An ongoing dialogue on HIV/AIDS, infectious diseases,
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?
March 28th, 2010
Kidneys: Fortunately, We Have Two
Here’s a case over in our Journal Watch: AIDS Clinical Care site: a man with suspected PCP develops rapidly progressive renal failure after being starting on both empiric PCP treatment with TMP-SMX and ART with TDF/FTC plus darunavir/ritonavir.
The specific questions at the end of the case were:
- What do you think is causing the renal failure?
- Would you continue empiric treatment for PCP or try to confirm the diagnosis?
- If you would continue empiric treatment, would you modify it?
- What would you do with his ART? Specifically, would you continue the tenofovir?
- What would be your preferred alternative regimen?
I ran into the nephrologist Jonathan Winston this weekend, who will providing his take on the case shortly. He asked me what actually happened.
Stay tuned …
[Edit: Outcome of case now posted here.]
March 24th, 2010
Now for Some Good News: TB Cases Continue to Decline
From the latest
This figure speaks for itself, but two sentences from the Editorial Note deserve highlighting:
The 11.4% decrease in reported TB rate in 2009 is the largest single-year decrease ever recorded. From 1953 to 1993, the single largest annual percentage decrease in TB case rate was 11.1% in 1956
Since I started my ID career in these dark days — when we were all expecting (and some were experiencing) a cataclysmic increase in TB nationwide — all I can say is … wow.
And I’m not a bit surprised that these remarkable data have thus far received such scant media coverage, because stories about Infectious Diseases are so much more exciting when they go in the opposite direction.
March 17th, 2010
This One Drives Me Crazy
In the debate over efforts to expand HIV testing by making it less “exceptional” and more like other important tests done in medical care — something I heartily endorse (no kidding) — comes one particular protest that makes absolutely no sense to me.
It goes something like this:
We cannot expand HIV testing before guaranteeing that all newly-diagnosed people can get access to care.
ARRGGGH!
In what other disease do we make this stipulation? Would we stop recommending cancer or diabetes or hypertension screening in poor communities because there is no guarantee that they will be “covered” if we find something?
Look, the desire to get everyone access to care is laudable. And we should plan for an increase in cases when testing expands, as has so impressively happened in Washington DC. But we’re hardly going to fix the whole health care system at the same time we change antiquated HIV testing laws.
It’s especially ironic that this keeps coming up in HIV. Is there another disease with so many safety nets in place for coverage as HIV/AIDS?
Some would argue — I would — that we have in HIV care a pretty impressive model for national health care.
So let’s get that law changed already, ok?
March 14th, 2010
MRSA Bacteremia Question Redux — and the “Answer”
As noted here, I recently had to answer a question on management of MRSA bacteremia as part of an every-10-year cycle of test-taking.
(For more on that joyous process, read this interesting debate here in the New England Journal of Medicine.)
The question seemed to have no obvious right answer, so I did what one is explicitly allowed to do in this phase of the process — in other words, I asked some experts for their advice.
As a reminder, the case is a guy with positive blood cultures for MRSA (vancomycin MIC 2.0) on hospital day 4 despite receiving vancomycin (trough 15) and having undergone resection of a mycotic aneursym on hospital day 3.
Choices were: 1) continue current vancomcyin dose; 2) increase vancomycin to achieve trough of 20; 3) change to daptomycin; 4) change to linezolid.
Expert Number One said the following:
What a terrible question. A classic case of “what is the writer thinking and how much does he/she know?” 4 is clearly wrong, but I wouldn’t be surprised to hear that this is what they want. If the MIC is really 2, you need a trough of 40, which is not an option, so 2 is wrong. Given that he is only 5 days out and average duration of bacteremia in this setting is 7 days or so, you could consider 1 with reassessment in 2 or 3 days (but this is not really given here) and with MIC of 2, probably won’t work. That leaves 3 by default, but with MIC of 2, there is a significant possibility of heteroresistance to bothvanco and dapto. A terrible question. I wouldn’t know how to guess what they want!
And Expert Number Two — who kindly allowed me to cite as Dr. Myoung-don Oh, who is the corresponding author of this paper — generously offered:
I think there are several issues to resolve.
#1. Is the patient failing on VCM therapy? I think it is too early to declare VCM failure in this case. (1)The median duration of MRSA bacteremia(or mycotic aneurysm) is >4 days (2) Even if we choose an optimum antibiotic, MRSA bacteremia would persist if infected focus is not removed). In this case, the aneurysm was resected on HD#3. Therefore, I would rather wait 2 more days to see if MRSA bacteremia persist.
March 10th, 2010
The Extraordinary Power of Placebo
Just published in the journal Neurology — not typically on my radar screen — is this remarkable study comparing pregabalin to placebo for HIV-related distal sensory peripheral neuropathy.
Here are the results:
At endpoint, pregabalin and placebo showed substantial reductions in mean Numeric Pain Rating Scale (NPRS) score from baseline: -2.88 vs -2.63, p = 0.3941.
(-snip-)
Individuals with HIV-associated neuropathy achieved NPRS treatment effect size similar to those in studies of diabetic peripheral and postherpetic neuralgia. However, the placebo group in the current study had a much higher NPRS change than in the diabetic peripheral neuropathy or postherpetic neuralgia studies
In other words, the pregabalin here worked great, but the placebo effect was so gargantuan that the placebo was just as good.
Writing in Journal Watch: AIDS Clinical Care, the always-astute Abbie Zuger has a theory why this happened:
Notably, this study is not the first in which a treatment for HIV-related peripheral neuropathy has elicited an unusually high placebo response. The reasons behind that phenomenon would be extremely interesting to pursue — might HIV-positive individuals have greater faith in the power of medication than do others?
I think she’s on to something important here. After all, in how many other diseases can patients so directly link the medications they are taking to their own survival?
And we clinicians who practice HIV medicine should keep this in mind when prescribing medications to our patients. Strong mutual conviction that something will work — from both provider and patient — may well be a self-fulfilling prophecy.
Why not leverage this for all it’s worth?
March 5th, 2010
Test Question on MRSA Bacteremia
I just happened to be taking a test the other day — something I do for fun every now and then, say every 10 years or so — and I came across this question (slightly condensed/changed to protect the innocent):
Man with history of IDU admitted with fever, has bacteremia due to MRSA (MIC 2 mcg/mL confirmed by E-test). Found to have mycotic aneurysm of superficial femoral artery. Aneurysm is resected surgically on hospital day 3. On vancomycin 1 gm IV q12 hours, vancomycin trough is 15 μg/mL. Blood cultures drawn on hospital day 4 turn positive the next day; patient is subjectively improved but still febrile. WBC has declined from 16k to 11K.
What is the best next step?
1. Continue current rx
2. Increase vancomycin dose to achieve trough of 20 mcg/mL
3. Change vancomycin to daptomycin
4. Change vancomycin to linezolid
So what’s the answer?
Does anyone really know what the best thing to do here is? For the record, I got it “wrong.”
Paul E. Sax, MD
Contributing Editor
NEJM Journal Watch
Infectious Diseases
Biography | Disclosures | Summaries
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