Backbones versus core agents in initial ART regimens: one game, two players
Journal of Antimicrobial Chemotherapy April 2016 V.71 N.4 P.856-861
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.
VRE and VSE Bacteremia Outcomes in the Era of Effective VRE Therapy: A Systematic Review and Meta-analysis Any impact of blips and low-level viraemia episodes among HIV-infected patients with sustained virological suppression on ART?