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	Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted hiv-1 drug resistance: an individual-patient- and sequence-level meta-analysis
	Rhee, Soo-Yon1; Blanco, Jose Luis2; Jordan, Michael R.3; Taylor, Jonathan4; Lemey, Philippe5; Varghese, Vici1; Hamers, Raph L.6,7; Bertagnolio, Silvia8; de Wit, TobiasF. Rinke6,7; Aghokeng, Avelin F.9
刊名	Plos medicine
	2015-04-01
卷号	12期号:4页码:29
ISSN号	1549-1676
DOI	10.1371/journal.pmed.1001810
通讯作者	Rhee, soo-yon(syrhee@stanford.edu)
英文摘要	Background regional 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. methods and findings 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-naive 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. conclusions 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.
WOS关键词	RESOURCE-LIMITED SETTINGS ; OLIGONUCLEOTIDE LIGATION ASSAY ; TREATMENT-NAIVE INDIVIDUALS ; SUB-SAHARAN AFRICA ; REVERSE-TRANSCRIPTASE ; VIROLOGICAL FAILURE ; ANTIRETROVIRAL TREATMENT ; TREATMENT PROGRAMS ; META-REGRESSION ; SOUTH-AFRICA
WOS研究方向	General & Internal Medicine
WOS类目	Medicine, General & Internal
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000354825700001
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2375180
专题	武汉病毒研究所
通讯作者	Rhee, Soo-Yon
作者单位	1.Stanford Univ, Dept Med, Stanford, CA 94305 USA 2.Univ Barcelona, Hosp Clin Univ, Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain 3.Tufts Univ, Sch Med, Boston, MA 02111 USA 4.Stanford Univ, Dept Stat, Stanford, CA 94305 USA 5.Univ Leuven, KU Leuven, Dept Microbiol & Immunol, Rega Inst Med Res Clin & Epidemiol Virol, Leuven, Belgium 6.Univ Amsterdam, Acad Med Ctr, Dept Global Hlth & Internal Med, NL-1105 AZ Amsterdam, Netherlands 7.Amsterdam Inst Global Hlth & Dev, Amsterdam, Netherlands 8.WHO, CH-1211 Geneva, Switzerland 9.Virol Lab CREMER IMPM, Yaounde, Cameroon 10.Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden
推荐引用方式 GB/T 7714	Rhee, Soo-Yon,Blanco, Jose Luis,Jordan, Michael R.,et al. Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted hiv-1 drug resistance: an individual-patient- and sequence-level meta-analysis[J]. Plos medicine,2015,12(4):29.
APA	Rhee, Soo-Yon.,Blanco, Jose Luis.,Jordan, Michael R..,Taylor, Jonathan.,Lemey, Philippe.,...&Shafer, Robert W..(2015).Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted hiv-1 drug resistance: an individual-patient- and sequence-level meta-analysis.Plos medicine,12(4),29.
MLA	Rhee, Soo-Yon,et al."Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted hiv-1 drug resistance: an individual-patient- and sequence-level meta-analysis".Plos medicine 12.4(2015):29.

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