Genetic Consequences of Antiviral Therapy on HIV-1

Arenas, Miguel

doi:10.1155/2015/395826

Cited by 14 publications

(8 citation statements)

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“…Again, note that the main catalytic sites of the integrase are aspartic and glutamic acids (Asp-64, Asp-116 and Glu-152) [48,49]. Comparing HIVin and HIVb, or VIRin and WAG, we also observed a few amino acid changes with an increase in their relative rate of change, such as isoleucine/methionine, isoleucine/leucine, leucine/methionine and serine/threonine (in HIVin) or cysteine/tyrosine (in VIRin), where the amino acids involved presented similar physicochemical properties, agreeing with selection pressure for the maintenance of the protein function [40,50,51].…”

Section: Novel Empirical Substitution Models For Hiv and General Virus Protease And Integrasesupporting

confidence: 75%

“…Actually, we benefited from the large number of sequences that are available for these proteins. Note that they have been frequently sequenced due to their relevant role as common antiretroviral drug targets [ 39 , 40 , 41 , 42 ]. Next, we found that the large number of sequences present in some method datasets (in particular, those with more than 10,000 sequences, which are 3 of the 4 method datasets) caused computational limitations that forced us to split them into 10 partitions with the same size ( Figure 1 ).…”

Section: Methodsmentioning

confidence: 99%

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HIV Protease and Integrase Empirical Substitution Models of Evolution: Protein-Specific Models Outperform Generalist Models

Amparo

Arenas

2021

Genes

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Diverse phylogenetic methods require a substitution model of evolution that should mimic, as accurately as possible, the real substitution process. At the protein level, empirical substitution models have traditionally been based on a large number of different proteins from particular taxonomic levels. However, these models assume that all of the proteins of a taxonomic level evolve under the same substitution patterns. We believe that this assumption is highly unrealistic and should be relaxed by considering protein-specific substitution models that account for protein-specific selection processes. In order to test this hypothesis, we inferred and evaluated four new empirical substitution models for the protease and integrase of HIV and other viruses. We found that these models more accurately fit, compared with any of the currently available empirical substitution models, the evolutionary process of these proteins. We conclude that evolutionary inferences from protein sequences are more accurate if they are based on protein-specific substitution models rather than taxonomic-specific (generalist) substitution models. We also present four new empirical substitution models of protein evolution that could be useful for phylogenetic inferences of viral protease and integrase.

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Section: Novel Empirical Substitution Models For Hiv and General Virus Protease And Integrasesupporting

confidence: 75%

Section: Methodsmentioning

confidence: 99%

HIV Protease and Integrase Empirical Substitution Models of Evolution: Protein-Specific Models Outperform Generalist Models

Amparo

Arenas

2021

Genes

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“…This represented a large increase in ART coverage, from 9.9% in 2003 to 96.6% in 2014, which coincided with a significant decrease in HIV/AIDS patient mortality from 11.6 to 2.6% [16]. However, with the increase in antiretroviral drug use, the frequency of adaptive mutations in HIV-1 has also increased, generating drug-resistant strains [19]. This has created severe clinical and epidemiological problems [20].…”

Section: Introductionmentioning

confidence: 99%

HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China

Zhao

Zhang

et al. 2017

AIDS Res Ther

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BackgroundTo understand HIV-1 drug resistance in 11 prefectures of Hebei Province, China, we implemented a cross-sectional HIV-1 molecular epidemiological survey.MethodsBlood samples were collected from 122 newly diagnosed drug-naïve HIV-1-positive individuals and 229 antiretroviral therapy (ART)-failure individuals from 11 prefectures in Hebei Province, China. Patient demographic data were obtained via face-to-face interviews using a standardized questionnaire when blood samples were collected. Genotyping of HIV-1 drug resistance (DR) was implemented using an in-house assay.ResultsIn this study, the overall prevalence of HIV-1 DR was 35.5%. The prevalence of HIV-1 DR in participants experiencing treatment failure and ART-naïve participants was 51.9 and 5.9%, respectively. Mutations in protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), and non-NRTI (NNRTIs), as well as dual and multiple mutations were extensively seen in participants experiencing treatment failure. The proportions of NNRTI mutations (χ2 = 9.689, p = 0.002) and dual mutations in NRTIs and NNRTIs (χ2 = 39.958, p < 0.001) in participants experiencing treatment failure were significantly higher than those in ART-naïve participants. The distributions of M184V/I and M41L mutations differed significantly among three main HIV-1 genotypes identified. Viral load, symptoms in the past 3 months, CD4 counts, transmission route, and the duration of ART were found to be associated with HIV-1 DR.ConclusionsOur results suggest that new prevention and control strategies should be formulated according to the epidemic characteristics of HIV-1-resistant strains in Hebei Province, where antiretroviral drugs are widely used.Electronic supplementary materialThe online version of this article (doi:10.1186/s12981-017-0133-3) contains supplementary material, which is available to authorized users.

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“…DRM is based on rapid viral evolution and high levels of genetic variability in HIV-1 [1,[12][13][14]. Long-term ARV therapy results in drug selective immune pressure on the HIV-1 population, which causes mutations of viral peptides as the virus attempts to escape the host immune system.…”

Section: Discussionmentioning

confidence: 99%

New drug resistance mutations of reverse transcriptase Human immunodeficiency virus type-1 gene in first-line antiretroviral-infected patients in West Sumatra, Indonesia

Efrida¹,

Nasrul²,

Parwati³

et al. 2018

Russ Open Med J

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Background -Antiretroviral (ARV) therapy has successfully reduced the transmission, morbidity, and mortality of Human immunodeficiency virus 1 (HIV-1) infection, but the appearance of drug resistance mutations (DRMs) is an obstacle to successful HIV management. DRMs against nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) have never been analyzed and reported in HIV-1 patients in Padang (West Sumatra, Indonesia). Objective -This study aimed to identify NRTI-and NNRTI-DRMs from HIV-1 proviral deoxyribonucleic acid (DNA) in HIV-infected patients who had received ARV therapy for >12 months at the Dr. M. Djamil General Hospital in Padang. Material and Methods -We isolated HIV-1 proviral DNA from blood samples from 105 HIV-1 patients who had undergone first-line ARV therapy for >12 months. Isolates were amplified via a nested PCR technique using two primer-specific types of reverse transcriptase (RT). The amplicon was electrophoresed on 0.8% agarose gel and then sequenced. Analysis of DRMs in the HIV-1 RT genes was based on the Standford HIV database. Results -The 17 isolates from 105 ARV-treated patients, eight RT genes were successfully sequenced, and DRM of RT inhibitors was found in one of the isolates (12.5%). The Stanford HIV database analysis detected three new DRMs at the 184th, 215th and 190th codon positions, causing three mutations: M184L and T215N (NRTI-DRMs) with low-level resistance to zidovudine, and G190D (NNRTI-DRM). Conclusion -We concluded that the new DRMs found in Padang, West Sumatra indicates the importance of genotypic resistance testing and the periodic evaluation of the effectiveness of ARV drugs currently in use.

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Genetic Consequences of Antiviral Therapy on HIV-1

Cited by 14 publications

References 94 publications

HIV Protease and Integrase Empirical Substitution Models of Evolution: Protein-Specific Models Outperform Generalist Models

HIV Protease and Integrase Empirical Substitution Models of Evolution: Protein-Specific Models Outperform Generalist Models

HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China

New drug resistance mutations of reverse transcriptase Human immunodeficiency virus type-1 gene in first-line antiretroviral-infected patients in West Sumatra, Indonesia

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