Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study

被引：201

作者：

Gregson, John ^{[3
]}

Tang, Michele ^{[2
]}

Ndembi, Nicaise ^{[4
]}

Hamers, Raph L. ^{[5
,6
]}

Rhee, Soo-Yon ^{[2
]}

Marconi, Vincent C. ^{[7
,8
]}

Diero, Lameck ^{[9
,10
]}

Brooks, Katherine ^{[11
]}

Theys, Kristof ^{[12
]}

de Wit, Tobias F. Rinke ^{[5
,6
]}

Arruda, Monica ^{[13
]}

Garcia, Frederico ^{[14
]}

Monge, Susana ^{[15
]}

Gunthard, Huldrych F. ^{[16
,17
]}

Hoffmann, Christopher J. ^{[18
,19
]}

Kanki, Phyllis J. ^{[20
]}

Kumarasamy, Nagalingeshwaran ^{[21
]}

Kerschberger, Bernard ^{[22
]}

Mor, Orna ^{[23
]}

Charpentier, Charlotte ^{[24
,25
,26
]}

Todesco, Eva ^{[27
]}

Rokx, Casper ^{[28
]}

Gras, Luuk ^{[29
]}

Halvas, Elias K. ^{[30
]}

Sunpath, Henry ^{[31
]}

Di Carlo, Domenico ^{[32
]}

Antinori, Antonio ^{[33
]}

Andreoni, Massimo ^{[34
]}

Latini, Alessandra ^{[35
]}

Mussini, Cristina ^{[36
]}

Aghokeng, Avelin ^{[37
]}

Sonnerborg, Anders ^{[38
,39
,40
]}

Neogi, Ujjwal ^{[38
,39
,40
]}

Fessel, William J. ^{[41
]}

Agolory, Simon ^{[42
]}

Yang, Chunfu ^{[43
]}

Blanco, Jose L. ^{[44
]}

Juma, James M. ^{[45
]}

Smit, Erasmus ^{[46
]}

Schmidt, Daniel ^{[47
]}

Watera, Christine ^{[48
]}

Asio, Juliet ^{[48
]}

Kirungi, Wilford

Tostevin, Anna ^{[49
,50
]}

El-Hay, Tal ^{[51
]}

Clumeck, Nathan ^{[52
]}

Goedhals, Dominique ^{[53
]}

van Vuuren, Cloete ^{[53
]}

Bester, Philip Armand

Sabin, Caroline ^{[54
]}

机构：

[1] UCL, Dept Infect, London WC1E 6BT, England

[2] Stanford Univ, Dept Med, Stanford, CA 94305 USA

[3] London Sch Hyg & Trop Med, Dept Stat, London, England

[4] Inst Human Virol Nigeria, Abuja, Federal Capital, Nigeria

[5] Univ Amsterdam, Acad Med Ctr, Amsterdam Inst Global Hlth & Dev, Dept Global Hlth, NL-1012 WX Amsterdam, Netherlands

[6] Univ Amsterdam, Acad Med Ctr, Dept Internal Med, NL-1012 WX Amsterdam, Netherlands

[7] Emory Univ, Rollins Sch Publ Hlth, Dept Global Hlth, Atlanta, GA 30322 USA

[8] Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA USA

[9] Moi Univ, Eldoret, Kenya

[10] Acad Model Providing Access Healthcare, Eldoret, Kenya

[11] Brown Univ, Alpert Med Sch, Div Infect Dis, Providence, RI 02912 USA

[12] KU Leuven Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, B-3000 Leuven, Belgium

[13] Univ Fed Rio de Janeiro, Inst Biol, LVM, BR-21941 Rio De Janeiro, Brazil

[14] Complejo Hosp Univ Granada, Granada, Spain

[15] CIBERESP, Madrid, Spain

[16] Univ Zurich, Div Infect Dis & Hosp Epidemiol, Zurich, Switzerland

[17] Univ Zurich, Inst Med Virol, Zurich, Switzerland

[18] Johns Hopkins Univ, Baltimore, MD USA

[19] Aurum Inst, Johannesburg, South Africa

[20] Harvard Univ, TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA

[21] VHS, YRGCARE Med Ctr, Chennai, Tamil Nadu, India

[22] Med Sans Frontieres Operat Ctr Geneva, Mbabane, Eswatini

[23] Israel Minist Hlth, Publ Hlth Serv, Cent Virol Lab, Jerusalem, Israel

[24] Univ Paris Diderot, Sorbonne Paris Cite, IAME, UMR 1137, Paris, France

[25] INSERM, IAME, UMR 1137, Paris, France

[26] Hop Bichat Claude Bernard, AP HP, Virol Lab, F-75018 Paris, France

[27] Hop La Pitie Salpetriere, Lab Virol, Paris, France

[28] Erasmus Univ, Med Ctr, Dept Internal Med Infect Dis, Rotterdam, Netherlands

[29] Stichting HIV Monitoring, Amsterdam, Netherlands

[30] Univ Pittsburgh, Pittsburgh, PA USA

[31] Ethekwini Dist Hlth Off, Kwa Zulu, South Africa

[32] Univ Roma Tor Vergata, Dept Expt Med & Surg, Rome, Italy

[33] INMI L Spallanzani, Infect Dis Unit, Rome, Italy

[34] Univ Hosp Tor Vergata, Clin Infect Dis, Rome, Italy

[35] San Gallicano Dermatol Inst, HIV AIDS Unit, Rome, Italy

[36] Azienda Osped Univ Policlin, Clin Infect Dis, Modena, Italy

[37] Virol Lab CREMER IMPM, Yaounde, Cameroon

[38] Karolinska Inst, Div Clin Microbiol, Stockholm, Sweden

[39] Karolinska Inst, Infect Dis Unit, Stockholm, Sweden

[40] Karolinska Univ Hosp, Stockholm, Sweden

[41] Kaiser Permanente Med Care Program Northern Calif, San Francisco, CA USA

[42] Ctr Dis Control & Prevent, Div Global HIV AIDS, Ctr Global Hlth, Atlanta, GA USA

[43] Ctr Dis Control & Prevent, Int Lab Branch, Div Global HIV AIDS, Ctr Global Hlth, Atlanta, GA USA

[44] Univ Barcelona, Inst Invest Biomed August Pi i Sunyer, Clin Univ, Barcelona, Spain

[45] Minist Hlth & Social Welf, Dar Es Salaam, Tanzania

[46] Publ Hlth England, Publ Hlth Lab, Birmingham, W Midlands, England

[47] Robert Koch Inst, Dept Infect Dis Epidemiol HIV AIDS STI & Blood Bo, Berlin, Germany

[48] Uganda Res Unit AIDS, Entebbe, Uganda

[49] Minist Hlth, Kampala, Uganda

[50] UCL, MRC Clin Trials Unit, London, England

来源：

LANCET INFECTIOUS DISEASES | 2016年 / 16卷 / 05期

基金：

英国惠康基金;

关键词：

TENOFOVIR DISOPROXIL FUMARATE; ANTIRETROVIRAL THERAPY; VIROLOGICAL FAILURE; HIV-1-INFECTED PATIENTS; NAIVE PATIENTS; EFAVIRENZ; EMTRICITABINE; LAMIVUDINE; TRANSMISSION; K65R;

D O I：

10.1016/S1473-3099(15)00536-8

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

Background Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after virological failure with first-line tenofovir-containing ART. Methods The TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI; efavirenz or nevirapine). We used an individual participant-level meta-analysis and multiple logistic regression to identify covariates associated with drug resistance. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene. Findings We included 1926 patients from 36 countries with treatment failure between 1998 and 2015. Prevalence of tenofovir resistance was highest in sub-Saharan Africa (370/654 [57%]). Pre-ART CD4 cell count was the covariate most strongly associated with the development of tenofovir resistance (odds ratio [OR] 1.50, 95% CI 1.27-1.77 for CD4 cell count <100 cells per mu L). Use of lamivudine versus emtricitabine increased the risk of tenofovir resistance across regions (OR 1.48, 95% CI 1.20-1.82). Of 700 individuals with tenofovir resistance, 578 (83%) had cytosine analogue resistance (M184V/I mutation), 543 (78%) had major NNRTI resistance, and 457 (65%) had both. The mean plasma viral load at virological failure was similar in individuals with and without tenofovir resistance (145 700 copies per mL [SE 12 480] versus 133 900 copies per mL [SE 16 650; p=0.626]). Interpretation We recorded drug resistance in a high proportion of patients after virological failure on a tenofovir-containing first-line regimen across low-income and middle-income regions. Effective surveillance for transmission of drug resistance is crucial. Copyright (C) The TenoRes Study Group. Open Access article distributed under the terms of CC BY.

引用

页码：565 / 575

页数：11

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