Top 10 HIV Clinical Developments of 2012

Simplify

A review of:

Frank J. Palella Jr., et al. SPIRIT Study: switching to Emtricitabine/Rilpivirine/Tenofovir DF (FTC/RPV/TDF) single-tablet regimen (STR) from a Ritonavir-boosted protease inhibitor and two nucleoside reverse transcriptase inhibitors (NRTIs) maintains HIV suppression and improves serum lipids in HIV-1 infected subjects at week 24. 19th International AIDS Conference; Washington, DC; July 22-27, 2012; Abstract TUAB0104.

Calvin J. Cohen, et al. Switching from efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) single tablet regimen (STR) to emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) STR in virologically suppressed, HIV-1 infected subjects. 13th European AIDS Conference; Belgrade; 2011; Abstract LBPS10/4.

I have never been one to mess much with success. In the past, I have played with the HIV therapies of patients doing well, and on more than a few occasions I have been burned. The viral load may go up despite the greater convenience and potency of the newer regimen. Maybe there is a pharmacy mixup, or the patient -- despite instructions that include pictures of suns and moons -- misunderstands and takes the medication wrong. I thought folks who did stuff like induction therapy followed by more compact maintenance regimens were meshuga, or had patient populations as obedient as border collies.

But I am now getting more adventurous. Mostly, I have had no choice: I could not stand by while patients on more cumbersome regimens labored on with twice-a-day dosing and a fistful of meds, while those entering care could walk out of their pharmacy with a three-month supply of HIV therapy that could fit in a Flintstones vitamin bottle. Plus there were the low-rumble side effects. So, out went the AZT/3TC. And those lopinavir/ritonavir refills? Replaced with once-a-day PI therapies. And it was good.

This year we have seen simplification go to a new level -- and, I must admit, I am hooked. Several studies show us that, in addition to moving from twice-a-day to once-a-day PI therapies, we can also take advantage of sleek new formulations for many (but certainly not all) of our patients.

For example, the SPIRIT study has, so far, showed us that taking folks on stable boosted PI-based therapies and switching them to TDF/FTC/rilpivirine can work. At 24 weeks, 94% of those who switched to TDF/FTC/rilpivirine had a viral load below 50 copies/mL compared to 90% of those who stayed on their entry regimen (achieving non-inferiority). Historic baseline viral load (i.e., before initiating the entry regimen) above or below 100,000 copies/mL did not influence the efficacy results, indicating that pre-treatment viral load (a prickly problem in the ECHO Trial) is not an issue when switching stably suppressed patients to this regimen. As expected, gastrointestinal symptoms and lipids improved with the switch from PI therapy. Another study looked at a switch to the same regimen from TDF/FTC/efavirenz, with similar reassuring results.

Now, these swaps are not for everyone, and we must recall our oath: primum non nocere. Those with, or likely to have, significant NNRTI mutations archived away -- as well as those who are either not adherent or on proton pump inhibitor therapies -- are not candidates for this particular switch.

With the Quad, we have an additional switch option, but less data to guide us. Again, common sense is advised. New drugs come with new risks for side effects, and drug interactions make combining the Quad with other HIV meds a setup for tears.

But, there will be more drugs to come. The availability of cobicistat as a stand-alone tablet in early 2013 will shake things up at the pharmacy. Ditto for the release of dolutegravir, a once-a-day integrase inhibitor. Coformulations will soon abound, making for even more seductive switches. It is all enough to make this reluctant switcher more of a cowboy when it comes to messing with my patient's meds.