Saturday, February 6, 2016

Dual Therapy Treatment Strategies for the Management of Patients Infected with HIV: A Systematic Review of Current Evidence in ARV-Naive or ARV-Experienced, Virologically Suppressed Patients

We reviewed the current literature regarding antiretroviral (ARV)-sparing therapy strategies to determine whether these novel regimens can be considered appropriate alternatives to standard regimens for the initial treatment of ARV-naive patients or as switch therapy for those patients with virologically suppressed HIV infection.

A search for studies related to HIV dual therapy published from January 2000 through April 2014 was performed using Biosis, Derwent Drug File, Embase, International Pharmaceutical Abstracts, Medline, Pascal, SciSearch, and TOXNET databases; seven major trial registries, and the abstracts of major conferences. Using predetermined criteria for inclusion, an expert review committee critically reviewed and qualitatively evaluated all identified trials for efficacy and safety results and potential limitations.

Sixteen studies of dual therapy regimens were critiqued for the ARV-naive population. Studies of a protease inhibitor/ritonavir in combination with the integrase inhibitor raltegravir or the nucleoside reverse transcriptase inhibitor lamivudine provided the most definitive evidence supporting a role for dual therapy. In particular, lopinavir/ritonavir or darunavir/ritonavir combined with raltegravir and lopinavir/ritonavir combined with lamivudine demonstrated noninferiority to standard of care triple therapy after 48 weeks of treatment. Thirteen trials were critiqued in ARV-experienced, virologically suppressed patients. The virologic efficacy outcomes were mixed. Although overall data regarding toxicity are limited, when compared with standard triple therapy, certain dual therapy regimens may offer advantages in renal function, bone mineral density, and limb fat changes; however, some dual combinations may elevate lipid or bilirubin levels.

The potential benefits of dual therapy regimens include reduced toxicity, improved tolerability and adherence, and reduced cost. Although the data reviewed here provide valuable insights into the effectiveness and tolerability of dual therapy regimens, it remains unclear whether these potential benefits can be maintained long-term. Appropriately powered studies with longer follow-up periods are needed to more definitively assess potential toxicity reduction advantages with dual therapy.

Below:  Efficacy of therapy by regimen in A) in ARV-naive, and B) ARV-experienced, virologically suppressed patients

Full article at:

Jean-Guy Baril
Clinique médicale du Quartier latin, Montreal, Quebec, Canada

Jonathan B. Angel
Division of Infectious Diseases, University of Ottawa and the Ottawa Hospital, Ottawa, Ontario, Canada

M. John Gill
Department of Medicine, University of Calgary, Calgary, Alberta, Canada

Joseph Gathe
Therapeutic Concepts, Houston, Texas, United States of America

Pedro Cahn
Fundación Huesped, Buenos Aires, Argentina

Jean van Wyk
AbbVie Inc., North Chicago, Illinois, United States of America

Sharon Walmsley
Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada

Sharon Walmsley
University of Toronto, Toronto, Ontario, Canada

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