Integrase resistance emergence with dolutegravir/lamivudine with prior HIV-1 suppression.
J Antimicrob Chemother
; 77(6): 1738-1740, 2022 05 29.
Article
en En
| MEDLINE
| ID: mdl-35274144
ABSTRACT
OBJECTIVES:
Integrase resistance has not been reported with co-formulated dolutegravir/lamivudine in clinical trials or real-life cohorts. We aim to report, to the best of our knowledge, the first case of selection of the key integrase mutation R263K in a subject treated with this regimen started as a switch strategy with undetectable plasma HIV-1 viraemia.METHODS:
Clinical case report.RESULTS:
A patient with long-term suppressed HIV-1 viraemia (<50â copies/mL) with no known risk factors for virological failure and never exposed previously to an integrase inhibitor developed virological failure (consecutive plasma HIV-1 RNA 149 and 272â copies/mL) with 322 CD4 cells/mm3 despite good treatment adherence. He was receiving the anticonvulsant clobazam, considered to have a potential weak interaction with dolutegravir, unlikely to require a dose adjustment. Plasma HIV-1 genotypic deep sequencing (Vela System) revealed the emergence of R263K (79.6%) and S230N (99.4%) mutations in the integrase region (intermediate resistance to dolutegravir, scoreâ=â30 Stanford HIVDB 9.0). The reverse transcriptase and protease regions could not be amplified due to low viral loads. PBMC DNA deep sequencing performed some months later revealed mutations M184I (14.29%) and M230I (6.25%) in the reverse transcriptase and G163R (9.77%) and S230N (98.8%) in the integrase. R263K was only found at extremely low levels (0.07%).CONCLUSIONS:
This case illustrates that integrase resistance can emerge in patients treated with co-formulated dolutegravir/lamivudine and raises awareness of the need to carefully consider and monitor drug-drug interactions, even when regarded as having a low potential, in subjects treated with dolutegravir/lamivudine.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Infecciones por VIH
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VIH-1
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Seropositividad para VIH
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Inhibidores de Integrasa VIH
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
/
Male
Idioma:
En
Año:
2022
Tipo del documento:
Article