Prevalence of Primary Drug Resistance Against HIV-1 Integrase Inhibitors in Canada

Ji, Hezhao; Patterson, Aileen P.; Taylor, Tracy; Rank, Claudia; Halverson, Jessica; Capiña, Rupert; Brooks, James; Sandstrom, Paul

doi:10.1097/qai.0000000000001649

Cited by 19 publications

(19 citation statements)

References 20 publications

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“…The prevalence of INSTI resistance reported in our study is similar to a recent study observing the prevalence of transmitted INSTI resistance in a Swiss HIV cohort [33] but is lower than those reported in other North American and European cohorts [15, 16, 27, 28]. This difference may in part be due to our method of defining drug resistance, which was restricted to individuals who had intermediate- to high-level INSTI resistance as defined by the Stanford University HIV Drug Resistance Database Genotypic Resistance Interpretation Algorithm version 7.0.1.…”

Section: Discussionsupporting

confidence: 89%

“…This difference may in part be due to our method of defining drug resistance, which was restricted to individuals who had intermediate- to high-level INSTI resistance as defined by the Stanford University HIV Drug Resistance Database Genotypic Resistance Interpretation Algorithm version 7.0.1. Other studies have defined INSTI resistance as individual [ 15 , 16 , 27 , 33 ] and/or cumulative [ 16 , 27 ] presence of mutations. Nevertheless, there is an increase in the prevalence of intermediate- to high-level INSTI resistance within our population from 2009 to 2016 (1 to 7 per 1000 ART-treated individuals), likely due to the increase in the number of individuals receiving INSTI-containing therapies.…”

Section: Discussionmentioning

confidence: 99%

“…There have been previous reports of transmitted and treatment-emergent INSTI resistance in clinical settings [ 15–18 ]. However, to better monitor and evaluate the current modalities of INSTI resistance and assess adequacy of INSTI resistance testing, more information is required about the change in yearly prevalence of INSTI resistance and the specific integrase mutations associated with INSTI resistance selected, in large clinical HIV populations.…”

mentioning

confidence: 99%

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Prevalence of Human Immunodeficiency Virus-1 Integrase Strand Transfer Inhibitor Resistance in British Columbia, Canada Between 2009 and 2016: A Longitudinal Analysis

Kamelian

Lepik

Chau

et al. 2019

Open Forum Infectious Diseases

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Background Integrase strand transfer inhibitors (INSTIs) are highly efficacious and well tolerated antiretrovirals with fewer adverse side-effects relative to other classes of antiretrovirals. The use of INSTIs raltegravir, elvitegravir, and dolutegravir has increased dramatically over recent years. However, there is limited information about the evolution and prevalence of INSTI resistance mutations in clinical human immunodeficiency virus populations. Methods Human immunodeficiency virus-1-positive individuals ≥19 years were included if they received ≥1 dispensed prescription of antiretroviral therapy (ART) in British Columbia between 2009 and 2016 (N = 9358). Physician-ordered drug resistance tests were analyzed and protease inhibitor (PI), reverse-transcriptase inhibitor (RT), and INSTI resistance were defined as having ≥1 sample with a combined, cumulative score ≥30 by Stanford HIV Drug Resistance Algorithm version 7.0.1. Results Although most ART-treated individuals were tested for PI and RT resistance, INSTI resistance testing lagged behind the uptake of INSTIs among INSTI-treated individuals (11% in 2009; 34% in 2016). The prevalence of INSTI resistance was relatively low, but it increased from 1 to 7 per 1000 ART-treated individuals between 2009 and 2016 (P < .0001, R2 = 0.98). Integrase strand transfer inhibitor resistance mutations increased at integrase codons 66, 97, 140, 148, 155, and 263. Conclusions The prevalence of INSTI resistance remains low compared with PI and RT resistance in ART-treated populations but is expanding with increased INSTI use.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Prevalence of Human Immunodeficiency Virus-1 Integrase Strand Transfer Inhibitor Resistance in British Columbia, Canada Between 2009 and 2016: A Longitudinal Analysis

Kamelian

Lepik

Chau

et al. 2019

Open Forum Infectious Diseases

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“…The development of new drugs that target different phases of the HIV-1 replication ensures the efficacy of ART regimens [ 9 ]. Drugs that target and block viral DNA integration have been included in patients’ antiretroviral regimens [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Short Communication: Integrase Strand Transfer Inhibitors Drug Resistance Mutations in Puerto Rico HIV-Positive Individuals

López

Tirado

Arias

et al. 2021

IJERPH

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The HIV-1 integrase viral protein is responsible for incorporating the viral DNA into the genomic DNA. The inhibition of viral integration into host cell DNA is part of recent therapeutic procedures. Combination therapy with protease and reverse transcriptase inhibitors has demonstrated good synergistic results in reducing viral replication. The purpose of this study is to assess the occurrence of integrase drug resistance mutations from the period comprising 2013 through 2018 in Puerto Rico (PR). We analyzed 131 nucleotide sequences available in our HIV genotyping database, and we performed drug resistance mutation analyses using the Stanford HIV Drug Resistance Database. Twenty-one sequences (16.03%) harbored major or resistance-associated mutations. We identified the Q148HKR, G140S, Y143R, N155H, S147G, and E138EA major drug resistance mutations and the D232DN, T97TA, E157Q, G163GART accessory mutations. We detected high-level drug resistance to Elvitegravir and Raltegravir (76.19% and 85.71%). Moreover, we identified sequences harboring drug resistance mutations that could provide resistance to Dolutegravir. The transmission of strains with integrase antiretroviral resistance has been previously documented in treatment naïve patients. Given the increase of patients treated with integrase inhibitors, surveillance of drug resistance mutations is an essential aspect of PR’s clinical management of HIV infection.

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“…12 Some data show that rare major INSTI mutations were found among primary infected HIV-1 patients in Europe, Venezuela, Canada, sub-Saharan Africa, and the US. [13][14][15][16][17] In China, few data are available on the prevalence of HIV-1 INSTI resistance among ART-naïve patients: no major INSTI drug resistance mutations and rare accessory INSTI drug resistance mutations (0.52%, 2/385) were found among 385 ARTnaïve individuals in Beijing; a total of 10 (1.95%) major INSTI drug resistance mutations and 8 (1.56%) accessory INSTI drug resistance mutations were found among 513 ART-naïve individuals in Yunnan. 18,19 Given that INSTIs are currently used in HIV-1-infected individuals in Guangdong, a developed province on the southern coast of China, it is essential to obtain the resistance status to this class of antiretrovirals, but there is no information about mutations related to INSTIs among HIV-1-infected individuals in Guangdong.…”

Section: Introductionmentioning

confidence: 99%

<p>Absence of Integrase Inhibitor-Associated Resistance Among Antiretroviral Therapy-Naïve HIV-1-Infected Adults in Guangdong Province, China, in 2018</p>

Lan¹,

Li²,

Chen³

et al. 2020

IDR

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Prevalence of Primary Drug Resistance Against HIV-1 Integrase Inhibitors in Canada

Cited by 19 publications

References 20 publications

Prevalence of Human Immunodeficiency Virus-1 Integrase Strand Transfer Inhibitor Resistance in British Columbia, Canada Between 2009 and 2016: A Longitudinal Analysis

Prevalence of Human Immunodeficiency Virus-1 Integrase Strand Transfer Inhibitor Resistance in British Columbia, Canada Between 2009 and 2016: A Longitudinal Analysis

Short Communication: Integrase Strand Transfer Inhibitors Drug Resistance Mutations in Puerto Rico HIV-Positive Individuals

<p>Absence of Integrase Inhibitor-Associated Resistance Among Antiretroviral Therapy-Naïve HIV-1-Infected Adults in Guangdong Province, China, in 2018</p>

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