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Tipo do documento: Artigo
Título: 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
Autor: Rhee, Soo-Yon
Blanco, Jose Luis
Jordan, Michael R.
Taylor, Jonathan
Lemey, Philippe
Varghese, Vici
Hamers, Raph L.
Bertagnolio, Silvia
Wit, Tobias F. Rinke de
Aghokeng, Avelin F.
Albert, Jan
Avi, Radko
Avila-Rios, Santiago
Bessong, Pascal O.
Brooks, James I.
Boucher, Charles A. B.
Brumme, Zabrina L.
Busch, Michael P.
Bussmann, Hermann
Chaix, Marie-Laure
Chin, Bum Sik
D’Aquin, Toni T.
Gascun, Cillian F. de
Derache, Anne
Descamps, Diane
Deshpande, Alaka K.
Djoko, Cyrille F.
Eshleman, Susan H.
Fleury, Herve
Frange, Pierre
Fujisaki, Seiichiro
Harrigan, P. Richard
Hattori, Junko
Holguin, Africa
Hunt, Gillian M.
Ichimura, Hiroshi
Kaleebu, Pontiano
Katzenstein, David
Kiertiburanakul, Sasisopin
Kim, Jerome H.
Kim, Sung Soon
Li, Yanpeng
Lutsar, Irja
Morris, Lynn
Ndemb, Nicaise
NG, Kee Peng
Paranjape, Ramesh S.
Peeters, Martine
Poljak, Mario
Price, Matt A.
Ragonnet-Cronin, Manon L.
Reyes-Terán, Gustavo
Rolland, Morgane
Sirivichayakul, Sunee
Smith, Davey M.
Soares, Marcelo Alves
Soriano, Vincent V.
Ssemwanga, Deogratius
Stanojevic, Maja
Stefani, Mariane Martins de Araújo
Sugiura, Wataru
Ssemwanga, Deogratius
Tanuri, Amilcar
Tee, Kok Keng
Truong, Hong-Ha M.
Van de Vijver, David A. M. C.
Vidal, Nicole
Chunfu, Yang
Yang, Rongge
Yebra, Gonzalo
Ioannidis, John P. A.
Vandamme, Anne-Mieke
Shafer, Robert W.
Abstract: 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 de- signing 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 Decem- ber 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 se- quences 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 tran-scriptase 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-asso-ciated 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 nevira-pine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resis-tance 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 lim-itations 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 resis-tance, 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.
País: Estados unidos
Unidade acadêmica: Instituto de Patologia Tropical e Saúde Pública - IPTSP (RG)
Citação: RHEE, Soo-Ton 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, San Franciso, v. 12, n. 4, e1001810, 2015.
Tipo de acesso: Acesso Aberto
Identificador do documento: 10.1371/journal.pmed.1001810
Identificador do documento: 10.1371/journal.pmed.1001810
Data de publicação: 7-Abr-2015
Aparece nas coleções:IPTSP - Artigos publicados em periódicos

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