An ongoing dialogue on HIV/AIDS, infectious diseases,
April 4th, 2012
Infectious Diseases Specialists Take the Best Medical Histories
In an era where control-c followed by control-v — that’s cut and paste, for those of you who don’t use keyboard shortcuts — is the prime method by which most clinicians write their medical notes, I’d like to come right out and brag that ID doctors take the best medical histories.
You could argue (as I have before) that we do this because we suffer from variable (but mostly extreme) degrees of OCD. Or that it’s because we have no billable procedure. Or that we’re just being kind to the clinicians responsible for dictating discharge summaries, and want to offer them a little spice for their otherwise routine narratives.
But in reality, we are motivated by a quest for that “a-ha!” moment, when some scrap of history leads to the diagnosis that — with this critical piece of information — becomes oh so obvious. At least to us.
You know the type:
- The avid golfer who develops cough, pneumonia, and erythema nodosum — and tells you she has just played in a golf tournament in Arizona. (After being informed she has coccidioidomycosis, her first question was why the diagnosis wasn’t made in the Minute Clinic she went to in Scottsdale. Good question!)
- The gardener who is evaluated for a series of bumps on his back — Nocardia brazilienses, of course — and tells you he regularly uses one of his trowels as a back scratcher at the end of his work day.
- The diabetic with a wound infection from Aeromonas hydrophila, who describes using week-old tap water he keeps by his bed to soak the gauze for his wet-to-dry dressings.
- The biology grad student with high fevers and a severe sore throat, who says he just came back from Burma, where he spent most of his days in the jungle setting up large tarps to collect urine from tree mammals. Diagnosis? Burmese Pharyngeal Fever, of course.
(I made that last one up — he just had strep throat. But the exposure history was awesome, wasn’t it?)
Making one of these diagnoses from the history is, for an ID doctor, the equivalent of resecting a large tumor successfully, or doing an emergency cardiac cath on a patient with an acute coronary syndrome, or performing a face transplant.
It’s our version of, “So we took him to the OR, and saved his life.”
So it was with interest that I read this case series on severe Pasturella multocida (notorious cat and dog bacteria) respiratory infections in three people who provided palliative care — to their pets! Summarized in Journal Watch by Abbie Zuger, the paper has these choice historical items from the cases:
A further detailed history revealed that the patient’s pet dog died several days previously, that the patient had provided palliative care to the terminally ill dog by dropper-feeding honey to the dog, and that the patient had co-consumed honey with the dog by licking the same dropper used to comfort-feed the dog…
Further history revealed that 2 weeks prior to her illness, the patient had provided palliative care to her dying cat by holding, hugging, and kissing the head of the cat and allowing the cat to lick her hands and arms …
Simply asking whether or not the patient had a pet would not have uncovered the defined association of these respiratory illnesses with palliative pet care. The patient with P. multocida uvulitis even denied having a pet (it had died 6 weeks previously) and only admitted to having provided palliative pet care when asked specifically if she had any animal contacts in the past 3 months.
So the next time someone makes fun of us for asking patients about their pets (current or, sniff, recently deceased), or travel, or dietary habits, or sexual escapades, or home improvement projects, or assorted hobbies, we should stand our ground — because ID doctors take the best medical histories.
Have I made my point?
March 30th, 2012
Our Obsession with Dental Antibiotic Prophylaxis and an E-mail from Mom
I have a regular, highly efficient email correspondence with my mother — who never really liked talking on the phone to begin with (neither do I), so email is perfect for us.
The topics we cover are mostly family stuff, and food — she’s a food writer, after all, so it might be a recipe worth trying or a recent restaurant find.
But yesterday it was this:
I went to have my teeth cleaned today and they wouldn’t do it unless I took an antibiotic because of the plate in my ankle. They gave it to me, I waited 25 minutes, and then had my teeth cleaned. Was that necessary?
Mom
Sigh.
Where do I begin? I considered responding with a terse, “Nope” — but what’s the fun in that? Plus, even though she never went to medical school, she seems to get medical concepts better than most MDs.
It’s broadly misconceived by dentists and orthopedists alike that the risk of antibiotics is lower than the risk of “seeding” an artificial joint or plate by the dental work.
Clearly wrong.
But that doesn’t stop them. And it’s because surgeons are much more worried about passive errors (not doing something) than they are about harming someone with an active error (medication side effect).
They’re surgeons, after all. Maddening.
Paul
For her added reading pleasure, I sent her this reference, and this editorial.
I’m sure she’s read every word.
March 27th, 2012
Latest Guidelines Recommend HIV Treatment for All
From the key “What’s New in the Guidelines” section of today’s Department of Health and Human Services update:
ART is recommended for all HIV-infected individuals. The strength of this recommendation varies on the basis of pretreatment CD4 cell count.
This recommendation replaces a rather confusing categorization on when to start ART that, not surprisingly, was widely misinterpreted — fortunately, it now has been retired in favor of this much clearer statement.
The main reasons for the change were 1) greater appreciation of the dangers of uncontrolled viral replication (see this paper, for example) and 2) the data from 052 confirming the powerful effect HIV treatment has on preventing transmission.
My personal experience is that the latter has turned out to be the main driver of early HIV treatment in clinical practice. When my patients with high CD4 cell counts are informed of this benefit, they have almost uniformly become more motivated to start treatment.
Perhaps that’s no surprise, but it’s important to remember that what was widely considered a “public health” benefit of ART seems to have personal benefits for most individuals as well. People prefer being less contagious to others.
Now let’s see if we can make this treatment happen — it sure will be a challenge, as lots of people with HIV are not even in care, and won’t be having these discussions with their providers.
March 22nd, 2012
More Confusion on Anal Cancer Screening
Screening for anal cancer in men who have sex with men (MSM) — with pap smears, high resolution anoscopy, with whatever test — is quite the quagmire.
As I’ve mentioned before, the proponents of screening cite the success of cervical cancer screening and the startling high rates of anal cancer among HIV+ MSM as reason enough for doing something.
(Exactly what we should be doing is far from clear.)
The naysayers, who are much less vocal, say there is no evidence that this screening actually reduces the rate of anal cancer, which is of course the endpoint of interest.
Now, over in Lancet Oncology, comes this paper entitled, “Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis.”
After reviewing a dizzying amount of data, the authors conclude:
Anal HPV and anal cancer precursors were very common in MSM. However, on the basis of restricted data, rates of progression to cancer seem to be substantially lower than they are for cervical pre-cancerous lesions. Large, good-quality prospective studies are needed to inform the development of anal cancer screening guidelines for MSM.
Not to beat a dead horse here, but the fact remains that just because we can screen for pre-cancerous lesions, doesn’t mean we should.
(For more on this fascinating dilemma, read this op-ed piece. Or this recent survey.)
And it is notable that two established HIV guidelines — those for prevention of opportunistic infections and for HIV primary care — do not endorse anal pap smear screening, awaiting just the sort of prospective studies called for in this paper.
March 22nd, 2012
Identity Crisis
As some of you might have noticed, due to a web snafu here at Mass Medical Society, I was briefly a gastroenterologist earlier this week:
Unfortunately, I don’t think this translated in a higher paycheck, even though scoping is much more lucrative than doing ID consults.
And while HIV and ID Observations is admittedly a blah name for a blog — fresh ideas anyone? — Gut Check on Gastroenterology is already taken!
March 15th, 2012
CROI 2012 Really Rapid Review — with CROI 2013 Dates!
Some highly subjective highlights — a Really Rapid Review™– from this year’s Number One Greatest Super Scientific HIV Conference, the 19th Conference on Retroviruses and Opportunistic Infections (CROI), which ended last week in Seattle:
- Need more evidence that maintaining a CD4 cell count > 500 is beneficial? This compelling analysis from the SMART and ESPRIT studies found that among virologically suppressed, ART-treated subjects with CD4 > 500, there was no evidence of a higher mortality rate compared to the general population (standardized mortality ratio, 1.0). Not so for CD4s 350-500, by the way.
- Of course, most patients don’t start ART until their CD4 is below 500, but as shown in this global view, starting CD4s have improved dramatically since 2002 — pretty much everywhere. Despite this improvement, the only country where the average starting CD4 is > 300 is the USA. Lots of work still to do here.
- Related: the San Francisco policy of recommending ART for all with HIV as a public health measure has substantially raised the CD4 at treatment initiation in that city. Suspect this will eventually turn out the be the case nationally as well, now that treatment as prevention has become more broadly accepted.
- Based on this CDC study, only 44% of patients diagnosed with HIV in the United States are receiving care. We’ve heard this story before, but it’s still a shock — and worth remembering that the number of people diagnosed with HIV and not in care greatly exceeds those who are not diagnosed. How to bring the 56% back into care is obviously an urgent challenge for us.
- Why did the FEM-PrEP study fail to show protection of TDF/FTC? As suspected, poor adherence was the answer — detectable drug levels were found in fewer than 50% of infected women assigned to active drug (mystery solved). These results reinforce my gut feeling about PrEP — namely, that it will be a niche intervention, not one that can be broadly implemented.
- Not many clinical trials of ART at this CROI, but the meeting featured results of two major trials on the coformulated TDF/FTC/elvitegravir/cobicistat — or “quad” — single-pill treatment. These studies demonstrated it was non-inferior to recommended regimens — TDF/FTC/EFV and TDF/FTC/ATV/r. The “quad” (what will it ultimately be called?) has been submitted for FDA review. (Disclosure: I presented the results on the former.)
- 96-week coverage of phase II data on dolutegravir — and it still looks really good. Phase III data later this year?
- D:A:D study on cardiovascular risk of atazanavir? “No worries,” as people of a certain age (e.g., all our ID fellows) like to say. And let me be the first (or next) person to question the use of colons between letters in “D:A:D” — why? And did they realize it would make it harder to search?
- D:A:D again, this time on renal issues. The culprits? TDF, ATV/r, and LPV/r. We’ve heard this before, with EuroSIDA (you’ve got to figure that some EuroSIDA patients are also in D:A:D) and other cohorts. Bottom line is that in older, medically complex patients with other co-morbid risk factors for renal disease, the TDF + boosted PI regimen is the one to monitor closely.
- The tenofovir pro-drug 7340 has plenty of antiviral activity. Plus, the low doses will allow novel co-formulations, including the single-pill combination of boosted PI 7340/FTC/DRV/cobi. Will it be safer than TDF? Studies are ongoing to answer this question.
- Treatment with abacavir (or efavirenz, at least initially) increases CRP. Grace McComsey, a top-notch clinical researcher, led this study (I’m a co-investigator), and we were surprised by the results. Why? Because other randomized studies (notably STEAL and HEAT) found nothing — though ACTG 5095 (in which all patients received ABC or EFV or both) did find that CRP went up. Clinical significance uncertain, of course, but it raises again the abacavir-cardiovascular risk issue, as does this in vitro study.
- More on inflammatory/immune activation/coagulation biomarkers: Switching a boosted PI to raltegravir improves these biomarkers. Again, clinical relevance? You decide.
- Remarkable presentation by Steve Grinspoon on levels of arterial inflammation — using PET scans — in patients with virologic suppression and no cardiovascular disease. The key result is that HIV patients have comparable inflammation to those with established atherosclerotic disease, significantly greater than HIV negative controls matched by Framingham risk. Incredible pictures, if you have time for the webcast.
- Can a drug that stimulates the latent HIV reservoir be the first step to cure? Maybe — though my impression watching this fascinating scientific presentation is that we’re still a long, Long, LONG way from actually using such a strategy in practice.
- Zoster vaccine for patients with HIV looks safe and immunogenic. Now the tough questions: Who do we give it to? All with HIV? Just those over 60? Over 50? Those with virologic suppression? Over a certain CD4 threshold? This is why we have vaccine guideline panels.
- Adding boceprevir or telaprevir to peg IF/RBV improves 12-week SVR rates in co-infected patients. No surprises here, but good to see.
- Those annoying boceprevir drug-drug interactions with boosted PIs didn’t seem to have much of an effect on treatment response — but still one can’t feel too comfortable about using boceprevir with boosted PIs anyway.
- Levels of what is likely the next HCV PI — the once-daily TMC435 — are dramatically reduced by efavirenz. Fortunately, rilpivirine, raltegravir, and tenofovir are okay. Since TMC435 is a big-time cyp3A4 substrate, drug-interactions studies with boosted PIs are critical.
- By contrast, the HCV NS5A inhibitor BMS-790052 — which is now called daclatasvir — has quite predictable interactions, at least with efavirenz and atazanavir/r, though some dose adjustment will be required.
- Interferon-free regimen in HCV monoinfected patients: 12 weeks of the nucleotide 7977 + ribivirin has looked extraordinary in genotype 2 and 3 patients. How about in genotype 1 null-responders? Initial responses (kinetics) were terrific, but relapse rates high, as reported previously in a press release. Seems a longer treatment course, or one additional drug, will be required for these difficult-to-treat patients. Still — an all-oral therapy without interferon? Music to my ears. Results of this 12-week combination in treatment-naive genotype 1 patients are eagerly awaited, as are the results of 7977 + daclatasvir.
Now for the non-scientific part:
- Dates of next year’s conference (March 2-8 2013, see above) announced. Hurray! And the new CROI website design is vastly improved, much more readable, with easier-to-find abstracts, webcasts, etc.
- Second time the conference has been in Seattle, last time 10 years ago. A beautiful city with great food and coffee everywhere — but the streets seem so empty and spread out compared to congested Boston, NYC, Philadelphia, Washington DC, etc!
- Conference center perfect for this meeting, with spacious meeting rooms and many hotels close by.
- During the large scientific sessions, a woman walked up and down the aisles astutely looking at the participants, periodically writing something in a notebook. What was she doing? Trying to catch people violating the “No Photos” policy? (Impossible.) Getting some ambulatory exercise in an unlikely location? Taking food orders? (“I’ll have a hot dog and a beer, thanks very much.”) Thinking about MIP-1 alpha? (I love saying that, even though I have no idea what it is.) Nope — she was counting the audience. There must be a better way.
- Backpacks this year for the abstract book. I generally like them, but I’ve stopped using the conference bags at the actual conference ever since someone walked away with mine thinking it was his — only to discover the error when he boarded his flight to Dallas. “Hi Paul, you know that laptop you’ve been missing …”
Time to rename this conference, “Conference on Retroviruses, Non-HIV Complications, and Hepatitis”? Maybe.
March 4th, 2012
Be Careful What You “Catch”
On the eve of the 19th Retroconference, or “CROI” — and I’m headed to Seattle right this moment — two baseball players have intersected with the world of Infectious Diseases.
Ike Davis of the Mets has Coccidioidomycosis (Valley Fever).
And Ryan Howard of the Phillies has an infection after achilles tendon surgery.
Bottom line, it’s quite obvious that Bud Selig needs to hire an ID specialist — and I know just the candidate.
March 1st, 2012
Post-Exposure Prophylaxis, the World’s Most Outdated HIV Guidelines, and What To Do About Them
Every time I cover HIV prevention in a lecture, it’s always kind of embarrassing to cite the “official” post-exposure prophylaxis (PEP) guidelines, which are here (non-occupational) and here (occupational).
That’s right, they were last updated in 2005, the year of Hurricane Katrina.
Yes — more than six years ago. The alternative choices seem particularly curious (read: don’t do it) today — indinavir/ritonavir or efavirenz for PEP? You’ve got to be kidding me.
Because here’s a short list of what’s happened since then related to the HIV prevention front:
- HPTN 052
- An HIV vaccine study that, marginal efficacy aside, at least gave us a sense of “community risk” in a low-moderate prevalence area
- iPrEx
- Landmark studies in perinatal prevention, such as this one
- That great wave of HIV drug development, which included darunavir, maraviroc, raltegravir, and etravirine
No, there’s not been much new on occupational risk of HIV acquisition, which fortunately remains incredibly rare –and has always been a relatively data-free zone. (For the record, this is pretty much it here.)
So what’s an ID/HIV specialist to do?
I’ve been told that the next round of PEP guidelines is in development, but frankly the existing guidelines have been out of date for so long that something/anything has to be done.
Hence I welcome the imminent publication of this paper on the use of tenofovir/FTC and raltegravir for non-occupational post-exposure prophylaxis.
Yes, the study is small, and there’s no control group; furthermore, given the rarity of transmission, it can’t really estimate the preventive efficacy of this intervention — we’ll probably never have that.
But it provides at least some support behind what we’ve been doing now for several months, which is frequently replacing lopinavir/r with raltegravir — leading to much better tolerability of the PEP regimen.
And our hospital is about to make it official. From my colleague Sigal Yawetz, who heads up our PEP program, comes the following:
First line empiric therapy, not pregnant, no renal problems: tenofovir/FTC, raltegravir
First line therapy, pregnant (or breast feeding, continues to breast feed though not recommended): zidovudine/3TC, lopinavir/r
First line therapy, abnormal renal function: zidovudine/3TC, raltegravir
For any exposure to known infected person: ART to be selected by HIV expert
There — PEP Guidelines updated!
February 26th, 2012
A Truly Bizarre “Systematic” Review
You know that tenofovir, emtricitabine, and efavirenz HIV regimen? The one that’s universally listed as one of the “Preferred,” or “Recommended” or “First-line” options in all HIV treatment guidelines in the universe?
And the regimen that is easily the most widely used in the USA today?
Well, here’s a surprising review from Cochrane Summaries, entitled “Effectiveness and safety of first-line tenofovir + emtricitabine + efavirenz for patients with HIV”:
We searched the Cochrane Central Register of Controlled Trials, EMBASE, GATEWAY, LILACS, PubMed, AEGIS, and the WHO prospective clinical trials registry in November 2011…Only one study [emphasis mine] involving 517 antiretroviral-naive HIV infected adults was included in this review.
The authors go on to conclude, “The effects and safety of TDF + FTC + EFV as first-line treatment for patients with HIV cannot be assessed on the basis of only one trial. Further studies evaluating the effects and safety of TDF + FTC + EFV as first-line treatment for patients with HIV are needed.”
Gosh.
This is so mind-bogglingly wrong that it’s almost as if the review appeared in the medical version of The Onion, if there were such a thing.
They write that their inclusion criteria for this review was “Randomized controlled trials that evaluated the effects and safety of TDF + FTC + EFV compared with other HAART regimens, as first-line treatment for patients with HIV.”
But maybe they used additional criteria — such as “Only studies published in a calendar year in which the St. Louis Cardinals won the World Series, and whose first author’s last name starts with the 7th letter of the alphabet will be considered for inclusion”, as the Gilead 934 study is the only one they chose.
Because for the record, there’s also this study (5202).
And this one (ECHO).
And if you want to include TDf + 3TC + EFV (why not), there’s this one (Gilead 903).
And this one (5142)…
I’m sure I’ve left something out. But you get the idea.
February 23rd, 2012
Hepatitis C and the “Retooling” of HIV/ID Specialists
The news that hepatitis C (HCV) has passed HIV as a cause of death in the United States got quite a bit of attention when it was first presented last year at ICAAC — and no doubt the published paper, in this week’s Annals of Internal Medicine, will also cause a stir.
In fact, I boldly predict that going forward, (approximately) 94.2% of HCV-related research grants, journal articles, and lay press articles will cite this paper, making it (for now) the “Palella NEJM 1998” of HCV.
(For those of you who don’t know Palella NEJM 1998, this was the first paper in a major medical journal to demonstrate the dramatic decline in HIV-related mortality due to effective HIV therapy. Figure 1 from that study is permanently emblazoned on HIV specialists’ retinas.)
But the Annals paper also reminded me — again — that there’s a significant retooling going on in the HIV/ID field to accommodate HCV. And for some docs and HIV organizations, it’s more than a retooling — it’s practically a comprehensive overhaul. What do I mean exactly? Some citations, some anecdotes:
- The International AIDS Society – USA is now officially known as the “International Antiviral Society – USA” and has HCV therapy as a major focus of its efforts.
- Two large HIV annual educational meetings — one led by Clinicial Care Options, the other called Opman — both now prominently include hepatitis as a substantial component of their conference agenda. In fact, both have even changed their names: “2012 Annual CCO HIV and Hepatitis C Symposium” and “Optimal Management of HIV Disease & Hepatitis“.
- Several of the larger clinical trials sites for HIV therapy now devote a significant proportion of their research efforts to HCV. The leader of a well-known site told me that nearly half of their studies are now HCV-related.
- Many clinical ID practices (including ours) now openly solicit patients with HCV (not just HIV/HCV co-infection).
Of course, it’s easy to see why this is happening. These HCV cases call for all the skills we’ve sharpened over 16 years of combination antiretroviral therapy — managing complex regimens, myriad side effects, virologic responses, resistance, and drug-drug interactions.
Then there’s the dynamic pace of HCV therapeutic research. Seemingly every week, there’s another major story, most of it happening too quickly for peer-reviewed medical journals. See here for an example.
Oh, and you get to cure people. Wow.
By contrast, HIV therapy is in a plateau phase, with few major recent advances in treatment. The top four recommended initial regimens haven’t changed since 2009, and they are all remarkably effective. Clinical sessions of HIV follow-up have been likened to “well-baby checks”, a startling turnaround from the drama of HIV practice just a few years ago.
Yawn. And I mean that in the best possible way. Patients are doing great!
So if HIV/ID specialists seem to be jumping on the HCV bandwagon, it’s completely understandable. Though whether gastroenterologists mind sharing this bandwagon with us is highly debatable — most would probably just as soon let us drive, given the current difference in compensation between endoscopy and office management of medically and socially complex patients.
Perhaps I should even rename this blog “HIV, HCV, and ID Observations”?
Nah, it still needs a complete name overhaul — and I’m waiting for some good suggestions.
Paul E. Sax, MD
Contributing Editor
NEJM Journal Watch
Infectious Diseases
Biography | Disclosures | Summaries
Learn more about HIV and ID Observations.
NEJM Journal Watch — Recent Infectious Disease Articles- Cryptococcosis Outcomes in People Without HIV Infection
- Mycoplasma pneumoniae in U.S. Schools: Trends and the Upshot
- Observations from ID and Beyond: Ten Interesting Things About Norovirus Worth Knowing
- Guidelines Revised in 2024 Detail Use of Antiretroviral Agents for Pediatric HIV Infection
- Preventing Multidrug-Resistant TB with Levofloxacin