An ongoing dialogue on HIV/AIDS, infectious diseases,
November 10th, 2008
Yes, Just a Case Report, but Incredibly Cool
At this year’s Retrovirus Conference (was it really this year’s conference, seems like much longer ago than that), there was a poster presentation summarizing a very unusual case. A man with HIV, stable on antiretroviral therapy, developed acute leukemia. He underwent an allogeneic bone marrow transplant — here’s the kicker — from a donor who was homozygous for the CCR5 delta 32 mutation. In other words, the donor’s CD4 cells were all but resistant to infection with CCR5-tropic virus.
All antiretrovirals were stopped at the time of transplant, and — amazingly — no rebound in HIV viremia occurred for a year. No virus found in plasma or PBMCs; no HIV found in bone marrow or in rectal biopsies. He remained HIV seropositive, but the virus was nowhere to be found.
When I presented this single case in summaries of the highlights of this year’s CROI, inevitably the response was astonishment, even though it was just one case. But then the case disappeared from view, and I don’t believe it has been published yet in a peer-reviewed journal.
Now the story has been updated in the Wall Street Journal — the patient is now off antivirals for over 600 days, still no virus rebound. Today it’s the most e-mailed piece in the Journal.
Just a hunch, but I think this is the closest thing we’ve come to a cure for HIV infection. Granted, it’s not practical to offer bone marrow transplants to the 33 million or so people infected with HIV in the world, never mind the difficulty of finding donors who are appropriate matches and have the delta 32 mutation (the mutation occurs in only approximately 5% of individuals, and is even rarer in persons of African and Asian descent).
Regardless, if ever there were a plausible target for gene therapy, the CCR5 delta 32 mutation seems like a great place to start.
November 2nd, 2008
The Big HIV News from ICAAC/IDSA
Tons of interesting stuff at this year’s combined ICAAC/IDSA meeting, most of it in non-HIV related Infectious Diseases. In aggregate, literally hundreds of posters, presentations, and symposia on MRSA, C diff, osteomyelitis, complicated UTIs, hospital-acquired pneumonia, antibiotic resistance … It’s a great meeting to catch up on general ID, and the literature review sessions alone are practically worth the price of admission.
But there are almost always a few major HIV-related studies presented as well, and this year was no exception. These two understandably got the most attention:
- Early antiretroviral therapy increases survival [Kitahata H-896b]. The NA-ACCORD study compared all-cause mortality among more than 8,000 patients with HIV followed since 1996. Compared with those starting therapy with a CD4 cell count between 200 and 350, patients starting with CD4s between 350 and 500 had a 70% reduction in the risk of death. Wow. [Addendum: Our astute editor at AIDS Clinical Care points out that this is really a 43% reduction, as the relative hazard for mortality for the group deferring is 1.7. Still wow.] Usual caveats on the limitations of cohort studies apply, but this was a very well done study with a huge sample size; its conclusions were further bolstered by the observation that virologic suppression rates did not differ between the two groups — implying comparable levels of medication adherence. Stay tuned for a similar analysis of those starting with a CD4 > 500 cells — whispers that we’ll see this info at next year’s CROI in Montreal. Will this be the final word on the “when to start treatment” question we’ve been debating now for two decades? Should pretty much every patients with HIV be on therapy? What will happen to the planned “START” randomized trial? I sense unless something truly unanticipated happens with drug toxicity, we’re going to be starting a lot of asymptomatic patients on treatment over the next few years.
- Raltegravir vs efavirenz as initial therapy [Lennox H-896a]. Can something be as good as efavirenz (essentially our current gold standard) for initial therapy? Apparently yes — raltegravir was “non-inferior*” to efavirenz when combined with TDF/FTC in a large phase III, double-blind study: Virologic suppression rates at 48 weeks were 86% for RAL compared to 82% for EFV. There were also lower rates of drug-related averse events in the raltegravir arm, with protocol-specified CNS toxicity occurring in 18% of efavirenz and 10% of raltegravir-treated subjects. We’ve been using the 2NRTI + NNRTI or PI approach as initial therapy for a long time — here at last is a new approach.
And for the record, I’m a big fan of this combined ICAAC/IDSA meeting, but it will be separate for at least the next two years at least. Oh well.
*The use of the term “non-inferior” always sounds like pedantic statistics-ese to me. 86% “non-inferior” to 82%? But it does mean something specific — best described to me as “not too much worse than”, with “too much worse” generally defined as within 10-12%. But the lower-limit of the 95% confidence interval can’t be below this 10-12%, and that’s where peculiar statements such as “86% is noninferior to 82%” come from.
October 27th, 2008
Antibiotics as Placebos?
(Not an ad.)
This article in the BMJ is geting lots of news: Out of 679 practicing physicians in the United States, about half admitted to prescribing placebos on a regular basis. A “small but notable proportion (13%) of physicians reported using antibiotics.”
My first instinct was surprise that the rate was this low, but then I remembered that public perception of this practice might not be so favorable. As a result, the appropriate MD response to this news is to be “shocked, schocked …” that placebos are being prescribed, and to express grave concern at the ethics of the practice. So undoubtedly some of the doctors surveyed in that study probably didn’t tell the truth.
From an ID perspective, reading that antibiotics are sometimes used as a placebo is hardly news at all. Since about half of the US population believes that antibiotics are helpful for the common cold, all a clinician has to do is prescribe a Z-pack for a runny nose to a patient expecting antibiotics, have that patient get better (colds do, after all get better eventually), and the practice is reinforced. This exact exchange must transpire hundreds of thousands of times a day in doctors’ offices and emergency rooms.
I’ve written here about one potential cure for this problem (C. diff), but it’s not exactly something you’d want instituted as a preventive measure.
Is there a way to exploit the placebo’s powerful effect in clinical practice that doesn’t seem so sneaky? And doesn’t expose patients to medication side effects? Here’s one: Our office has a terrific coffee/tea maker, and I’ve found that handing a patient with a bad cold a cup of freshly made green tea in a nice mug works wonders. I don’t believe we ever covered that in medical school.
October 18th, 2008
Back to School, Day 2
During the course, often the best questions and anecdotes come during the breaks. Here are a few:
- Tons of questions about our favorite nemesis, MRSA. What works for chronic carriers? How do you manage family members who you suspect would be culture-positive (and the source of recurrences), but are not your patient? What if the vet won’t culture the family dog? What are the guidelines for infection control in the outpatient setting? What is the best non-linezolid (which still costs > $150/day) oral antibiotic? What’s the right dose of trimethoprim-sulfa? (Many advocates for two double-strength tablets twice daily.) Number of definitive answers to any of the above questions? None. I guess misery loves company.
- A primary care MD working at a college health clinic gave me some insight into just how far we still have to go to make those revised HIV testing guidelines a reality. In this campus-based practice, if one of the students requests an HIV test, or the clinician thinks an HIV test is indicated, several restrictions are in place that go way beyond the state-mandated requirement for written informed consent. First, extensive pre-test counseling is required; second, only one of the providers is allowed to order the test (so the student must return to see that clinician if he is not available that day); third, mention of HIV testing in the medical record is forbidden; and fourth, the results of the test do not appear in the student’s chart. (They are kept in some locked remote location, no doubt.) Hey, can we stop this madness already? Is there any evidence that such policies help anyone? (The MD at our course was complaining about them, not surprisingly.) Of note, the revised HIV testing recommendations — explicitly outlining the rationale for eliminating barriers to testing — are now over two years old.
- Only two course participants thought I was Paul Farmer. Interestingly, one of them thought I was Paul Farmer immediately after he gave his lecture, during the coffee break, when the real thing was standing right across the room. My clue she had the wrong Paul Edward was when she told me my work inspired her to apply to medical school when she was growing up in Port-au-Prince. There are definitely worse people one could be mistaken for — back when I had more hair (lots more hair), someone thought I was a dead ringer for this guy. Yikes.
October 15th, 2008
Back to School, Day 1
We offer two post-graduate courses each year, one entitled Infectious Diseases in Primary Care, and the other AIDS Medicine: An Intensive Case-Based Course. The Primary Care one started today, the AIDS course starts on Monday.
(Both are equally fascinating. I am entirely unbiased.)
What is so striking is that the participants — and content — barely overlap at all. Topics for primary care course:
- Antibiotics
- UTIs
- Pneumonia
- Sore throats/colds
- Immunizations
You get the idea. For the AIDS course?
- Acute HIV infection
- Management of treatment-naive patients
- Interpretation of resistance testing
- Metabolic complications of therapy
- Legal and ethical considerations of HIV care
I suppose I should not find the lack of overlap surprising, given papers such as this one, citing that 62% of family practitioners refer their AIDS patients to specialists immediately — a big change from 1994, when only 18% did. (Even 62% seems low …)
But the irony is that with improved antiretroviral therapy — the very thing that drove some generalists away from HIV care due to its complexity — HIV patients are living longer, and hence are in greater need of the kind of care delivered best by primary care clinicians.
So maybe what we really need is a primary care course for HIV specialists?
October 8th, 2008
The French Win This One
The 2008 Nobel Prize in Medicine goes to and
For the record, if you search the Nobel press release for the word “Gallo”, you won’t find it mentioned anywhere.
Why is this notable? Seems like ancient history, but actually two groups in 1983 claimed they discovered the virus that causes AIDS, both finding a human retrovirus — the one we now know as HIV. The French group called it “lymphadenopathy-associated virus” or LAV, and the Americans (led by Robert Gallo) “human T-lymphotropic virus III” or HTLV-III. We now know it was the same virus — indeed, due to “lab contamination,” sometimes literally the same — and that the French were first, but maybe (am being generous here) the Americans were a bit more practical (and certainly louder) about the implications of the discovery.
An academic truce of sorts ensued many years later — this was much less entertaining, but perhaps a good thing for international relations, at least until “Freedom Fries.”
October 1st, 2008
Deadlines of Note
Just a reminder of some interesting deadlines/events out there, in case you were too wrapped up sharpening pencils for tomorrow’s Vice Presidential debate:
- As of today, Medicare will no longer reimburse hospitals for medical errors — which includes some hospital-acquired infections. According to this article, several other payors (including private insurers) are using this as a precedent for them to do the same. No doubt the desired outcomes — fewer errors, better outcomes, lower costs — are something we all want, but could it be that insurance companies view these outcomes with slightly different motivations than the people actually experiencing and delivering the health care? (Just a hunch.) Plus, some of these errors are more amenable to systems and behavioral changes than others. Mistakes such as wrong-limb surgery, retained devices during operations, or transfusions of the incorrect blood type are simply not the same as a nosocomial infection in a highly debilitated or immunocompromised patient. Great review of the complexity of this issue here in this week’s JAMA.
- Abstracts for the 16th Retrovirus Conference (CROI 2009) are due today at 5:30pm. As a regular attendee of HIV/ID conferences over the years (and, darn it, frequent rejectee of submitted abstracts), I can state unequivocally that the standards set by CROI for abstract acceptance must be the highest in our field. Moreover, once accepted, abstracts face an incredibly high hurdle to be chosen for oral presentations. Notable examples of this from the 2008 conference include the abacavir/DAD/cardiovascular disease study (published as a major paper in Lancet just a week later), and a large randomized clinical trial comparing abacavir/3TC with tenofovir/FTC. Both of these studies were posters, not oral presentations! This is a tough club to get into, that’s for sure.
- (Warning, no ID/HIV content to follow.) Tonight at 6:30 PM EST, the Chicago Cubs — the best team in National League this year — start their “quest” for their first World Series title since 1908. Yes, that’s a hundred years! Can there be any baseball fan with a pulse out there who isn’t rooting for them at least a little?
September 29th, 2008
Required Reading: The Value of ID Specialists
In the most recent issue of Clinical Infectious Diseases, there’s a comprehensive review of the value of an ID specialist from the perspective of non-patient care activities.
Covered in particular are:
- Antibiotic stewardship
- Infection control
- Monitoring rates of nosocomial infections
- Managing health care worker “well-being and exposures”
Also included are tables listing dozens of studies quantifying the value of these activities. It’s an impressive paper, running 12 pages long and including over a hundred references.
What might be most useful, however, is a section entitled, “Putting the Data to Use Effectively in a Negotiation.” Here, in best Business School 101-ese, is a step-by-step approach to making the case for our value to hospitals or other health-care centers. Such negotiating skills are not taught in medical school, residency, or fellowship, and suspect that many of us could use this nice primer.
So if you can’t define “BATNA” (hint: it’s got nothing to do with rabies), I highly recommend this paper.
September 27th, 2008
Crunchy Frog?
One of the ID fellows just received this curbside consult:
A primary care doctor paged me because a patient of his just discovered a dead frog in the salad she was eating, and wanted to know what to do.
How about, “Don’t eat it!”
But there are definitely some things in our field you just can’t look up — not even in UpToDate. And as a nerdy male of a certain age, I had the immediate impulse to ask if the salad dressing on this salad was lark’s vomit, but refrained.
You think Cardiologists get questions like these? I think not. They don’t know what they’re missing.
Paul E. Sax, MD
Contributing Editor
NEJM Journal Watch
Infectious Diseases
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