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
| Original language | English (US) |
|---|---|
| Pages (from-to) | 592-600 |
| Number of pages | 9 |
| Journal | International Journal of Antimicrobial Agents |
| Volume | 54 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 2019 |
Funding
Funding: This study was supported by grants from Fundacão de Amparo à Pesquisa do Estado de São Paulo (FAPESP, São Paulo, Brazil) [grant 13/11323-5 to RSD], the Brazilian National Research Council (CNPq, Brazil) [grant CNPq/cura 454700/14-8 to RSD ], and the Deutsches Zentrum für Infektionsforschung (DZIF, Braunschweig, Germany) [04.704 to ML and 04.810 to ML and OF]. ViiV Healthcare (Brentford, UK) and Torino Pharma (San Diego, CA, USA) donated some of the study drugs. AS is supported by the Italian Ministry of Financial Affairs (Rome, Italy); ILS is supported by the DZIF and the Alexander von Humboldt-Stiftung (Bonn, Germany). The funders had no role in study design, data collection and analysis, the decision to present the data, or preparation of the manuscript. The authors are thankful to Dr Shailendra Rathore (UCL, London, UK) for computational assistance in mathematical simulations; to Dora@hivforum (http://hivforum.info/forum/index.php) for providing an expert activist's feedback on the manuscript; and to Eric Verdin (Buck Institute, Novato, CA, USA) for providing the OGH construct. The authors are also thankful to Torino Pharma (San Diego, CA, USA) for providing auranofin and to ViiV Healthcare (Brentford, UK) for providing dolutegravir and maraviroc. Special thanks to the volunteers involved in the trial. Funding: This study was supported by grants from Fundac?o de Amparo ? Pesquisa do Estado de S?o Paulo (FAPESP, S?o Paulo, Brazil) [grant 13/11323-5 to RSD], the Brazilian National Research Council (CNPq, Brazil) [grant CNPq/cura 454700/14-8 to RSD], and the Deutsches Zentrum f?r Infektionsforschung (DZIF, Braunschweig, Germany) [04.704 to ML and 04.810 to ML and OF]. ViiV Healthcare (Brentford, UK) and Torino Pharma (San Diego, CA, USA) donated some of the study drugs. AS is supported by the Italian Ministry of Financial Affairs (Rome, Italy); ILS is supported by the DZIF and the Alexander von Humboldt-Stiftung (Bonn, Germany). The funders had no role in study design, data collection and analysis, the decision to present the data, or preparation of the manuscript. Competing interest: AS, ML and ILS are inventors of patents covering the use of auranofin in HIV-1 infection. All other authors declare no competing interests. Ethical approval: The protocol was approved by the Human Subjects Review Committee of the Federal University of Sao Paulo (Sao Paulo, Brazil) [approval no. 10757312.0.0000.5505].
Keywords
- Antiproliferative agent
- Disease-modifying antirheumatic agent
- HIV cure
- HIV reservoir
- Proviral DNA
- Viral evolution
ASJC Scopus subject areas
- Microbiology (medical)
- Infectious Diseases
- Pharmacology (medical)
