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

Rodrigues, Rosangela; Vazquez, Carla; Colares, Jeová Keny Baima; Custódio, R. M.; Filho, Francisco Bonásser; Souza, Lenice do Rosário de; Gianna, Maria Clara; Marques, Cristiano Correa de Azevedo; Brígido, Luis Fernando de Macedo

doi:10.1590/s0074-02762005000100018

Cited by 14 publications

(18 citation statements)

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“…The high prevalence of TAMs (67.24%) was similar to that reported in São Paulo (73%). 24 The K65R mutation was not reported in most national studies and has occurred in less than 1% of the patients in this study. At Brazilian Northeast region this mutation was seen in 3.4% of patients and, specifi cally in the state of Ceará, in 5.9% of cases.…”

Section: Discussionmentioning

confidence: 49%

“…23 In the other Brazilian studies, L90M was also the most frequent, present in 26 to 37% of the cases. 20,21,23,24,44 Compared with international data, these patients present lower prevalence of wild-type virus, probably because in other sites -where genotype was available earlier in the setting of virologic failure -more wild-type virus can be demonstrated. Other reason may be the lower exposure to less effective regimens, including less than two active agents.…”

Section: Discussionmentioning

confidence: 74%

“…21,23,25,26 Only one national study showed even higher prevalence of wildtype virus (15.3%). 20 The most prevalent mutation occurred at codon 184 (68.31%), as reported in São Paulo (64%), 24 Rio de Janeiro (67%), 23 and Northeast Brazil (66%). 25 In Santos, from 2006, this mutation was even more prevalent (88%).…”

Section: Discussionmentioning

confidence: 87%

“…20 From 2004 to 2007, many other authors showed data from the prevalence of antiretroviral resistance in adults from Bahia, São Paulo, Rio de Janeiro, Federal District and North Eastern states. [21][22][23][24][25][26][27] The aim of this study is to analyze the genotypic profile of patients tested for resistance in the Brazilian state of Paraná, in order to determine the frequency of RT and PR mutations among patients failing ART.…”

Section: Introductionmentioning

confidence: 99%

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HIV-1 genotypic resistance profile of patients failing antiretroviral therapy in Paraná, Brazil

Toledo¹,

Carvalho²,

Romagnoli³

et al. 2010

Braz J Infect Dis

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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 profi le 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 nonnucleoside analogue reverse transcriptase inhibitors related mutations, which were more prevalent in this study. Previous exposure to antiretroviral drugs was associated with genotypic resistance to specifi c drugs, leading to treatment failure in HIV patients.

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Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

HIV-1 genotypic resistance profile of patients failing antiretroviral therapy in Paraná, Brazil

Toledo¹,

Carvalho²,

Romagnoli³

et al. 2010

Braz J Infect Dis

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“…The identification of specific drug resistance mutations is increasingly used to avoid antiretroviral drugs that retain only minimal residual activity in favor of other residual activity that is likely to be either fully or almost fully active. Previous national and regional surveillance studies on the prevalence of mutation conferring antiretroviral drug resistance were carried out in large centers in Brazil (3,4,(6)(7)(8)(9)(10). All of these studies have shown a low frequency of wild-type HIV-1 isolates and a high prevalence of virus strains containing resistance mutations among treated patients failing HAART.…”

Section: Introductionmentioning

confidence: 99%

Frequency and diversity of human immunodeficiency virus type 1 mutations associated with antiretroviral resistance among patients from Southern Brazil failing highly active antiretroviral therapy (HAART)

Saad

Morimoto²,

Wiechmann³

et al. 2010

Int J Mol Med

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Abstract. The human immunodeficiency virus type 1 (HIV-1) epidemic in Brazil is spreading to small municipalities as well as the innermost parts of the country and scarce information has been reported on the frequency of HIV-1 resistanceassociated mutations in these areas. To determine the frequency and diversity of the HIV-1 antiretroviral resistance-associated mutations among patients failing highly active antiretroviral therapy from Londrina in Southern Brazil, 127 HIV-1 genotyping tests that were assayed during January 2000 to July 2008 from 108 patients were evaluated. Sixty-nine patients (63.9%) were male and 39 (36.1%) were female and the age ranged from 10 to 68 years (mean, 40.8±9.2). All of them showed at least one HIV-1 antiretroviral resistance-associated mutation and in 72 (56.7%) genotyping tests, mutations for the three antiretroviral classes were detected simultaneously. Mutations associated with resistance to protease inhibitor (PI) were detected in 124 tests (97.6%), the main ones were L90M in 28 (22.0%), V82A in 27 (21.2%), M46I in 26 (20.5%), and I54V in 23 (18.1%). The main mutations associated with nucleoside reverse transcriptase inhibitor (NRTI) resistance were M184V in 82 (64.6%), and the thymidine analog mutations were D67N in 51 (40.1%) tests, K70R in 45 (35.4%), T215Y in 40 (31.5%), and M41L in 38 (30.0%). The most frequent major mutations associated with resistance to nonnucleoside RT inhibitors (NNRTI) were K103N in 47 (37.0%), G190A in 11 (8.7%), and G190S in 2 (2.6%) tests. Mutations associated with reduced susceptibility to NRTI and IP simultaneously were observed in 46 (36.2%) tests. The results obtained may contribute to the improvement of the treatment strategies and the management of the antiretroviral drug therapy of HIV-1-infected patients from this Brazilian region, reducing public costs for antiretroviral drugs which have not been efficient in therapy.

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HIV‐1 protease function and structure studies with the simplicial neighborhood analysis of protein packing method

Zhang

Kaplan

Tropsha³

2008

Proteins

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The Simplicial Neighborhood Analysis of Protein Packing (SNAPP) method was used to predict the effect of mutagenesis on the enzymatic activity of the HIV-1 protease (HIVP). SNAPP relies on a four-body statistical scoring function derived from the analysis of spatially nearest neighbor residue compositional preferences in a diverse and representative subset of protein structures from the Protein Data Bank. The method was applied to the analysis of HIVP mutants with residue substitutions in the hydrophobic core as well as at the interface between the two protease monomers. Both wild type and tethered structures were employed in the calculations. We obtained a strong correlation, with R2 as high as 0.96, between ΔSNAPP score (i.e., the difference in SNAPP scores between wild type and mutant proteins) and the protease catalytic activity for tethered structures. A weaker but significant correlation was also obtained for non-tethered structures as well. Our analysis identified residues both in the hydrophobic core and at the dimeric interface (DI) that are very important for the protease function. This study demonstrates a potential utility of the SNAPP method for rational design of mutagenesis studies and protein engineering.

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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

Abstract: Antiretroviral resistance mutations (ARM) are one of the major obstacles for pharmacological human immuno-

Cited by 14 publications

References 14 publications

HIV-1 genotypic resistance profile of patients failing antiretroviral therapy in Paraná, Brazil

HIV-1 genotypic resistance profile of patients failing antiretroviral therapy in Paraná, Brazil

Frequency and diversity of human immunodeficiency virus type 1 mutations associated with antiretroviral resistance among patients from Southern Brazil failing highly active antiretroviral therapy (HAART)

HIV‐1 protease function and structure studies with the simplicial neighborhood analysis of protein packing method

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