Resistance to the most recent protease and non-nucleoside reverse transcriptase inhibitors across HIV-1 non-B subtypes

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Hauptverfasser: Anta L, Blanco JL, Llibre JM, García F, Pérez-Elías MJ, Aguilera A, Pérez-Romero P, Caballero E, Vidal C, Cañizares A, Gutiérrez F, Dalmau D, Iribarren JA, Soriano V, De Mendoza C
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Veröffentlicht: Zenodo 2025
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author Anta L
Blanco JL
Llibre JM
García F
Pérez-Elías MJ
Aguilera A
Pérez-Romero P
Caballero E
Vidal C
Cañizares A
Gutiérrez F
Dalmau D
Iribarren JA
Soriano V
De Mendoza C
author_facet Anta L
Blanco JL
Llibre JM
García F
Pérez-Elías MJ
Aguilera A
Pérez-Romero P
Caballero E
Vidal C
Cañizares A
Gutiérrez F
Dalmau D
Iribarren JA
Soriano V
De Mendoza C
contents <div> <div>Objectives</div> <p>Limited data are available on resistance to etravirine, rilpivirine, darunavir and tipranavir in patients infected with HIV-1 non-B subtypes, in which natural polymorphisms at certain positions could influence the barrier and/or pathways to drug resistance.</p> </div> <div> <div>Methods</div> <p>FASTA format sequences from the reverse transcriptase and protease genes recorded within the Spanish Drug Resistance database (ResRIS) were examined.</p> </div> <div> <div>Results</div> <p>From 8272 genotypes derived from 5930 different HIV-1 patients included in ResRIS, 5276 genotypes had complete treatment information. Overall, 85% were from antiretroviral-experienced subjects and 7.5% belonged to HIV-1 non-B subtypes: CRF02_AG, C, F and G being the most prevalent variants. For etravirine, only G190A was more prevalent in B than non-B subtypes, whereas V90I and V179E were more frequent in non-B than B subtypes. For rilpivirine, V108I and Y188I were more frequent in B than non-B subtypes, whereas V90I was more prevalent in non-B subtypes. Despite these differences, the overall prevalence of resistance did not differ significantly when comparing etravirine or rilpivirine in B versus non-B subtypes (11.3% versus 7.4%, <em>P</em> = 0.13, and 10.5% versus 7.4%, <em>P</em> = 0.23, respectively). Despite more frequent natural polymorphisms in non-B than B subtypes at tipranavir resistance positions, the prevalence of tipranavir resistance was greater in B than non-B subtypes (11% versus 4.3%, <em>P</em> = 0.004), reflecting a greater antiretroviral exposure in the former. Darunavir resistance did not differ significantly when comparing B and non-B subtypes (5.8% versus 5.5%, <em>P</em> = 0.998).</p> </div> <div> <div>Conclusions</div> <p>The rate of resistance to the most recently approved protease and non-nucleoside reverse transcriptase inhibitors is low in antiretroviral-experienced patients, regardless of the HIV-1 subtype.</p> </div>
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spellingShingle Resistance to the most recent protease and non-nucleoside reverse transcriptase inhibitors across HIV-1 non-B subtypes
Anta L
Blanco JL
Llibre JM
García F
Pérez-Elías MJ
Aguilera A
Pérez-Romero P
Caballero E
Vidal C
Cañizares A
Gutiérrez F
Dalmau D
Iribarren JA
Soriano V
De Mendoza C
<div> <div>Objectives</div> <p>Limited data are available on resistance to etravirine, rilpivirine, darunavir and tipranavir in patients infected with HIV-1 non-B subtypes, in which natural polymorphisms at certain positions could influence the barrier and/or pathways to drug resistance.</p> </div> <div> <div>Methods</div> <p>FASTA format sequences from the reverse transcriptase and protease genes recorded within the Spanish Drug Resistance database (ResRIS) were examined.</p> </div> <div> <div>Results</div> <p>From 8272 genotypes derived from 5930 different HIV-1 patients included in ResRIS, 5276 genotypes had complete treatment information. Overall, 85% were from antiretroviral-experienced subjects and 7.5% belonged to HIV-1 non-B subtypes: CRF02_AG, C, F and G being the most prevalent variants. For etravirine, only G190A was more prevalent in B than non-B subtypes, whereas V90I and V179E were more frequent in non-B than B subtypes. For rilpivirine, V108I and Y188I were more frequent in B than non-B subtypes, whereas V90I was more prevalent in non-B subtypes. Despite these differences, the overall prevalence of resistance did not differ significantly when comparing etravirine or rilpivirine in B versus non-B subtypes (11.3% versus 7.4%, <em>P</em> = 0.13, and 10.5% versus 7.4%, <em>P</em> = 0.23, respectively). Despite more frequent natural polymorphisms in non-B than B subtypes at tipranavir resistance positions, the prevalence of tipranavir resistance was greater in B than non-B subtypes (11% versus 4.3%, <em>P</em> = 0.004), reflecting a greater antiretroviral exposure in the former. Darunavir resistance did not differ significantly when comparing B and non-B subtypes (5.8% versus 5.5%, <em>P</em> = 0.998).</p> </div> <div> <div>Conclusions</div> <p>The rate of resistance to the most recently approved protease and non-nucleoside reverse transcriptase inhibitors is low in antiretroviral-experienced patients, regardless of the HIV-1 subtype.</p> </div>
title Resistance to the most recent protease and non-nucleoside reverse transcriptase inhibitors across HIV-1 non-B subtypes
url https://doi.org/10.1093/jac/dkt146