It has been well over a year since the concept of using dolutegravir (Tivicay) plus lamivudine (Epivir) as initial antiretroviral therapy (ART) was introduced to the world, and for some of us it is still a tough idea to get used to. Decades of indoctrination to hit hard with a three- or four-drug strategy have been difficult to shake. In addition, initial treatment with these two agents requires faith in the potency and resistance barrier of dolutegravir, which was slow at first but is growing.
The fate of this ART-lite strategy has been riding on a small study of 20 treatment-naïve patients in Argentina: the PADDLE study. Last year, the study team showed us remarkably brisk responses among those enrolled, with all participants achieving an undetectable viral load after eight weeks of therapy.
This summer, week 48 data were presented, and 18 of the 20 participants had maintained viral suppression. Of the two who were not suppressed, one was a suicide and the other, who had an HIV RNA level >100,000 copies/mL at screening, experienced virologic failure but re-suppressed on dolutegravir plus lamivudine without intensification or switch.
The Bottom Line
The PADDLE study is not quite the HIV therapeutics equivalent of landing a human on Mars. Rather, it's more like the small rover that touched down on the planet and kicked up red dust. Gusty and going where no ART has gone before, PADDLE has pushed our boundaries and imagination. For sure, the features of dolutegravir are essential to this regimen's simplicity, underscoring the need to consider not only antiretroviral quantity but also quality. Larger studies, of course, will need to confirm the PADDLE results before we embrace this and similar two-drug regimens, and these are underway -- but already what we have seen opens a brave new world where potent therapy could be cheaper and certainly safer than some of the big-guns we are now deploying.
What are some other top clinical developments of 2016? Read more of Dr. Wohl's picks.
David Alain Wohl, M.D., is a professor in the Division of Infectious Diseases at the University of North Carolina at Chapel Hill, director of the North Carolina AIDS Training and Education Center and site leader of the University of North Carolina Chapel Hill AIDS Clinical Research Site.