S/GSK1349572, a new integrase inhibitor for the treatment of HIV: promises and challenges.

INTRODUCTION: The recent introduction of integrase inhibitors (INIs) into the HIV treatment armentarium has had a significant impact on HIV treatment. However, at present, raltegravir twice daily is the only licensed INI featuring a lower genetic barrier compared with boosted protease inhibitors. S/GSK1349572 represents a new INI in current development. It is a once-daily, unboosted INI with low pharmacokinetic variability and predictable exposure-response relationship. Phase IIb studies in antiretroviral-naïve patients have demonstrated non-inferiority to efavirenz-based HIV therapy. Phase II studies in INI-experienced patients show partially retained activity in vivo. Overall, the safety profile of S/GSK1349572 in all studies completed has been very favorable. AREAS COVERED: A Pubmed and Medline search was carried out on all articles on S/GSK1349572 from 2005 to 2010, including recent abstract presentations from major HIV conferences (CROI 2010, WAC2010, EACS2009, HIV10 and ICAAC2010). The reader will become acquainted with the unique properties of this new INI and will understand the current promises and challenges of the data available from S/GSK1349572. EXPERT OPINION: S/GSK1349572 represents a new, unboosted, once-daily INI in development with distinct pharmacokinetics and resistance profile, which has showed promising potency and tolerability in the first clinical studies.

Vicriviroc, a new CC-chemokine receptor 5 inhibitor for treatment of HIV: properties, promises and challenges.

IMPORTANCE OF THE FIELD: Although HIV has become a treatable disease with near to normal life expectancy, the quest for the development of better tolerated drugs with simple dosing schedules and a high barrier to the emergence of drug resistance remains. Vicriviroc is a small-molecule chemokine receptor antagonist that inhibits the binding of R5-tropic HIV-1 to host cells at the CC-chemokine receptor 5 (CCR5) co-receptor, thus, preventing viral entry. CCR5 inhibitors are believed to possibly decrease inflammation from the immune system and thereby offer additional properties further to their antiretroviral efficacy. AREAS COVERED IN THIS REVIEW: This review is based on a PubMed search covering the years 2005 - 2010 for pharmacokinetic, pharmacological and clinical data of vicriviroc. WHAT THE READER WILL GAIN: In this review, the pharmacokinetic, pharmacological and clinical data of vicriviroc are presented. Moreover, the potential role of vicriviroc in the growing HIV armamentarium is discussed. TAKE HOME MESSAGE: Vicriviroc is being developed to be administered in combination with a ritonavir-boosted protease inhibitor for patients with R5-tropic virus. Early clinical trials have established the safety of vicriviroc in both treatment-naive and -experienced R5-tropic HIV-1 infected individuals. Recently, two Phase III clinical trials in treatment-experienced patients failed to prove its superiority over available HIV medications. Phase III trials for treatment-naive patients are still under planning. Clearly, more favorable study results are needed to move vicriviroc into drug registration and approval.