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May 15th, 2014

CDC Recommends Broader Use of Pre-Exposure Prophylaxis — Can We Make It Happen?

Making a much stronger and more comprehensive statement than their earlier “Guidance,” the CDC is now recommending tenofovir/FTC (Truvada) for all Americans at high risk for HIV. More specifically, they recommend it for a broad range of people who have certain risk factors (click to see full size image):

Guidance for PrEP

One certainly gets why this was done — as summarized nicely in this Times piece, it’s easy to be “frustrated that the number of H.I.V. infections in the United States has barely changed in a decade, stubbornly holding at 50,000 a year, despite 30 years of official advice to rely on condoms to block transmission.”

Plus, we know that PrEP really does work, provided people take it. An encouraging report from CROI this year found that adherence was nearly 80% among MSM seeking PrEP in three U.S. cities (Miami; Washington, DC; San Francisco).

And I have been surprised that we haven’t yet seen much of a decline in HIV incidence, even with a broader number of our patients in care receiving suppressive antiretroviral therapy, which essentially eliminates the risk of transmission to others.

However, it’s clear that the epidemic is being sustained by those not in care, which is why PrEP is so important. It also raises the first of several major challenges for clinicians, as the highest rate of HIV in the USA right now is in a population that tends not to access care on a regular basis — young, African-American MSM.

Other challenges:

  • The risk assessment will have to be done on the front lines of care — that is, by primary care clinicians — as HIV-negative, at-risk patients do not see HIV/ID specialists.
  • These PCPs will have to get comfortable prescribing tenofovir/FTC. It’s not that it’s complicated (“take one pill daily”), it’s just that it’s not a medication they currently use.
  • They will also be responsible for monitoring both adverse events and (very importantly), incident HIV and other sexually transmitted infections.

Because of these issues, in the few years since PrEP became an option for HIV prevention, we’ve been offering our PCPs a one-time ID consult to discuss the risks and benefits, with a strategy for further follow-up outlined for the primary provider.

So can PrEP be more broadly adopted? I think we (meaning the patchwork U.S. healthcare system) can pull this off.

But it won’t be easy.

May 3rd, 2014

The Top Items from the Revised DHHS HIV Treatment Guidelines

A sparkling, shiny new revision of the DHHS HIV Treatment Guidelines was released this week (thanks Alice Pau!), and provides plenty to read and think about — 285 pages, if you’re counting.

A few ways to navigate this gargantuan effort more efficiently — the What’s New section, the recommendations summarized here, and the tables here.

But if you want the Monarch Notes/CliffsNotes version (clearly an analogy soon to be as outdated as dial phones, fax modems, and 8-track tapes), here’s one perspective (mine, not the panel’s) on the most important changes:

  • After two years of virologic suppression, frequency of CD4 monitoring reduced — and for those with CD4 > 500, it’s now “optional.” Everyone knows it makes no sense to modify treatment based on CD4 results alone in their patients on suppressive therapy, so it’s liberating to have this now formalized in treatment guidelines. Soon quality improvement programs, ADAPs, and others (patients?) will stop nagging us for CD4s in these situations. By the way, “optional” means “if it makes you and/or your patient feel better to check it, go ahead and do so.” It doesn’t mean that there are new guidelines for what to do with the results when the CD4 comes back 840, or 570, or 750, or 1001. And that’s because you should do nothing.
  • More recommended initial regimens! As per the late 2013 update, there are now seven recommended regimens — the “core four” from 2009 (TDF/FTC + EFV, or ATV/r, or DRV/r, or RAL), plus the three other integrase options:  TDF/FTC + EVG/c or DTG, and ABC/3TC + DTG. And now there’s an entirely new category for those with HIV RNA < 100,000, CD4 > 200, which for me predominantly exists for TDF/FTC/RPV. (ABC/3TC + EFV and ATV/r are also in there.) In fact, there are so many recommended regimens that the “preferred” term has been dropped, the alternative options relatively few in number (4), and many drugs (ZDV, FPV, MVC, SQV, NVP) no longer recommended at all. Makes sense to retire them, right? Why would you ever choose one of these for initial therapy in 2014?
  • The “Regimen Simplification” section is now called, “Regimen Switching in the Setting of Viral Suppression.” That’s a much better title, and not only that, the entire section has been extensively revised. If you read the PDF versus the HTML version and are looking for the yellow highlighting showing what has changed in this section, it’s intentionally left out when so much is altered — too distracting.
  • A whole new section on cost considerations. Gingerly treading into these potentially contentious waters, the section mentions cost sharing, prior authorizations, generic ART, lab testing (again), and the wholesale prices of various ART components.

Plenty more in there, of course. Now get reading!

April 27th, 2014

Why ID/HIV Specialists Rank Last in MD Salaries

Here’s a figure from Medscape listing 2013 physician compensation:

MD Compensation Report

Now a median of $174,000/year is hardly chump change, so I don’t expect much in the way of sympathy on these data. On the other hand, someone has to to be last, and note that our income hasn’t increased a bit since the last time I commented on this survey three years ago.

So it’s worth taking a few moments listing the top reasons why we rank so low, most of them probably as obvious to you as the antibiotic of choice for treatment of syphilis. Then we’ll once again end on a happier note.

Reason #1:  Doctors in the USA are paid the most for doing procedures.  A famous ID doctor once said, “No one ever got rich from doing a gram stain.” And even though I just made that quote up, it’s definitely true. We ID doctors barely do any procedures, and the few we can do are comparatively low ticket items such as PAP smears, CSF exams, minor wound care, I and D, etc. Some ID/HIV specialists have added various procedures to their practice to offset this deficit, such as screening for anal dysplasia in their HIV positive patients using high resolution anoscopy, doing fecal microbiota transplants for C diff, or providing injections of facial fillers for lipoatrophy — that last one most certainly a cash business. However, these enterprising (and for the first two, strong-stomached) ID docs are the exception, not the rule.

Reason #2:  Productivity of doctors is still measured in volume. In a fee-for-service, count-the-RVUs system, the more patients you see the more you get paid. And I suspect there are few cases less amenable to high volume service than those referred to ID/HIV doctors. Consider these:  Fever of unknown origin (clinic or hospital/ICU setting). Spinal osteomyelitis/epidural abscess. New HIV diagnosis (especially with advanced disease/complications). Acute endocarditis. Lyme disease (real or imagined). Recurrent UTIs in patients with GU anatomic abnormalities or spinal cord injury. Fever in the returning traveler. Non-tuberculous mycobacterial lung infection. Infectious complication following major surgery. Tuberculosis of any sort. Sexually transmitted infections. Transplant-related infections. And on and on and on …

Reason #3:  Many of the time-consuming services ID doctors provide have no billing code. Which means, simply, you can’t charge for your work. Did you spend an hour searching for a critical culture result done at an outside hospital? Maybe it was the orthopedics consult on a patient with a septic hip, now in your hospital with essentially zero information in the chart. And once this patient is treated, who’s going to arrange his/her post-discharge IV antibiotics? The lab test follow-up?  The vancomycin levels?  That’s right, it’s you, Dr. Bugsndrugs, and not Dr. Breakbone who can bill plenty for the time in the OR, while you can only hope your documentation on the initial consult note meets appropriate complexity criteria for a C4 or C5. (Don’t forget the review of systems.) The rest of the work listed above (aside from that first note) is essentially gratis. On a different case, did you spend an eternity searching for the resistance genotype done in 1999, relegated to the proverbial dust heap — but now it’s absolutely crucial to find it as you try to craft a new HIV regimen for a patient with significant side effects? What’s the billing code for that? And don’t get me started on curbside consults — just read this.

There are certainly other reasons for the low salary: low income means you can’t invest in money-making imaging/scanners (just a few have a FibroScan), there’s no ID-drug equivalent to Lucentis, a high proportion of us work on salary for a hospital/clinic rather than in private practice, and many participate in infection control/quality improvement programs that earn points for citizenship but rarely salary.

Yet despite the low revenue, we still seem to be doing great with two key questions — if we had to do it all over again, would we:

1) Choose to go into medicine [that is, still become a doctor]?
2) Choose the same specialty?

Here, low-ish revenues notwithstanding, we do pretty darn well, finishing second among specialties in question #1, and eighth in question #2. All of which means we’re pretty satisfied with our jobs — hardly surprising given that we have the privilege of working in such an interesting field. Money isn’t everything.

Take it away, boys!

April 24th, 2014

Pioneering Measles Vaccine Researcher Has Anecdotes, Insight, Perspective, and Generosity to Spare

people_measles5In the new IDSA/Oxford University Press journal Open Forum Infectious Diseases (OFID), we plan to interview a series of great figures in ID about their experiences, posting them as podcasts with accompanying scripts.

Our first interview is with Dr. Samuel Katz, a key figure in development of the measles vaccine, and it can be heard here.

It’s timely for several reasons. First, World Immunization Week starts today; second, MMWR just released a summary of the staggering health benefits of the “Vaccines for Children” program, created 20 years ago in response to the last big measles outbreak in this country; and third, the Annals of Internal Medicine has just published a thoughtful commentary on the difficulty of identifying measles in an era when so few clinicians have ever seen a case.

I encourage you to listen to the full interview, but here are some highlights:

  • What it was like working in the lab of Nobel laureate John Enders
  • How they tested the attenuated measles virus first in monkeys, and then on themselves (!)
  • Planning and conducting the first clinical trial
  • Expansion of the vaccine to international use
  • How Dr. Katz views the anti-vaccine movement

There are some great stories in there, all suffused with an extraordinary generosity of spirit and humility. You’ve heard the phrase “humble to a fault”? We’ve got a prime candidate in Dr. Samuel Katz!

After all, what other medical advances have had quite the health benefits of a safe, highly effective vaccine — especially for a disease as contagious and potentially serious as measles? Or, to extract some key data from the MMWR cited above:

Because of vaccination, approximately 322 million illnesses, 21 million hospitalizations, and 732,000 premature deaths will be prevented among children born during [the past 20 years], at a cost savings to society of $1.38 trillion.

That pretty much says it all.


April 12th, 2014

Unwittingly, HCV “News” Brackets Our Current Treatment Era on Successive Days

I’ve already told you what a fan I am of Physician’s First Watch, the daily email summary of hot medical news provided by my colleagues here at the Massachusetts Medical Society.

If you haven’t signed up, you must do so — let’s play a short tune (always a favorite) for background music while you head over there and take care of it. I’ll still be here when you get back:

Linus and Lucy by Vince Guaraldi on Grooveshark

Finished? Great.

Anyway, this week the diligent First Watchers sent me this on Thursday:

The World Health Organization has issued its first recommendations on screening for and treating hepatitis C infection … Pegylated interferon with ribavirin is the recommended treatment.

Interferon plus ribavirin? Blast from the past.

Now of course the WHO guidelines are much more nuanced than that — the full document includes discussions of telaprevir, boceprevir, simeprevir, and sofosbuvir.

But on a day-to-day basis right now, in places lucky enough to have access to the newest drugs, sofosbuvir is part of every recommended regimen, so it’s startling to see interferon and ribavirin listed alone. And barely mentioned at all is the sofosbuvir plus simeprevir combination — a regimen astoundingly free of side effects, and arguably the treatment of choice today for virtually everyone with genotype 1 if drug costs were no issue. (Which they most emphatically are.)

By contrast, First Watch sent this off the very next day:

An 8-week course of sofosbuvir and ledipasvir was not inferior to a 12-week course, or to an 8-week course that also added ribavirin … Another research group studied the combination of a protease inhibitor (ABT-450)… plus two inhibitors of hepatitis C virus replication (ombitasvir and dasabuvir) for 12 weeks … [Both studies had] response rates of roughly 95%.

They were referring, of course, to two remarkable studies (here and here) just published in the New England Journal of Medicine, showing us what’s soon to come: both a sofosbuvir/ledipasvir single pill regimen for just 8 weeks, and an interferon-free approach that doesn’t include sofosbuvir at all.

So in the future we’ll have choices between several excellent options.

Now get over to the First Watch site and sign up. You won’t regret it.

April 8th, 2014

Would “HIV Controllers” Benefit from Antiretroviral Therapy?

Let me start with a disclosure — I’m the co-PI (along with Jon Li and Florencia Pereyra) on a study addressing the very question in the title.

The reason for this post is that the topic has been the beneficiary of some terrific coverage in Nature Medicine, both of this research question specifically and the whole topic of HIV controllers in general. Highly recommended.

Everyone who practices HIV medicine has encountered at least one of these lucky few who have low or even undetectable blood HIV RNA without antiretroviral drugs. And as you know, these HIV controllers represent a small subset of those with HIV — estimates vary, but it’s almost certainly < 1%.

Our message to them for years was that they didn’t need treatment, because they are already doing essentially the same thing with their own immune system.

But now there’s a body of evidence that this HIV control may have a downside, specifically an excess of immune activation and inflammation — which can, over the long term, have adverse effects on health. Cardiovascular disease (here and here). Lymphoid fibrosis. And a surprising report at CROI this year found a higher rate of hospitalization among HIV controllers compared to a control group of HIV patients who are receiving ART.

So would HIV controllers benefit from HIV treatment? That’s what we’re trying to answer — more details of the study, ACTG A5308, right here.

And if you have a few minutes, listen to this interview from Nature Medicine. It’s chock-full of thoughtful questions, and my best attempt to answer them!

April 5th, 2014

$0 for 30 Minutes of My Time? Sign Me Up!

Best e-mail survey ever, my second invitation from them — hence a “friendly reminder”:

Dear Sax,

This is a friendly reminder about the online study we recently invited you to – X5328963_HCV

Approximate interview length: 30 minutes
Honorarium: $0
Estimated end date: 2014.06.22

By clicking the survey link below, you agree to participate under the terms specified above.

Start survey.

Once complete, please click the link below to check your account balance and redeem any outstanding honoraria.

Honorarium survey

Thank you for your time — your views are important to us.


Doctors get a lot of survey requests, but this is the first time I’ve received one that has so accurately estimated the dollar value of an ID specialists’ time.

Let’s see — if I do a hundred of these, what would my net be? Still zero?

Oh well. At least my views are important to them.

(Full disclosure: Survey links changed — last one to a candidate for the funniest four minutes… oh, just watch it.)

March 29th, 2014

Opening Day ID Link-o-Rama

19C_baseballSeveral ID/HIV tidbits to keep you entertained until Sunday night’s opening “day” — for baseball that is.

(I hear there’s some sort of basketball tournament going on as well.)

Away we go!

  • Female-to-female sexual transmission of HIV is extremely uncommon — though one such case was diagnosed at our hospital over 20 years ago — but this most recent report from Texas is probably the strongest case report to date, with both convincing behavioral and phylogenetic evidence of the transmission. Note that the infected partner had stopped HIV treatment in 2010, and had an HIV RNA of 82,000.
  • Thoughtful and interesting piece in the New York Times by noted health-care economist Uwe E. Reinhardt about the controversy over the price of sofosbuvir. Good primer on cost-effectiveness as well. The challenge here is that sofosbuvir is both an incredibly expensive drug and an incredible advance on what we had previously. Quandary indeed.
  • We ID doctors do love ceftriaxone — almost as much as we love doxycycline — and at least anecdotally, have been pushing this envelope of this third generation cephalosporin by using it more and more for Staph aureus infections. This report of high rates of ceftriaxone resistance among MSSA isolates might give us pause, however. Important caveat: no link to clinical outcomes in ceftriaxone-treated patients.
  • Taking acetaminophen with phenylephrine — a common combination “cold remedy” — can significantly raise phenylephrine levels, potentially to dangerous levels. One of the great ironies in your drug store is the vast array of cold medicines for sale — when basically none of them works at all. Because if one did work, don’t you think that would be the one we’d all use?
  • Speaking of colds, I’d bet one of the most common questions primary care providers (and ID doctors) get is, “Is it safe to exercise when I have a cold?” Thoughtful response here on the Mayo Clinic site, which I will instantly adopt.
  • Some of my friends were surprised when I didn’t comment on this latest flurry of news about the dangers of cat bites. Hey, stuff like this is ho-hum to us ID docs, we know already that cat bites are bad — but cat-to-human transmission of tuberculosis? Now that’s news! Importantly, this was M. bovis, which responds nicely to standard TB treatment. So add Mycobacterium bovis to toxoplasmosis, Bartonella spp (cat scratch disease), Pasteurella multocida … here, kitty kitty!
  • So the “Five Second Rule” for food dropped on the floor is real: “Time is a significant factor in the transfer of bacteria from a floor surface to a piece of food.” Extraordinary! Either that, or these British researchers have way too much time on their hands. Note that carpet is safer from a microbe perspective if fluffier. For a paranoid’s view of the whole issue, plus a scientist in an oh-so natty outfit, watch this.
  • Want to make your head spin? Read the methods section in this study on the use of xenodiagnosis for Lyme disease. It can be tough going at times (“Ticks were crushed and tested by PCR and injection of the lysate subcutaneously into an SCID mouse and/or by isothermal amplification followed by PCR and electrospray ionization mass spectroscopy, IA/PCR/ESI-MS,” egad), so this commentary is a big help — especially with this statement: “…detection of borrelial DNA by xenodiagnosis is not tantamount to detection of viable spirochetes.” Agree.

Back to baseball. Here’s the best story from Spring Training, the stray dog (Hank) who wandered into the Brewers’ training facility. Sure beats some guy with a mustache sliding into a mug of beer:

March 12th, 2014

Really Rapid Review — CROI 2014, Boston

CROI2014logoDespite the winter that would never end, intrepid HIV/ID researchers and clinicians arrived in Boston for this year’s Conference on Retroviruses and Opportunistic Infections –or more accurately, Conference on Retroviruses and Flaviviridae (little ID joke there) — which just finished last week. Not that it was easy — a winter storm roared eastward as the conference got started, leading to cancellation of dozens of flights headed this way from the Mid-Atlantic states. This was followed by many numb fingers and toes from our unseasonably frosty weather — it was 9 degrees F one morning, a balmy 12 degrees the next.

As usual, CROI was densely packed with scientific presentations and posters; some could argue that the content of one CROI includes as much information as the remainder of the HIV conferences put together. Certainly it feels that way sometimes, especially when there are synchronous “can’t miss” presentations — just try to be in two places simultaneously, especially when one of the slide session rooms is full. Check out the conference site for web casts and, eventually, many of the posters.

(Can’t directly link the abstracts yet — I put the abstract numbers in brackets after each citation — but you can get the full program here.)

Organized roughly (very roughly) by clinical trials, cure research, complications, epidemiology, and miscellaneous interesting studies, here is a Really Rapid Review™ of CROI 2014, brought to you in Technicolor by …oh, let’s get on with it already, and be sure to read to the very end for the top HIV study of the year, as well as a terrific video clip:

  • Success with an NRTI-sparing regimen? Could it be? In the NEAT study, a fully powered randomized clinical trial, darunavir/r plus raltegravir was noninferior to darunavir/r plus TDF/FTC. But — and there are several buts — there was again quite poor performance of the DRV/r plus RAL in those with high viral load/low CD4 (around one-third failed), and more resistance on failure. Plus, aside from some renal markers, was it better in any way? Not really. Can’t seeing using this regimen much based solely on this trial [84LB].
  • When combined with TDF/FTC, raltegravir was significantly better than both darunavir/r and (especially) atazanavir/r, with the relatively poor result of the atazanavir/r arm driving by lots of discontinuations for jaundice [85]. Why so high in this study?  A theory: Give people the option to switch and stay in the study, and they’ll take it. Note that virologic outcomes were the same. Lipids, bone outcomes also better with raltegravir [779LB, 746].
  • In a phase II dose-finding study, the investigational NNRTI MK-1439 — hereafter to be known as doravirine — was potent and well tolerated [92LB]. Guess the big question for its development is how much we need a new NNRTI — none of our current options is perfect, true, but they are pretty good. And what will be the three-letter abbreviation of doravirine? “DRV” is already taken!
  • In the LATTE study — how can you not love that name? — a two-drug maintenance treatment of the v-e-r-y long half-life integrase inhibitor 744 and rilpivirine, both given orally, worked quite well [91LB]. There was only one case of treatment failure with resistance, occurring in a study subject who was on a heavily calorie-restricted diet — not good for rilpivirine! These results set up the potential for a future combination strategy using injectable long-acting preparations of each drug — once-monthly injections, anyone? And will that be a niche intervention or transformative antiretroviral strategy? You decide.
  • For patients starting TDF/FTC/EFV, giving vitamin D and calcium significantly reduced the degree of bone mineral loss with ART initiation [133]. But is it enough to warrant doing it for everyone? And would it work if EFV were not the drug, which induces vitamin D metabolism? Somehow I’m just so biased against supplements, my gut feeling is to hold off for now in making this standard practice. Read the rest of this entry »

March 10th, 2014

CROI Is Over — and a Baby Once Again Takes Center Stage

One of our fellows asked me this AM when I was posting a RRR (Really Rapid Review™) of CROI 2014, and my response was to clear my throat, make some vague excuses, and curse the respiratory viruses that seem as perpetual as the cold weather this year.

It’s in the works, promise — but in the meantime, did you see the New York Times Editorial Page yesterday? Under the title, “Great Hope for Babies With H.I.V.”, the editorial cites the case reported at CROI last week of a second baby possibly “cured” of HIV after starting ART soon after birth.

Why do I use the word possibly and put the word “cured” in quotes? From the Times:

The baby, now 9 months old, has no signs of virus in her blood that can be detected by the most highly sophisticated tests. She cannot be considered “cured” or even “in remission” because she is still taking the drugs.

Yes, that bolding is mine.

Isn’t it incredible how much attention this case has received, despite that oh-so-important fact?

Prediction:  One day we will be treating all babies born to HIV-infected mothers who are not receiving ART with combination therapy, at least initially.

But until we have more than a few of these anecdotes — especially those that have stopped treatment and not experienced viral rebound — let’s calm down already.

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

NEJM Journal Watch
Infectious Diseases

Biography | Disclosures | Summaries

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