ArticleAntimicrobial agents and chemotherapy2014
Effect of suberoylanilide hydroxamic acid (SAHA) administration on the residual virus pool in a model of combination antiretroviral therapy-mediated suppression in SIVmac239-infected indian rhesus macaques.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 44 citations in OpenAlex.
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- Antibody-based CCR5 blockade protects Macaques from mucosal SHIV transmission.Nature communications · 2021Article
- Antibody-mediated depletion of viral reservoirs is limited in SIV-infected macaques treated early with antiretroviral therapy.The Journal of clinical investigation · 2021Article
- Review
- Virologic and Immunologic Features of Simian Immunodeficiency Virus Control Post-ART Interruption in Rhesus Macaques.Journal of virology · 2020Article
- The Landscape of Persistent Viral Genomes in ART-Treated SIV, SHIV, and HIV-2 Infections.Cell host & microbe · 2019Article
- TLR7 agonist administration to SIV-infected macaques receiving early initiated cART does not induce plasma viremia.JCI insight · 2019Article
- Impacts of HIV Cure Interventions on Viral Reservoirs in Tissues.Frontiers in microbiology · 2019Review
- Antibody-Mediated CD4 Depletion Induces Homeostatic CD4Journal of virology · 2018Article
- Ultrasensitive Immunoassay for Simian Immunodeficiency Virus p27AIDS research and human retroviruses · 2018Article
- Short-Term Pegylated Interferon α2a Treatment Does Not Significantly Reduce the Viral Reservoir of Simian Immunodeficiency Virus-Infected, Antiretroviral Therapy-Treated Rhesus Macaques.Journal of virology · 2018Article
- Wake me up before you go: a strategy to reduce the latent HIV reservoir.AIDS (London, England) · 2018Article
- Defining total-body AIDS-virus burden with implications for curative strategies.Nature medicine · 2017Article
- Genetically-barcoded SIV facilitates enumeration of rebound variants and estimation of reactivation rates in nonhuman primates following interruption of suppressive antiretroviral therapy.PLoS pathogens · 2017Article
- In Vivo Models of Human Immunodeficiency Virus Persistence and Cure Strategies.The Journal of infectious diseases · 2017Review
- In vitro effects of the small-molecule protein kinase C agonists on HIV latency reactivation.Scientific reports · 2016Article
- Article
- Multi-dose Romidepsin Reactivates Replication Competent SIV in Post-antiretroviral Rhesus Macaque Controllers.PLoS pathogens · 2016Article
- Antiretroviral Therapy in Simian Immunodeficiency Virus-Infected Sooty Mangabeys: Implications for AIDS Pathogenesis.Journal of virology · 2016Article
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Authors and funding
24 authors at 5 institutions in 1 country.
Funding
Abstract
Nonhuman primate models are needed for evaluations of proposed strategies targeting residual virus that persists in HIV-1-infected individuals receiving suppressive combination antiretroviral therapy (cART). However, relevant nonhuman primate (NHP) models of cART-mediated suppression have proven challenging to develop. We used a novel three-class, six-drug cART regimen to achieve durable 4.0- to 5.5-log reductions in plasma viremia levels and declines in cell-associated viral RNA and DNA in blood and tissues of simian immunodeficiency virus SIVmac239-infected Indian-origin rhesus macaques, then evaluated the impact of treatment with the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA; Vorinostat) on the residual virus pool. Ex vivo SAHA treatment of CD4(+) T cells obtained from cART-suppressed animals increased histone acetylation and viral RNA levels in culture supernatants. cART-suppressed animals each received 84 total doses of oral SAHA. We observed SAHA dose-dependent increases in acetylated histones with evidence for sustained modulation as well as refractoriness following prolonged administration. In vivo virologic activity was demonstrated based on the ratio of viral RNA to viral DNA in peripheral blood mononuclear cells, a presumptive measure of viral transcription, which significantly increased in SAHA-treated animals. However, residual virus was readily detected at the end of treatment, suggesting that SAHA alone may be insufficient for viral eradication in the setting of suppressive cART. The effects observed were similar to emerging data for repeat-dose SAHA treatment of HIV-infected individuals on cART, demonstrating the feasibility, utility, and relevance of NHP models of cART-mediated suppression for in vivo assessments of AIDS virus functional cure/eradication approaches.
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