Switch Frenzy: A Top HIV Clinical Development of 2016

Options breed choice, and as safer, better tolerated and more convenient antiretrovirals (ARV) have become available, they have tempted us to manipulate even effective HIV regimens. With a critical mass of such options at hand, we are increasingly discussing the merits of "simplification" with our patients -- trading in old, stodgy regimens for sleek new models. It could be argued that the current switch-mania started in earnest with co-formulation of the pharmacological booster cobicistat (Tybost) with darunavir (Prezista), and with atazanavir (Reyataz), as darunavir/cobicistat (Prezcobix) and atazanavir/cobicistat (Evotaz) respectively. This allowed us to gleefully abandon ritonavir (Norvir) and end a marriage that we had been seeking to leave for years. Even the diehards holding on to their beloved four-pill-a-day lopinavir/ritonavir (Kaletra) finally broke down and accepted a single tablet in their stead -- and their bowels have thanked them ever since. But the availability of tenofovir alafenamide fumarate (TAF, Vemlidy) in a slew of co-formulations has really gotten the switch party hopping.

The replacement of tenofovir disoproxil fumarate (TDF, Viread) with TAF wherever TDF is found grants a wish high on an HIV provider's list. A TDF-like drug with better renal and bone safety means we do not have to obsess about creatinine creep or T scores. Taking up less physical space helps clinch the deal for lateral swap-outs of TAF for TDF, with only the looming specter of prior authorization standing in the way. Switching, though, is not just about TAF. The single tablet of abacavir/lamivudine/dolutegravir (Triumeq) has been useful for those of the guanosine analogue persuasion, and a number of recent studies demonstrate more novel and radical modifications to successful regimens that can be accomplished, providing more convenience with less medicine.

Major recent studies of virologically suppressed patients whose antiretroviral therapy (ART) was switched are listed in the table.

The Bottom Line

Messing with successful ART, once eschewed as playing cowboy/girl, is now required as part of good care. With improvements in ART, I look at each patient's regimen to determine whether it is optimal. For example, those who initiated ART a decade ago may have been started on a boosted protease inhibitor (PI) regimen despite having no baseline drug resistance. It is unlikely that, were they to enter care today, most of these patients would leave with a prescription for darunavir or atazanavir. As these patients' age increases, so too does their risk of drug interactions and polypharmacy. Therefore, a discussion regarding regimen revamping is warranted. For others, longer-term toxicity, such as elevated lipids and osteopenia, or even persistent low-level intolerability that was just coped with, can be addressed through a swap.

What switch studies also tell us is that maintaining suppression of HIV is easier than achieving an undetectable viral load, and that even some forms of very minimal ART can keep a lid on HIV replication. This is nicely illustrated in the LATTE-2 trial, in which two agents with low-to-moderate barriers to drug resistance were able to maintain viral suppression following more standard induction therapy.

It is remarkable to stand back and reflect that, for this once fatal and contagious viral infection that took so many people, we now have treatment options that are more potent and safer than all our old handful-of-M&Ms cocktails yet no bigger than a Tic Tac or baby aspirin. Treatment will continue to advance, as described below. As it does, we should be mindful of how far we have come and that we are still dealing with a virus that continues to hurt and kill.

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.