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Geographic and Temporal Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted HIV-1 Drug Resistance

2015-04-01Artigo científico Acesso aberto
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dc.contributor.authorRhee, Soo Yon
dc.contributor.authorBlanco, Jose Luis
dc.contributor.authorJordan, Michael R.
dc.contributor.authorTaylor, Jonathan
dc.contributor.authorLemey, Philippe
dc.contributor.authorVarghese, Vici
dc.contributor.authorHamers, Raph L.
dc.contributor.authorBertagnolio, Silvia
dc.contributor.authorde Wit, Tobias F Rinke
dc.contributor.authorAghokeng, Avelin F.
dc.contributor.authorAlbert, Jan
dc.contributor.authorAvi, Radko
dc.contributor.authorAvila-Rios, Santiago
dc.contributor.authorBessong, Pascal O.
dc.contributor.authorBrooks, James I.
dc.contributor.authorBoucher, Charles A B
dc.contributor.authorBrumme, Zabrina L.
dc.contributor.authorBusch, Michael P.
dc.contributor.authorBussmann, Hermann
dc.contributor.authorChaix, Marie Laure
dc.contributor.authorChin, Bum Sik
dc.contributor.authorD’Aquin, Toni T.
dc.contributor.authorDe Gascun, Cillian F.
dc.contributor.authorDerache, Anne
dc.contributor.authorDescamps, Diane
dc.contributor.authorDeshpande, Alaka K.
dc.contributor.authorDjoko, Cyrille F.
dc.contributor.authorEshleman, Susan H.
dc.contributor.authorFleury, Herve
dc.contributor.authorFrange, Pierre
dc.contributor.authorFujisaki, Seiichiro
dc.contributor.authorHarrigan, P. Richard
dc.contributor.authorHattori, Junko
dc.contributor.authorHolguin, Africa
dc.contributor.authorHunt, Gillian M.
dc.contributor.authorIchimura, Hiroshi
dc.contributor.authorKaleebu, Pontiano
dc.contributor.authorKatzenstein, David
dc.contributor.authorKiertiburanakul, Sasisopin
dc.contributor.authorKim, Jerome H.
dc.contributor.authorKim, Sung Soon
dc.contributor.authorLi, Yanpeng
dc.contributor.authorLutsar, Irja
dc.contributor.authorMorris, Lynn
dc.contributor.authorNdembi, Nicaise
dc.contributor.authorNG, Kee Peng
dc.contributor.authorParanjape, Ramesh S.
dc.contributor.authorPeeters, Martine
dc.contributor.authorPoljak, Mario
dc.contributor.authorPrice, Matt A.
dc.contributor.authorRagonnet-Cronin, Manon L.
dc.contributor.authorReyes-Terán, Gustavo
dc.contributor.authorRolland, Morgane
dc.contributor.authorSirivichayakul, Sunee
dc.contributor.authorSmith, Davey M.
dc.contributor.authorSoares, Marcelo A.
dc.contributor.authorSoriano, Vincent V.
dc.contributor.authorSsemwanga, Deogratius
dc.contributor.authorStanojevic, Maja
dc.contributor.authorStefani, Mariane A.
dc.contributor.authorSugiura, Wataru
dc.contributor.authorSungkanuparph, Somnuek
dc.contributor.authorTanuri, Amilcar
dc.contributor.authorTee, Kok Keng
dc.contributor.authorTruong, Hong Ha M
dc.contributor.authorvan de Vijver, David A M C
dc.contributor.authorVidal, Nicole
dc.contributor.authorYang, Chunfu
dc.contributor.authorYang, Rongge
dc.contributor.authorYebra, Gonzalo
dc.contributor.authorIoannidis, John P A
dc.contributor.authorVandamme, Anne Mieke
dc.contributor.authorShafer, Robert W.
dc.contributor.institutionGlobal Health and Tropical Medicine (GHTM)
dc.contributor.institutionInstituto de Higiene e Medicina Tropical (IHMT)
dc.contributor.institutionTB, HIV and opportunistic diseases and pathogens (THOP)
dc.contributor.pblPLOS - Public Library of Science
dc.date.accessioned2018-05-14T22:02:21Z
dc.date.available2018-05-14T22:02:21Z
dc.date.issued2015-04-01
dc.descriptionPMID: 25849352 WOS:000354825700001
dc.description.abstractRegional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes.We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05–1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06–1.25), North America (OR = 1.19; 95% CI: 1.12–1.26), Europe (OR = 1.07; 95% CI: 1.01–1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12–1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92–1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions—a proxy for recent infection—yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs—K101E, K103N, Y181C, and G190A—accounted for >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling.Most TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent2015073
dc.identifier.doi10.1371/journal.pmed.1001810
dc.identifier.issn1549-1277
dc.identifier.otherPURE: 1731636
dc.identifier.otherPURE UUID: e4db9171-9230-4bca-8d0b-4a03ac251c9b
dc.identifier.otherScopus: 84930531525
dc.identifier.otherWOS: 000354825700001
dc.identifier.otherPubMed: 25849352
dc.identifier.urihttp://www.scopus.com/inward/record.url?scp=84930531525&partnerID=8YFLogxK
dc.identifier.urlhttps://www.scopus.com/pages/publications/84930531525
dc.language.isoeng
dc.peerreviewedyes
dc.subjectBiotechnology
dc.subjectBiochemistry
dc.subjectMolecular Biology
dc.subjectCell Biology
dc.subjectSDG 3 - Good Health and Well-being
dc.titleGeographic and Temporal Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted HIV-1 Drug Resistanceen
dc.title.subtitleAn Individual-Patient- and Sequence-Level Meta-Analysisen
dc.typejournal article
degois.publication.issue4
degois.publication.titlePLoS Medicine
degois.publication.volume12
dspace.entity.typePublication
rcaap.rightsopenAccess

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