Among patients who are HIV-positive, dolutegravir and low-dose efavirenz are more tolerable and effective than standard-dose efavirenz, while dolutegravir offers slight improvement regarding viral suppression efficacy and tolerability, according to a meta-analysis published in the Lancet HIV.

The systematic review was conducted to inform a component of the new World Health Organization (WHO) Consolidated HIV Treatment Guidelines. Steve Kanters, MSc, from the University of British Columbia in Vancouver, and colleagues sought to assess the comparative effectiveness of recommended antiretroviral therapy (ART) regimens for HIV in ART-naive patients. They searched for randomized clinical trials published through July 5, 2015, and compared recommended antiretroviral regimens in treatment-naive adults and adolescents (aged 12 years or older) with HIV. Data were extracted on trial and patient characteristics, as well as the primary outcomes of viral suppression, mortality, AIDS-defining illnesses, discontinuations, discontinuations due to adverse events, and serious adverse events.


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A total of 5,865 citations were identified through database searches and other sources; 34,032 patients were randomly assigned to 161 treatment groups. For viral suppression at 48 weeks, compared with efavirenz, the researchers found that the odds ratio (OR) for viral suppression was 1.87 with dolutegravir and 1.40 with raltegravir. Low-dose efavirenz was similar to all other treatments regarding viral suppression.

Low-dose efavirenz and integrase strand transfer inhibitors “tended to be protective of discontinuations due to adverse events relative to normal-dose efavirenz,” noted the investigators. Dolutegravir (OR, 0.26) had the most protective effect relative to efavirenz in network meta-analyses, followed by low-dose efavirenz (OR, 0.39). The researchers made no conclusions about serious adverse events and noted that low event rates also limited the quality of evidence for mortality and AIDS-defining illnesses.

“The efficacy and safety of ART has substantially improved with the introduction of newer drug classes of antiretrovirals that are now available to patients and HIV care providers,” stated the researchers. “Their improved tolerance could be part of a larger solution to improve retention, which is a challenge, particularly in low-income and middle-income country settings.

“With improved efficacy and safety, and in view of WHO’s public health approach to the ART scale-up, steps to improve ease of care and equitability are needed before these treatments can be appointed as the preferred first-line regimens,” they concluded.


  1. Kanters S, Vitoria M, Doherty M, et al. Comparative efficacy and safety of first-line antiretroviral therapy for the treatment of HIV infection: a systematic review and network meta-analysis. Lancet HIV. 2016 Sep 6. doi: 10.1016/S2352-3018(16)30091-1.