Abstract
ObjectiveWe 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.MethodsA 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 s, 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.ResultsSixteen 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.ConclusionsThe 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.
Highlights
In the late 1980s/early 1990s, the sequential use of nucleoside reverse transcriptase inhibitor (NRTI) monotherapy and dual therapies in patients with HIV infection rapidly led to treatment failure because of the emergence of resistance-associated mutations [1]
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
Current treatment guidelines continue the convention of preferred combination antiretroviral therapy (cART) based on combining a dual NRTI backbone with a third “anchor” agent, such as a ritonavir (r)-boosted protease inhibitor (PI; PI/r), a non-nucleoside reverse transcriptase inhibitor (NNRTI), or an integrase inhibitor [2,3,4]
Summary
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. Data Availability Statement: All data can be found in the manuscript
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