Potential impact of the antirheumatic agent auranofin on proviral HIV-1 DNA in individuals under intensified antiretroviral therapy: Results from a randomised clinical trial

Author(s):Show less -

Diaz, Ricardo Sobhie ^[1] ; Shytaj, Iart Luca ^{[2, 3]} ; Giron, Leila B. ^{[4, 1]} ; Obermaier, Benedikt ^{[2, 3]} ; Libera, Jr., Ermelindo Della ^[1] ; Galinskas, Juliana ^[1] ; Dias, Danilo ^[1] ; Hunter, James ^[1] ; Janini, Mario ^[1] ; Gosuen, Gisele ^[1] ; Ferreira, Paulo Abrao ^[1] ; Sucupira, Maria Cecilia ^[1] ; Maricato, Juliana ^[1] ; Fackler, Oliver ^{[2, 3]} ; Lusic, Marina ^{[2, 3]} ; Savarino, Andrea ^[5] ; Grp, SPARC Working

Affiliation

^[1] Univ Fed Sao Paulo, Infect Dis Dept, BR-04021001 Sao Paulo - Brazil

^[2] Heidelberg Univ Hosp, Dept Infect Dis, D-69120 Heidelberg - Germany

^[3] German Ctr Infect Res, D-69120 Heidelberg - Germany

^[4] Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 - USA

^[5] Ist Super Sanita, Dept Infect Dis, Viale Regina Elena 299, I-00161 Rome - Italy

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS; v. 54, n. 5, p. 592-600, NOV 2019.
• Web of Science Citations: 2

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. (C) 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved. (AU)

• FAPESP's process: 13/11323-5 - Multi interventional study exploring HIV-1 residual replication: a step towards HIV-1 eradication and sterilizing cure
• Grantee: Ricardo Sobhie Diaz
• Support Opportunities: Regular Research Grants