An ongoing dialogue on HIV/AIDS, infectious diseases,
November 7th, 2011
Can We All Agree That This Is Stupid? Thank You.
If this report isn’t an urban legend, then it’s pretty clear some people need a brain transplant:
The Facebook group is called “Find a Pox Party in Your Area.” According to the group’s page, it is geared toward “parents who want their children to obtain natural immunity for the chicken pox.” …On the page, parents post where they live and ask if anyone with a child who has the chicken pox would be willing to send saliva, infected lollipops or clothing through the mail.
One topic I’ve tended to steer clear from is whole vaccine controversy.
How could I be rational? I’m an Infectious Diseases specialist married to a pediatrician! I believe that the benefits of vaccines — especially for childhood diseases — so overwhelmingly outweigh the risks that I can’t really engage in a polite debate about it.
So each time I’m about to write something about the vaccine issue, I hear Dana Carvey’s voice saying, “Not gonna do it … Wouldn’t be prudent.”
And I write nothing.
But sending infected lollipops in the mail? Some things just deserve open ridicule, and this is one of them.
November 5th, 2011
A Mysteriosis about Listeriosis
For obvious reasons, listeriosis has been much in the news recently. The latest information from CDC on the Colorado cantaloupe outbreak cites 139 cases and 29 deaths.
The recent outbreak aside, however, actual cases of listeriosis are pretty rare. We easily could go months in our hospital without seeing a single case, and we have the largest obstetrical service in New England.
Which brings me to the mystery part: Why is medical student knowledge about listeria so high?
I meet with the medical students to review basics of antibiotics at the beginning of every rotation. Depending on the time of year and the number of prior clinical rotations they’ve done, they have variable amounts of ID knowledge before they get here.
But all of them know about listeria. And they know a lot about it.
- Causative organism? (Listeria monocytogenes — check)
- Dietary risk factors? (deli meats, soft cheeses, now cantaloupes — check)
- Population at risk? (pregnant women, transplant patients, and the elderly — check)
- Clinical manifestations? (meningitis, sepsis, gastroenteritis — check)
- Antibiotic of choice? (ampicillin — check)
They seem to know way more about listeria than they do about far more common infections, such as Strep pneumoniae or Epstein-Barr virus.
It’s the oddest thing. Any proposed explanations for this remarkable expertise would be most welcome.
October 29th, 2011
Will An Antiretroviral Patch Help Adherence? Doubtful …
This little nugget came up recently, found by our Journal Watch Executive Editor:
Preliminary research suggests that a patch could deliver an AIDS drug to patients … The researchers successfully used transdermal patches to administer 96 percent of an AIDS drug to simulated skin over a week. “Still, the important limitation of pills, regardless of how few there are or even how minimal the side effects, is adherence,” Johnston [the investigator] noted. Research has shown that many patients, if not most, don’t take their pills all the time.
Setting aside for a moment the fact that most patients actually do take their medications just fine, thank you — and that this particular transdermal HIV drug delivery system hasn’t even been tested on animals, let alone humans — I have always wondered about the assumption that novel drug delivery systems would improve adherence.
Seems to me that the major problem with non-adherent patients isn’t that they can’t take pills.
It’s that they won’t take them.
And I strongly suspect that most would make the same choice when it comes to putting on a patch every day (or even every week).
October 26th, 2011
Xigris is Gone — Not That Many ID Docs Will Notice
From the FDA comes this news:
FDA notified healthcare professionals and the public that on October 25, 2011, Eli Lilly and Company announced a worldwide voluntary market withdrawal of Xigris [drotrecogin alfa (activated)]. In a recently completed clinical trial (PROWESS-SHOCK trial), Xigris failed to show a survival benefit for patients with severe sepsis and septic shock.
Some quick (and non-scientific) thoughts on these perhaps no-so-surprising turn of events:
The use of various adjunctive therapies in acute sepsis has a long and mostly checkered history. ACTH-directed glucocorticoids, mineralocorticoids, intensive insulin therapy, disparate antibody treatments (most famously anti-endotoxin antibodies) — none has really worked very well. Now we can add recombinant human activated protein C — Xigris — to the list of disappointing (and sometimes dangerous) therapies. In failure there may be opportunity, but treatment of sepsis is one tough nut to crack.- I know trade names are frowned upon in academic medicine, but is there anyone who actually said, “drotrecogin alpha (activated)”? What kind of word is “drotrecogin”? Is there a “Drotrecogin Beta (Activated),” and is it a space ship? The use of the parenthetical post-name word — “(activated)” — is particularly cumbersome.
- Finally, how many ID doctors ever literally prescribed this drug? In our institution, the use of drotecogin alpha … oh you know, Xigris … was overwhelmingly in the hands of the intensivists. They would consult us sometimes after giving it to their critically-ill patients for advice on the usual ID issues (choice of antibiotics, source of fever, whether to change the lines). I only remember being specifically asked, “should we give it” a few times, and am certain I never ordered it.
Meanwhile, “Xigris” happens to be a terrific name. Kudos to whatever advertising brainiac thought of that one.
I’m sure he/she cashed the check for these services many years ago.
October 25th, 2011
Important Reminder: Don’t Eat Raw Garden Slugs
From the pages of the New York Times, courtesy of ProMED, comes this case report:
An Australian man has been hospitalized for more than a month in serious condition as a result of eating two garden slugs on a dare…The 21-year-old Sydney man apparently contracted a rat lungworm parasite from the slugs, which pick it up from rodent droppings. The parasite, a nematode called Angiostrongylus cantonensis, can cause fatal brain swelling.
From the perspective of an Infectious Diseases doctor, the surprising thing isn’t that a person would actually eat a raw garden slug — or even, as in this case, eat two raw garden slugs. After all, in our field one regularly hears of risk-taking behavior that, to quote a particular novel, “… runs to Z and beyond!”
Nope — my favorite part of the case report is this line:
“We hope this will help to remind others to avoid eating raw slugs,” the moderator, Eskild Petersen, said.
And with that, Public Health Crisis averted.
October 19th, 2011
Going, Going, Gone … HIV Treatment Failure Is Disappearing in People Who Take Their Meds
World Series time, hence the baseball reference in the title.
(Doesn’t take much.)
But over in Lancet Infectious Diseases — which has turned out to be a terrific journal, by the way — there’s a study reminding us that advances in HIV treatment in the late 2000s were truly spectacular.
The goal of the paper was to track the outcome of patients with “triple-class virologic failure” (TCVF) over the course of the last decade. Using data from 24 European cohorts, the investigators had access to over 90,000 patients, out of whom 2722 failed treatment with regimens that at some point contained the original three drug classes: NRTIs, PIs, and NNRTIs.
Rates of virologic suppression after TCVF steadily increased over the decade, from 19.5% in 2000 to 57.9% in 2009, and both AIDS complications and deaths declined. Significant predictors of virologic suppression by multivariable analysis included later calendar year, transmission category (MSM did the best), low viral load, and high CD4.
Those who had previously been able to achieve virologic suppression before TCVF were also more likely to be successfully treated — this clearly being a marker for good adherence. And although “past performance is no guarantee of future results,” it sure can be useful regardless. You have to assume that most of the 40% or so who did not achieve virologic suppression simply didn’t take their meds.
So what’s missing from their analysis?
Notably, because our objective was mainly descriptive, we did not attempt to further adjust for time-dependent variables such as access to new drugs …
In other words, the single most important factor for improved treatment outcomes in the 2000s — the introduction of darunavir, raltegravir, maraviroc, and etravirine — is left out.
(They also didn’t include data on resistance or adherence, but I suspect the former was tough to find, and the latter probably didn’t change all that much.)
So these results are either truly remarkable (if you follow HIV from a distance) or, if you are actively practicing HIV medicine day-to-day, are so obvious you can legitimately wonder why they did the study in the first place.
Both reactions are appropriate.
October 4th, 2011
Hormonal Contraception MAY Increase Risk of HIV
From the pages of Lancet Infectious Diseases, a study from Africa:
We aimed to assess the association between hormonal contraceptive use and risk of HIV-1 acquisition by women and HIV-1 transmission from HIV-1-infected women to their male partners … Among 1314 couples in which the HIV-1-seronegative partner was female, rates of HIV-1 acquisition were 6·61 per 100 person-years in women who used hormonal contraception and 3·78 per 100 person-years in those who did not (adjusted hazard ratio 1·98, 95% CI 1·06—3·68, p=0·03). Among 2476 couples in which the HIV-1-seronegative partner was male, rates of HIV-1 transmission from women to men were 2·61 per 100 person-years in couples in which women used hormonal contraception and 1·51 per 100 person-years in couples in which women did not use hormonal contraception (adjusted hazard ratio 1·97, 95% CI 1·12—3·45, p=0·02).
We’ve heard this story before, that hormonal contraception may increase the risk of HIV acquisition. The mechanism is unclear — vaginal thinning, increased HIV replication in genital secretions, something else — but undoubtedly part of it may be the simple fact that women receiving hormonal contraception must be less likely to use condoms.
In fact, that last factor is pretty darn likely, and why the results cannot be considered definitive — even though condom use was controlled for in the study.
Lack of concrete proof notwithstanding, women should be counseled that hormonal contraception could increase the risk of HIV acquisition and transmission — and hence it’s even more important that condom use be emphasized, especially in high HIV prevalence regions.
October 4th, 2011
Spanish HIV Vaccine Story Gets Lots of Attention — Here’s Why
If you’re looking for a good way to pass the time while running errands, traveling, or walking to work, I highly recommend the Freakonomics podcasts, which have taught me all sorts of interesting things.
Such as the fact that suicide is more common than murder in the USA, but gets way less attention. And how a restaurant can recover from serving a salad with a mouse in it. (Yes, waiter, there’s a mouse in my salad.) Or how much do our efforts to be better parents really matter? Not as much as we’d like to think, I’m afraid.
Which brings me to their comprehensive review of people who predict the future — markets, politics, sports, agriculture, you name it. Turns out that the kind of people most likely to make an accurate prediction are the ones who pretty much tell you what you already expect. But they’re too boring — anyone can say things will turn out the obvious way — so we have an insatiable demand for people who go the opposite route, making surprising predictions that go far out on a limb, foretelling something shocking or incredible.
And paradoxically, rather than taking these bold pundits to task for being wrong, we mostly forget about them until they get it right — at which point, we proclaim them geniuses. What sports fan of a certain age can forget Joe Namath’s shocking prediction in 1969 that the Jets would beat the Colts in Super Bowl III? (They did.)
And it didn’t matter that the guy predicting the 2008 market collapse had been saying the same thing every year for more than a decade, now he’s known as the guy who got it right! What vision!
(As for baseball prognostication, don’t get me started. Hmm, could be trouble.)
Which brings me to this HIV vaccine research done by a group of investigators in Spain, which has generated a fair bit of news coverage:
Researchers at the Spanish Superior Scientific Research Council (CSIC) have successfully completed Phase I human clinical trials of a HIV vaccine that came out with top marks after 90% of volunteers developed an immunological response against the virus. The MVA-B vaccine draws on the natural capabilities of the human immune system and “has proven to be as powerful as any other vaccine currently being studied, or even more”, says Mariano Esteban, head researcher from CSIC’s National Biotech Centre.
With the caveat that I am not an HIV vaccine researcher, I was surprised at how much news these early data generated — mostly because the study only involved 26 people.
And, to be blunt, also because the first report of the research in English occurred in the on-line “journal” called “Gizmag“. Unless there’s a report at a scientific meeting or journal I’m missing.
Regardless, it’s safe to say it will be hard to know when one of these highly-touted advances in the HIV vaccine effort actually turns out to be the real thing.
Someone making this prediction will eventually be right. Problem is that these could be the people just as likely — or more likely — to get it wrong.
October 3rd, 2011
CASCADE: When to Start, (Yet) Another Take
As we await the enrollment, analysis, and results of the START study — which is randomizing patients with CD4>500 to start HIV therapy vs waiting until the CD4 falls to 350 — much of the research on “when to start” ART in patients with high CD4’s comes from observational studies. Several have already been published (NA-ACCORD, ART-CC, CAUSAL), but one limitation of each of them is that none could accurately assess duration of HIV infection.
Enter “CASCADE“, or “Concerted Action on SeroConversion to AIDS and Death in Europe”. CASCADE includes patients from Europe, Australia, and Canada only if they have a defined date of HIV acquisition, thereby limiting effects of lead-time bias. In order to get at the when-to-start question, the investigators constructed something called “nested subcohorts” between 1996 and 2009, comparing the outcomes of those who started ART vs. those who didn’t.
The results? Out of 9,455 patients, starting ART (vs deferring) was associated with a lower risk of developing AIDS or death for those with a CD4 cell count < 500 — but not for those who started between 500-799. An interesting aspect of this study is that they were able to calculate a “number needed to treat” (NNT) to prevent progression. Over 3 years of follow-up, 21 and 34 patients would need to start treatment to prevent one patient from progressing to AIDS or death in those with CD4s between 200-349 and 350-499 respectively.
Usual caveats of observational studies apply — most notably that no such study can control for all factors between those who started ART vs those who didn’t that would influence outcome — but the results are helpful nonetheless, as the benefits of therapy before the CD4 cell count falls to < 350 shown here have been consistently seen in multiple studies. Furthermore, the NNT data to prevent AIDS or death — 34 for CD4 between 350-499 — place the benefits of treating these patients as even greater than what we accomplish with statin therapy for hypercholesterolemia to prevent MIs, which is estimated as 40-70.
Bottom line: Treating patients with CD4 350-500 and no symptoms may not be as exciting giving ART to someone with advanced HIV disease, but it sure makes good clinical sense.
Paul E. Sax, MD
Contributing Editor
NEJM Journal Watch
Infectious Diseases
Biography | Disclosures | Summaries
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