Article information
Abstract
Antiretroviral therapy (ART) has reduced morbidity and mortality related to human immunodeficiency virus (HIV) infection, but in spite of this advance, HIV mutations decrease antiretroviral susceptibility, thus contributing to treatment failure in patients. Genotyping HIV-1 allows the selection of new drugs after initial drug failure. This study evaluated the genotypic profile of HIV-1 isolates from treated (drug-experienced) patients in Paraná, Brazil. The prevalence of mutations in reverse transcriptase (RT) and protease (PR) genes were assessed. We analyzed 467 genotypes of patients with HIV-1 viral loads above 1,000 copies/mL. Mutations at HIV-1 RT and PR genes and previously used ART regimens were recorded. The most prevalent RT mutations were: 184V (68.31%), 215YF (51.6%), 103NS (46%), 41L (39.4%), 67N (38.54%), 210W (23.5%), 190ASE (23.2%), and 181C (17.4%). PR mutations were 90M (33.33%), 82ATFS (29%), 46I (26.8%) and 54V (22.2%). The prevalence of mutations was in line with previous national and international reports, except to non-nucleoside analogue reverse transcriptase inhibitors related mutations, which were more prevalent in this study. Previous exposure to antiretroviral drugs was associated with genotypic resistance to specific drugs, leading to treatment failure in HIV patients.
Keywords:
HIV-1
genotype
antiretrovirals
drug-experienced patients
Full text is only available in PDF
References
[1.]
S. Okie.
Fighting HIV – lessons from Brazil.
N Engl J Med, 11 (2006), pp. 1977-1981
[2.]
Brazilian Program for STD/AIDS. Response + Magazine 2008: Experiences of the Brazilian AIDS Programme. Brasília, Brazil: Ministry of Health, 2008:80. [cited 2009 february 12] Available from: http://aids.gov.br/data/documents/storedDocuments
[3.]
S. Vella, L. Palmisano.
The Global Status of Resistance to Antiretroviral Drugs.
Clin Infect Dis, 41 (2005), pp. S239-S246
[4.]
J.M. Coffin.
HIV population dynamics in vivo: implications for genetic variation, pathogenesis and therapy.
Science, 267 (1995), pp. 483-489
[5.]
D.J. Hu, T.J. Dondero, M.A. Rayfield, et al.
The emerging genetic diversity of HIV. The importance of global surveillance for diagnostics, research, and prevention.
JAMA, 275 (1996), pp. 210-216
[6.]
A.K.N. Iversen, R.W. Shafer, K. Wehrly, et al.
Multidrugresistant human immunodeficiency virus type I strains resulting from combination antiretroviral therapy.
J Virol, 70 (1996), pp. 1086-1090
[7.]
B. Ledergerber, M. Egger, M. Opravil, et al.
Clinical progression and virological failure on highly active antiretroviral therapy in HIV-1 patients: a prospective cohort study.
Lancet, 353 (1999), pp. 863-868
[8.]
R.W. Shafer, M.A. Winters, S. Palmer, T.C. Merigan.
Multiple concurrent reverse transcriptase and protease mutations multidrug resistance of HIV-1 isolates from heavily treated patients.
Ann Intern Med, 128 (1998), pp. 906-911
[9.]
B.A. Larder, G. Darby, D. Richman.
HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy.
Science, 243 (1989), pp. 1731-1734
[10.]
B.A. Larder, S.D. Kemp.
Multiple mutations in HIV-1 reverse transcriptase confer high-level resistance to Zidovudine (AZT).
Science, 246 (1989), pp. 1155-1158
[11.]
Shafer RW, Rhee SY, Zioni R, Liu T, Kiuchi M. Stanford University HIV drug resistance database. [cited 2008 october 2] Available from: http://hivdb.stanford.edu/pages/asi/releaseNotes
[12.]
V.A. Johnson, F. Brun-Vézinet, B. Clotet, et al.
Update of the drug resistance mutations in HIV-1: December 2008.
Top HIV Med, 16 (2008), pp. 138-145
[13.]
M.S. Hirsch, H.F. Günthard, J.M. Schapiro, et al.
Antiretroviral drug resistance testing in adult HIV-1 infection: 2008 recommendations of an International AIDS Society-USA panel.
Clin Infect Dis, 47 (2008), pp. 266-285
[14.]
C. Tamalet, J. Fantini, C. Tourres, N. Yahi.
Resistance of HIV-1 to multiple antiretroviral drugs in France: a 6-year survey (1997-2002) based on an analysis of over 7000 genotypes.
AIDS, 17 (2003), pp. 2383-2388
[15.]
P. Scott, E. Arnold, B. Evans, et al.
Surveillance of HIV antiretroviral drug resistance in treated individuals in England: 1998-2000.
J Antimicrob Chemother, 53 (2004), pp. 469-473
[16.]
S.Y. Rhee, T. Liu, J. Ravela, M.J. Gonzales, R.W. Shafer.
Distribution of Human Immunodeficiency Virus Type 1 Protease and Reverse Transcriptase Mutation Patterns in 4,183 Persons Undergoing Genotypic Resistance Testing.
Antimicrob Agents Chemother, 48 (2004), pp. 3122-3126
[17.]
D.D. Richman, S.C. Morton, T. Wrin, et al.
The prevalence of antiretroviral drug resistance in the United States.
AIDS, 18 (2004), pp. 1393-1401
[18.]
S.Y. Rhee, W.J. Fessel, A.R. Zolopa, et al.
HIV-1 Protease and reversetranscriptase mutations: correlations with antiretroviral therapy in subtype B isolates and implications for drug-resistance surveillance.
J Infect Dis, 192 (2005), pp. 456-465
[19.]
S. Napravnik, J.R. Keys, E.B. Quinlivan, D.A. Wohl, O.V. Mikeal, JJ Eron Jr.
Triple-class antiretroviral drug resistance: risk and predictors among HIV-1-infected patients.
AIDS, 21 (2007), pp. 825-834
[20.]
A. Tanuri, E. Caridea, M.C. Dantas, et al.
Prevalence of mutations related to HIV-1 antiretroviral resistance in Brazilian patients failing HAART.
J Clin Virol, 25 (2002), pp. 39-46
[21.]
F. Bahia, C. Pedroso, E.M. Netto, R. Figueiredo, L. Pinto Neto, C. Brites.
Evaluation of the Genotypic Pattern of HIV-1 Resistance in AIDS Patients Failing Antiretroviral Therapy.
Braz Journal Infec Dis, 8 (2004), pp. 281-289
[22.]
D.M. Cerqueira, R.M. Amorim, R.R. Silva, G.N. Camara, M.M. Brígido, C.R. Martins.
Antiretroviral resistance and genetic diversity of human immunodeficiency virus type 1 isolates from the Federal District, Central Brazil.
Mem Inst Oswaldo Cruz, 99 (2004), pp. 877-882
[23.]
J.C. Couto-Fernandez, C. Silva-de-Jesus, V.G. Veloso, et al.
Human immunodeficiency virus type 1 (HIV-1) genotyping in Rio de Janeiro, Brazil: assessing subtype and drug-resistance associated mutations in HIV-1 infected individuals failing highly active antiretroviral therapy.
Mem Inst Oswaldo Cruz, 100 (2005), pp. 73-78
[24.]
R. Rodrigues, C.M.P. Vazquez, J.K. Colares, et al.
Antiretroviral resistance mutations in human immunodeficiency virus type 1 infected patients enrolled in genotype testing at the Central Public Health Laboratory, São Paulo, Brazil: preliminary results.
Mem Inst Oswaldo Cruz, 100 (2005), pp. 97-102
[25.]
A.M. Cavalcanti, H.R. Lacerda, A.M. Brito, S. Pereira, D. Medeiros, S. Oliveira.
Antiretroviral resistance in individuals presenting therapeutic failure and subtypes of the human immunodeficiency virus type 1 in the Northeast Region of Brazil.
Mem Inst Oswaldo Cruz, 102 (2007), pp. 785-792
[26.]
M.S. Medeiros, E.A. Arruda, R.L. Guerrant, et al.
Genotype testing and antiretroviral resistance profiles from HIV-1 patients experiencing therapeutic failure in northeast Brazil.
Braz J Infect Dis, 11 (2007), pp. 390-394
[27.]
D.J. de Sa-Filho, M.S. Soares, V. Candido, et al.
HIV type 1 pool gene diversity and antiretroviral drug resistance mutations in Santos, Brazil.
AIDS Res Hum Retroviruses, 24 (2008), pp. 347-353
[28.]
R.W. Shafer, J.M. Schapiro.
HIV-1 drug resistance mutations: an updated framework for the second decade of HAART.
AIDS Rev, 10 (2008), pp. 67-84
[29.]
M.S. Hirsch, F. Brun-Vézinet, R.T. DAquila, et al.
Antiretroviral drug resistance testing in adult HIV-1 infection: recommendations of an International AIDS Society-USA Panel.
JAMA, 283 (2000), pp. 2417-2426
[30.]
R.T. DAquila, J.M. Schapiro, F. Brun-Vézinet, et al.
Update on Drug Resistance Mutations in HIV-1. International AIDS Society – USA Resistance Mutations Project Panel.
Top HIV Med, 9 (2001), pp. 31-33
[31.]
R.T. DAquila, J.M. Schapiro, F. Brun-Vézinet, et al.
Update on Drug Resistance Mutations in HIV-1. International AIDS Society – USA Resistance Mutations Project Panel.
Top HIV Med, 9 (2001), pp. 21-23
[32.]
R.T. DAquila, J.M. Schapiro, F. Brun-Vézinet, et al.
Drug resistance mutations in HIV-1. International AIDS Society – USA Drug Resistance Mutations Group.
Top HIV Med, 10 (2002), pp. 11-15
[33.]
R.T. DAquila, J.M. Schapiro, F. Brun-Vézinet, et al.
Drug resistance mutations in HIV-1.
Top HIV Med, 10 (2002), pp. 21-25
[34.]
R.T. DAquila, J.M. Schapiro, F. Brun-Vézinet, et al.
Drug resistance mutations in HIV-1.
Top HIV Med, 11 (2003), pp. 92-96
[35.]
V.A. Johnson, F. Brun-Vézinet, B. Clotet, et al.
International AIDS Society-USA Drug Resistance Mutations Group. Drug resistance mutations in HIV-1.
Top HIV Med, 11 (2003), pp. 215-221
[36.]
V.A. Johnson, F. Brun-Vézinet, B. Clotet, et al.
Update of the drug resistance mutations in HIV-1: 2004.
Top HIV Med, 12 (2004), pp. 119-124
[37.]
V.A. Johnson, F. Brun-Vézinet, B. Clotet, et al.
Update of the drug resistance mutations in HIV-1: 2005.
Top HIV Med, 13 (2005), pp. 51-57
[38.]
V.A. Johnson, F. Brun-Vezinet, B. Clotet, et al.
Update of the drug resistance mutations in HIV-1: Fall 2005.
Top HIV Med, 13 (2005), pp. 125-133
[39.]
V.A. Johnson, F. Brun-Vézinet, B. Clotet, et al.
Update of the drug resistance mutations in HIV-1: Fall 2006.
Top HIV Med, 14 (2006), pp. 125-130
[40.]
V.A. Johnson, F. Brun-Vézinet, B. Clotet, et al.
Update of the drug resistance mutations in HIV-1: 2007.
Top HIV Med, 15 (2007), pp. 119-125
[41.]
V.A. Johnson, F. Brun-Vezinet, B. Clotet, et al.
Update of the Drug Resistance Mutations in HIV-1: Spring 2008.
Top HIV Med, 16 (2008), pp. 62-68
[42.]
D.R. Bangsberg, E.P. Acosta, R. Gupta, et al.
Adherence-resistance relationships for protease and non-nucleoside reverse transcriptase inhibitors explained by virological fitness.
AIDS, 20 (2006), pp. 223-231
[43.]
M.C. Sucupira, I.E. Souza, L.J. Costa, M.A. Scheinberg, R.S. Diaz.
Antiretroviral treatment failure and HIV-1 genotypic resistance in São Paulo, Brazil.
Antivir Ther, 6 (2001), pp. 263-264
[44.]
U.M. Parikh, D.C. Barnas, H. Faruki, J.W. Mellors.
Antagonism between the HIV-1 reverse-transcriptase mutation K65R and thymidine-analogue mutations at the genomic level.
J Infect Dis, 194 (2006), pp. 651-660
[45.]
O. Gallego, L. Ruíz, A. Vallejo, B. Clotet, M. Leal, V. Soriano.
Rate of virological treatment failure and frequencies of drug resistance genotypes among human immunodeficiency virus-positive subjects on antiretroviral therapy in Spain.
J Clin Microbiol, 40 (2002), pp. 3865-3866
[46.]
M. Zazzi, P. Corsi, A. Gonnelli, et al.
Evolution of the prevalence of HIV drug resistance patterns over 9 years of HAART and its relation with changes in the failing treatment regimens: an analysis of a large Italian database. XV International HIV Drug Resistance Workshop; Sitges, Spain.
Antivir Ther, (2006), pp. S137
[47.]
M. Violin, A. Galli, S. Corvasce, et al.
Study of antiretroviral resistance in treated patients with virological failure (START study): an Italian survey over the period 2003-2005. XV International HIV Drug Resistance Workshop; Sitges, Spain.
Antivir Ther, (2006), pp. S132
[48.]
D. Pillay, H. Green, R. Matthias, et al.
Estimating HIV-1 drug resistance in antiretroviral-treated individuals in the United Kingdom.
J Infect Dis, 192 (2005), pp. 967-973
[49.]
D. Costagliola, D. Descamps, L. Assoumou, Agence Nationale de Recherches sur le SIDA et les Hepatites Virales (ANRS) AC11 Resistance Study Group, et al.
Prevalence of HIV-1 drug resistance in treated patients: a French nationwide study.
J Acquir Immune Defic Syndr, 46 (2007), pp. 12-18
[50.]
S. Di Giambenedetto, L. Bracciale, M. Colafigli, et al.
Declining prevalence of HIV-1 drug resistance in treatment-failing patients: a clinical cohort study.
Antivir Ther, 12 (2007), pp. 835-839
[51.]
J. Vercauteren, K. Deforche, K. Theys, et al.
The incidence of multidrug and full class resistance in HIV-1 infected patients is decreasing over time (2001-2006) in Portugal.
Retrovirology, 5 (2008), pp. 1-8
Copyright © 2010. Elsevier Editora Ltda.. All rights reserved
