Determination of Drug Resistance and Virus Typology in HIV-1-Positive Pediatric Patients in Istanbul, Turkey

Background: The advent of resistance-associated mutations in HIV-1 is a barrier to the success of the ARTs. Objective: In this study, the abundance of HIV-1 infection in Iranian children, and also detection of the TDR in naïve HIV-1 infected pediatric (under 12 years old) were evaluated. Materials: From June 2014 to January 2019, a total of 544 consecutive treatment-naïve HIV-1- infected individuals enrolled in this study. After RNA extraction, amplification, and sequencing of the HIV-1 pol gene, the DRM and phylogenetic analysis were successfully performed on the plasma specimens of the ART-naïve HIV-1-infected-children under 12 years old. The DRMs were recognized using the Stanford HIV Drug Resistance Database. Results: Out of the 544 evaluated treatment-naïve HIV-1-infected individuals, 15 (2.8%) cases were children under 12 years old. The phylogenetic analyses of the amplified region of pol gene indicated that all of the 15 HIV-1-infected pediatric patients were infected by CRF35_AD, and a total of 13.3% (2/15) of these children were infected with HIV-1 variants with SDRMs (one child harbored two related SDRMs [D67N, V179F], and another child had three related SDRMs [M184V, T215F, and K103N]), according to the last algorithm of the WHO. No PIs-related SDRMs were observed in HIV-1-infected children. Conclusion: The current study demonstrated that a total of 13.3% of treatment-naïve HIV-1-infected Iranian pediatrics (under 12 years old) were infected with HIV-1 variants with SDRMs. Therefore, it seems that screening to recognize resistance-associated mutations before the initiation of ARTs among Iranian children is essential for favorable medication efficacy and dependable prognosis.

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The Determination of HIV-1 RT Mutation Rate, Its Possible Allosteric Effects, and Its Implications on Drug Resistance

10.20944/preprints202002.0099.v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Joshua Yi Yeo ◽

Ghin Ray Goh ◽

Chinh Tran-To Su ◽

Samuel Ken-En Gan

Keyword(s):

Drug Resistance ◽

Mutation Rate ◽

Treatment Resistance ◽

Investigation Methods ◽

Immunodeficiency Virus ◽

Assay Methods ◽

Emerging Viral Diseases ◽

Hiv 1

The high mutation rate of human immunodeficiency virus type 1 (HIV-1) plays a major role in treatment resistance from the development of vaccines to long-lasting drugs. In addressing the crux of the issue, various attempts to estimate the mutation rate of HIV-1 resulted in a large range of 10-5 - 10-3 errors/bp/cycle due to the use of different types of investigation methods. In this review, we discuss the different assay methods, their findings on the mutation rates of HIV-1 and how the location of these mutations can be further analyzed for their potential allosteric effects to reveal potentially new inhibitors with different pharmacodynamics that can be used to circumvent fast occurring HIV drug resistance. Given that HIV is one of the fastest mutating viruses, it is a good model for comprehensive study of its mutations that can give rise to much horizontal understanding towards overall viral drug resistance as well as emerging viral diseases.

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HIV-1 DRUG RESISTANCE ASSESSMENT IN PEDIATRIC PATIENTS

VIRUS Reviews & Research ◽

10.17525/vrr.v14i2.29 ◽

2009 ◽

Vol 14 (2) ◽

Author(s):

Sandra R. R. Simonetti ◽

Dirce B. De Lima ◽

Hermann G. Schatzmayr ◽

Bruno R. Simonetti ◽

Denise C. N. Sztajnbok ◽

...

Keyword(s):

Drug Resistance ◽

Pediatric Patients ◽

Resistance Assessment ◽

Hiv 1

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Contribution of Gag and Protease to HIV-1 Phenotypic Drug Resistance in Pediatric Patients Failing Protease Inhibitor-Based Therapy

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02682-15 ◽

2016 ◽

Vol 60 (4) ◽

pp. 2248-2256 ◽

Cited By ~ 14

Author(s):

Jennifer Giandhari ◽

Adriaan E. Basson ◽

Katherine Sutherland ◽

Chris M. Parry ◽

Patricia A. Cane ◽

...

Keyword(s):

Drug Resistance ◽

Amino Acid ◽

Pediatric Patients ◽

Site Directed Mutagenesis ◽

Directed Mutagenesis ◽

Amino Acid Substitutions ◽

Resistance Mutations ◽

Phenotypic Resistance ◽

Protease Resistance ◽

Hiv 1

ABSTRACTProtease inhibitors (PIs) are used as a first-line regimen in HIV-1-infected children. Here we investigated the phenotypic consequences of amino acid changes in Gag and protease on lopinavir (LPV) and ritonavir (RTV) susceptibility among pediatric patients failing PI therapy. The Gag-protease from isolates from 20 HIV-1 subtype C-infected pediatric patients failing an LPV and/or RTV-based regimen was phenotyped using a nonreplicativein vitroassay. Changes in sensitivity to LPV and RTV relative to that of the matched baseline (pretherapy) sample were calculated. Gag and protease amino acid substitutions associated with PI failure were created in a reference clone by site-directed mutagenesis and assessed. Predicted phenotypes were determined using the Stanford drug resistance algorithm. Phenotypic resistance or reduced susceptibility to RTV and/or LPV was observed in isolates from 10 (50%) patients, all of whom had been treated with RTV. In most cases, this was associated with protease resistance mutations, but substitutions at Gag cleavage and noncleavage sites were also detected. Gag amino acid substitutions were also found in isolates from three patients with reduced drug susceptibilities who had wild-type protease. Site-directed mutagenesis confirmed that some amino acid changes in Gag contributed to PI resistance but only in the presence of major protease resistance-associated substitutions. The isolates from all patients who received LPV exclusively were phenotypically susceptible. Baseline isolates from the 20 patients showed a large (47-fold) range in the 50% effective concentration of LPV, which accounted for most of the discordance seen between the experimentally determined and the predicted phenotypes. Overall, the inclusion of thegaggene and the use of matched baseline samples provided a more comprehensive assessment of the effect of PI-induced amino acid changes on PI resistance. The lack of phenotypic resistance to LPV supports the continued use of this drug in pediatric patients.

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The Determination of HIV-1 RT Mutation Rate, Its Possible Allosteric Effects, and Its Implications on Drug Resistance

Viruses ◽

10.3390/v12030297 ◽

2020 ◽

Vol 12 (3) ◽

pp. 297 ◽

Cited By ~ 3

Author(s):

Joshua Yi Yeo ◽

Ghin-Ray Goh ◽

Chinh Tran-To Su ◽

Samuel Ken-En Gan

Keyword(s):

Drug Resistance ◽

Mutation Rate ◽

Treatment Resistance ◽

Therapeutic Drugs ◽

Investigation Methods ◽

Immunodeficiency Virus ◽

Assay Methods ◽

Emerging Viral Diseases ◽

Hiv 1

The high mutation rate of the human immunodeficiency virus type 1 (HIV-1) plays a major role in treatment resistance, from the development of vaccines to therapeutic drugs. In addressing the crux of the issue, various attempts to estimate the mutation rate of HIV-1 resulted in a large range of 10−5–10−3 errors/bp/cycle due to the use of different types of investigation methods. In this review, we discuss the different assay methods, their findings on the mutation rates of HIV-1 and how the locations of mutations can be further analyzed for their allosteric effects to allow for new inhibitor designs. Given that HIV is one of the fastest mutating viruses, it serves as a good model for the comprehensive study of viral mutations that can give rise to a more horizontal understanding towards overall viral drug resistance as well as emerging viral diseases.

Download Full-text