“The Dallas Buyers Club” Takes on AIDS, Peer Patients, and Not Taking “No” for An Answer

If you’re a doctor or nurse of a certain age, the Dallas Buyers Club will jog memories. If you’re among those who lost a loved one or friend to AIDS maybe 20 or 30 years ago, or not, this new film might wrench your heart. Anyone watching will be pushed to think hard about drug development today, the slow pace of progress for metastatic breast cancer and other young life-takers, and the FDA’s role in sanctioning, or blocking, treatments for adults with terminal illness.

Dallas Buyers Club image from FOCUS films copy

scene from “the Dallas Buyers Club” (Focus Films)

The movie draws loosely on the story of Ron Woodroof, a Texan rodeo rider who developed AIDS around 1985. A rail-thin Matthew McConaughey, who says he dropped nearly 50 pounds for this role, somehow nails the look of young, HIV-infected men who were filing into hospitals and clinics back then. After absorbing his diagnosis and said prognosis of 30 days to live, the cowboy teams up with Rayon, a (fictitious) transgender woman portrayed, memorably, by Jared Ledo. Together with an oddball group of sympathetic accomplices, the pair set up shop, to procure and distribute unapproved medications the doctors won’t prescribe. Jennifer Garner plays a sympathetic young physician, Dr. Eva Saks, who in the movie crosses lines a bit incredibly, too personally in the second half, to help the AIDS patients and commiserate. But otherwise the film is spot-on. It captures the desperation, determination and clinging together of people, then, affected by what was incurable disease.

One question that sticks with me, as a physician reflecting on the story, is how unclear it is which drugs, exactly, helped the protagonist. Woodroof, as depicted in the film, briefly takes AZT and then moves on to all kinds of substances including DDC (Zalcitabine) from Mexico, interferon of unknown purity or dose from Japan, protein supplements and more. Through a mix of stuff he lives until 1992, seven years beyond what the doctors first told him to expect. An old-school clinical trialist, almost any of my former teachers, and anyone who appreciates evidence-based medicine (as I do, for the record) would know and state and insist that you can’t draw any conclusions based on what happened to the movie’s protagonist, or Woodroof in real life.

On the other hand, clinical trials are painfully slow. Published trials can be flawed. Even if they’re randomized and well-analyzed, the findings can be hard to interpret when it comes to a single patient’s course and well-being. What’s a dying man to do?

Another relevant point, for people affected by almost any health problem, is the extent to which the patients took charge in the Dallas Buyers Club. They found and shared information about their disease independently of their physicians. The image of an AIDS patient using an old computer in a library, looking up articles about his condition, anticipates patient networks of which there are hundreds, on-line and in communities, today.

I came away from this movie feeling optimistic. Because when I was a student, 30 years ago, I wouldn’t have believed that a man afflicted by AIDS, as McConaughey portrays, could now, likely, live for a long time.

#hope, and happy Thanksgiving,


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Visiting an Exhibit on Early AIDS at the New York Historical Society

School’s back in session. With fall approaching, your author has resumed teaching and attending lectures. Today I had the chance to visit the New-York Historical Society where an exhibit, AIDS in New York: The First Five Years is winding down. The display closes in two days.

A group advocating AIDS research marches down Fifth Avenue in June, 1983. (Mario Suriani/AP) - NYHS image

A group advocating AIDS research marches down Fifth Avenue in June, 1983. (M. Suriani/AP image) NYHS 

The opening scene, by the first room’s entrance, is breathtaking in a way. There’s a huge picture of men, countless, basking in the sun on a Hudson pier. The men looked relaxed, comfortable and healthy – blissfully unaware of what lies ahead. The exhibit takes you through the late 70’s club scene, with just a few pictures of that, and then moves to confusing and odd reports of unusual infections in homosexual men, intravenous drug addicts, hemophiliacs and Haitians. The show moves on into the early 80’s, when science steps in slowly, and most politicians keep away.

What’s clear is that most doctors didn’t know what was going on. The young men weren’t sure either. There were rumors but also credible denials about a disease affecting the community. Gradually, the city’s Department of Health and CDC started tracking the problem. There were protests, and activists, and friends helping friends to die. There was no therapy back then, except to temper some of the infections and treat the once-rare cancers we were seeing with strange frequency.

I had the fortune of walking through the exhibit today among a group of suburban high school students – kids who were born after the invention of anti-retroviral therapy. Their questions – some simple and others intense, and the relatively young guide’s recounting of her experiences during the early AIDS years, made me realize how crucial is this history. It was a terrifying health problem, then.

Yes, the historical society’s exhibit is neat and tidy. I remember, well, caring for young people who died, hopelessly. The gravity of the epidemic isn’t captured. But it’s a worthwhile review, nonetheless – especially for its bits on low-end media, like typed bulletins from the early Gay Men’s Health Crisis and early posters on safe sex. Those frank messages provided the only information some people at risk received about the emerging disease. The display includes a few passages and images having to do with patients helping patients. That was the best part.

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NEJM Reports on 2 New Drugs for Hepatitis C

Last week’s NEJM delivered an intriguing, imperfect article on a new approach to treating hepatitis C (HCV). The paper’s careful title, Preliminary Study of Two Antiviral Agents for Hepatitis C Genotype 1, seems right. The analysis, with 17 authors listed, traces the response of 21 people with hepatitis C (HCV) who got two new anti-viral agents, with or without older drugs, in a clinical trial sponsored by Bristol-Meyers Squibb.

The 21 study participants all had chronic infection by HCV genotype 1, a strain that’s common in North America and relatively resistant to standard treatment. All subjects were between 18 and 70 years old, with a measurable level of HCV RNA in the blood, no evidence of cirrhosis, and no response to prior HCV treatment (according to criteria detailed in the paper). In the trial, 11 patients received a combination regimen of daclatasvir (60 mg once daily, by mouth) and asunaprevir (600 mg, twice daily by mouth) alone; the other 10 patients took the experimental drugs along with 2 older meds for HCV – Peginterferon (Pegasys, an injectible drug by Roche) and Ribavirin (Copegus, a pill, by Roche).

The main finding is that the 10 patients assigned to take 4 drugs all did strikingly well in terms of reducing detectable HCV in their blood over the course of 24 weeks. There was a dramatic response, also, in 4 of the 11 patients assigned to the new drugs only. An accompanying editorial highlighted the work as a Watershed Moment in the Treatment of Hepatitis C. The medical significance is that they’ve demonstrated proof of principle: by “hitting” a resistant HCV strain with multiple anti-viral drugs simultaneously, they could reduce it to undetectable levels.

The first question you have to ask about this report is why the NEJM – the most selective of medical journals – would publish findings of an exploratory analysis of two new pills paired with two older drugs for HCV. The best answer, probably, is that the virus infects some 4 million people in the U.S. and approximately 180 million people worldwide, according to the study authors. HCV can cause liver damage, cirrhosis, liver cancer (which is usually fatal) and, occasionally blood disorders.

The new drugs derive from some interesting science. This, maybe, also is a factor in why the article was published in the NEJMDaclatasvir (BMS-790052) blocks a viral protein, NS5A, that’s essential for HCV replication. The second new drug, asunaprevir (BMS-650032) inhibits a viral protease, NS3.

I have several concerns about this report. One is that the researchers screened 56 patients for possible registration but enrolled only 21 on the trial; according to a supplementary Figure 1, 35 potential subjects (over half) didn’t meet criteria for eligibility. This disparity makes any once-researcher wonder about bias in selecting patients for enrollment. If you’re a pharmaceutical company and want to show a new drug or combo is safe, you’re going to pick patients for a trial who are least likely to experience or display significant toxicity.

Toxicity seems like it could be problematic. Diarrhea, fatigue and headaches were common among the study subjects. Worrisome is that 6 patients (of 21, that would be 28.5% of those on the trial) had liver problems manifest by at least one enzyme (the ALT) rising over 3 times the normal limit.

Further complicating the picture is there’s no indication of how these new drugs mesh with the two drugs approved for HCV in 2011: Vic­trelis (boceprevir) and Incivek (telaprevir).

Given all these limitations, you might wonder about BMS’s influence at the Journal or, more likely, the manuscript’s peer reviewers. The 17 study authors, and the editorialist, separately, disclose a host of industry ties.

What I’m thinking, as much as I’m critical of this research work, is that this is probably the way of the future – smaller, pharma-funded studies of targeted new drugs in complicated combinations. Many will be authored by academics with ties to industry, if not put forth directly by company-employed researchers. These quick-and-promising studies in select patient groups will be routine. And while advocates push for rapid publication of new clinical research in patients with resistant, disabling diseases, it’ll be hard for physicians and patients to interpret these kinds of data.

So these particular findings may turn out to be true and life-saving, or not. The bigger concern is this: It would be helpful if the journals would take a really tough stance on full disclosure of authors and editors ties to industry. As Merrill Goozner has emphasized, the Physician Payment Sunshine Act – a small component of the 2010 HCR legislation – has important implications for academic medicine and reporting of clinical research studies.

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Magic Johnson is Alive 20 Years after Announcing He Had HIV

Yesterday’s Washington Post Sports has a clip from CNN, 20 years ago, when basketball star Magic Johnson announced on TV that he had HIV, the virus that causes AIDS. The date was Nov 7, 1991.

“Where were you when Magic made his announcement? What were your thoughts on Johnson and HIV/AIDS that day and how have they changed?” asks Matt Brooks in his column.

I can’t quite recall where I was. Probably I was at the hospital working, possibly even taking care of a patient with HIV. But I do remember thinking how much courage it must have taken for him to come out with it.

He understood, likely, that he would die soon, and his doctors probably thought the same. There were only two antiviral drugs approved for HIV back then. There was so much stigma, and fear.

Today you can see and listen to him in an interview on ESPN.

It’s great to see Magic Johnson back in the news, even if it’s (just) in a sports sections, and to be reminded that he’s alive, doing OK. The condition we thought was a death sentence has become a chronic illness, with so many drugs available for treatment it’s hard to keep track.

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Gregg Allman Stars in Hepatitis C Awareness Campaign, with Merck

This weekend I learned that Gregg Allman, of the Allman Brothers, has hepatitis C. Not just that; he underwent a liver transplant last year for treatment of liver cancer. This information came my way via CNN, in a clip narrated by Dr. Sanjay Gupta. The cable TV crew filmed the old rocker in Macon, Georgia, at the band’s Big House.

Gregg Allman, performing in 2010 (Wikimedia Commons)

“He’s taping a public service announcement for the drug company Merck, about hepatitis C,” Gupta says 40 seconds or so into the clip (italics added, ES).

Hepatitis C stays silent in many carriers, meaning that most people with the virus are unaware of their infected state. The liver-infecting virus spreads most often by contaminated needles, sexual relations or transfusion of infected blood. Over time, the virus tends to cause liver damage and blood problems including anemia and, rarely, a condition called mixed cryoglobulinemia. In patients with long-standing hepatitis C, there’s a significantly elevated risk of developing liver cancer.

For two decades there have been a few, fairly effective anti-viral drugs available for hepatitis C. Treatment generally reduces patients’ anemia and liver disease, which leads them to feel better, and also reduces the risk of the long-term effects of infection, including liver cancer. Last month the FDA approved two new drugs for hep C: Victrelis (boceprevir), manufactured by Merck, and Incivek (telaprevir), by Vertex Pharmaceuticals.

While I have no formed opinion as to which of these new drugs is most effective or less toxic or more affordable in the long term for patients with hepatitis C, I do find it strange that Gregg Allman will be singing for Merck.

Eat a Peach (album cover)

The ethics of this are complicated: On the one hand, it might be a good thing for a music icon to raise public awareness about hepatitis C, so that more people at risk might get tested and then treated early before they develop severe liver disease and cancer, and would feel better. Gregg Allman is in a position to spread that message effectively: “If I have hep C, you might have hep C. Let me tell you about it…” (somewhat in the style of Magic Johnson, on HIV).

On the other hand, the notion of a post-transplant musician serving as the public’s primary source for information on hepatitis C seems preposterous, especially if he’s tied in with a pharmaceutical company with a stake in the matter. The situation is reminiscent of Sally Fields starring in commercials for Boniva, an osteoporosis drug.

You might ask yourself – and it’s not a trivial exercise – who can best, and objectively, inform the public about viral liver infections and the potential benefits of treatment: doctors? (we harbor biases; many have industry ties); patient peers? (Allman is a heightened example, but he’s hardly objective about this, either); newspapers? (or radio…

Will Allman’s be wasted words? (Hard to resist.) Really I’m not sure.

But I might go to Allman’s concert for the American Liver Foundation, at the Beacon Theater, scheduled for July 27.

All for now.




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Looking Back on ‘The Normal Heart,’ and Patients’ Activisim

A few weeks ago I saw The Normal Heart, a play about the early, unfolding AIDS epidemic in NYC and founding of the Gay Men’s Health Crisis. The semi-autobiographical and now essentially historical work by Larry Kramer first opened at the Public Theater in 1985.

Cover of the paperback, published by “Plume,” from Wikipedia

The story takes on the perspective of a young man who’s seeing the death of too many of his friends and neighbors from a strange and previously-unknown disease. As much as the situation is disturbing, and frightening, and shattering of the gay men’s barely decade-old freedom to behave as they choose, most of the protagonist’s associates just can’t deal with it. Nor can other, potentially sympathetic officials like Mayor Koch, health officials at the CDC and NIH.

Among the men who form GMHC, in this drama, there’s a mixed crew. Some say they’re  embarrassed by the attention the illness drew to some gay men’s behavior. Many stay fully or half-closeted, understandably insecure in their jobs. They worry about discrimination and rejection by families, landlords and even doctors, some who were reluctant to take on patients with this disease. Some of the affected men and their friends, straightforwardly, fear death; others are in plain denial about what’s going on in their community.

The scenes unfold between 1981 and 1984, more or less the time when I moved to Manhattan, lived downtown, applied and matriculated at NYU’s medical school. Many of the first clinical cases, i.e. patients, I saw, were young men with HIV and Kaposi’s sarcoma, one of the first conditions associated with the outbreak and that’s featured in the play – the appearance of maroon or violet-colored, usually but not always flat, often elongate, spots on the skin. The AIDS patients tended to have anemia, either from immune blood disorders or, more often, infection in the bone marrow. As a hematologist-to-be, I was intrigued.

Then and now, looking back, it’s hard not to respect those men’s activism, especially those who, with Kramer, created the AIDS Coalition to Unleash Power (ACT UP). They were impatient with the pace of research and physicians’ protocols, and spoke out so emphatically about their needs: for more research; for prevention and treatment; for easier access to new drugs; and, simply, for good medical care.

The play closes soon in New York;  its producers are said to be planning a tour and a London production of the work. Patients and their advocates, of all backgrounds and particular concerns, might take notes.

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Human Milk For Sale, Where’s the FDA?

The June issue of Wired carries a feature on the Booming Market for Human Breast Milk. You can read about the under-the-counter and over-the-Internet sale of “liquid gold” with a typical asking price in the range of $1 to $2.50 an ounce.
Here’s a taste, from the article:

…“rich, creamy breast milk!” “fresh and fatty!”… Some ship coolers of frozen milk packed in dry ice. Others deal locally, meeting in cafés to exchange cash for commodity…

Late last year, the FDA issued a warning about feeding your child human milk from strangers. Still, the stuff’s barely regulated.

milk containers, Wired Magazine, June 2011

As much as I think it’s a good idea for women to breast feed their babies as best they can, I was pretty shocked to learn about this unregulated industry.  Mainly because if a woman who donates milk is infected with a virus, like HIV or HTLV-1, the milk often contains the virus. The infant can absorb the virus and become infected. Feeding human breast milk from an unknown donor is kind of like giving a child a blood transfusion from a stranger, unchecked by any blood bank.

I’m not sure why Wired ran this story, which is admittedly interesting. Maybe it’ll push the FDA to take a more aggressive stance on this matter, as it should.

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A New E. Coli Outbreak, Hemolytic-Uremic Syndrome, and Eating In or Out

There’s a newly-identified E. coli strain that’s causing a serious illness called hemolytic uremic syndrome (HUS). The recent cases, mainly in northern Europe, have been attributed to eating raw vegetables like cucumbers, lettuce and tomato. So far, authorities aren’t sure of the exact source.

Like any stomach bug, these bacteria can cause diarrhea, fever and other symptoms related to the gut. When people develop HUS, the kidneys fail and they may need dialysis. (Uremic Syndrome refers to uremia, when toxins normally cleared by the kidneys circulate in the bloodstream and cause problems in other body parts.)

blood smear reveals fragmented red blood cells (schistocytes), image from Wikimedia Commons

The “H” in HUS is for hemolytic, which describes how red blood cells are destroyed in the bloodstream. This occurs sometimes from effects of a bacterial toxin, such as might happen upon ingestion of a toxic strain of E. coli bacteria. This condition results in jaundice – a visible yellowing of the eyes and skin, and anemia – a paucity of red blood cells.

According to NatureNews, the culprit’s genome has been sequenced. It encodes broad-spectrum beta-lactamases. This means these toxic E. coli will, in general, resist antibiotics that exert their antiseptic powers by means of beta-lactam rings.

What’s my take-home message, as a home-maker and mom?

If I were traveling in areas affected now, I wouldn’t panic or change my plans. But I would avoid eating salad and any raw fruits or vegetables that can’t be peeled. I’d be mindful of foods like guacamole and salsa with fresh cilantro or other imperfectly-washed ingredients. Better to order cooked food, especially in restaurants where you don’t know who’s rinsing the greens.

The same rules apply at home, except that I’ll eat salad and fresh vegetables that I’ve prepared diligently.

Hand-washing after touching any part of a toilet, bathroom sink or faucet is always wise. The point is to avoid accidentally putting germs in your mouth that come from animal or human feces.


My next post will be on another topic, entirely.

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New Findings on Leprosy and Armadillos

A surprise lesson arrived in my snail mailbox today: the April 28 issue of NEJM includes a fascinating research paper on a probable cause of leprosy in the southern U.S. New, detailed genetic studies show that armadillos, long-known to harbor the disease, carry the same strain as occurs in some patients; they’re a likely culprit in some cases.

Dr. Gerhard Henrik Armauer Hansen, who identified the bacteria causing leprosy

Dr. Gerhard Henrik Armauer Hansen, who identified the bacteria causing leprosy

For those who didn’t go to med school: Leprosy is a chronic, infectious disease cause by Mycobacterium leprae. In my second year we were told to refer to the illness as Hansen’s disease. We learned that some people are more susceptible to it than others, possibly due to inherited immunological differences, a point that is reiterated in the current article.

The World Health Organization reports there are under 250,000 cases worldwide every year. Here in the U.S., Hansen’s disease is quite rare, with about 150 new cases reported annually according to the study authors. The condition wasn’t evident in the Americas before Columbus’ travels, but by the mid-18th Century it was affecting some settlers near New Orleans. Today, most cases in the U.S. arise in travelers and others who’ve lived or worked abroad in regions where leprosy is endemic. About a third crop up in people who’ve never left the country, and these cases tend to cluster in the southeastern U.S.

Leprosy tends to affect the skin, and what the NEJM investigators first did was examine skin biopsy specimens from patients who live in the U.S. and hadn’t traveled. It’s been known for decades that armadillos can carry these bacteria, and so the researchers took specimens from wild armadillos in five southern states, and analyzed the M. leprae bacterial genomes. They matched. Then they looked at more patients’ samples, and also analyzed M. leprae sequences from patients in other parts of the world.

The conclusion is that wild armadillos and some leprosy patients in the southern U.S. are infected with an identical strain of the bacteria that causes leprosy. From this information, the authors infer that armadillos are a reservoir for this stigmatizing germ, and that they may be the source of some patients’ infections.

So the news is that leprosy may be a zoonosis.

A personal note –

Only once I saw a patient with Hansen’s disease, at the Bellevue dermatology clinic, when I was a fourth-year student. She was an elderly woman from China. Her face, which I can picture now, had classic leonine features. The resident caring for her,  an intern with a plan to become a dermatologist, prescribed antibiotics.

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Passover Preparations, and Good Housekeeping

There’s so much medical stuff I’d like to write on today. The thing is, it’s almost Passover. I’ve just got a few hours to finish readying our home for the holiday.

And so this will be the topic for today’s ML, on home-making:

Part of the Passover preparation is, in my mind, like spring cleaning: we scrub surfaces in the kitchen, pantry and elsewhere; we shake out all the rugs and vacuum or sweep extra carefully; we go through old foods and decide what’s worth keeping or should be discarded. We remove all bits of bread, and then set a minor flame (I use a match) to, symbolically and really, burn the last crumb.

I’m reminded of the spring of 1987, when I spent the second half of Passover in a small apartment in Cochabamba, Bolivia, where I followed an endocrinologist in his rounds and learned about so-called tropical diseases: malaria, Chagas, amoeba and other parasites I hadn’t seen first-hand before. There was running water for only 4 hours early each day in the place where I stayed; I learned to gather, boil it and apply iodine to sterilize it before washing my few dishes. There I ate matzah I’d stashed in my suitcase. (Later on in my journey, its well-known constipating effects proved beneficial.)

The main public hospital in Cochabamba held patients in old-fashioned, long rectangular rooms with 15 or 20 beds along each side. Ventilation came by breezes through the open windows, and patients’ families were responsible for giving them food. Nurses – nuns, really – kept the place clean; they swept under each bed daily. No blankets or sheets touched the floor; it was immaculate.

I know there are people out there who think a sterile home breeds diseases – like asthma and peanut allergies and maybe even Hodgkin’s; the notion is that somehow it’s good to get our immune systems exposed at an early age to lots of bacteria and other organisms, so they won’t respond too vigorously to nature’s tiniest offerings. While there may be a germ of truth in some of these arguments (for the record, I don’t agree with most, and am fearful of the harmful bugs and parasites that can be lethal if ingested), I do think that for the most part, we could do a better job on the hygiene front.

At the AHCJ meeting I attended a session on food safety. There was a lot of discussion of how the FDA, USDA and other agencies are and aren’t tracing sources of contamination in the food supply, from large and small (excluded from some regulations) growers and manufacturers, and what to do about imported foods, which are screened now for radioactivity as well as for unwanted germs.

The way I see it is this: We’re responsible for our health to the extent that our behavior can reduce our risk of illness. Keeping a clean home, and washing food thoroughly, and cooking it carefully, are things we can do to reduce the odds of getting sick. Nothing’s full-proof, and I don’t mean to suggest that if someone develops hemolytic uremic syndrome from eating contaminated spinach or bad ground beef that it’s their fault.

But maybe we’ve become lazy as a culture, or just too rushed: we buy prepared food and pre-“washed” salad. We grow accustomed to the dust behind a bed-board or bookcase that’s hard to move; we don’t flip the couch cushions periodically and clean what’s under there, as perhaps our grandmothers would have, should they have been sufficiently fortunate to have upholstered furniture.

I admit that I’m very imperfect in all of this, that my home is far from absolutely clean, and that I sometimes eat salad in restaurants where I doubt it’s been quite so-well washed as I’d like or want to know. There is surely some dust on this laptop, and I fear now there may be a crumb of bread that’s escaped the feather’s final sweep.

But I’ll do my best, and sign off now, and enjoy the holiday with my family.

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