In Vitro Susceptibility of HIV Isolates with High Growth Capability to Antiretroviral Drugs
It has been considered that reduced susceptibility to antiretroviral drugs is influenced by drug adherence, drug tolerance and drug-resistance-related mutations in the HIV genome. In the present study, we assessed the intrinsic high viral growth capability as a potential viral factor that may influe...
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/23/15380 |
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| author | Alfredo A. Hinay Kyosuke Kanai Akeno Tsuneki-Tokunaga Mizuki Komatsu Elizabeth O. Telan Seiji Kageyama |
| author_facet | Alfredo A. Hinay Kyosuke Kanai Akeno Tsuneki-Tokunaga Mizuki Komatsu Elizabeth O. Telan Seiji Kageyama |
| author_sort | Alfredo A. Hinay |
| collection | DOAJ |
| description | It has been considered that reduced susceptibility to antiretroviral drugs is influenced by drug adherence, drug tolerance and drug-resistance-related mutations in the HIV genome. In the present study, we assessed the intrinsic high viral growth capability as a potential viral factor that may influence their susceptibility to antiretroviral drugs using an in vitro model. Phytohemagglutinin-activated peripheral blood mononuclear cells (1.5 × 10<sup>6</sup> cells) were infected with HIV isolates (10<sup>6</sup> copies/mL). The culture was carried out at different concentrations (0.001–20 μM) of 13 synthetic antiretroviral compounds (six nucleoside/nucleotide reverse transcriptase inhibitors, one non-nucleoside reverse transcriptase inhibitor, four integrase inhibitors, and two protease inhibitors), and HIV production was assessed using HIV-RNA copies in culture. The 90% inhibitory concentration (IC<sub>90</sub>) and pharmacokinetics of an antiretroviral agent were used as parameters to determine the reduced antiretroviral drug susceptibility of HIV isolates with high growth capability to synthetic antiretroviral compounds. The high growth capability of HIV isolates without any known drug resistance-related mutation affected their susceptibility to tenofovir (IC<sub>90</sub> = 2.05 ± 0.40 μM), lamivudine (IC<sub>90</sub> = 6.83 ± 3.96 μM), emtricitabine (IC<sub>90</sub> = 0.68 ± 0.37 μM), and efavirenz (IC<sub>90</sub> = 3.65 ± 0.77 μM). These antiretroviral drugs showed IC<sub>90</sub> values close to or above the maximum plasma concentration against HIV isolates with high growth capability without any known drug resistance-related mutation. Our results may contribute to the development of effective strategies to tailor and individualize antiretroviral therapy in patients harboring HIV isolates with high growth capability. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:44:52Z |
| publishDate | 2022-12-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c4ad8d55ed97409ea0418c93c3b28e172023-11-24T11:18:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123231538010.3390/ijms232315380In Vitro Susceptibility of HIV Isolates with High Growth Capability to Antiretroviral DrugsAlfredo A. Hinay0Kyosuke Kanai1Akeno Tsuneki-Tokunaga2Mizuki Komatsu3Elizabeth O. Telan4Seiji Kageyama5Division of Virology, Department of Microbiology and Immunology, Faculty of Medicine, Tottori University, Yonago 683-8503, JapanDivision of Virology, Department of Microbiology and Immunology, Faculty of Medicine, Tottori University, Yonago 683-8503, JapanDivision of Virology, Department of Microbiology and Immunology, Faculty of Medicine, Tottori University, Yonago 683-8503, JapanDivision of Virology, Department of Microbiology and Immunology, Faculty of Medicine, Tottori University, Yonago 683-8503, JapanNational Reference Laboratory, STD AIDS Cooperative Central Laboratory, San Lazaro Hospital, Manila 1003, Metro Manila, PhilippinesDivision of Virology, Department of Microbiology and Immunology, Faculty of Medicine, Tottori University, Yonago 683-8503, JapanIt has been considered that reduced susceptibility to antiretroviral drugs is influenced by drug adherence, drug tolerance and drug-resistance-related mutations in the HIV genome. In the present study, we assessed the intrinsic high viral growth capability as a potential viral factor that may influence their susceptibility to antiretroviral drugs using an in vitro model. Phytohemagglutinin-activated peripheral blood mononuclear cells (1.5 × 10<sup>6</sup> cells) were infected with HIV isolates (10<sup>6</sup> copies/mL). The culture was carried out at different concentrations (0.001–20 μM) of 13 synthetic antiretroviral compounds (six nucleoside/nucleotide reverse transcriptase inhibitors, one non-nucleoside reverse transcriptase inhibitor, four integrase inhibitors, and two protease inhibitors), and HIV production was assessed using HIV-RNA copies in culture. The 90% inhibitory concentration (IC<sub>90</sub>) and pharmacokinetics of an antiretroviral agent were used as parameters to determine the reduced antiretroviral drug susceptibility of HIV isolates with high growth capability to synthetic antiretroviral compounds. The high growth capability of HIV isolates without any known drug resistance-related mutation affected their susceptibility to tenofovir (IC<sub>90</sub> = 2.05 ± 0.40 μM), lamivudine (IC<sub>90</sub> = 6.83 ± 3.96 μM), emtricitabine (IC<sub>90</sub> = 0.68 ± 0.37 μM), and efavirenz (IC<sub>90</sub> = 3.65 ± 0.77 μM). These antiretroviral drugs showed IC<sub>90</sub> values close to or above the maximum plasma concentration against HIV isolates with high growth capability without any known drug resistance-related mutation. Our results may contribute to the development of effective strategies to tailor and individualize antiretroviral therapy in patients harboring HIV isolates with high growth capability.https://www.mdpi.com/1422-0067/23/23/15380human immunodeficiency virusantiretroviral drugsviral growth capability |
| spellingShingle | Alfredo A. Hinay Kyosuke Kanai Akeno Tsuneki-Tokunaga Mizuki Komatsu Elizabeth O. Telan Seiji Kageyama In Vitro Susceptibility of HIV Isolates with High Growth Capability to Antiretroviral Drugs International Journal of Molecular Sciences human immunodeficiency virus antiretroviral drugs viral growth capability |
| title | In Vitro Susceptibility of HIV Isolates with High Growth Capability to Antiretroviral Drugs |
| title_full | In Vitro Susceptibility of HIV Isolates with High Growth Capability to Antiretroviral Drugs |
| title_fullStr | In Vitro Susceptibility of HIV Isolates with High Growth Capability to Antiretroviral Drugs |
| title_full_unstemmed | In Vitro Susceptibility of HIV Isolates with High Growth Capability to Antiretroviral Drugs |
| title_short | In Vitro Susceptibility of HIV Isolates with High Growth Capability to Antiretroviral Drugs |
| title_sort | in vitro susceptibility of hiv isolates with high growth capability to antiretroviral drugs |
| topic | human immunodeficiency virus antiretroviral drugs viral growth capability |
| url | https://www.mdpi.com/1422-0067/23/23/15380 |
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