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Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART

dc.rights.licenseopenen_US
dc.contributor.authorDERACHE, A.
dc.contributor.authorIWUJI, C. C.
dc.contributor.authorDANAVIAH, S.
dc.contributor.authorGIANDHARI, J.
dc.contributor.authorMARCELIN, A. G.
dc.contributor.authorCALVEZ, V.
dc.contributor.authorDE OLIVEIRA, T.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDABIS, Francois
dc.contributor.authorPILLAY, D.
dc.contributor.authorGUPTA, R. K.
dc.date.accessioned2020-06-05T09:19:34Z
dc.date.available2020-06-05T09:19:34Z
dc.date.issued2019-02-01
dc.identifier.issn1460-2091 (Electronic) 0305-7453 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/7758
dc.description.abstractEnObjectives: The WHO recently recommended the use of a new first-line ART containing dolutegravir. We investigated the efficacy of NRTI backbones (tenofovir or abacavir with a cytosine analogue) in low- and middle-income countries where there is significant prior exposure to antiretrovirals and drug resistance to NRTIs. Methods: Within the treatment-as-prevention study in South Africa, we selected participants with available next-generation sequencing (NGS) data for the HIV-1 pol gene at trial entry; they were either ART initiators (n = 1193) or already established on ART (n = 94). NGS of the HIV-1 pol gene was carried out using MiSeq technology; reverse transcriptase drug resistance mutations (DRMs) were detected at 5% (DRM5%) and 20% (DRM20%) for all 1287 participants. Genotypic susceptibility was assessed using the Stanford HIVDB resistance interpretation algorithm. Results: NRTI DRM20% and DRM5% were detected among 5/1193 (0.4%) and 9/1193 (0.8%) of ART initiators, respectively. There was tenofovir exposure in 73/94 (77.7%) of those established on ART, with full susceptibility to abacavir in 57/94 (60.6%) and 56/94 (59.6%) for DRM20% and DRM5%, respectively, while 67/94 (71.3%) and 64/94 (68.1%) were fully susceptible to tenofovir, respectively. The differences between tenofovir and abacavir were not statistically significant at the 20% or 5% variant level (P = 0.16 and 0.29, respectively). NGS detection of variants at the 5% level increased detection of K65R in both naive and treated groups. One of 607 integrase sequences carried a DRM20% (Q148R). Conclusions: Dolutegravir with a cytosine analogue plus tenofovir or abacavir appears to have similar efficacy in South Africans naive to ART. NGS should be considered in HIV drug resistance surveillance.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/us/
dc.subject.enIDLIC
dc.title.enPredicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART
dc.title.alternativeJ Antimicrob Chemotheren_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1093/jac/dky428en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed30380053en_US
bordeaux.journalJ Antimicrob Chemotheren_US
bordeaux.page473-479en_US
bordeaux.volume74en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - U1219en_US
bordeaux.issue2en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.exportfalse
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=J%20Antimicrob%20Chemother&rft.date=2019-02-01&rft.volume=74&rft.issue=2&rft.spage=473-479&rft.epage=473-479&rft.eissn=1460-2091%20(Electronic)%200305-7453%20(Linking)&rft.issn=1460-2091%20(Electronic)%200305-7453%20(Linking)&rft.au=DERACHE,%20A.&IWUJI,%20C.%20C.&DANAVIAH,%20S.&GIANDHARI,%20J.&MARCELIN,%20A.%20G.&rft.genre=article


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