HIV and ID Observations

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.

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.

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.

Interested in researching the cause of AIDS?  Well go ahead and give NetBase Solutions’ healthBase a try, but don’t expect much in the way of filtering:

One of the most unfortunate examples is when you type in a search for “AIDS,” one of the listed causes of the disease is “Jew.” Really. The ridiculousness continues. When you click on Jew, you can see proper “Treatments” for Jews, “Drugs And Medications” for Jews and “Complications” for Jews. Apparently, “alcohol” and “coarse salt” are treatments to get rid of Jews, as is Dr. Pepper!

To be fair, the site seems to have cleaned up its act quite a bit since this report — here’s an example of a search I just did.  Most of the results are now much more plausible, but there’s still some wacky stuff there.  HIV is the number two cause of AIDS (number two?), and number five is “Abbott” — and I don’t they’re referring to the guy up there in the baseball uniform.

Look, I’m all for using the internet for medical information, and acknowledge I can barely function without it these days.  But this kind of advanced search engine takes lots and lots of human oversight, and for now the swarm of medical data out there in web-land can be as misleading as it is vast.

(Hat tip to Graeme M for the link.)

So says the Institute of Medicine’s recommendations for protection of health care workers:

Healthcare workers (including those in non-hospital settings) who are in close contact with individuals with nH1N1 influenza or influenza-like illnesses should use fit-tested N95 respirators … Employers should ensure that the use and fit testing of N95 respirators be conducted in accordance with OSHA regulations.

Every so often — well, more like constantly — my wife (the primary care pediatrician in full-time practice) reminds me what life is like seeing patients outside of a tertiary care, academic medical setting.

Her response to this recommendation to use N95 respirators for evaluation of all “influenza-like illness”?

Amazement, incredulity, bafflement, dismay.  Seeing as waiting rooms of pediatricians’ offices in the winter are filled with kids with cough, runny nose, and fever, I can certainly understand her response.  If these guidelines were followed literally, everyone in these offices would have to wear such a mask virtually all day — never mind the high cost and short supply of N95s, the logistics of fit-testing everyone, the effect on provider morale, etc.

In short, since following this recommendation is currently impossible, one possible response would be to refer all such patients to hospitals.  Bad for everyone.

Let’s hope when the CDC reviews these guidelines, they can provide some more practical (i.e., actually do-able) advice for people in practice.

From the FDA Advisory:

There have been postmarketing reports of cases of Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme, as well as hypersensitivity reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including hepatic failure. Intelence therapy should be immediately discontinued when signs and symptoms of severe skin or hypersensitivity reactions develop.

These rare — but potentially life-threatening — reactions have been reported with all the NNRTIs.  From my extremely unsophisticated perspective (the less said about my biochemistry performance in med school the better), the molecular structure of these drugs look quite different.

So what is it with this drug class?

A few ID/HIV items to cover before summer “unofficially” ends (Sept 1?  Kids back at school?  Labor Day?):

• Will US Public Health officials recommend infant male circumcision to prevent HIV?  They might be considering such a move, but I suspect it will not be strongly promoted.  After all, none of the studies demonstrating its efficacy have been done in developed countries, and the pattern of the US epidemic — predominantly gay men and women of infected male partners — excludes the very group circumcision has been shown to protect:  circumcised heterosexual men.  Look for lots of CDC-ese in these guidelines, with terms such as “consider” and “might choose” and “be offered.”
• Getting lots of questions from my patients about the H1N1 vaccine.  Some decent interim answers here.  When available?  (Don’t know yet.)  Who will get it?  (The young, pregnant women, those at risk for severe flu)  Will there be enough?  (Maybe.)  Will the regular flu vaccine still be needed?  (Yes.)  Will this season’s flu vaccination programs/clinics/sites be civilized affairs with minimal panic, anger, waiting lines, frustration?  (I hope so, but the media will do their best to portray the situation otherwise.)
• Anyone see this movie on chronic Lyme?  Would love to hear your impressions.  I have not seen it — but this will definitely be a Netflix choice when it a appears on DVD.  (Note that I did not link to Netflix; I’m a big fan, but they are the most egregious purveyors of annoying pop-up ads in the universe right now.)
• How’s this for a new definition of contagious?  Be reassured:  my little teaser photo has been thoroughly autoclaved.

Enjoy the sunshine …

Read all about it here:

As of August 17, 2009, written (signature) consent is no longer required for HIV testing in the VHA. Instead, patients will provide verbal informed consent prior to HIV testing. Furthermore, scripted pre-test and post-test counseling are no longer mandated.

Since the VA is the largest HIV provider in the nation — and has an exceptional electronic medical record/database — it will be fascinating to see how this policy influences new case detection, linkage to care, and whether there are any negative repurcussions.

Nice page of FAQs here.  And though you’re sick of hearing from me on this issue, I totally agree with this move.

This might seem bizarre, but one of the reasons I chose to go into Infectious Diseases as a field was the names of the diseases (and often the micro-organisms that caused them) sounded so darn cool.

For example, if you were a science fiction writer you could hardly come up with a better-sounding name for a mysterious disease than “toxoplasmosis.”  Or its full name, “Toxoplasma gondii”.

Major Pribulon, I’d advise against taking your Colonial Defense Armada into Sector 18, Ambrilla Zone — I hear reports of a widespread outbreak of TOXOPLASMOSIS.

Wow, that sounds scary.

Anyway, from the only toxoplasma diagnostic reference lab in the United States — the one at Stanford, founded by Jack Remington, now headed by Jose Montoya — comes this fascinating paper on risk factors for acquiring toxoplasmosis in this country.  It’s a case-control study using 148 newly-acquired cases from their serology lab, comparing them with 413 negative controls.  Here are the significant risks:

• eating raw ground beef or rare lamb
• eating locally cured, dried, or smoked meat
• working with meat
• drinking unpasteurized goat’s milk
• having 3 or more (!) kittens
• eating raw oysters, clams, or mussels

Interesting that having 1 or 2 kittens was not a risk factor, and neither was gardening.  Raw shellfish consumption is one I hadn’t heard before; there are several plausible explanations:

Oysters, clams, and mussels are filter feeders that concentrate T. gondii, as has been shown under experimental conditions. Sea otters in California have been found to be infected with T. gondii, and it is likely that they are often infected by eating mollusks, which filter T. gondii from seawater. The seawater in California is thought to be contaminated by T. gondii oocysts that originate from cat feces, survive or bypass sewage treatment, and travel to the coast through river systems.

And don’t forget:  stay out of the Ambrilla Zone, Sector 18.

Over on the CID web site, they have the revised version of the “IDSA Primary Care Guidelines for the Management of Persons Infected with Human Immunodeficiency Virus”. It’s a great document, filled with useful references and a particularly strong table where to find other consensus guidelines (diabetes, hyperlipidemia, mental health, others).

My vote for what will be most commonly-cited part of the guidelines it Table 5 (Recommended Baseline Lab Tests) — though Table 9 (Vaccines) could be a close second.

Some potential areas of controversy:

• No recommendation for routine screening for osteoporosis
• No recommendation for routine anal pap smears in MSM
• LP for all patients with late-latent syphilis or syphilis of unknown duration

Regarding the bone density, I suspect this will will be recommended one day, though agree for now it’s premature.

However, I’m sure there are many who will be surprised that the anal paps are not routinely recommended.  Solid quote:

Anal cytologic screening (ie, anal Pap smears) in HIV infected women and MSM is not considered to be the standard of care at this time but is being performed in some health care centers. Additional studies of screening and treatment protocols for anal dysplasia are in progress to clarify this issue.

Seems that it is done uniformly at clinics that have enthusiasts, or zealots — plus a high-resolution anoscopy plus biopsy protocol.  (”If you’re at Disneyland, you go on the rides.”)   We don’t really know yet whether this screening prevents cancer.

For the LP issue — I know it’s in the STD Guidelines, but do you really LP all such cases in your HIV patients?