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An ongoing dialogue on HIV/AIDS, infectious diseases,
March 10th, 2014
One of our fellows asked me this AM when I was posting a RRR (Really Rapid Review™) of CROI 2014, and my response was to clear my throat, make some vague excuses, and curse the respiratory viruses that seem as perpetual as the cold weather this year.
It’s in the works, promise — but in the meantime, did you see the New York Times Editorial Page yesterday? Under the title, “Great Hope for Babies With H.I.V.”, the editorial cites the case reported at CROI last week of a second baby possibly “cured” of HIV after starting ART soon after birth.
Why do I use the word possibly and put the word “cured” in quotes? From the Times:
The baby, now 9 months old, has no signs of virus in her blood that can be detected by the most highly sophisticated tests. She cannot be considered “cured” or even “in remission” because she is still taking the drugs.
Yes, that bolding is mine.
Isn’t it incredible how much attention this case has received, despite that oh-so-important fact?
Prediction: One day we will be treating all babies born to HIV-infected mothers who are not receiving ART with combination therapy, at least initially.
But until we have more than a few of these anecdotes — especially those that have stopped treatment and not experienced viral rebound — let’s calm down already.
February 27th, 2014
From the CROI website:
We are pleased to announce that CROI 2015 has been scheduled!
Location: Seattle, WA, USA
Dates: Monday, February 23 to Thursday, February 26, 2015
Details and schedules: Will be posted in early summer 2014
Love their exclamation point. Yahoo indeed! Kudos to the conference organizers for getting the dates out early this year.
Meanwhile, for those of you planning to attend next week’s conference in Boston, I bring you this bit of chilling news. On the plus side, the whole convention center is interconnected with most of the conference hotels, or just a short walk away.
But for some travel anxiety, especially for those planning on arriving Monday, here’s a good place to start.
Hey, since we can’t change the weather, might as well complain about it.
February 23rd, 2014
The proportion of participants with a viral load below 200 copies per mL at week 48 was 94·1% for efavirenz 400 mg and 92·2% for 600 mg (difference 1·85%, 95% CI −2·1 to 5·79). CD4 T-cell counts at week 48 were significantly higher for the 400 mg group than for the 600 mg group (mean difference 25 cells per μL, 95% CI 6—44; p=0·01).
The 400 mg dose was better tolerated, too. For the record, these data are far more convincing than prior dose-reducing strategies with other antiretrovirals (stavudine, zidovudine, ritonavir come to mind). The results of the study were no doubt outstanding.
So these results have huge implications internationally, where efavirenz-based regimens are the default first-line choice for essentially all treatment naive patients. A lower dose will make treatment cheaper, coformulations easier, the pills smaller, and the sun will shine brighter, too.
Here in the USA? As of today, these data are of limited value, and here’s why:
- As first-line therapy, efavirenz is overwhelmingly given as part of coformulated TDF/FTC/EFV (Atripla), which as you know includes 600 mg. Decreasing to 400 mg means increasing the number of pills, both because this splits up the coformulation and because EFV comes in 200 mg capsules.
- If we’re after similar efficacy and better tolerability, there are several other non-efavirenz first-line options that do the same thing, and are easy to take, too — notably TDF/FTC/rilpivirine, TDF/FTC/elvitegravir/cobicistat, and TDF/FTC or ABC/3TC + dolutegravir.
- Until a generic version of efavirenz is approved, there’s not all that much benefit from a cost perspective — though I do hear that TDF/FTC/EFV pricing has been going up.
- The 400 mg dose is not FDA approved for treatment.
So for now, I stick with my opinion about the waning of the efavirenz era – a drug which has been on an extraordinary run dating back its approval in 1998.
However, if the 400 mg dose does get FDA approved, and if there are future coformulations with EFV using this dose, and if these data are confirmed to lower toxicity while maintaining virologic efficacy, then efavirenz might make a comeback.
But it’s a long shot.
February 13th, 2014
It’s safe to say that most of the perspectives on Derek Jeter’s retiring from baseball will not be written by ID doctors, so let me seize the opportunity. And since it’s always risky to dwell on players from a certain team while living in Boston — I have friends for whom a central component of their identity is Hatred for the Yankees — this will be less about Jeter’s retirement and more about how the news made me feel.
In a word — old.
You see, I was at the game when Jeter hit his first major league home run — opening day in Cleveland, April 2 1996, weather a balmy 38 degrees. That was a remarkable year on many fronts, both personal and professional, as my daughter was born, Boston experienced its snowiest winter ever, HIV became suddenly treatable (How About That!), and well, the Yankees won the World Series, in part thanks to their rookie shortstop.
So what was it like to be an ID doctor 18 years ago? Let’s take a look at the Way Back Machine, and I caution those of a certain age that this is guaranteed to make you feel downright ancient:
- You were still doing gram stains in a hospital lab that was on the patient floors.
- Aminoglycosides were a regular part of “triples” — you know, amp, gent, clinda.
- Amphotericin B had no liposomal formulation, and was co-administered with all kinds of magic potions (diphenhydramine, meperidine, hydrocortisone, pixie dust) to make it better tolerated.
- Erythromycin was used as an actual antibiotic — sometimes even intravenously.
- Ritonavir was used as an actual antiretroviral, and the dose was 600 mg twice daily (yes kids, you read that right).
- Severe C diff was extremely uncommon, and almost never happened in an outpatient.
- Community-acquired MRSA might be presented at an ID case conference given its rarity.
- There was hardly any vancomycin-resistant enterococcus — good thing, too, since there was no linezolid.
- If you wanted a quinolone to treat community-acquired pneumonia, you were out of luck — levofloxacin wasn’t approved until December 1996.
- If your patient needed indinavir, he/she needed to get it from a single mail-order pharmacy called “Statscript.”
- No echinocandins, oseltamivir, tigecycline, cefepime, daptomycin.
- Some days you spent half of your time on rounds looking for X-rays. These were actual films, viewed on a light box — or, if you were in the radiology department, on those noisy contraptions that rotated light boxes. (What did they do with those things?)
- These numbers/letters meant nothing: HLA-B*5701, HPTN 052, K65R, E138K, CCR5, CXCR4, Q80K, PrEP, TDF.
- Target vancomycin trough level: 5-10.
- Some people were actually taking ddC — which, despite the medical “information” from Dallas Buyers Club, was a pretty horrible medication.
- Best place for drug information was often the “PDR”. If you’ve never heard of it, don’t ask.
I could go on like this all day, but why not finish on a high note?
February 5th, 2014
- Long piece in the New York Review of Books — all doctors subscribe, of course — by Arnold (Bud) Relman, describing his experience as a 90-year-old who survives a fall. Riveting, moving, and typically curmudgeonly stuff from the ex-Editor-in-Chief of the New England Journal of Medicine. But this line deserves emphasis: “During the day I was visited on rounds by teams of physicians. They spent most of their time outside my room, studying and discussing the data on their mobile computers.“
- How do interns spend their time in the era of electronic medical records? Let’s look at the data — “Interns spent 12% of their time in direct patient care, 64% in indirect patient care, 15% in educational activities, and 9 % in miscellaneous activities. Computer use occupied 40% of interns’ time.“
- Or, for a more poetic description, read Abraham Verghese’s brilliant description of the “iPatient”: “On my first day as an attending physician in a new hospital, I found my house staff and students in the team room, a snug bunker filled with glowing monitors … the demands of charting in the electronic medical record (EMR), moving patients through the system, and respecting work-hour limits led residents to spend an astonishing amount of time in front of the monitor.”
- One of my colleagues in General Medicine, Jeff Linder (who parenthetically does some nice ID-related work too), found that the number one barrier to use of electronic medical records during an outpatient visit was loss of eye contact with patients — which does not surprise me a bit.
- The solution? Get a medical scribe to join you in the exam room so you can actually look at the patient while taking the history. This is the money quote from this wonderful New York Times piece: “For decades, physicians pinned their hopes on computers to help them manage the overwhelming demands of office visits. Instead, electronic health records have become a disease in need of a cure, as physicians do their best to diagnose and treat patients while continuously feeding the data-hungry computer.” FYI, after reading this piece, every single colleague of mine wants a scribe now.
- The hospital periodically receives patient surveys from these guys. The leading complaint, of course, is parking — this is Boston, after all. But in the Top Five Complaints is also something along the lines of, “That doctor seemed more interested in the computer than in me.”
- Department of Oversharing: I recently saw a doctor for an eye issue, and he was very competent and nice. He spent 90% of the visit (aside from the exam part) entering what I was telling him into his electronic medical record. The computer was situated far to his left, so he was facing away from me the entire time; I could have put on this hat, he never would have noticed.
OK, so I’m nearly done. Except to comment that we used to be able to take notes while facing our patients, and that this allowed a kind of organic eye contact that seems all but impossible in the electronic medical record era. Note that I won my 8th Grade Typing Competition (72 words/minute, thank you), so don’t blame inadequate keyboarding skills.
And since this started with a dog (dare you to click on the image above) and eye contact, I might as well say that they run rings around both cats and us electronic medical records-obsessed doctors when it comes to this skill.
Enjoy more dog magic in this wonderful documentary:
January 30th, 2014
Older person, many medical problems. Probably is on hemodialysis, with the vascular surgeons having some difficulty with access. There’s diabetes, of course, and cardiovascular disease, and oh yeah, a mechanical aortic valve that’s around 10 years old. Some toes are missing from prior surgical treatment of osteomyelitis.
Now? Fever and mental status changes have brought him/her to the hospital, and 100% of the umpteen blood cultures done since admission are positive for MRSA. They remain positive even though the MIC to vancomycin is 1.0 and the trough concentration of the drug is 18.
Since starting on vancomycin, the patient has improved somewhat, but continues to have fevers and, yes, positive blood cultures. Lots of them — it’s been days. Vancomycin MIC is checked again, and it remains unchanged. Maybe even it’s 0.5 this time. An exhaustive search for a removable focus of infection has yielded nothing — no abscess, no valvular vegetations/root abscess, no spinal osteomyelitis, clots. A cardiac surgeon has been consulted, and passes on the opportunity to replace the valve, thank you very much. The dialysis AV fistula is functioning, for now, but is not red or draining.
So the question is this:
With persistent MRSA bacteremia despite “appropriate” vancomycin therapy, should the antibiotics be changed?
Lots of options out there. Linezolid. Daptomycin. Ceftaroline (off label, of course). Combination therapy, with the idea that more should be better, naturally. You could add gentamicin (really?), or rifampin (biofilms!), or do a vancomycin/beta-lactam combination.
Let’s hear from you — vote on these options (as I said, there are lots of them this time), then comment away.
January 21st, 2014
OK, gang. You did such a bang-up job on Question #1 that I can’t resist getting another consult.
Here’s the case: Patient in intensive care, has been there for some time — at least a week, probably weeks. Perhaps he/she had surgery (especially abdominal surgery) that didn’t go well, or has severe cardiovascular disease, or multiple trauma from an MVA, or suffered a large intracerebral hemorrhage or stroke. There have been several antibiotic “courses” directed at fevers of too many origins.
Each day you see the patient, and each day there’s a fever — generally 100.5 or a bit higher. Normotensive. Nothing obvious on exam. Labs show a WBC of 11-15 — in other words, not normal but not horribly abnormal either. LFTs are fine.
All bacterial cultures are unrevealing. Several sputum cultures, however, are positive for Candida; a urine culture (from a foley catheter) is positive also. If the patient has an abdominal drain, it has a few yeast in there too. Imaging is non-specifically abnormal — some pleural effusions, but no obvious pneumonia; CT shows no abscess.
So here’s the question:
Should patients in the ICU be given systemic treatment for Candida spp. if they have positive cultures from multiple sites other than blood?
Or just go ahead and vote, and have at it in the comments section.
January 15th, 2014
Unanswerable Questions in Infectious Diseases: The Abdominal Collection and Duration of Antibiotic Therapy
Each time I attend on the inpatient service, the number of questions for which we just don’t have a definitive answer continues to amaze me. And here’s the most remarkable part — many of them come up all the time!
In that spirit, I will post a series of these quandaries, and you, the brilliant readers, will offer your answers or, barring a definitive answer, your individual approach.
Let’s start with this one:
How long should we continue antibiotics in someone with infected abdominal collection and a percutaneous drain?
You know the situation — peritonitis from perforation, or diverticular abscess, or a surgical mishap, and now the interventional radiologists have kindly placed a drain into the infected collection. (Or, more commonly, multiple drains into the multiple collections.) The patient, once critically ill, is improving — albeit slowly — and the resident, surgical PA, and surgeon all want to know the answer to the above question.
Low grade fevers — 99.5 F or so — continue. There might be an ongoing anastomotic leak, there might not. There is no plan for more surgery. White blood cell count is down from 25K to 15K. Platelets are slowly rising.
Yes, this is a specific variant on the age-old “How long should we treat?” question. I’ve opined on this before, but now we’re getting specific. These IDSA guidelines say “4-7 days,” but that implies rapid source control, no ongoing leak, everything going smoothly.
(And these smooth-sailing cases rarely trigger an ID consult.)
So what do you do in this particular situation? Please vote and comment — especially if you don’t like any of these answers!
January 2nd, 2014
- Interesting, balanced piece in the New York Times about the slow uptake for PrEP, in particular among gay men. This caught my eye: “Certainly, fewer people have tried PrEP than many experts had anticipated.” I wonder who those experts were? Seems this always was going to be a relatively niche intervention.
- Fascinating editorial in the latest New England Journal of Medicine about preserving antibiotics, which includes this amazing statistic: Almost 80% of antibiotic use in the United States is for livestock. And here’s a great slide for your next talk on antibiotic resistance. Don’t those cows worry about upsetting their microbiome?
- Speaking of antibiotic resistance, I neglected to highlight this extraordinary CDC report on Antibiotic Resistant Threats when it first came out this year. The top three, with threat levels of “Urgent,” are C. difficile, Carbapenem-resistant Enterobacteriaceae (look at this chilling map), and Drug-resistant Neisseria gonorrhoeae. Sounds about right — but I’d have substituted MRSA for the last one — way greater clinical impact. MRSA’s threat level, by the way, is listed as “Serious.”
- Is some chronic low back pain caused by bacterial infection? According to this paper, and this randomized trial of amox-clav, the answer is clearly yes! An editorial rightly describes the implications of these studies for spine surgeons and pain specialists — never mind patients — as “momentous.” Yes, these are the winners of The Most Surprising Studies in ID, 2013. Confirmation of these findings by other investigators eagerly awaited. (What an understatement.)
- These three deaths from Lyme carditis are most worrisome — the patients were really young (26–38 years old), and though two of three had some pre-existing cardiac disease, they were overall pretty healthy. Fortunately, a review of 20,000 pathology specimens at a tissue bank did not find any additional cases, suggesting that Lyme carditis as a cause of death is rare indeed. Still, wouldn’t it be great if the Lyme vaccine for humans were available again?
- As more HIV drugs become generic, this should mean cost-savings, right? Not always, according to this remarkable (and disheartening) report. Lesson: If you don’t like the price of a generic drug, it pays to shop around for the best price. And if you live near a Costco Pharmacy, give them a try, even if you’re not a member — their pharmacies are available to all, with consistently low prices.
- SPOILER ALERT — if you haven’t seen the movie Philomena, just skip to the trailer below and read no further. But if you’re on the fence, you must see it, since it could have been the best film of 2013 — entertaining, well-acted, funny, heartbreaking. Just great. I cite it here on this site because one major plot turn occurs when the main character’s long-lost son is found to have died of AIDS — and though she is naturally very sad, her response was completely non-judgmental in a very non-Hollywood way. I was expecting the typical moral outrage, and was pleasantly surprised that it never came.
Stay warm, everyone, and Happy New Year!
December 24th, 2013
At the IDSA meeting in 2012, John Bartlett gave a lecture called, “Infectious Diseases Update for the HIV Provider” — what a great title — which was, as usual, information-packed, practical, well-referenced, and just plain fun. It also occurred to me at the time that there is probably no other person on the planet who could give this lecture, and made me vow to write something about what a treat it is chatting with John at ID meetings or other events.
For those of you who don’t keep up with the celebrities in Infectious Diseases, John was Chief of the Division of Infectious Diseases at Johns Hopkins for 26 years, stepping down in 2006. He was also the Co-Chair and one of the founding members of the Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents, a position that we’ve just learned he is leaving this year.
But John is much, much more than these titles. John is the true Renaissance Man of Infectious Diseases, the person in our field who somehow seems to know something — and usually a lot of something — about everything.
You want some examples? How many ID doctors are true experts in all of the following distinct topics?
- Clostridium difficile
- Respiratory tract infections
- Antimicrobial resistance
- Anaerobic pulmonary infections
I’m fairly certain the answer is “Just one — John Bartlett”, and I’m no doubt doing him a disservice by leaving off several other areas of expertise that should be added to the list. Most of us ID doctors would make a career out of one of these topics.
The other impressive thing about John is that he’s a true visionary. Says his long-time former colleague Joel Gallant:
John is a man of incredible vision. He always knows what the next big thing will be, and embraces it long before it becomes the next big thing. There are many examples: managed care, bioterrorism, medical education on the internet (before he knew how to turn on his own computer), pandemic flu, and of course HIV/AIDS. Back when most hospitals, university medical centers, and ID divisions were running away from the AIDS epidemic, John took it on, both as a scientific priority and a moral imperative. With the help of Frank Polk and the Hopkins president, he established an outpatient AIDS clinic and an inpatient AIDS ward—both of which were way ahead of their time.
This last part is well worth reading again, which is why I bolded it. To start an HIV program at Hopkins in the 1980s was a truly brave move; many hospital administrators (possibly at Hopkins and definitely elsewhere — ahem, looking at you one particular Harvard hospital) strongly opposed opening HIV clinics or inpatient services, as they feared the stigma such a clinical and research focus would bring to their institutions. John discusses these early days in more detail here.
Finally, is there a person better at combining both the practical and the scholarly aspects of Infectious Diseases than John G. Bartlett? And someone who does it with such excitement? Not a chance — think of his numerous guidebooks … his “Game Changers” or “Hot Topics in ID” lectures at IDSA … his end-of-the-year summaries (here’s a good one for 2013, didn’t know there was a Mimivirus!) … his “Awards”, such as this one for most important bacterium, of all things.
You can just sense how fascinating he finds each of these topics, and that enthusiasm inevitably makes us excited too — a key quality of a great teacher.
John will be missed on the Guidelines panel, but we will always know where to find him at our ID meetings — sitting toward the front at a major plenary session, taking careful notes in longhand on a large yellow pad.
Hey, he doesn’t want to miss anything!
(One in a very occasional series.)