ArticleRetrovirology2010
Response of a simian immunodeficiency virus (SIVmac251) to raltegravir: a basis for a new treatment for simian AIDS and an animal model for studying lentiviral persistence during antiretroviral therapy.
Article in Retrovirology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 38 citations in OpenAlex.
- Clinical and virological effects of the integrase inhibitor raltegravir in cats with naturally progressive feline leukaemia virus infection.Journal of feline medicine and surgery · 2026Article
- Allogeneic MHC-matched T-cell receptor α/β-depleted bone marrow transplants in SHIV-infected, ART-suppressed Mauritian cynomolgus macaques.Scientific reports · 2022Article
- Effects of therapeutic vaccination on the control of SIV in rhesus macaques with variable responsiveness to antiretroviral drugs.PloS one · 2021Article
- Multifaceted HIV integrase functionalities and therapeutic strategies for their inhibition.The Journal of biological chemistry · 2019Review
- Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection.Nature communications · 2019Article
- Correlates of Protection Against SIVEBioMedicine · 2018Article
- Antiviral Activity of Bictegravir and Cabotegravir against Integrase Inhibitor-Resistant SIVmac239 and HIV-1.Antimicrobial agents and chemotherapy · 2017Article
- Retroviral DNA Integration.Chemical reviews · 2016Review
- Short Communication: Comparative Evaluation of Coformulated Injectable Combination Antiretroviral Therapy Regimens in Simian Immunodeficiency Virus-Infected Rhesus Macaques.AIDS research and human retroviruses · 2016Article
- Nonhuman Primates and Humanized Mice for Studies of HIV-1 Integrase Inhibitors: A Review.Pathogens & immunity · 2016Review
- Characterization of the Drug Resistance Profiles of Integrase Strand Transfer Inhibitors in Simian Immunodeficiency Virus SIVmac239.Journal of virology · 2015Article
- Detection of Simian Immunodeficiency Virus in Semen, Urethra, and Male Reproductive Organs during Efficient Highly Active Antiretroviral Therapy.Journal of virology · 2015Article
- Pharmacokinetic profile of raltegravir, elvitegravir and dolutegravir in plasma and mucosal secretions in rhesus macaques.The Journal of antimicrobial chemotherapy · 2015Article
- Effect of HIV-1 integrase resistance mutations when introduced into SIVmac239 on susceptibility to integrase strand transfer inhibitors.Journal of virology · 2014Article
- Chronic binge alcohol consumption does not diminish effectiveness of continuous antiretroviral suppression of viral load in simian immunodeficiency virus-infected macaques.Alcoholism, clinical and experimental research · 2014Article
- Effect of combination antiretroviral therapy on Chinese rhesus macaques of simian immunodeficiency virus infection.AIDS research and human retroviruses · 2013Article
- Investigational treatment suspension and enhanced cell-mediated immunity at rebound followed by drug-free remission of simian AIDS.Retrovirology · 2013Article
- Considerations in the development of nonhuman primate models of combination antiretroviral therapy for studies of AIDS virus suppression, residual virus, and curative strategies.Current opinion in HIV and AIDS · 2013Review
- Comprehensive in vitro analysis of simian retrovirus type 4 susceptibility to antiretroviral agents.Journal of virology · 2013Article
- Characterization of peripheral and mucosal immune responses in rhesus macaques on long-term tenofovir and emtricitabine combination antiretroviral therapy.Journal of acquired immune deficiency syndromes (1999) · 2012Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn this study we successfully created a new approach to ART in SIVmac251 infected nonhuman primates. This drug regimen is entirely based on drugs affecting the pre-integration stages of replication and consists of only two nucleotidic/nucleosidic reverse transcriptase inhibitors (Nt/NRTIs) and raltegravir, a promising new drug belonging to the integrase strand transfer inhibitor (INSTI) class.
resultsIn acutely infected human lymphoid CD4+ T-cell lines MT-4 and CEMx174, SIVmac251 replication was efficiently inhibited by raltegravir, which showed an EC90 in the low nanomolar range. This result was confirmed in primary macaque PBMCs and enriched CD4+ T cell fractions. In vivo monotherapy with raltegravir for only ten days resulted in reproducible decreases in viral load in two different groups of animals. When emtricitabine (FTC) and tenofovir (PMPA) were added to treatment, undetectable viral load was reached in two weeks, and a parallel increase in CD4 counts was observed. In contrast, the levels of proviral DNA did not change significantly during the treatment period, thus showing persistence of this lentiviral reservoir during therapy.
conclusionsIn line with the high conservation of the three main amino acids Y143, Q148 and N155 (responsible for raltegravir binding) and molecular docking simulations showing similar binding modes of raltegravir at the SIVmac251 and HIV-1 IN active sites, raltegravir is capable of inhibiting SIVmac251 replication both in tissue culture and in vivo. This finding may help to develop effective ART regimens for the simian AIDS model entirely based on drugs adopted for treatment in humans. This ART-treated AIDS nonhuman primate model could be employed to find possible strategies for virus eradication from the body.
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Registered trials
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