As 2019 draws to a close, TheBodyPro takes stock of the year's most noteworthy developments in HIV. And not just any developments: We're looking specifically at those with the largest impact for people who provide HIV care and services in the U.S. In this series, veteran clinician-researcher David Alain Wohl, M.D., guides us through the new research and other important moments of 2019 that have the greatest potential to alter the HIV clinical landscape in the months and years to come.
Islatravir (formerly MK-8591 and, before that, EFdA) is an NRTTI. That is not a typo: It is a nucleoside reverse transcriptase translocation inhibitor, an adenosine analogue with a novel one-two punch mechanism that confers a very high barrier to resistance. It is also really potent in miniscule amounts for long periods of time.
These properties can certainly get an imagination going. But, for now, the clinical trial data on islatravir have been mostly limited to daily administration with doravirine (Pifeltro), an NNRTI made by the same company developing islatravir.
At the IAS Conference on HIV Science this summer, the results of a phase II, dose-ranging study of islatravir plus doravirine in treatment-naive participants were presented. Four arms were included: three featured differing dosages of islatravir, and the fourth served as a control using doravirine plus emtricitabine/tenofovir disoproxil fumarate (FTC/TDF, Truvada). Each arm had roughly 30 participants.
In the first part of the study, the islatravir plus doravirine arms also had lamivudine (3TC, Epivir) on board until week 24, at which time participants with an undetectable viral load dropped the 3TC and coasted along with the other two drugs. All but a handful made it to the part of the study in which the 3TC was dropped.
At 24 weeks post-simplification, 1 or 2 people in each of the four study arms had virologic failure, albeit with plasma HIV RNA levels less than 80 copies/mL; none met criteria for resistance testing. Overall, islatravir plus doravirine was well tolerated.
The Bottom Line on Islatravir's Potential as a Future Antiretroviral
Islatravir is so potent that for it to be taken with doravirine once a day, the NRTTI has to be lightly sprayed onto the doravirine tablet. This is clearly an antiretroviral not built for daily administration. But then what is it destined for? Is it only to be Starsky to doravirine's Hutch? Or will islatravir become a once-weekly oral med without an obvious dance partner? Data have been presented on its potential as an implantable for long-term treatment or prevention. Is that where this is headed?
Is the answer all of the above?
The development pathway(s) of this interesting agent will be important to watch; it is hard to predict given its wide potential. At the same time, it is not the only promising novel treatment/prevention antiretroviral; while careful and calibrated study of any new agent is important, its relevance can decay if others get there first.