An ongoing dialogue on HIV/AIDS, infectious diseases,
November 8th, 2012
Steroids for Bell’s Palsy and the ID Doctor
OK, let’s imagine you’ve just gotten a call/email/text from one of your colleagues about Bell’s palsy; he/she is a busy PCP who periodically asks you very reasonable ID questions.
I suspect it went something like this:
COLLEAGUE: Hi Friendly ID Doctor, quick question — I have a patient with Bell’s palsy — wondering whether to give him steroids.
FRIENDLY ID DOCTOR: Steroids? Absolutely not! Don’t you know that a host of infectious diseases cause Bell’s palsy, including Lyme, HSV, VZV, HIV, syphilis [and other obscure diagnoses I’m too tired or too forgetful to list]. Have you excluded these?
COLLEAGUE: Well, I just read that the neurologists are recommending steroids …
FRIENDLY ID DOCTOR: I’d get Lyme titers, and start the patient on doxycycline and high-dose valacyclovir. In addition, [insert boilerplate language about the limitations of curbside ID consults here].
COLLEAGUE: But the neurologists say antiviral therapy doesn’t really work. And doxycycline? Why?
LESS-FRIENDLY ID DOCTOR: Never mind — how about you call a neurologist and ask what to do?
Every so often, something comes along that shows that you are absolutely and completely and totally biased in your approach to a problem by your perspective. Whoppingly biased, if that’s a word. I confess that Bell’s palsy is one of those things.
(I didn’t even know that the preferred term is now “Bell palsy”, without the possessive. Sounds weird. I’m sticking with “Bell’s”.)
To me — and probably to most Infectious Diseases specialists — a patient with Bell’s is an ID problem worth solving.
But to the vast majority of the rest of the world, including these new guidelines and the great swath of primary care providers and neurologists, it’s “an acute, peripheral facial paresis of unknown cause.”
Emphasis mine.
And after reading this evidence–based review, I confess that the data supporting the use of steroids for Bell’s palsy are far stronger than those for antiviral agents or, with my New England bias, doxycycline, which was not even mentioned in the guidelines. Oh well.
Nonetheless, for providers who see a new case, especially in the warm months, please humor me — send a Lyme titer. And at least think about those other ID diagnoses that cause Bell’s.
I mean Bell.
November 7th, 2012
Vitamins and the Department of Bad Timing
Now that the election is over, we can get back to something that really matters — namely vitamins, and specifically whether they really help people.
Last month there was a large, well-done study from Tanzania showing that mega-doses of vitamins not only didn’t help those HIV starting ART, but they actually were harmful — LFTs went up, and there was a non-significant trend towards more deaths among the sickest patients who got the vitamins.
Granted, I’ve never been a fan of high-dose supplements, but given these results, and the fact that they cost a boatload of money, I came out pretty strongly against them. Spend the money on real food — you know, the stuff we evolved as a species to eat — not the shiny capsules from GNC that come in plastic bottles with pseudoscientific labels.
Then, that same day I had fun blasting mega-vitamins, this study came out showing that a single multivitamin daily reduces the risk of cancer in men.
And the papers are in the same journal. Jeeze.
First, in my defense, it’s high doses of vitamin that I really object to — the list of studies showing that mega-supplements do no good (and may do harm) is not short. Second, while this particular multivitamin study (part of the giant Physicians’ Health Study II) showed a cancer prevention benefit, even the authors acknowledge that the effect size was small, and that cancer-related and overall mortality were similar. Third, this separate analysis of that same study showed no benefit in prevention of cardiovascular disease.
So for our patients wedded to taking something, let’s leave it as “take a daily multivitamin — if you must.”
And by the way, Mitt, those Lyme Disease flyers in Virginia didn’t do the trick.
October 28th, 2012
Dolutegravir and the 88% Rule
In the latest treatment-naive trials of elvitegravir and dolutegravir, there’s a striking consistency in the results of the “test” regimen. Here are the studies, with the percentage of responders by treatment arm:
- Study 102: TDF/FTC/EFV (84%) vs. TDF/FTC/EVG/c (88%) — non-inferior
- Study 103: TDF/FTC + ATV/r (87%) vs. TDF/FTC/EVG/c (90%) — non-inferior
- SPRING-2: TDF/FTC or ABC/3TC + RAL (85%) vs. DTG (88%) — non-inferior
- SINGLE: TDF/FTC/EFV (81%) vs. ABC/3TC + DTG (88%) — ABC/3TC + DTG — superior
The last of these, the SINGLE study, is the only one where there’s superiority in the primary outcome for the experimental arm, here ABC/3TC + dolutegravir. As the lead investigator Sharon Walmsley note, this favorable result was largely due to a significantly higher proportion of subjects in the TDF/FTC/EFV group discontinuing therapy for adverse events (10% vs 2%), as rates of virologic failure were similar between arms. ABC/3TC + dolutegravir also was better than TDF/FTC/EFV from both the immunologic and resistance perspective.
And though cross study comparisons are frowned upon by purists, we can’t resist. Just a quick glance at all four of the EVG and DTG arms, and you can easily see that an 88% response rate is the new price of admission for any treatment-naive regimen.
Anything shy of the high 80s, and there has to be something else very special about the treatment — for example, better tolerability, much lower cost, better long-term safety, it helps you become a virtuoso violinist — to make it compete with options for therapy we already have, or will have soon.
October 17th, 2012
It’s Time to Tell Our Patients to Stop Their Vitamin Supplements
Over in JAMA, there’s a large study out today that (yet again) failed to demonstrate a benefit of vitamins.
Over 3000 patients with HIV in Tanzania were randomized to receive either high-dose or standard-dose multivitamin supplementation, in addition to “HAART” (ugh). Though the study was planned for 24 months, it was stopped early by the Data Safety and Monitoring Board due to a higher rate of LFT abnormalities in the high-dose vitamin group. Not only that, the sickest patients — those with BMI < 16 — seemed to do even worse on the mega-dose, with a higher risk of death that almost reached statistical significance (relative risk 1.36; 95% CI, 0.93-1.98; p=.11).
One could quibble with the generalizability of the results to current standard of care in well-resourced areas — for example, the most common regimen was d4T, 3TC, and nevirapine, used in nearly 60% — but it’s hard to imagine how this makes the results less convincing. After all, one would expect that vitamin supplementation would be more important in settings where malnutrition and advanced HIV disease are highly prevalent.
So what should we do?
I’ve been keeping quiet with my patients who insist on taking handfuls of vitamins, despite their having access to real food and nothing at all to suggest dietary insufficiency. With this study, however, I will strongly encourage them to save their money — the only people benefiting from their daily intake are those in the $27-billion dollar/year vitamin industry.
October 16th, 2012
Some Liver Meeting “Wow!” Studies Start to Emerge
The Liver Meeting, the annual meeting of the American Association for the Study of Liver Disease, does not take place until November 9-13, in Boston.
But if you want a preview, a couple of notable studies have already been “announced” in the press.
Specifically, there’s this:
Abbott today announced initial results from “Aviator,” a phase 2b study of its interferon-free, investigational regimen for the treatment of hepatitis C (HCV). Initial results show sustained virological response at 12 weeks post treatment (SVR12) in 99 percent of treatment-naïve (n=77) and 93 percent of null responders (n=41) for genotype 1 (GT1) HCV patients taking a combination of ABT-450/r, ABT-267, ABT-333 and ribavirin for 12 weeks, based on an observed data analysis.
That regimen contains 5 drugs — HIV/ID docs will recognize the “/r” as familiar short hand for ritonavir boosting — but it’s hard to beat those response numbers. Note especially the 93% cure rate in interferon null responders — amazing.
If 5 drugs seems like too many, there’s also this:
[Bristol-Myers Squibb] said 94 percent of patients who took a combination of three experimental drugs, daclatasvir, asunaprevir, and BMS-791325, were cured in a 12-week study. Those patients did not take interferon or ribavirin.
Looks like it’s going to be an interesting meeting. That sentence may be the understatement of the year.
October 15th, 2012
ID Doctors are Clueless about Treating Helicobacter
Every so often, we’ll get a referral from a gastroenterologist about a refractory case of Helicobacter pylori.
Usually the patient has been treated multiple times, and still has symptoms and a positive test. Naturally a referral to a specialist in Infectious Diseases seems warranted.
But the reality is that this is like the IV nurse contacting the July intern with a tricky IV, telling the newly minted doc that since he/she (the nurse) can’t get the IV in, the intern should give it a try.
Ha.
Because the fact is that most ID doctors know little if anything about treating helicobacter, which is overwhelmingly diagnosed and managed by primary care doctors and gastroenterologists.
The ID doc can read the guidelines as well as the next guy, but we have little hands-on experience with treatment. So choosing between the multiple different regimens, selecting the right PPI and dose, giving the right length of therapy, and deciding whether to use bismuth are practical skills we most definitely lack. Suffice to say it’s no accident that this study was covered in Journal Watch Gastro rather than Journal Watch ID.
I was reminded of this gap in our knowledge the other day with this exchange with one of my colleagues:
GI doc: Hey Paul, I have a question about Helicobacter treatment.
Me: OK …
[I’m worried. Should I tell him he might as well be asking his office receptionist?]
GI doc: I saw your patient John Smith, he’s on HIV treatment with blank, blank, and blank.
[He horribly mangles the regimen, which is tenofovir/FTC and boosted darunavir. I’m feeling better already.]
Here’s my question — what can I give him that won’t interact?
Me: Just avoid clarithromycin — it interacts with the darunavir and ritonavir.
[Amazingly, he’s asked me about the only thing I could possibly answer about helicobacter without looking it up.]
GI doc: Fine, I’ll use Pylera.
[I have absolutely no idea what that is. Time to come clean.]
Me: I have absolutely no idea what that is.
For the record, Pylera is a combination of bismuth, tetracycline, and metronidazole. Learn something new every day.
It’s pretty easy to understand why we know next to nothing about helicobacter — the disease used to require an endoscopy and biopsy for diagnosis. Regardless, it’s quite humbling to acknowledge that yes, there’s this fascinating (and very cool looking) bacterial infection out there about which most ID doctors have little if any expertise.
Perhaps that will change as rates of antibiotic resistance rise, especially if complex culturing and susceptibility testing are required. We’re really good at that stuff.
October 13th, 2012
More Questions from “ID in Primary Care” Course
Some additional excellent questions from the course:
- For someone who has had 3 doses of hepatitis B vaccine but does not have the antibody, should we just go ahead and give another 3 shots?
A: (Per vaccine guru Howard Heller): The guidelines say to just go ahead and give another 3 shots but if the initial series was many years before then I usually give one booster dose and recheck antibody level 2 weeks later. If there is a robust response then I stop. And always consider the possibility of and screen for chronic infection as a possible reason for why the patient did not “respond” to the first series of shots. - If someone has a history of receiving 2 doses of MMR but they do not have antibodies, do you just give them one dose of MMR or 2 doses?
A: If they have documentation of the 2 previous doses or if their history is very reliable, then one dose. If there is any doubt about the reliability, then give 2. - My patient had a positive HIV ELISA, and an indeterminate Western blot. What should I do next?
A: As I wrote here, you must exclude acute HIV infection with an HIV RNA (viral load). And if that’s negative, it also would make sense to exclude HIV-2 with a differentiation assay. If both are negative, then it’s a false positive ELISA. Would repeat again in a month just to make sure. - How long is a person contagious with shingles?
A: When the lesions are crusted over, there’s no further viral replication and the person is no longer contagious. - Can a person get mononucleosis twice?
A: They can only get EBV-related mononucleosis once, but other infections that can mimic acute EBV mono include CMV, toxoplasmosis, and HIV. - Why do people think you look like Paul Farmer? You have a much stronger resemblance to Steve Buscemi.
A: Umm … Thank you… or not? (Above image with permission of www.mattleese.com.) Just in time for Halloween!