Major drug resistance mutations to HIV-1 protease inhibitors (PI) among patients exposed to PI class failing antiretroviral therapy in São Paulo State, Brazil


Autoři: Giselle de Faria Romero Soldi aff001;  Isadora Coutinho Ribeiro aff001;  Cintia Mayumi Ahagon aff001;  Luana Portes Ozório Coelho aff001;  Gabriela Bastos Cabral aff001;  Giselle Ibette Silva López Lopes aff001;  João Leandro de Paula Ferreira aff001;  Luís Fernando de Macedo Brígido aff001aff001
Působiště autorů: Núcleo de Doenças de Vinculação Sanguínea ou Sexual, Laboratório de Retrovírus, Centro de Virologia, Instituto Adolfo Lutz, São Paulo, São Paulo, Brazil aff001
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223210

Souhrn

Background

Protease inhibitors (PI) are especially important in salvage therapy. Previous treatment failure with a PI containing regimen may elicit resistance mutations, reducing PI susceptibility and limiting treatment options. The aim of this study was to describe major PI mutations among patients exposed to at least one PI to evaluate predictors of mutation emergence and the impact of subtypes on resistance.

Methodology

Partial HIV-1 pol sequences (Sanger Sequencing) from patients exposed to PI with virological failure were genotyped from January 2014 to December 2017. Drug resistance mutations (DRM), antiretroviral susceptibility (GSS) and subtypes, along clinical and laboratory parameters, were evaluated using logistic regression to access the predictors of mutation emergence.

Results

In 27.5% (466/1696) of the cases at least one major PI mutations was identified, most commonly M46 (14.7%), V82 (13.8%) and I54 (13.3%). Mutations to NRTI and NNRTI were observed in 69.6% and 59.9%, respectively, of the 1696 sequences. Full activity to darunavir was predicted in 88% (1496/1696), but was only 57% among those with at least one PI-DRM. Subtype C sequences had less major PI-DRMs (10%, 9/87) compared to B (28%, 338/1216) or F (35%, 58/168) (p <0.001) but adjusted analysis suggested that this association is not independent from a shorter treatment time and fewer regimens (OR 0.59, Confidence Interval 95: 0.2–2.5, p = 0.48). Subtype F, together with NRTI mutations and longer time on treatment was associated to presence of PI-DRM, to a lower darunavir GSS and to mutations at codon I50.

Conclusions

Among patients with PI-DRM, full activity to darunavir was compromised in almost half of the cases and efforts to detect failure at earlier time are warranted, particularly for HIV-1 subtype F that showed association to the emergence of resistance, with potential impact in protease inhibitors sequencing. Furthermore, NRTI mutations may serve as an indicative of sufficient adherence to allow PI-DRM emergence.

Klíčová slova:

Antimicrobial resistance – Antiretroviral therapy – Genotyping – HIV-1 – Microbial mutation – Mutation databases – Viral load – Protease inhibitors


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PLOS One


2019 Číslo 10

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