An ongoing dialogue on HIV/AIDS, infectious diseases,
February 26th, 2009
Meningococcal Resistance to Ciprofloxacin
Ciprofloxacin-resistant Neisseria meningitidis has now been documented in the United States. Here’s a nice summary in Journal Watch, with two different perspectives.
I suppose we shouldn’t be surprised, but it did take a while. (At least compared to that other famous neisseria-bug, Neisseria gonorrhoeae.)
Oh well.
Why is this important? As every practicing ID doc/primary care provider/public health official knows, nothing strikes fear into a community quite like a case of invasive meningococcal disease. Since household contacts of these cases have a many-fold increased risk of developing the disease, preventive therapy is recommended for any close contact — with “close” being defined nicely by one infection-control practitioner I know as “coughing distance.”
But we all know that prophylaxis extends way beyond this — not surprisingly, many more people request and get preventive therapy than actually need it, and in part this is because it’s so easy to do: a single dose of ciprofloxacin.
Now this needs to be reconsidered. Although it’s up to each local department of health to determine the recommended preventive therapy, I suspect it won’t be long before we’re all back to rifampin (four doses over two days, drug interactions) or a shot of ceftriaxone (ouch).
February 13th, 2009
CROI 2009: Greatest Hits
Fresh back from lovely Montreal, where the temperature (I’m glad to report) climbed into the balmy 40’s …
Here’s a rapid-fire listing of the Greatest Hits. As I’m sure to be leaving something off this list, happy to accept other suggestions:
- Interleukin-2 does not work. The ESPRIT and SILCAAT studies are over. Yes, the CD4’s increase, but compared to antiretroviral therapy alone, there’s absolutely no clinical benefit, and plenty of side effects.
- Should we be starting antiretroviral therapy at even higher CD4s? At ICAAC, the NA-ACCORD group said starting before 350 improved survival; here they said it was 500! The ART-CC disagreed, slightly (their estimate was around 350).
- Switching from lopinavir/r to raltegravir increases the risk of virologic failure in suppressed patients. Likely explanation: undetected NRTI resistance at baseline. This study should have no bearing on the use of raltegravir in either treatment-naive or treatment-experienced patients — essentially, the drug must be used with at least one other fully active agent. (Oh yeah, the lipids improved, not surprisingly.)
- Treating HIV during TB treatment increases survival compared with waiting until TB therapy is completed. One of the most interesting things about this study is that TB treatment outcomes were similar — but those who delayed therapy obviously had HIV disease progression. By contrast, a small study of cryptococcal meningitis from Zambia suggested that early ART was harmful — the first time early ART has been associated with worse outcomes.
- Treating HIV significantly reduces the risk of HIV transmission to a seronegative partner. This study from Zambia and Uganda involved nearly 3000 discordant couples (!), and the effect was dramatic — especially when one considers that HIV therapy was only given if clinically indicated (i.e., not to prevent transmission).
- …But the risk of transmission is not zero. Some studies showed persistent HIV shedding in semen despite effective antiretroviral therapy. No surprise — but this doesn’t diminish my enthusiasm for #5 above, as the reduction in risk from treatment is huge.
- Antivirals and cardiovascular disease. D:A:D is updated, and continues to implicate abacavir, and a French Hospital Database study does the same — and both now cite lopinavir/r as associated with increased risk as well. An ACTG database study does not find an association with abacavir, but a prospective randomized switch trial (to ABC/3TC or TDF/FTC) does — in the updated analysis, the difference was statistically significant. Regarding abacavir, pathogenesis studies were all over the place — split about evenly whether positive or negative. Peter Reiss gave a sensational summary on this complex issue — web cast highly recommended if you have 15 minutes to spare.
- Lopinavir/r is better than nevirapine for women who previously received single-dose nevirapine. This might seem intuitively obvious, but it answers an important question that has generated enormous controversy over the years. (Plus the first author is a beloved colleague.)
- Two non-ritonavir boosters are introduced. (Details here and here.) Yes, data are early, but something without the GI and lipid effects would be welcome indeed. Whether we really will need PK boosters at all remains an open question, but for now they clearly are needed for PIs and the investigational integrase inhibitor elvitegravir.
- A microbicide works. Sort of.
So what’s missing? Not a single phase III study of a novel agent, nor a phase IV comparative trial of existing drugs done in the developed world.
Yes, it’s a very “quiet” phase in HIV drug development — too quiet. If this poster is a harbinger of what’s coming with integrase resistance, let’s hope it’s not quiet for long.
February 11th, 2009
CROI 2010 Dates and Location Announced
February 16-20, 2010, San Francisco — at least according to John Mellors during his opening remarks here in Montreal.
Is it really one day longer? [Update — no, it’s Feb 17-20.] Really during the week of Presidents’ Day? (School vacation week in New England … but I realize you can’t make everyone happy with schedules.)
In other words, regardless …
February 4th, 2009
Brush with Greatness: Bruce Walker
Bruce Walker has just received a $100 million grant from Terry and Susan Ragon to start a vaccine research institute, with a focus on finding an HIV vaccine. The news of this gift (which as you can imagine has been floating around these parts for some time) is all the more remarkable since it comes at a time when philanthropic efforts are declining precipitously, for obvious reasons.
So what kind of person is Bruce Walker? Aside from his being a genuinely nice guy, several words come to mind: Exuberant, optimistic, energetic. He’s done brilliant translational research in the field of HIV pathogenesis and — no small matter — can explain his work clearly and engagingly to non-lab scientists.
In fact, it may be this last skill that ultimately enabled him to get this incredibly generous gift. Sure, he has the scientific credentials, with literally hundreds of published papers and numerous prestigious grants.
But there are other folks like that in academic medical centers.
Which brings me back to what I think makes Bruce so special. He can describe his research with enthusiasm and clarity to just about anyone — other basic researchers, clinicians, journalists, high school undergraduates, Bill Gates, Elizabeth Taylor, and no doubt the guy he meets in his neighborhood who is out just walking his dog. I’m not kidding.
No matter how abstruse the immunology, he always brings it back to how this work could help — is going to help — actual human beings.
So congratulations to Bruce. After a year of major setbacks on the vaccine research front, this bit of good news is welcome indeed.
(Second in a very occasional series.)
February 1st, 2009
Whither PEPFAR?
Mark Dybul will no longer be running the President’s Emergency Plan for AIDS Relief, or PEPFAR, the multi-billion dollar international program for HIV treatment program started by Bush in 2003.
Some are happy. Others are not.
(Note the exquisite use of euphemism — he was “required to submit his resignation“, not “fired.”)
Experts on global HIV treatment can debate the pros and cons of this move, but can anyone truly be surprised? In this most highly politicized of diseases, how could we expect otherwise?
Right from the start, I viewed PEPFAR as kind of like a lifesaving medication that had a few side effects that you wished weren’t present, but was, well, lifesaving — so you dealt with it. Sure, critics might (and did) carp at the abstinence education requirement, the restrictions on treatment for “sex workers” (some say this isn’t the preferred term now, if not help me with this), and the fact that PEPFAR was set up independently from other already established treatment programs. And what about the 40+ million Americans without insurance? Why no PEPFAR-equivalent for them?
But it’s hard to argue with the results — In some of the world’s poorest nations, millions got HIV treatment who previously could not.
So say what you will about the politics of this recent move, PEPFAR was a groundbreaking piece of legislation by Bush, and Dybul was its on-the-ground leader. And given the past track record of some Repubicans on this disease, for these accomplishments they must get some credit.
January 29th, 2009
Too Many Options: What Actually Happened
We recently published a case in AIDS Clinical Care entitled “Too Many Options”, describing a patient with longstanding HIV infection, virologic failure, and resistance to NRTIs, NNRTIs, and PIs.
Fortunately, resistance and tropism testing gave him several options for a new drug regimen — including darunavir, etravirine, maraviroc, enfuvirtide, and — if one believes phenotypic NRTI susceptibility with multiple TAMs — several NRTIs.
And what did our three experts suggest? Three different regimens:
- Sharon Walmsley: darunavir/r, maraviroc, and etravirine (three drugs — not counting ritonavir)
- Tim Wilkin: darunavir/r, raltegravir, maraviroc, and tenofovir/FTC (five drugs)
- Graeme Moyle: darunavir/r, raltegravir, and maraviroc (three drugs, but different from Sharon’s selection)
Now these are smart, highly-experienced clinicians, physicians who are active in clinical research, know the literature extremely well, and actually see patients. (Funny how that last part is sometimes left out.) Each of them provided sound reasons for their (varying) choices.
And what did we do with this patient? (Or one very much like him … obviously some details changed as per HIPAA mandate.)
We offered him the chance to enroll in the clinical study ACTG 5241 (mentioned by Tim), which takes patients like this, gives them an optimal regimen — then randomizes them to receive or not to receive NRTIs.
(I don’t think it will ruin the study to mention that the “flip of the coin” gave him the “No Nukes” option.)
I sure hope we learn something from this study. While we know that regimens should contain “two (preferably three)” active agents, beyond that there’s plenty of uncertainty out there.
January 25th, 2009
Just Twenty Days Until Pitchers and Catchers Report …
As the temperature in Boston again falls below 10 degrees, my thoughts longingly turn to baseball — and how a locally unpopular team is making a foray into the world of Infectious Diseases:
The potential of a serious staph infection affecting a member of the team has not been lost on the New York Yankees. According to a provider of disinfecting sports coating, the Yankees have been proactive in their quest to keep the new stadium as clean as possible.
“Of course they want to protect their investments, but they also want to minimize any bacterial infection anywhere in the new stadium to protect the fans,” said Craig Andrews, CEO of CSG Sportscoatings. “They are the most proactive of any organization in Major League Baseball in protecting their facilities for players and fans.”
Andrews said all public bathrooms and concession areas, along with the home and visiting clubhouses, weight rooms, lounges, showers, coaches’ rooms, dugouts and bullpens, are being treated.
Whether these coatings actually work is open to debate — regular cleaning of surfaces with detergent-based cleaners or disinfectants seems most important in locker rooms — but regardless, I can just hear it now.
Yankee fan: “Great, now Texeira, Sabathia, Jeter, and A-Rod can stay healthy.”
Red Sox fan: “This will probably spawn the super-bug that will end civilization.”
Football fan: “Who cares?”
January 22nd, 2009
Fear of Vaccines: Not Just Parents
Fear of vaccines are legion among many parents, with enormous public health resources devoted to defusing this fear and trying to debunk common myths. I find this site particularly useful.
(Talk about a “hot button” topic. Read this to get an idea about how passionate views on vaccine safety can be. Wow.)
This fear, however, isn’t limited to parents. With the updated adult immunization schedule just released, I thought I would share a recent e-mail I received from a very experienced internist:
A man with nasal polyps on inhaled steroids regularly, requests Zostavax. Would you counsel avoiding the injection out of concern for him developing disseminated zoster with the vaccination, or is this not a concern? Would the vaccine have any effect on the likelihood of lung cancer recurrence, which was surgically resected last year?
The answer to the first question is easy — no. (Guidelines here, reviewed by me here.)
But the second question? Why would someone worry that the zoster vaccine would cause a relapse of cancer? Is there yet any biologic or epidemiologic data that could possibly link immunization with cancer recurrence or progression?
Yet if the vaccine is given, and the cancer then recurs, will the patient — and his doctor — connect the two?
One of the first lessons in Statistics 101 is that correlation does not mean causation. But boy this is a hard lesson to learn.
January 17th, 2009
Salmonella, CDC, and How to Prevent a Cold
Today’s ID/HIV Link-o-Rama is being brought to you from the frozen tundra of Boston, MA:
- This past summer’s salmonella outbreak that sickened more than 1000 people was linked to raw jalapeno and serrano peppers. In the current one, the suspected culprit is contaminated peanut butter. Aside from the fact that raw hot peppers and peanut butter in a jar are both uncooked, I can hardly think of any two foods as being more dissimilar. (“Would you like some hot salsa with your peanut butter?”) Count food safety as one of the formidable challenges for the newcomers to the FDA (along with perhaps updating their clunky web site).
- Another government-agency transition will be taking place at the CDC, as current chief Julie Gerberding will be stepping down. (Can’t seem to find this info on their now-excellent site — maybe waiting for the official day, Jan 20 2009.) Her tenure will be forever linked to her strong position during the anthrax attacks of 2001, which led to her subsequent appointment — plus charges that she softened her position on global warming to match that of President Bush. And there was a notable appearance in this famous Journal of Epidemiology.
- The pneumococcal vaccine has significantly reduced cases of pneumonia in infants, and meningitis in both children and adults. The current rate of pneumococcal meningitis is 0.79 case per 100,000 persons, confirming what I always tell our ID fellows — that bacterial meningitis is a rare entity indeed, so it’s no wonder we are consulted on virtually every case. It doesn’t matter that choosing the right antibiotic is usually easy; these cases are terrifying.
- Add a reduced risk of colds to the (long) list of benefits associated with a good night’s sleep. Study volunteers (yes, people volunteered for this) were 3-fold more likely to get a cold after a rhinovirus challenge if they slept less than 7 hours a night. I am not by nature one of those paranoid ID doctors who believes that the world is filled with nasty micro-critters just waiting to strike — in fact, I’m relatively laissez-faire on most ID-related issues. (Eating in Mexico City, for example.) However, I’m terrified of colds (am convinced the severity of colds is proportional to nose size) and can think of few greater motivations for getting enough sleep than this latest research.
- Speaking of cold — cold weather, that is — the high temperature in Montreal yesterday was -4.0 degrees Fahrenheit. As I write this, it is a comparatively balmy 1 degree above zero. Say what you will about the CROI organizers, they are a hardy bunch. This year’s meeting should make those Februaries in Chicago seem like a trip to the Caribbean.
Stay warm!
Paul E. Sax, MD
Contributing Editor
NEJM Journal Watch
Infectious Diseases
Biography | Disclosures | Summaries
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