An ongoing dialogue on HIV/AIDS, infectious diseases,
November 7th, 2009
A Career in Infectious Diseases and “The Next Big Thing”
I was working with a medical intern in clinic this past week who is potentially interested in ID. After seeing our 3rd consecutive stable HIV patient, he asked me what I thought the next big challenge would be in our field — especially since HIV treatment has been “solved.”
“Solved” might be stating it a bit strongly — after all, we still have no cure, the drugs aren’t perfect, not everyone can get them, there’s no vaccine, etc — but he had a point. Many of the research questions on HIV treatment are now about moving things forward incrementally, and it’s hard to imagine an advance anytime soon along the lines of combination therapy in the mid 1990s, or even the second wave of newer treatments that become available in 2006-8.
So what’s the answer to his question? I compiled a brief list, shown below in no particular order:
- Highly drug-resistant bacteria — MRSA, carbapenemase-producing gram negatives, etc.
- Influenza, obviously, plus other SARS-like respiratory viruses
- Hepatitis C, though we’ll have to take this back from the hepatologists — I doubt they’ll mind — with nearly a hundred novel treatments in development
- Infections associated with therapeutic immunosuppression — TNF blockers, other biologics
- Food safety
- Device-related infections
- Novel diagnostics — PCR, other amplification techniques, direct antigen detection methods, etc
- Finding the next infectious cause of some idiopathic or autoimmune disease — some helicobacter-like discovery regarding Crohn’s, or multiple sclerosis, or sarcoid
(Not on my list are issues specifically related to ID in resource-limited settings, because that’s not what I do.)
I’m sure I’m missing something, but it’s a start.
October 31st, 2009
Would Changing Restrictive HIV Testing Laws Improve Survival?
Emphatically yes — to the tune of >600,000* years of life gained nationwide. So says a nifty paper being presented at the annual IDSA meeting today by Mike April, under the direction of Rochelle Walensky.
(*Original abstract said 549,437, cited in the link; number at the actual presentation, though, was 609,656.)
Bottom line is that laws that limit HIV testing (such as requiring written consent, ahem) lead to later diagnoses, and hence shorter projected life span for those with HIV. As always with such models, one could quibble with certain assumptions, but the results remain robust through a wide range of sensitivity analyses.
In fact, the only way that switching to an opt-out testing policy could fail to improve survival is if opt-out discouraged a large group of people from getting tested at all — for which there’s not the slightest bit of evidence whatsoever.
Are you listening Massachusetts? I think you are .
October 20th, 2009
Well That Was Fast! HIV Vaccine Trial Published
Remember the HIV vaccine trial press release? The one announcing the first-ever positive result?
Then the backlash, with people questioning how the analyses were done, and reported?
Now, less than a month later, we have the scientific presentation and the paper appear on the same day.
Read all about it here and here.
If you want the view from 10,000 feet (why is that the chosen altitude for that cliche?), here it is:
- The vaccine strategy combines two vaccine generally thought to be ineffective on their own — canarypox ALVAC-HIV and glycoprotein 120 AIDSVAX B/E — in a “prime and boost” approach
- Over 16,000 patients are enrolled in Thailand in a placebo-controlled trial
- The “modified intention-to-treat” analysis, which excludes those who are found to be HIV positive at entry, shows a modest but statistically significant protective effect, reducing the infection rate by about 30%
- There is a trend towards a protective effect in the intention-to-treat and per protocol analyses
- In those who were vaccinated and became infected, there was no effect on CD4 cell count or HIV RNA
Numerous questions remain, many of them summarized in this accompanying editorial: Why did it work when the individual strategies didn’t? How durable is the protection? How do the strains causing infection relate to those in the vaccine? Did the per-protocol analysis fail to show a significant protective effect solely because of a smaller sample size? Would the vaccine work if tested on higher-risk populations? What effect will this study have on the ongoing vaccine development effort, both in the lab and in trials?
Answers to some of these questions may be forthcoming. Regardless, the surprising results of this study serve as a reminder of just how mysterious the immune system remains — despite some incredibly smart people working on it with lots of resources.
Because if you asked the vaccine cognoscenti to vote a little over a year ago on which strategy in clinical trials would end up with a positive result — the “prime and boost” one published today or the adenovirus vector approach — the latter would have won in a landslide.
October 17th, 2009
Is Chronic Fatigue Syndrome Another Retroviral Disease?
Here’s a surprising report in Science:
Studying peripheral blood mononuclear cells (PBMCs) from CFS patients, we identified DNA from a human gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV), in 68 of 101 patients (67%) compared to 8 of 218 (3.7%) healthy controls … These findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of CFS.
I confess, I had never even heard of “xenotropic murine leukemia virus-related virus” (wow that’s a mouthful) before this report, but apparently virologists have been aware of it for some time, due to a possible association with prostate cancer.
The story behind the Whittemore Peterson Institute reporting these findings is almost as interesting as the paper itself. From their web site:
In September of 2004, a group of dedicated citizens and clinicians proposed the concept of a medical institute for the millions of patients in the US suffering from the disorders known as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), fibromyalgia and other closely related illnesses. They were concerned by the lack of available doctors to understand and serve the growing numbers of patients with these complex chronic illnesses.
According to the coverage of the story in the Times, the Institute got its start with a several million dollar donation from Annette and Harvey Whittemore, whose child has been suffering from CFS for over twenty years. The Times piece goes on to quote Dr. William Reeves from CDC, who sounds quite skeptical about the findings.
“We and others are looking at our own specimens and trying to confirm it,” he said, adding, “If we validate it, great. My expectation is that we will not.”
My take on all this? Despite our being down this road before on CFS — EBV, HHV-6, candida, enterovirus, parainfluenza, Lyme, to list a few putative causes — without much to show for it scientifically, I’m all for having multiple groups working on trying to find the cause of this awful disorder, even if it seems likely that there is more than one cause.
And judging from some of the pained, angry, and frustrated comments posted here, I’m clearly not alone.
October 12th, 2009
AIDS Vaccine: Maybe not Effective After All
Well, that didn’t take long:
Researchers from the U.S. Army and Thailand announced last month they had found the first vaccine that provided some protection against HIV. But a second analysis of the $105 million study, not disclosed publicly, suggests the results may have been a fluke, according to AIDS scientists who have seen it.
In short, two additional analyses (intention-to-treat and per protocol) do not show a statistically significant protective effect. In other words, the study subjects who followed the protocol most closely (per protocol) had less protection from the vaccine strategy.
What the …
But even in the original report, the protective effect didn’t seem all that great — statistically significant, yes, but maybe not clinically significant — so when you add how cumbersome this vaccine is to administer (and probably to manufacture), as well as these new findings, the likelihood of this vaccine strategy making its way to clinical use seems vanishingly small.
So what can we still hope from this study?
At best, some understanding of the correlates of protection. Maybe.
October 5th, 2009
No Baseball Tonight
“Are you writing another funny blog post because there’s no baseball?” asks my son J.
As “funny” is very much in the eye of the beholder, that remains to be seen. But here are a few things on my mind the last few days:
- No data supporting N95 over surgical masks for flu. One huge logistical issue dodged — at least for now. But Consumer Reports, that darling of objective reporting, seems to think they’re just great. Since “minimax” is the operative strategy for infection control, look for this controversy to go on for a bit.
- Speaking of flu, I’ve been hearing for weeks (from a certain someone) how chaotic this H1N1 vaccine situation will be in pediatric practices. And here’s proof.
- LONG (wow) piece on E. coli O157:H7. Not unreasonable, given the potential severity of the illness and the tortuous route hamburgers take en route to our kitchens. (Yuck.) Did I mention before that this is one of the few ID issues that my wife and I take a hard line on? Make those burgers well-done, thank you.
- Hey, did you catch the 10AM agenda in tomorrow’s General Court of the Commonwealth of Massachusetts? Can’t miss that.
- Finally, did a throat infection bring down the mighty Tyrannosaurus rex? Perhaps if the dinosaur doc sent a “hold” tube to the lab, they can make the diagnosis retrospectively.
Good luck Tigers/Twins fans!
September 30th, 2009
The Battle for Colonic Microflora
My two favorite newspapers (New York Times and Wall Street Journal — sorry, hometown paper) have just covered opposite ends of a topic on the edges of ID practice — namely, colonic micro-organisms.
Too few?
Too many?
Wrong type?
In the Times, a review of the probiotic debate:
Probiotics are live micro-organisms that work by restoring the balance of intestinal bacteria and raising resistance to harmful germs… So what health problems can probiotics really help? After gathering at a Yale workshop to review the available evidence, a panel of 12 experts concluded that there was strong evidence that several probiotic strains could reduce diarrhea, including that associated with antibiotic use. Several studies have also suggested that certain probiotics may be useful for irritable bowel syndrome.
I suspect the “experts” were gathered specifically because they had interest in this topic, and hence may be predisposed to a favorable review of the data. Still, there might be something to it, and I’m crazy about yogurt — full summary of their report here, which was published in 2008.
Far more fringey, however, is the whole “colon cleansing” craze, covered in the WSJ:
The typical American diet of processed foods, pharmaceuticals, stress and lack of exercise is clogging up our lower intestinal tracts, leaving them inflamed and lined with waste—and leaking toxins into the body that cause problems ranging from headaches and chronic fatigue to arthritis and cellulite. All that “stubborn fecal matter” also contributes to bulging bellies and expanding waistlines, cleansing proponents claim.
Eliminating the buildup, either with supplements or laxatives, or by flushing the colon with warm water—a practice known as “hydrotherapy” or “colonics”—can dramatically improve a person’s health and well-being, proponents claim …
Gastroenterologists pooh-pooh [I did not make that up!] many of these claims …
What follows is a very thoughtful review — and a clear debunking — of what seems to be a major form of quackery out there. For example, here are the claims of one such service:
Colon cleansing benefits intestinal tract problems, absorption, bowel disease, constipation, digestive system, parasites, yeast infection. Helps control blood pressure, restores pH balance, restores proper digestion, reduces bad odors. Colon cleansing also clears intestinal blockage, relieves bloating, helps purify blood, kills bad bacteria, viruses. These are just of few of the many benefits one can receive by cleaning the intestinal tract.
The problem, of course, is the scientific data backing up these claims are pretty much non-existent. But hey, it’s just $25 for the “Oxygenated Colon Cleanser,” and $35 for the “Super-Oxygenated.” FREE SHIPPING!
Ultimately, I think one of the gastroenterologists quoted in the WSJ piece really nails it here:
“There is a degree of obsession that goes along with this,” says Dr. Landzberg… Even “natural” laxatives, such as the plants senna and cascara, can harm the bowel, Dr. Landzberg says, adding, “The public has grown increasingly wary of the side effects of pharmaceuticals. I would like to see people bring that same degree of healthy skepticism to ‘natural’ products.”
Wise words indeed.
September 25th, 2009
MRSA in Pets
As every card-carrying ID specialist knows, hardly anything is more common these days than patients with — and questions about — methcillin-resistant Staph aureus, or MRSA.
And one question I’ve been hearing increasingly these days is “Could I be getting my recurrent infection from Rufus?”
To which the answer is, unfortunately, yes.
(I had a dog named Rufus. No offense intended to people out there actually named Rufus.)
Now along comes this article in the New York Times, which no doubt will stimulate the economy by prompting massive sales of hand-sanitizers, plus a flurry of trips to the vet to have Otto cultured.
(That’s Otto — our cat — in the picture, FYI.)
The article is self-explanatory — pets get MRSA, they can spread it to their owners and back — but did they have to put this caption under the picture of the dog?
INFECTION Don Graff of Belle Mead, N.J., with his English setter, Sunny. The dog contracted MRSA after a spider bite [emphasis added] but was given medication and has improved.
Spider bite! If there’s one thing this medical writer should have figured out in her background research for the piece, it’s that MRSA infections are frequently mistaken for spider bites.
And I’d bet good money that Sunny (the English setter in the Times story) never had one — for which I’m sure he’s quite relieved.
September 24th, 2009
HIV Vaccine Study Shows Promise …
So says this press release by the US Military HIV Research Program:
A Phase III clinical trial involving more than 16,000 adult volunteers in Thailand has demonstrated that an investigational HIV vaccine regimen was safe and modestly effective in preventing HIV infection. According to final results released by the trial sponsor, the U.S. Army Surgeon General, the prime boost combination of ALVAC® HIV and AIDSVAX® B/E lowered the rate of HIV infection by 31.2% compared with placebo … In the final analysis, 74 placebo recipients became infected with HIV compared to 51 in the vaccine regimen arm. The efficacy result is statistically significant. The vaccine regimen had no effect on the amount of virus in the blood of volunteers who became HIV-infected during the study.
This is great news, of course; we’ve become so used to hearing gloom and doom about HIV vaccine studies that one can’t help but be excited, despite the relatively low (but statistically significant) rate of protection.
Still, one suspects such a combination vaccine could be logistically difficult to manufacture and administer , especially since one arm of the strategy employs the live-canarypox virus ALVAC vector, and 5 injections were required.
Plus there is the issue of cross-clade protection — the vaccine was designed to protect against the most common strains circulating in Thailand (B and E). While B is quite common in North America and Western Europe, is is far less so in Sub-Saharan Africa, where the HIV epidemic is the most severe.
Nonetheless, if you put this news along with the proven protective effects of male circumcision and HIV treatment — the latter I believe to be greatly underestimated by the medical and non-medical community — things are definitely looking up in the HIV prevention arena.
Further details on the study will be presented at the AIDS Vaccine Conference, October 19-22 in Paris — interestingly a return to the same city where HIV was discovered.
Paul E. Sax, MD
Contributing Editor
NEJM Journal Watch
Infectious Diseases
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