Resistance to the integrase strand transfer inhibitors raltegravir and elvitegravir is often due to well-identified mutations in the integrase gene. However, the situation is less clear for patients who fail dolutegravir treatment. Furthermore, most in vitro experiments to select resistance to dolutegravir have resulted in few mutations of the integrase gene. We performed an in vitro dolutegrav...

BACKGROUND This study evaluated the pharmacokinetics of a granule formulation of dolutegravir developed as an alternative to tablets for use in paediatric populations. METHODS A randomized, open-label study in healthy adults was carried out. Subjects received five treatments in a crossover design: a single dose of dolutegravir 50 mg as a tablet and dolutegravir 50 mg in 10 g of granule admini...

Dolutegravir is the newest integrase strand transfer inhibitor to be approved for the treatment of human immunodeficiency virus (HIV) infection. Dolutegravir is equivalent or superior to existing treatment regimens in both treatment-naïve and treatment-experienced patients including those with previous raltegravir or elvitegravir failure. The consistent efficacy coupled with excellent tolerabil...

The pharmacokinetics, metabolism, and excretion of dolutegravir, an unboosted, once-daily human immunodeficiency virus type 1 integrase inhibitor, were studied in healthy male subjects following single oral administration of [(14)C]dolutegravir at a dose of 20 mg (80 μCi). Dolutegravir was well tolerated, and absorption of dolutegravir from the suspension formulation was rapid (median time to p...

BACKGROUND/AIMS The viral integrase enzyme inhibitor dolutegravir is utilized for the treatment of immunodeficiency virus (HIV) infection. Knowledge on cytotoxicity of dolutegravir is limited. The present study thus explored, whether dolutegravir is able to trigger suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylser...

BACKGROUND Dolutegravir is approved for the treatment of HIV-1 patients exposed to other integrase inhibitors, but the decision to use dolutegravir in this setting should be informed by drug resistance testing. OBJECTIVES This study determined the extent of disagreement in predicted residual dolutegravir activity after raltegravir use, and identified individual mutational patterns for which u...

This study evaluated dolutegravir pharmacokinetics (PK) in subjects with moderate hepatic impairment compared to matched, healthy controls. In this open-label, parallel-group study, eight adult subjects with moderate hepatic impairment (Child-Pugh Score 7-9) and eight healthy subjects matched for gender, age, and body mass index received a single dolutegravir 50-mg dose. Following dosing, 72-ho...

AIM Dolutegravir is the newest integrase inhibitor approved for HIV treatment and has demonstrated potent antiviral activity in patient populations with a broad range of treatment experience. This analysis aimed to characterize the population pharmacokinetics of dolutegravir in treatment-naive patients and to evaluate the influence of patient covariates. METHODS A population pharmacokinetic m...

In the SPRING-2 trial, dolutegravir showed noninferiority to raltegravir, another integrase inhibitor, in antiretroviral-naive adults with HIV-1 infection. In the SINGLE trial, dolutegravir showed superiority over a non-nucleoside reverse transcriptase inhibitor, efavirenz. The next obvious step of the dolutegravir targeted strategy was to compare dolutegravir with a boosted protease inhibitor ...

BACKGROUND Dolutegravir (S/GSK1349572) is a new HIV-1 integrase inhibitor that has antiviral activity with once daily, unboosted dosing. SPRING-1 is an ongoing study designed to select a dose for phase 3 assessment. We present data from preplanned primary and interim analyses. METHODS In a phase 2b, multicentre, dose-ranging study, treatment-naive adults were randomly assigned (1:1:1:1) to re...