Backbones versus core agents in initial ART regimens: one game, two players

March 27, 2016 at 10:01 am

Journal of Antimicrobial Chemotherapy April 2016 V.71 N.4 P.856-861

Editor’s Choice

Josep M. Llibre, Sharon Walmsley, and Josep M. Gatell

1HIV Unit and ‘Lluita contra la SIDA’ Foundation, University Hospital Germans Trias I Pujol, Badalona, Spain

2Universitat Autònoma de Barcelona, Barcelona, Spain

3Infectious Diseases, University Health Network, University of Toronto, Toronto, Canada

4Infectious Diseases & AIDS Units, Hospital Clinic/IDIBAPS, University of Barcelona, Barcelona, Spain

Reliance on usually two NRTIs together with a third agent appears to be necessary to adequately control HIV replication, but continued research is needed to develop agents with lower toxicity, longer dosing intervals, lower cost and alternative routes of administration.

The advances seen in ART during the last 30 years have been outstanding. Treatment has evolved from the initial use of single agents as monotherapy. The ability to use HIV RNA as a surrogate marker for clinical outcomes allowed the more rapid evaluation of new therapies. This led to the understanding that triple-drug regimens, including a core agent (an NNRTI or a boosted PI) and two NRTIs, are optimal.

These combinations have demonstrated continued improvements in their efficacy and toxicity as initial therapy. However, the need for pharmacokinetic boosting, with potential drug–drug interactions, or residual issues of efficacy or toxicity have persisted for some agents. Most recently, integrase strand transfer inhibitors, particularly dolutegravir, have shown unparalleled safety and efficacy and are currently the core agents of choice.

Regimens that included only core agents or only backbone agents have not been as successful as combined therapy in antiretroviral-naive patients. It appears that at least one NRTI is needed for optimal performance and lamivudine and emtricitabine may be the ideal candidates.

Several studies are ongoing of agents with longer dosing intervals, lower cost and new NRTI-saving strategies to address unmet needs.

PDF

http://jac.oxfordjournals.org/content/71/4/856.full.pdf

Entry filed under: Antirretrovirales, HIV/SIDA, HIV/SIDA HAART, Infecciones virales. Tags: .

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