The Conference on Retroviruses and Opportunistic Infections (CROI) returned to Seattle this past week for its 24th meeting. It's the 4th time CROI has been held in Seattle, an excellent city for a meeting of this size, which includes "only" 4200 people. The convention center is pleasant and user-friendly -- big but not cavernous, actually encourages interactions with colleagues -- and there are numerous hotels and restaurants within walking distance, plus more Starbucks per square foot than any place on the planet.
From a content perspective, the big change for CROI 2017 was the return of numerous studies on antiretroviral therapy, studies involving both approved and investigational agents. The last several years, by contrast, had relative dominance of pre-exposure prophylaxis and hepatitis C studies. With PrEP, one had the sense at the meeting that we're now waiting for the next strategies (long-acting injectables, for example).
As for hepatitis C, well that's been all but solved (except for the implementation part). How do you improve on 97%-plus cured. Hooray!
On to the summary, a Really Rapid Review of the most interesting studies at the conference (at least from one perspective, ahem). Links are to the conference website (as usual excellent), abstract #'s are in brackets, and be sure to check out some of the oral presentations here. The list is roughly organized into epidemiology/prevention, treatment, cure, and opportunistic infections. Please tell me what I missed in the comments section.
And, because I was involved in a few of the studies listed below, for full disclosure I've inserted a special Puppy text emoticon to draw attention to that fact. ੯ੁૂ‧̀͡u (Make sure you click on them. Woof.)
New HIV infections in the USA continue to decline . From 2008-2014, the annual number of HIV infections dropped 3.6% per year, and the percentage of persons with undiagnosed infection declined at around the same rate. That's the good news. The bad news is that new infections continue to increase in young black and Hispanic men who have sex with men. For the record, we're down to 37,600 cases/year in the USA, and I expect this will continue to drop since PrEP use didn't really start until 2014.
In treatment-naive patients, the investigational NNRTI doravirine was non-inferior to boosted darunavir [45LB]. 84% vs 80% < 50/copies at week 48, with a trend toward doravirine being better with very high (>500,000) baseline HIV RNA. Favorable aspects of this treatment included once-daily dosing, few CNS side effects, and a better metabolic profile that darunavir. Only 1 of 364 doravirine-treated patients developed resistance, a low number for NNRTI strategy; none did in the darunavir arm. And note the abbreviations -- "DOR" vs "DRV"! A coforumulated DOR/TDF/3TC tablet is in development. ੯ੁૂ‧̀͡u
TAF superior to TDF after 144 weeks . The most important safety finding is that 0/866 on TAF vs 12 (11 if you remove "bladder spasm")/867 on TDF developed clinically significant renal issues, a difference that is highly statistically significant. ੯ੁૂ‧̀͡u
Should we be sending baseline integrase genotypes before starting therapy ? Based on this modeling study, the answer is a resounding NO, for three reasons: 1) the prevalence of transmitted integrase resistance is fortunately still very low (see above); 2) DTG-based regimens will likely succeed even when resistance to first-generation INSTIs is present; and 3) even if virologic failure occurs, it will delay use of a salvage regimen only briefly. ੯ੁૂ‧̀͡u
Many novel drugs in various stages of development. These include (deep breath) ibalizumab [449LB] (anti-CD4 monoclonal antibody), PRO140  (different humanized anti-CD4 monoclonal antibody), UB-421 [450LB] (yet another monoclonal antibody that blocks viral entry), elsulfavirine [452LB] (NNRTI with 8-day half-life), MK-8591  (potent and very long acting NRTI), GS-PI1  (an unboosted once-daily protease inhibitor), GS-9131  (NRTI with activity against essentially all NRTI-resistant isolates), and GS-CA1  (capsid inhibitor that in vitro is more potent than any other antiretroviral agents). Wow that's a lot!
Does ART with integrase inhibitors increase the risk of immune reconstitution inflammatory syndrome (IRIS)? The answer is yes, based on two studies conducted in non-TB endemic regions ( and ). As DTG-based regimens are increasingly adopted world-wide, we should expect IRIS incidence to increase. And count me in the group that thinks this is a good thing -- IRIS is a marker for faster virologic response and immunologic recovery. (Not everyone agrees.)
If you're interested in watching webcasts of interesting plenary or symposium talks, I can strongly recommend Demetre Daskalakis on ending the HIV epidemic in NYC (he has more energy than the rest of the 4199 CROI attendees combined), Charlie Flexner on long-acting ART (he dispelled several "myths"), and Carl June on how cellular treatments of cancer might apply to the HIV cure effort.
One caveat to this last talk is that Dr. June neglected to mention that there's huge difference in acceptable risk between someone with refractory metastatic cancer versus stable HIV infection. So I'm mentioning it for him.
See you at next year's CROI in Boston!
Paul E. Sax, M.D., is director of the HIV Program and Division of Infectious Diseases at Brigham and Women's Hospital in Boston.
This article was provided by NEJM Journal Watch. NEJM Journal Watch is a publication of the Massachusetts Medical Society.
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