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March 15th, 2012
CROI 2012 Really Rapid Review — with CROI 2013 Dates!
Some highly subjective highlights — a Really Rapid Review™– from this year’s Number One Greatest Super Scientific HIV Conference, the 19th Conference on Retroviruses and Opportunistic Infections (CROI), which ended last week in Seattle:
- Need more evidence that maintaining a CD4 cell count > 500 is beneficial? This compelling analysis from the SMART and ESPRIT studies found that among virologically suppressed, ART-treated subjects with CD4 > 500, there was no evidence of a higher mortality rate compared to the general population (standardized mortality ratio, 1.0). Not so for CD4s 350-500, by the way.
- Of course, most patients don’t start ART until their CD4 is below 500, but as shown in this global view, starting CD4s have improved dramatically since 2002 — pretty much everywhere. Despite this improvement, the only country where the average starting CD4 is > 300 is the USA. Lots of work still to do here.
- Related: the San Francisco policy of recommending ART for all with HIV as a public health measure has substantially raised the CD4 at treatment initiation in that city. Suspect this will eventually turn out the be the case nationally as well, now that treatment as prevention has become more broadly accepted.
- Based on this CDC study, only 44% of patients diagnosed with HIV in the United States are receiving care. We’ve heard this story before, but it’s still a shock — and worth remembering that the number of people diagnosed with HIV and not in care greatly exceeds those who are not diagnosed. How to bring the 56% back into care is obviously an urgent challenge for us.
- Why did the FEM-PrEP study fail to show protection of TDF/FTC? As suspected, poor adherence was the answer — detectable drug levels were found in fewer than 50% of infected women assigned to active drug (mystery solved). These results reinforce my gut feeling about PrEP — namely, that it will be a niche intervention, not one that can be broadly implemented.
- Not many clinical trials of ART at this CROI, but the meeting featured results of two major trials on the coformulated TDF/FTC/elvitegravir/cobicistat — or “quad” — single-pill treatment. These studies demonstrated it was non-inferior to recommended regimens – TDF/FTC/EFV and TDF/FTC/ATV/r. The “quad” (what will it ultimately be called?) has been submitted for FDA review. (Disclosure: I presented the results on the former.)
- 96-week coverage of phase II data on dolutegravir — and it still looks really good. Phase III data later this year?
- D:A:D study on cardiovascular risk of atazanavir? “No worries,” as people of a certain age (e.g., all our ID fellows) like to say. And let me be the first (or next) person to question the use of colons between letters in “D:A:D” — why? And did they realize it would make it harder to search?
- D:A:D again, this time on renal issues. The culprits? TDF, ATV/r, and LPV/r. We’ve heard this before, with EuroSIDA (you’ve got to figure that some EuroSIDA patients are also in D:A:D) and other cohorts. Bottom line is that in older, medically complex patients with other co-morbid risk factors for renal disease, the TDF + boosted PI regimen is the one to monitor closely.
- The tenofovir pro-drug 7340 has plenty of antiviral activity. Plus, the low doses will allow novel co-formulations, including the single-pill combination of boosted PI 7340/FTC/DRV/cobi. Will it be safer than TDF? Studies are ongoing to answer this question.
- Treatment with abacavir (or efavirenz, at least initially) increases CRP. Grace McComsey, a top-notch clinical researcher, led this study (I’m a co-investigator), and we were surprised by the results. Why? Because other randomized studies (notably STEAL and HEAT) found nothing — though ACTG 5095 (in which all patients received ABC or EFV or both) did find that CRP went up. Clinical significance uncertain, of course, but it raises again the abacavir-cardiovascular risk issue, as does this in vitro study.
- More on inflammatory/immune activation/coagulation biomarkers: Switching a boosted PI to raltegravir improves these biomarkers. Again, clinical relevance? You decide.
- Remarkable presentation by Steve Grinspoon on levels of arterial inflammation — using PET scans — in patients with virologic suppression and no cardiovascular disease. The key result is that HIV patients have comparable inflammation to those with established atherosclerotic disease, significantly greater than HIV negative controls matched by Framingham risk. Incredible pictures, if you have time for the webcast.
- Can a drug that stimulates the latent HIV reservoir be the first step to cure? Maybe — though my impression watching this fascinating scientific presentation is that we’re still a long, Long, LONG way from actually using such a strategy in practice.
- Zoster vaccine for patients with HIV looks safe and immunogenic. Now the tough questions: Who do we give it to? All with HIV? Just those over 60? Over 50? Those with virologic suppression? Over a certain CD4 threshold? This is why we have vaccine guideline panels.
- Adding boceprevir or telaprevir to peg IF/RBV improves 12-week SVR rates in co-infected patients. No surprises here, but good to see.
- Those annoying boceprevir drug-drug interactions with boosted PIs didn’t seem to have much of an effect on treatment response — but still one can’t feel too comfortable about using boceprevir with boosted PIs anyway.
- Levels of what is likely the next HCV PI — the once-daily TMC435 — are dramatically reduced by efavirenz. Fortunately, rilpivirine, raltegravir, and tenofovir are okay. Since TMC435 is a big-time cyp3A4 substrate, drug-interactions studies with boosted PIs are critical.
- By contrast, the HCV NS5A inhibitor BMS-790052 — which is now called daclatasvir — has quite predictable interactions, at least with efavirenz and atazanavir/r, though some dose adjustment will be required.
- Interferon-free regimen in HCV monoinfected patients: 12 weeks of the nucleotide 7977 + ribivirin has looked extraordinary in genotype 2 and 3 patients. How about in genotype 1 null-responders? Initial responses (kinetics) were terrific, but relapse rates high, as reported previously in a press release. Seems a longer treatment course, or one additional drug, will be required for these difficult-to-treat patients. Still — an all-oral therapy without interferon? Music to my ears. Results of this 12-week combination in treatment-naive genotype 1 patients are eagerly awaited, as are the results of 7977 + daclatasvir.
Now for the non-scientific part:
- Dates of next year’s conference (March 2-8 2013, see above) announced. Hurray! And the new CROI website design is vastly improved, much more readable, with easier-to-find abstracts, webcasts, etc.
- Second time the conference has been in Seattle, last time 10 years ago. A beautiful city with great food and coffee everywhere — but the streets seem so empty and spread out compared to congested Boston, NYC, Philadelphia, Washington DC, etc!
- Conference center perfect for this meeting, with spacious meeting rooms and many hotels close by.
- During the large scientific sessions, a woman walked up and down the aisles astutely looking at the participants, periodically writing something in a notebook. What was she doing? Trying to catch people violating the “No Photos” policy? (Impossible.) Getting some ambulatory exercise in an unlikely location? Taking food orders? (“I’ll have a hot dog and a beer, thanks very much.”) Thinking about MIP-1 alpha? (I love saying that, even though I have no idea what it is.) Nope — she was counting the audience. There must be a better way.
- Backpacks this year for the abstract book. I generally like them, but I’ve stopped using the conference bags at the actual conference ever since someone walked away with mine thinking it was his — only to discover the error when he boarded his flight to Dallas. “Hi Paul, you know that laptop you’ve been missing …”
Time to rename this conference, “Conference on Retroviruses, Non-HIV Complications, and Hepatitis”? Maybe.