Increased dose of dolutegravir as a potential rescue therapy in multi-experienced patients

Davide Ferrari, Vincenzo Spagnuolo, Monica Manca, Alba Bigoloni, Camilla Muccini, Giuseppe Banfi, Massimo Locatelli, Antonella Castagna

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a human immunodeficiency virus (HIV) integrase inhibitor (INI), is efficacious in INI-resistant patients at the 50 mg twice daily (BID) dose. However, DTG response was most reduced in subjects carrying resistance-associated mutations at position G140 and Q148. These mutations can cause a 10-20-fold reduced susceptibility to DTG as well as a 96% lower odds of achieving HIV-1 RNA <50 copies/mL at week 24 if compared with those with no mutations at these positions.

METHODS: Five multi-experienced patients harboring the mutation complex G140-Q148, resistant to at least three drug classes, and previously exposed to DTG 50mg BID, were treated with an increased dose of DTG (100 mg BID) in association with an optimized background regimen (OBR) based on their individual viral genotyping assays. The blood concentration of DTG was measured in order to determine whether a solubility issue is related with this high dosage.

RESULTS: Four out of five patients attained a HIV-1 RNA <50 copies/mL at week 48 and no relevant adverse events were detected. The measured DTG blood concentration was that expected for the administered dosage, ruling out any solubility concerns.

CONCLUSIONS: For the first time 100 mg BID of DTG were administered to five multi-experienced patients harboring the mutation complex G140-Q148. Although a small number of patients were tested, the results show a potential for an high-dose regimens of DTG as a rescue therapy in patients harboring INSTI resistant viruses.

Original languageEnglish
Pages (from-to)69-72
Number of pages4
JournalAntiviral Therapy
Volume24
Issue number1
Early online dateOct 24 2018
DOIs
Publication statusPublished - 2019

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