Baseline Susceptibility of Primary HIV-2 to Entry Inhibitors
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| Název: | Baseline Susceptibility of Primary HIV-2 to Entry Inhibitors |
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| Autoři: | Borrego, Pedro, Calado, Rita, Marcelino, José M., Bártolo, Inês, Rocha, Cheila, Cavaco-Silva, Patricia, Doroana, Manuela, Antunes, Francisco, Maltez, Fernando, Caixas, Umbelina, Barroso, Helena, Taveira, Nuno |
| Přispěvatelé: | Repositório Comum, Repositório da Universidade de Lisboa |
| Zdroj: | Antiviral Therapy. 17:565-570 |
| Informace o vydavateli: | SAGE Publications, 2011. |
| Rok vydání: | 2011 |
| Témata: | Male, 0301 basic medicine, Cyclohexanes/pharmacology, Amides/therapeutic use, Anti-HIV Agents, HIV Fusion Inhibitors/pharmacology, HCC INF, HIV Infections/drug therapy, HIV Infections, Microbial Sensitivity Tests, Cyclohexanes/therapeutic use, Enfuvirtide, HIV Envelope Protein gp41/therapeutic use, Maraviroc, Inhibitory Concentration 50, 03 medical and health sciences, Cyclohexanes, HIV Fusion Inhibitors, HSJ MED, Anti-HIV Agents/pharmacology, inhibitors, Humans, Amides/pharmacology, Peptide Fragments/therapeutic use, Quaternary Ammonium Compounds/therapeutic use, 0303 health sciences, Peptide Fragments/pharmacology, Triazoles/pharmacology, Quaternary Ammonium Compounds/pharmacology, HIV Fusion Inhibitors/therapeutic use, HIV Envelope Protein gp41/pharmacology, Triazoles, Amides, HIV Envelope Protein gp41, Peptide Fragments, 3. Good health, HIV-2/drug effects, Quaternary Ammonium Compounds, HIV-1/drug effects, Anti-HIV Agents/therapeutic use, CCR5 Receptor Antagonists, HIV-2, HIV-1, HIV Infections/virology, Female, Triazoles/therapeutic use |
| Popis: | Background The baseline susceptibility of primary HIV-2 to maraviroc (MVC) and other entry inhibitors is currently unknown. Methods The susceptibility of 19 HIV-2 isolates obtained from asymptomatic and AIDS patients and seven HIV-1 clinical isolates to the fusion inhibitors enfuvirtide (ENF) and T-1249, and to the coreceptor antagonists AMD3100, TAK-779 and MVC, was measured using a TZM-bl cell-based assay. The 50% inhibitory concentration (IC50), 90% inhibitory concentration (IC90) and dose–response curve slopes were determined for each drug. Results ENF and T-1249 were significantly less active on HIV-2 than on HIV-1 (211- and 2-fold, respectively). AMD3100 and TAK-779 inhibited HIV-2 and HIV-1 CXCR4 tropic (X4) and CCR5 tropic (R5) variants with similar IC50 and IC90 values. MVC, however, inhibited the replication of R5 HIV-2 variants with significantly higher IC90 values (42.7 versus 9.7 nM; P+ T-cells. Conclusions T-1249 is a potent inhibitor of HIV-2 replication indicating that new fusion inhibitors might be useful to treat HIV-2 infection. Coreceptor antagonists TAK-779 and AMD3100 are also potent inhibitors of HIV-2 replication. The reduced sensitivity of R5 variants to MVC, especially in severely immunodeficient patients, indicates that the treatment of HIV-2-infected patients with MVC might require higher dosages than those used in HIV-1 patients, and should be adjusted to the disease stage. |
| Druh dokumentu: | Article |
| Popis souboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 2040-2058 1359-6535 |
| DOI: | 10.3851/imp1996 |
| Přístupová URL adresa: | http://repositorio.chlc.min-saude.pt/bitstream/10400.17/2417/1/Antiviral%20Therapy%202011.pdf https://pubmed.ncbi.nlm.nih.gov/22293827 https://www.ncbi.nlm.nih.gov/pubmed/22293827 https://europepmc.org/abstract/MED/22293827 http://comum.rcaap.pt/bitstream/10400.26/4993/1/Borrego%20et%20al%20%20Antiviral%20Therapy%202011.pdf http://www.intmedpress.com/journals/avt/abstract.cfm?id=1996&pid=48 https://repositorio.chlc.min-saude.pt/bitstream/10400.17/2417/1/Antiviral%20Therapy%202011.pdf https://pubmed.ncbi.nlm.nih.gov/22293827/ https://hdl.handle.net/10400.26/4993 https://hdl.handle.net/10451/59111 http://hdl.handle.net/10400.17/2417 |
| Rights: | URL: https://journals.sagepub.com/page/policies/text-and-data-mining-license |
| Přístupové číslo: | edsair.doi.dedup.....5436ab91c7957e9b24f768dbac3da4fd |
| Databáze: | OpenAIRE |
Nájsť tento článok vo Web of Science | Abstrakt: | Background The baseline susceptibility of primary HIV-2 to maraviroc (MVC) and other entry inhibitors is currently unknown. Methods The susceptibility of 19 HIV-2 isolates obtained from asymptomatic and AIDS patients and seven HIV-1 clinical isolates to the fusion inhibitors enfuvirtide (ENF) and T-1249, and to the coreceptor antagonists AMD3100, TAK-779 and MVC, was measured using a TZM-bl cell-based assay. The 50% inhibitory concentration (IC50), 90% inhibitory concentration (IC90) and dose–response curve slopes were determined for each drug. Results ENF and T-1249 were significantly less active on HIV-2 than on HIV-1 (211- and 2-fold, respectively). AMD3100 and TAK-779 inhibited HIV-2 and HIV-1 CXCR4 tropic (X4) and CCR5 tropic (R5) variants with similar IC50 and IC90 values. MVC, however, inhibited the replication of R5 HIV-2 variants with significantly higher IC90 values (42.7 versus 9.7 nM; P+ T-cells. Conclusions T-1249 is a potent inhibitor of HIV-2 replication indicating that new fusion inhibitors might be useful to treat HIV-2 infection. Coreceptor antagonists TAK-779 and AMD3100 are also potent inhibitors of HIV-2 replication. The reduced sensitivity of R5 variants to MVC, especially in severely immunodeficient patients, indicates that the treatment of HIV-2-infected patients with MVC might require higher dosages than those used in HIV-1 patients, and should be adjusted to the disease stage. |
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| ISSN: | 20402058 13596535 |
| DOI: | 10.3851/imp1996 |