Resistance-Associated Mutations and Polymorphisms among Integrase Inhibitor-Naïve HIV-1 Patients in Kuwait

Chehadeh, Wassim; Albaksami, Osama; John, Sonia Elezebeth; Al‐Nakib, W.

doi:10.1159/000484692

Cited by 5 publications

(3 citation statements)

References 35 publications

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“…Indeed, in our study we analysed HIV-1 strains isolated from INSTI-naive children, thus excluding the effect of INSTI drugs on the selection process of these mutations. Furthermore, previous studies evaluating the variability of the IN gene revealed that amino acid variations at codon 138 (E138A/D/K/T) could arise from G-to-A hypermutation resulting from APOBEC-mediated RNA editing, 42 and also from natural polymorphism during viral replication 41 , 43 . Further in vivo and in vitro studies are thus needed to better understand the clinical significance of these naturally occurring unusual DRMs in INSTI-naive children.…”

Section: Discussionmentioning

confidence: 99%

High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO

Bouassa

Mossoro-Kpinde

Gody

et al. 2019

Journal of Antimicrobial Chemotherapy

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Objectives The predictive efficacy of integrase (IN) strand transfer inhibitors (INSTIs) was investigated in HIV-infected children born to HIV-infected mothers in Africa. Methods Plasma was collected at the Complexe Pédiatrique of Bangui, Central African Republic, from INSTI-naive children ( n = 8) and adolescents ( n = 10) in virological failure (viral load >1000 copies/mL) after 5 years of first- and/or second-line combination ART (cART). IN, reverse transcriptase (RT) and protease (P) genes were genotyped and drug resistance mutations (DRMs) to INSTIs, NRTIs, NNRTIs and PIs were interpreted using the Stanford algorithm. Results Successful IN, RT and P genotypes were obtained for 18, 13 and 15 children (median age 11 years, range 5–18; 8 were female), respectively. Two (2/18; 11.1%) viruses from children treated with a first-line regimen had INSTI DRMs at codon 138 (E138K and E138T), which is known to harbour major resistance mutations, and also had the accessory mutations L74I, G140K, G140R and G163R. The majority (16/18; 88.9%) of HIV-1 IN sequences demonstrated full susceptibility to all major INSTIs with a high frequency of natural polymorphic mutations. Most (12/15; 80%) genotyped viruses harboured at least one major DRM conferring resistance to at least one of the WHO-recommended antiretroviral drugs (NNRTIs, NRTIs and PIs) prescribed in first- and second-line regimens. Conclusions INSTIs could be proposed in first-line regimens in the majority of African children or adolescents and may constitute relevant therapeutic alternatives as second- and third-line cART regimens in HIV-infected children and adolescents living in sub-Saharan Africa.

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Section: Discussionmentioning

confidence: 99%

High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO

Bouassa

Mossoro-Kpinde

Gody

et al. 2019

Journal of Antimicrobial Chemotherapy

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“…The ABI 3500 Genetic Analyzer (Applied Biosystems, Foster City, CA) was used to determine the nucleotide sequences of 5' and 3' DNA strands as described previously. 18 The identification of HIV-1 subtype and mutations associated with resistance to protease inhibitors, reverse transcriptase inhibitors and InSTIs, was done using the Stanford University genotypic resistance interpretation algorithm. 21 Statistical analysis.…”

Section: Hiv-1 Genotyping and Drug Resistance Assessmentmentioning

confidence: 99%

“…17 Major non-polymorphic mutations that confer resistance to InSTIs were not detected in 53 InSTI-naı¨ve patients. 18 Given the scarce information on HIV-1 drug resistance in real clinical settings, especially in the Arabian Gulf region, we aimed in this report to characterize the patterns of mutations detected among patients who did not achieve viral suppression following 48 weeks of treatment with InSTI-based regimen.…”

Section: Introductionmentioning

confidence: 99%

Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting

Chehadeh

Albaksami

Al-Shammari

2020

Antivir Chem Chemother

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Background With the advent of next generation integrase strand transfer inhibitors, the rates of virologic failure in treated subjects are expected to decrease. In this study, we analyzed the mutation patterns leading to virologic failure before and after starting integrase strand transfer inhibitor-based regimen as first-line or salvage therapy. Methods Between 2016 and 2019, blood samples were received from 258 patients with HIV-1 infection. Plasma HIV-1 RNA concentrations, and pol gene sequences were determined at baseline, and 16–48 weeks of treatment with integrase strand transfer inhibitor-based regimen. Only patients who did not achieve viral suppression at 48 weeks of integrase strand transfer inhibitor-based treatment were eligible for the current study. Results Virologic failure was observed in seven patients on raltegravir-based regimen. All patients with virologic failure but one were infected with CRF01_AE virus subtype. Raltegravir based-regimen was offered as first-line therapy for four patients, and as salvage therapy for three patients. M184V mutation associated with high level resistance to lamivudine and emtricitabine was detected in six out of seven patients. Primary mutations (Y143C, N155H, T66I, G118R, E138K) conferring high level resistance to raltegravir were detected in only three patients. Pre-existing polymorphic integrase mutation (T97A) was detected in two patients. Furthermore, two patients reported low adherence to treatment. Conclusions Emergence of primary mutations in the integrase gene can account for virologic failure in less than half of patients on raltegravir-based regimen. Low adherence to treatment, pre-existing accessory mutations, and resistance to reverse transcriptase inhibitors may have some role in virologic outcome.

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Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia

Oroz

Begovać

Planinić

et al. 2019

Sci Rep

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Molecular epidemiology of HIV-1 infection in treatment-naive HIV-1 infected persons from Croatia was investigated. We included 403 persons, representing 92.4% of all HIV-positive individuals entering clinical care in Croatia in 2014–2017. Overall prevalence of transmitted drug resistance (TDR) was estimated at 16.4%. Resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside RTI (NNRTIs) and protease inhibitors (PIs) was found in 11.4%, 6.7% and 2.5% of persons, respectively. Triple-class resistance was determined in 2.2% of individuals. In addition, a single case (1.0%) of resistance to integrase strand-transfer inhibitors (InSTIs) was found. Deep sequencing was performed on 48 randomly selected samples and detected additional TDR mutations in 6 cases. Phylogenetic inference showed that 347/403 sequences (86.1%) were part of transmission clusters and identified forward transmission of resistance in Croatia, even that of triple-class resistance. The largest TDR cluster of 53 persons with T215S was estimated to originate in the year 1992. Our data show a continuing need for pre-treatment HIV resistance testing in Croatia. Even though a low prevalence of resistance to InSTI was observed, surveillance of TDR to InSTI should be continued.

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Resistance-Associated Mutations and Polymorphisms among Integrase Inhibitor-Naïve HIV-1 Patients in Kuwait

Cited by 5 publications

References 35 publications

High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO

High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO

Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting

Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia

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