An ongoing dialogue on HIV/AIDS, infectious diseases,
May 14th, 2010
The Luxury of the START Study … and Running Out of ART in Uganda
Over on our Journal Watch AIDS Clinical Care site, we did a poll asking about the ongoing START study:
In the START study, HIV-infected patients with CD4 counts greater than 500 cells per cubic mm are being randomized to start antiretroviral therapy right away or to wait until the CD4 count falls to 350 cells per cubic mm or below. If there were a START study site in your community, would you refer eligible patients to it?
87% said they would — which is interesting, since the study is having trouble enrolling, at least in some sites. If the study succeeds, we may learn definitively if treatment should be started at CD4 cell counts > 500, a longstanding debate in the field.
But the dilemma posed by the START study stands in sharp contrast to this life and death news about HIV treatment programs running out of money in Sub-Saharan Africa:
The global war on AIDS has racked up enormous successes over the past decade, most notably by providing drugs for millions of infected people in developing countries who would be doomed without this life-prolonging treatment. Now the campaign is faltering …
Although the number of Ugandans receiving drug treatments jumped from fewer than 10,000 a decade ago to nearly 200,000 today, hundreds of thousands more Ugandans need the drugs and likely can’t get them because clinics now routinely turn new patients away.
In the context of a limited supply of medications, the best approach to providing HIV treatment is to treat the sickest first — patients such as those described here in this NY Times article. But after the drugs run out, then what?
All of which goes to show that even the option of doing the START study is an incredible luxury, and that a person needing treatment for HIV is very very lucky to live here and not in Sub-Saharan Africa.
May 9th, 2010
Amusing Medical Cartoons … and Humor in Medicine
Someone pointed out this cartoon to me.
What an eloquent depiction of the interior dialogue of a young doctor as she considers various non-medical careers.
Brilliant!
Which led me to thinking more broadly about humor in medicine, about which I quickly remembered that anyone writing about humor (as opposed to writing humorously) will be instantly unfunny.
Sorry.
So let me be brief, and say that I hung around with a bunch of people in college who made cartoons like these their principal means of communication. And that crude art notwithstanding, there’s a real talent to to it.
And most of these are great.
I wonder what she/he (I assume she?) thinks of ID specialists …
May 4th, 2010
Zoster Vaccine Underutilized
From the Annals of Internal Medicine:
Eighty-eight percent of providers recommend herpes zoster vaccine and 41% strongly recommend it, compared with more than 90% who strongly recommend influenza and pneumococcal vaccines. For physicians in both specialties [Internal Medicine and Family Practice], the most frequently reported barriers to vaccination were financial.
From my admittedly biased perspective as an ID doctor, recommending the zoster vaccine is a no-brainer. The cases of zoster I see are severe, and complicated, and people with post-herpetic neuralgia (who sometimes find their way erroneously to our clinic) are miserable.
But I’m also biased in that I’m not in a private, independent practice, and hence not responsible for getting reimbursed for giving a vaccine with irregular insurance coverage and finicky storage requirements.
So my guess is that were the vaccine universally covered (i.e., “free”), that there would be much broader uptake.
After all, for most Americans over 60, which is more likely to prevent illness — the zoster vaccine or the tetanus booster?
May 2nd, 2010
Learning from Clinical Trials with Limited “Generalizability”
In the ongoing debate about when to start antiretroviral therapy in our sickest patients — those with acute opportunistic infections — comes this study from Zimbabwe of early vs. deferred ART in patients with cryptococcal meningitis:
The median durations of survival were 28 days and 637 days in the early and delayed ART groups, respectively (P
=
.031, by log‐rank test). The risk of mortality was almost 3 times as great in the early ART group versus the delayed ART group (adjusted hazard ratio, 2.85; 95% confidence interval, 1.1–7.23). The study was terminated early by the data safety monitoring committee.
In sum, early ART made a terrible situation even worse: 3-year survival for the early ART group was only 22%, vs 46% in the deferred therapy group.
The challenges of applying this study to clinical practice here are numerous, including use of non-amphotericin therapy for cryptococcal CNS disease, lack of protocol-directed management of suspected raised intracranial pressure or immune reconstitution inflammatory syndrome (IRIS), and the highly unstable social and political situation in the country at that time.
Still — sometimes a study’s findings are so overwhelming that that there is something to be learned, issues of limited generalizabilty notwithstanding.
I suspect here it’s that ART should be deferred for at least a couple of weeks in patients with crytpotoccal meningitis, giving the amphotericin/5FC time to bring down the organism burden. Importantly, this slight delay would still be consistent with the “early” ART strategy of A5164, where the median time to start therapy was 12 days after OI treatment.
At least that’s what I’ll be doing until the results of this study are available.
April 24th, 2010
Choosing an Official State Microbe
Wisconsin has selected Lactococcus lactis as its official state microbe:
The people of the state of Wisconsin, represented in senate and assembly, do enact as follows: SECTION 1. 1.10 (3) (t) of the statutes is created to read: 1.10 (3) (t) The bacterium Lactococcus lactis is the state microbe. SECTION 2. 1.10 (4) of the statutes is amended to read: 1.10 (4) The Wisconsin Blue Book shall include the information contained in this section concerning the state song, ballad, waltz, dance, beverage, tree, grain, flower, bird, fish, animal, domestic animal, wildlife animal, dog, insect, fossil, mineral, rock, soil, fruit, and tartan, and microbe.
As any self-respecting Packer fan could tell you, Lactococcus lactis is a critical part of making cheese, in particular the state’s famous cheddar.
And though the bill passed last week, I have three remaining very important questions:
- What were the other contenders? When I think Wisconsin and microbes (which I do several times a day), probably the first bug that occurs to me is Borrelia burgdorferi (Wisconsin is a notable non-New England/Mid-Atlantic epicenter for Lyme Disease), followed shortly thereafter by Diphyllobothrium latum (think various marinated and uncooked fish popular in northern European diets). Did these get any votes?
- What will Massachusetts choose? I could see Erysipelothrix rhusiopathiae, though perhaps Maine has a stronger claim to this lobster-related bacterium than we do — we’d better have a back-up in place, such as Babesia microti or Cyclospora cayetanensis, though for the latter the reference might be a bit obscure.
- Will other states go for the obvious choices? Legionella pneumophila for Pennsylvania, Coccidioides immitis for Arizona, Vibrio vulnificus for Louisiana, etc. You get the idea.
Finally, note that Wisconsin has both a state mineral and a state rock. In these tough economic times, you would think one or the other would be sufficient.
April 22nd, 2010
Should Transmission of HIV be a Crime?
Not according to Journal Watch editor and New York Times writer Abigail Zuger, writing here in the Times. She’s referring to the recent Darren Chiacchia case, where his former partner has filed a legal complaint that Chiacchia did not disclose having HIV — potentially a first-degree felony in Florida.
Were it a matter of science alone, all those AIDS statutes could be rescinded tomorrow. But the science was only a small part of the panic that created them. And effective treatment has not altered the rest of that potent emotional brew: the virus still sows terror, uncertainty, shame and endless complications, whether the infection is concealed or revealed…
Now we think we know better, but do we really? We blame that coughing woman in the subway for our cold, the giant meat company for our food poisoning, all manner of chemicals and electromagnetic radiation for our cancers, and fast-food outlets for ourdiabetes and heart disease. We cannot experience illness without casting around for blame.
Yet at the same time we believe deeply in prevention. Surely if we watch our diets and get our mammograms and colonoscopies, wash our hands, take whatever vitamin is foremost in the news and eat our burgers well done, we can avert bad things. Whole generations have now grown up knowing that sensible people “play safe,” with the overriding implication that if you catch a sexually transmitted disease, you have no one to blame but yourself.
Then the key point:
And so whose fault is a new H.I.V. infection, really? Is it mine, for giving it to you, or is it yours, for being stupid and cavalier enough to get it?
(Sorry for the lengthy quotes, she’s such a great writer it was irresistible.)
I mostly agree with Abbie that effective treatment of HIV has changed the risk equation profoundly, and that what originally motivated these laws — transmission of HIV was murder! — no longer holds. But remember that some (most?) might think that transmission of any infection — herpes, syphilis, MRSA, salmonella from peanut butter, hepatitis A from spinach — is potentially a crime, provided there’s evidence of deceit or negligence.
And people holding this view will continue to see these HIV statutes as completely justified. As a result, don’t expect them to be removed from the books anytime soon.
April 14th, 2010
Maraviroc Rarely Used for Treatment-Naive Patients
Over in Journal of Infectious Diseases, the MERIT study was recently published (with Chuck Hicks’ Journal Watch summary here), demonstrating that maraviroc is non-inferior to efavirenz — provided that the enhanced-sensitivity tropism test is used to select appropriate candidates.
(The MERIT study began in 2004-5. Don’t think I’ll ever forget that, since the investigator meeting overlapped with this memorable series. Notable event pictured.)
Despite these favorable results from the trial — and the FDA approval of the drug for treatment-naive patients — I agree with Chuck that mariviroc will get little use in this population, if only because the “preferred” alternatives (efavirenz, atazanavir/r, darunavir/r, raltegravir) are so incredibly good.
Our reader poll (right side of page) confirms how rarely the drug is prescribed as initial therapy. I suspect that some of the respondents who said they have given the drug to these patients did so within a clinical trial, which would make the response even lower.
Will maraviroc — or another CCR5 antagonist — ever have widespread use in HIV treatment?
Call me an optimist, but I envision that these drugs will be part of an aggressive eradication strategy, somehow based on the remarkable case of “cure” following bone marrow transplantation from a CCR5-negative donor.
Hey, I can dream can’t I? Red Sox fans certainly did in 2004.
April 10th, 2010
Why Are Doctors Still Carrying Beepers?
I was going through security at the airport the other day, and tossed my beeper into one of those gray bins — along with the device that should make the beeper superfluous, a cell phone.
“I didn’t know anyone used beepers anymore,” said the 30-something guy behind me.
What could I say? That doctors also use typewriters, buggy whips, and ice boxes?
But those are really the wrong comparisons — better is something more early-90s, like this “mobile phone.” For a while back then, beepers were quite the status symbol among the junior high school set — especially if they were made of clear, teal-colored plastic.
And while teenagers have long ago moved on, virtually every doctor I know still carries a beeper. One of my un-named colleagues (at and un-named hospital in an un-named city) became so frustrated by having to carry two devices that he hacked into his hospital’s paging system. He now gets pages on his cell phone as text messages.
(He says texts over cell phones are sent via the same technology as pages. Who knew?)
This article discusses some reasons why beepers have certain advantages over other wireless systems. But that was two years ago, and given advances in cellular technology, I find it hard to believe those advantages wouldn’t quickly be overshadowed by all the obvious benefits of a cell phone, particularly a modern smart device.
I, for one, would be happy to trade mine in. Just say the word.
April 4th, 2010
San Francisco Public Health: Treatment Recommended for All with HIV
Could there be anything more interesting than the start of the baseball season?
Maybe, because this is quite something:
In a major shift of HIV treatment policy, San Francisco public health doctors have begun to advise patients to start taking antiviral medicines as soon as they are found to be infected, rather than waiting — sometimes years — for signs that their immune systems have started to fail.
Yes, the field is heading in this direction, but thus far no one has had the guts actually to recommend universal treatment as policy.
In the early 2000s, I often referred to this review by my friend and colleague Keith Henry for why we might want to hold off on starting treatment for as long as possible. How did we get from there to a policy to treat everyone? Selected highlights:
- 2006: SMART study stopped — intermittent therapy is worse than continuous treatment, including the risk of non-AIDS complications. In other words, toxicity of ART notwithstanding, untreated HIV is worse.
- 2006: One-pill a day treatment (TDF/FTC/EFV) approved. It wasn’t and still isn’t for for everyone, but it definitely was the next chapter in making treatment much easier to take, a far cry from the handful of toxic pills we prescribed in the late 1990’s.
- 2007: SMART “naive” analysis is presented at the Sydney IAS meeting, (link is to published paper) showing that even for those starting SMART with high CD4’s but not on therapy, intermittent treatment was worse.
- 2008: The famous “Swiss Statement” proclaimed that patients with undetectable HIV RNA on treatment cannot transmit HIV to others. (If you read French, here is the original.) A series of studies — some in serodiscordant couples, some population-based, some just mathematical models — have followed, all essentially demonstrating that HIV treatment is more effective than any other preventive strategy we currently have.
- 2009: NA-ACCORD is presented at CROI, concluding that deferring therapy until the CD4 falls below 500 cells is associated with a nearly two-fold increased risk of death. The paper is then published in the NEJM, adding credibility to the statistical gyrations required to do such an analysis.
That’s not a comprehensive list, of course, but these and other data led to a change in the latest HIV treatment guidelines, which despite raising the CD4 threshold for starting therapy, still do not go as far as the proposed San Francisco recommendations.
Is their room for uncertainty? You bet:
James D. Neaton of the University of Minnesota School of Public Health, contends that a rigorous, randomized clinical trial is needed to show whether early intervention works. The risks of early treatment — giving powerful drugs to people at low risk of disease — – could outweigh the “modest predicted benefit,” Dr. Neaton wrote in an e-mail message. “That is why we do randomized trials.”
And more:
Dr. Lisa C. Capaldini, who runs an AIDS practice in the Castro district, also has strong reservations. “H.I.V. behaves differently in different people,” she said. Although Dr. Capaldini recognizes that today’s drugs are a vast improvement over earlier therapies, the program, she said “is not ready for prime time.”
San Francisco has always had a distinctive role in the history of the HIV epidemic.
Why should now be any different?
March 31st, 2010
C diff Guidelines: Metronidazole Still Preferred?
IDSA and The Society for Healthcare Epidemiology of America (SHEA) have published Clinical Practice Guidelines for Clostridium difficile infection.
Not surprisingly, it’s a comprehensive, extensively-referenced document that will be an invaluable resource, especially since the previous version is approximately 15 years old.
But with the caveat that I’m not an expert in this area, these particular treatment recommendations continue to perplex me:
Metronidazole is the drug of choice for the initial episode of mild‐to‐moderate Clostridium difficile infection (CDI). The dosage is 500 mg orally 3 times per day for 10–14 days.
Vancomycin is the drug of choice for an initial episode of severe CDI. The dosage is 125 mg orally 4 times per day for 10–14 days.
In what other diseases do we recommend something different for mild vs. severe infection, when both are oral options? I understand there is a cost difference, but since the data on treatment of severe CDI demonstrate the superiority of vancomycin, is this the right approach? Especially since oral vancomycin is better tolerated?
Or are we still going through this widely-quoted (and frankly kind of politically incorrect!) mom vs mother-in-law dilemma?
With the intention of being provocative, what would you take if you had C diff?
Paul E. Sax, MD
Contributing Editor
NEJM Journal Watch
Infectious Diseases
Biography | Disclosures | Summaries
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