An ongoing dialogue on HIV/AIDS, infectious diseases,
January 8th, 2012
Journal Club: In Early HIV Infection, Little Reason to Delay Therapy
Every experienced HIV clinician will recognize the following new-patient scenario:
- At least one, but often several negative HIV antibody tests in the past, generally due to being in a “high risk” group.
- Recent non-specific viral-type illness that, in hindsight, was undoubtedly acute HIV infection, undiagnosed.
- Now completely recovered, but found to be newly HIV antibody positive.
- Physical exam normal, CD4 500 or higher, HIV RNA in the moderate range (10-100K).
How should patients like these be managed? Specifically, should antiretroviral therapy be started, or should they be observed?
Over in Journal of Infectious Diseases, the so-called Setpoint study — a randomized strategy trial — investigated whether a 36-week period of treatment would delay the need to go on continuous HIV therapy, compared with observation. After 130 of a planned 150 patients were enrolled, a Data Safety Monitoring Board elected to stop the study due to this key finding: “… the higher rate of progression to needing treatment in the Deferred Treatment group (50%) versus the Immediate Treatment (10%) group.”
Importantly, the findings would have been even stronger in favor of Immediate Treatment if more up-to-date CD4 thresholds (500 rather than 350) were used as a criterion to start therapy. (The study was designed in the mid 2000s.)
How do these results influence practice? As I’ve noted before, patients diagnosed with recently-acquired HIV infection should be counseled that even if treatment is deferred, there is a high likelihood they will need to start treatment relatively soon.
It’s also time to retire the “you may have 10 years before needing to go on therapy” counseling, something we might have been prone to do in the past to soften the blow of someone hearing that they’re HIV positive. This kind of delay is highly unlikely, and may be limited to the small fraction of patients who have very low HIV RNA and very high CD4s.
January 4th, 2012
How Does Herpes Treatment Trigger a Positive Test for Performance-Enhancing Drugs?
Here’s my guess on how many of this blog’s readers know the following “facts”:
- Acyclovir and related drugs are used to treat herpes: nearly 100%
- Ryan Braun, superstar left fielder for the Milwaukee Brewers, is facing a 50 game suspension for testing positive for elevated levels of a “banned substance”, most likely testosterone: 10%
- Braun has disputed the results, stating that it’s a false-positive caused by treatment he’s receiving for a “private medical issue”: 1%
- That medical issue is widely rumored to be herpes: 0.01%
Now I should mention that I am a huge Ryan Braun fan, not only because of his stellar play, and his nickname (“The Hebrew Hammer”, one Braun shares with Hammerin’ Hank Greenberg), but also because he bears an uncanny resemblance to my nephew.
But it’s that last bullet point I can’t quite figure out — treatment of herpes is incredibly safe. How in the world would it lead to an elevated level of testosterone?
Turns out, it doesn’t.
But a quick search of “acyclovir” and “testosterone”, plus a perusal of an actual book — the irreplacable The Use of Antibiotics — finds that there are some obscure animal studies suggesting that anti-herpes drugs could do the reverse, i.e., lower testosterone levels.
From the book:
Dose-related testicular atrophy and abnormalities of spermatogenesis were noted in mice, rats and dogs treated on repeated occasions with either famciclovir or penciclovir …
All of which leads me to the very speculative conclusion that some doctors could be providing testosterone supplementation to their patients receiving anti-herpes therapy.
Which is, frankly, a completely bogus indication, way more “out there” as a practice than the typical off-label use of approved medications.
But that’s the only way I can connect the dots here.
In other words, something’s not right — the test result, the diagnosis, the prescribing practice — we just don’t know what that is yet.
January 3rd, 2012
Prevnar Now Approved for Adults — But Should We Start Using It?
From the FDA (and thanks to Physician’s First Watch for reporting the news):
Prevnar 13, a pneumococcal 13-valent conjugate vaccine, was approved today by the U.S. Food and Drug Administration for people ages 50 years and older to prevent pneumonia and invasive disease caused by the bacterium, Streptococcus pneumoniae.
As shown in multiple studies, Prevnar has dramatically lowered the incidence of pneumococcal disease, both in immunized children and also non-immunized children and adults through “herd immunity.” The shift to infections with non-Prevnar covered serotypes has been of some concern, but clearly this vaccine has had a major beneficial effect — something harder to prove with the older, less immunogenic polysaccharide vaccine.
So should we use start using Prevnar in adults?
When I have difficult vaccination questions, I turn to several reliable sources:
- My wife — pediatricians must give 100X (or more) vaccines than adult doctors
- The Immunization Action Coalition, especially their “Ask the Experts” section
- Howard Heller, my friend, ID Colleague, and Chief of Medicine at MIT Health Services, and adult immunization clinical expert
Howard kindly responded to my query this morning, and here’s his take:
We should still use the 23-valent pneumococcal vaccine (Pneumovax, PPS23) for adults until and unless the ACIP changes their recommendations. Although the conjugated vaccine induces higher antibody levels it has not yet been shown to decrease incidence of pneumonia, invasive disease or death. That study is underway. They will also be reviewing the data on the effect that Prevnar-13 in children has had on herd immunity and the prevalence of the various serotypes in invasive pneumococcal disease in adults. The advantage of the 23-valent vaccine is that it covers 10 serotypes that are not covered by PCV13. Stay tuned.
Thank you for that curbside, Howard — let me know if you have any questions about antiretroviral therapy!
December 28th, 2011
Why We Still Need HIV/ID Specialists
Over on Journal Watch AIDS Clinical Care, we periodically publish a tricky case — always drawn from clinical practice — then ask some experts how they would manage it, and why.
The most recent case pretty much has it all:
- Multiple prior regimens
- Multi-class drug resistance
- Metabolic complications
- Bad allergy history, one event nearly requiring hospitalization
- Disfiguring lipoatrophy
- History of treatment discontinuation
In fact, the case is so complicated that our Executive Editor said it made her “head hurt.” She’s just lucky the guy doesn’t have hepatitis C.
Fortunately, Graeme Moyle and Karam Mounzer kindly agreed to take it on. Given the complexity of the case, not surprisingly they came up with two different treatment approaches.
And patients like this are a reminder why, even in this era of single-pill-daily-for-HIV-treatment and 80-90% of patients in care virologically suppressed, we HIV/ID specialists still have a job.
December 24th, 2011
Making a List and Checking it Twice, Then Making Sure 052 is On It
How big a news story was HPTN 052, which demonstrated that HIV treatment reduced transmission by at least 96%?
(I like to emphasize that “at least” bit, since it’s likely that none of the study subjects with undetectable HIV RNA levels transmitted to their partners — the one case that did transmit did so before virologic suppression.)
Well, sources as disparate as Science and Time magazine both chose 052 for their “Top 10” in this year’s review of scientific breakthroughs. Science even put 052 as #1, something that you can bet we’ll have in common with this august periodical when Journal Watch AIDS Clinical Care publishes its own “Top Stories” next week.
But a Bronx Cheer out to Scientific American, which not only excluded 052, but then mentioned the following as a runner up:
…the report of a new target against HIV, in which a doorway to infection (the so-called CCR5-receptor on immune cells) is blocked.
CCR5 blockade a “new target”? That news is so 2002.
December 18th, 2011
Let’s Just Say I’m Glad the Grades Don’t Count
"Teacher, we are eager to learn."
A friend alerted me to this test of scientific literacy.
Give it a try — no google cheating — and let me know how you do.
And even though I got the first 5 questions right, my final score (to be disclosed in the comments, eventually) left little doubt that I was an English major in college.
Yeah, that’s my excuse.
December 14th, 2011
No HIV in Pepsi? Now THAT’S a Relief
How reassuring to be treated with the following news:
An SMS has been circulating that Pepsi products are contaminated with HIV but Permanis Sandilands Sdn Bhd has clarified that this is a hoax. Its marketing vice-president Hemalatha Ragavan said there was no truth to it. She urged people not to believe such claims.
I have a couple of thoughts about this breaking story.
First, we all know that texting — without other confirmation — is now the preferred current medium for obtaining important health information. And you can see how the text reads like the work of a highly-respected public health official:
for d next few days, do not drink any product from pepsi company like pepsi, tropicana juice, slice, 7up, coca cola, etc,,as a worker from the company has added his blood contaminated with HIV. watch NDtv …please 4ward this 2 every 1 u care about…..ok. Please note seriously
Second, the company issuing the denial — “Permanis Sandilands Sdn Bhd” — should think up a new slogan. “Come on board, it’s time to be COOL, have FUN and DARE FOR MORE!” is not not going to cut it among hip Malaysians.
December 11th, 2011
An Unlikely Interviewee Discusses “Six-Class” HIV Drug Resistance
He’d never acknowledge it, but in our field, it’s no secret this guy is something of a rock star.
I can think of several key principles in HIV pathogenesis and treatment that he and his research group have discovered, or elucidated most clearly, or simply explained the best — largely through his unique ability to link smart clinicians and laboratory scientists.
In other words, translational research at its finest.
Note I’m not using his name, since he’d definitely not approve of of any of this. Which is why I was particularly lucky to get him to agree to this interview, where we discuss those patients who, despite our numerous treatment options, are unfortunate enough to have HIV that is resistant to everything. “Six class” antiviral resistance.
No, he didn’t agree because I have incriminating photos or other dirt. But he owed me, since I was able to give him the correct date for his lecture at IDSA — the date was changed, and no one told him. (A recurrent nightmare of mine, by the way.)
Thanks again, SD.
December 8th, 2011
Big TB Prevention Study Important, Highly Relevant — Even Here
As I’ve noted before, tuberculosis is disappearing from the United States — which means that the bulk of cutting-edge research in TB (both clinical and basic science) has little relevance to US-based practitioners.
But over in NEJM, a much-anticipated TB study is published today that is highly relevant:
We conducted an open-label, randomized noninferiority trial comparing 3 months of directly observed once-weekly therapy with rifapentine (900 mg) plus isoniazid (900 mg) (combination-therapy group) with 9 months of self-administered daily isoniazid (300 mg) (isoniazid-only group) in subjects at high risk for tuberculosis. Subjects were enrolled from the United States, Canada, Brazil, and Spain … Tuberculosis developed in 7 of 3986 subjects in the combination-therapy group (cumulative rate, 0.19%) and in 15 of 3745 subjects in the isoniazid-only group (cumulative rate, 0.43%), for a difference of 0.24 percentage points.
Just how relevant is this study?
At the risk of over sharing, I would have been eligible to participate: Back in medical school, I cared for an elderly man with cough, weight loss, and lung cancer — only he didn’t have lung cancer, he had TB (oops). My next TB skin test was positive when I started internship, and I was advised to take 9 months of preventive therapy with INH.
Only I didn’t — not initially. For whatever reason, I somehow deluded myself into thinking it was a false-positive (just a little redness … right) and continued blithely on this path through both residency and ID fellowship.
Not smart, I know. Selfish, foolish youth.
Only when I became an actual ID specialist did it finally click. Needing another skin test before starting my job, I could no longer ignore the 15 mm welt on my arm. Nor could I bear the thought of harming my patients, never mind the painful irony and public health nightmare that would ensue if an ID specialist got active TB — headline: “ID Doc Infects Dozens; Ignored Advice He Gave Others.”
I finally took the INH. Oh, and it was no big deal.
But if I had the choice back then of 12 doses, taken once a week? Somehow this seems just so much easier, and I suspect I would have accepted treatment sooner had this option been available.
And as this short-course regimen enters formal treatment guidelines, I have a hunch it will be widely adopted — without the recommended directly observed component.
Do you agree?
December 4th, 2011
Images are Back
This site has been looking awfully plain the last couple of weeks. No pictures!
The reason? You figure it out.
But now we’ve got an exciting new treasure-trove of images, and I’m going to take advantage of this resource and provide some very exciting visuals for your enjoyment.
Like this one, if you’re feeling cold:
And this one too, if you’re hungry:
And finally, this one if you want to look at slugs again:
Some fun, eh?
You’re welcome.
Paul E. Sax, MD
Contributing Editor
NEJM Journal Watch
Infectious Diseases
Biography | Disclosures | Summaries
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