe: Ricardo Sobhie Diaz, Iart Luca Shytaj, Leila B. Giron, Benedikt Obermaier, Ermelindo della Libera, Juliana Galinskas, Danilo Dias, James Hunter, Mario Janini, Gisele Gosuen, Paulo Abrão Ferreira, Maria Cecilia Sucupira, Juliana Maricato, Oliver Fackler, Marina Lusic, Andrea Savarino, SPARC Working Group
• E-Jahr: 2019
• Jahr: 5 August 2019
• Umfang: 9 S.
• Fussnoten: Gesehen am 29.11.2019
• Titel Quelle: Enthalten in: International journal of antimicrobial agents
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1991
• Jahr Quelle: 2019
• Band/Heft Quelle: 54(2019), 5, Seite 592-600
• ISSN Quelle: 1872-7913
• DOI: doi:10.1016/j.ijantimicag.2019.08.001
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Antiproliferative agent
• Sach-SW: Disease-modifying antirheumatic agent
• Sach-SW: HIV cure
• Sach-SW: HIV reservoir
• Sach-SW: Proviral DNA
• Sach-SW: Viral evolution
• K10plus-PPN: 1683818865

Abstract

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]