Publication
In Vitro Evaluation of Novel Reverse Transcriptase Inhibitors TAF (Tenofovir Alafenamide) and OBP-601 (2,3-Didehydro-3-Deoxy-4-Ethynylthymidine) Against Multi-Drug Resistant Primary Isolates of HIV-2
| dc.contributor.author | Bártolo, I | |
| dc.contributor.author | Borrego, P | |
| dc.contributor.author | Gomes, P | |
| dc.contributor.author | Gonçalves, F | |
| dc.contributor.author | Caixas, U | |
| dc.contributor.author | Pinto, I | |
| dc.contributor.author | Taveira, N | |
| dc.date.accessioned | 2021-08-12T11:42:18Z | |
| dc.date.available | 2021-08-12T11:42:18Z | |
| dc.date.issued | 2019 | |
| dc.description.abstract | New antiretroviral drugs are needed to treat HIV-2 infected patients failing therapy. Herein, we evaluate the activity of novel reverse transcriptase inhibitors tenofovir alafenamide (TAF) and OBP-601(2,3-didehydro-3-deoxy-4-ethynylthymidine) against primary isolates from HIV-2 infected patients experiencing virologic failure. TAF and OBP-601 were tested against twelve primary isolates obtained from nine drug-experienced patients failing therapy and three drug naïve patients using a single-round infectivity assay in TZM-bl cells. The RT-coding region of pol was sequenced and the GRADE algorithm was used to identify resistance profiles and mutations. TAF and OBP-601 inhibited the replication of almost all isolates at a median EC50 of 0.27 nM and 6.83 nM, respectively. Two isolates showed moderate-level resistance to OBP-601 or TAF and two other isolates showed high-level resistance to OBP-601 or to both drugs. With one exception, all resistant viruses had canonical nucleoside reverse transcriptase inhibitors (NRTIs)-associated resistance mutations (K65R, N69S, V111I, Y115F, Q151M and M184V). Our results show that TAF has potent activity against most multi-drug resistant HIV-2 isolates and should be considered for the treatment of HIV-2 infected patients failing therapy. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | Antiviral Res. 2019 Jan;161:85-89. | pt_PT |
| dc.identifier.doi | 10.1016/j.antiviral.2018.10.018. | pt_PT |
| dc.identifier.uri | http://hdl.handle.net/10400.17/3819 | |
| dc.language.iso | eng | pt_PT |
| dc.publisher | Elsevier | pt_PT |
| dc.subject | HSJ MED | pt_PT |
| dc.subject | Humans | pt_PT |
| dc.subject | Adenine / analogs & derivatives | pt_PT |
| dc.subject | Adenine / pharmacology | pt_PT |
| dc.subject | Anti-HIV Agents / pharmacology | pt_PT |
| dc.subject | Drug Discovery | pt_PT |
| dc.subject | Drug Resistance, Multiple, Viral | pt_PT |
| dc.subject | HIV-2 / drug effects | pt_PT |
| dc.subject | Mutation | pt_PT |
| dc.subject | Microbial Sensitivity Tests | pt_PT |
| dc.subject | Reverse Transcriptase Inhibitors / pharmacology | pt_PT |
| dc.subject | Virus Replication / drug effects | pt_PT |
| dc.title | In Vitro Evaluation of Novel Reverse Transcriptase Inhibitors TAF (Tenofovir Alafenamide) and OBP-601 (2,3-Didehydro-3-Deoxy-4-Ethynylthymidine) Against Multi-Drug Resistant Primary Isolates of HIV-2 | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 89 | pt_PT |
| oaire.citation.startPage | 85 | pt_PT |
| oaire.citation.title | Antiviral Research | pt_PT |
| oaire.citation.volume | 161 | pt_PT |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | article | pt_PT |
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