OBJECTIVE To evaluate the antiviral activity, safety, pharmacokinetics, and pharmacokinetics/pharmacodynamics of dolutegravir (DTG), a next-generation HIV integrase inhibitor (INI), as short-term monotherapy. DESIGN A phase IIa, randomized, double-blind, dose-ranging study. METHODS In this study, INI-naive, HIV-1-infected adults currently off antiretroviral therapy were randomized to receiv...

A model of reservoir activation and viral replication is introduced accounting for the production of 2-LTR HIV-1 DNA circles following antiviral intensification with the HIV integrase inhibitor raltegravir, considering contributions of de novo infection events and exogenous sources of infected cells, including quiescent infected cell activation. The model shows that a monotonic increase in meas...

Article history: Received 11 October 2016 Accepted 11 October 2016 Available online 13 October 2016 formation on the impact of different ART regimens on inflammatory biomarkers linked with mortality remains, however, very limited. Recently, integrase inhibitors have shown to improve inflammation or immune activation markers when compared to non-nucleoside reverse transcriptase inhibitors. In pa...

In order to analyze the clinical relevance of the pharmacokinetic interactions between vinblastine and antiretrovirals described in literature, we evaluated all HIV-infected patients with Hodgkin's lymphoma treated with vinblastine-containing regimens and combination antiretroviral therapy, in a single clinical center. The use of protease inhibitors was independently associated with WHO grade I...

Raltegravir is the first licensed compound in 2007 of the new integrase inhibitor drug class. At the dose of 400 mg twice daily, raltegravir showed a potent antiviral action in antiretroviral-naïve patients when associated with tenofovir and emtricitabine. Raltegravir was also found to be highly active in antiretroviral-experienced patients with virological failure and displaying multiresistant...

Raltegravir, the only integrase (IN) inhibitor approved for use in HIV therapy, has recently been licensed. Raltegravir inhibits HIV-1 replication by blocking the IN strand transfer reaction. More than 30 mutations have been associated with resistance to raltegravir and other IN strand transfer inhibitors (INSTIs). The majority of the mutations are located in the vicinity of the IN active site ...

BACKGROUND GSK1265744 (744) is an HIV-1 integrase inhibitor in clinical development as a long-acting (LA) injectable formulation. This study evaluated plasma and tissue pharmacokinetics after single-dose administration of 744 LA administered by intramuscular (IM) or subcutaneous injections. METHODS This was a phase I, open-label, 9-cohort, parallel study of 744 in healthy subjects. 744 was ad...

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...