Philip Alcabes discusses myths of health, disease and risk.

HIV, Contraception, and (More) Unethical Conduct by U.S. Researchers

Brava! to Caitlin Gerdts and Divya Vohra at Daily Beast for a superb, and much-needed, dissection of the flaws in this week’s heavily hyped Lancet study by Heffron et al.  The study purported to show elevated HIV risk associated with hormonal contraceptive use among women in parts of Africa (abstract here, subscription needed for full text).  The NY Times ran a front-page story, claiming that

[t]he most popular contraceptive for women in eastern and southern Africa, a hormone shot given every three months, appears to double the risk the women will become infected with H.I.V.

and almost everybody else (as diversely situated in newsworld as the Atlantic, CNN health blog, Catholic News Agency, and Voice of America) joined the NYT in failing to examine it critically.

Gerdts and Vohra add the essential context that was missed by the newsmedia:  about a half-million women die during or because of childbirth each year, almost all of them in poor countries.

At RH Reality Check, Jodi Jacobson summarizes the main cautions about the Heffron study, and points to a Guttmacher Institute white paper.  She takes into account concerns about high maternal and infant mortality in parts of Africa, the harms associated with complications of pregnancy and unsafe abortions, and, of course, the substantial possibility of vertical transmission of HIV in places where antiretroviral therapy isn’t universally available.

To claim that poor women should give more weight to the rather remote risk of acquiring a virus that might cause serious illness years down the road than to the dangers of pregnancy itself in the near term is to reduce real women to automata.  Facing dire straits they might be, but they’re supposed to be reasoning machines, programmed to engage in the AIDS industry’s preferred calculus, risk.

A quick summary of the shortcomings of the Heffron et al. research:  comparing users of hormonal contraception to nonusers, the difference in actual risk of acquiring or transmitting HIV was very small, amounting to 1 to 3 new infections per one hundred contraceptive users over and above the infection rate for nonusers.  And it’s impossible to say that these excess infections were actually attributable to the contraceptive — because the study wasn’t a clinical trial.  A great many aspects of social setting, relationships, health, and welfare of the study subjects would have been different between contraception users and nonusers, some of which would undoubtedly account for differences in rate of HIV transmission.

And since all of the subjects were in so-called discordant couples — one partner infected with HIV, the other not — it would be unusual to expect no HIV transmission at all.

Unless, of course, the subjects had been offered antiretroviral therapy, ART.  But this the researchers did not do.  They referred eligible subjects to HIV clinics.  They seem not to have checked whether people who needed ART were getting it.  They seem not to have offered ART to women who got pregnant, either.  Certainly, their Lancet article makes no report of doing so.

I wondered if this was too much to expect of researchers — so I asked the students taking my course on global AIDS and human rights.  Undergraduates, I find, generally have a clearer sense of ethics than most medical researchers.

Even the students who felt that the Heffron study was worth doing and basically sound were troubled by the researchers’ lack of curiosity as to whether HIV-infected subjects were getting the ART drugs they needed.  And most of the students thought this was a disabling ethical fault, which should have caused human subjects committees to make the researchers redesign the study.  One student pointed out that the Bill and Melinda Gates Foundation, one of the study’s funding sources, could easily afford to pay for antiretroviral therapy for all of the roughly 2,000 HIV-infected people in the study.

In the end, my students had the questions that Marcia Angell raised in her editorial in the New England Journal of Medicine in 2011 (PDF at this link angell editorial nejm 2000 ):  Don’t physician researchers have the same responsibility to study subjects that they do to their own patients?  And therefore, when their subjects lack resources to obtain effective therapy for treatable conditions, don’t the researchers have a moral obligation to make the therapies available?

Heffron et al. didn’t do this.  They watched HIV-infected people transmit HIV to their partners (the researchers provided HIV testing and counseling about avoiding transmission — but they don’t make clear whether they notified uninfected partners that they might be in harm’s way).  They did little to prevent transmission.  Notably, they didn’t offer ART to people with low CD4 counts.  Nor did they offer post-exposure prophylaxis to uninfected people who had had intercourse with an infected partner.  They just watched.

On this account, the Heffron study wasn’t only flawed — it was so questionable on ethical grounds that the Lancet should be ashamed to have published it.  And the funders — the NIH as well as the Bill & Melinda Gates foundation — censured.

 

 

Bean Counting HIV Infections

Larry Kramer told the NY Times today that there is no  AIDS policy in the U.S.  To which  Kevin Fenton, the aimless director of CDC’s AIDS efforts, replied, non-sequitur-ly, “CDC is not resting.”

The occasion was CDC’s publication in PLOS One of new figures claiming that the annual number of new HIV infections in the U.S. is only around 50,000.

And if you read the CDC’s new Fact Sheet on HIV infection, just posted, you find out that

The current level of HIV incidence in the United States is likely not sustainable. Prevention efforts in recent years have successfully averted significant increases in new HIV infections, despite the growing number of people living with HIV and AIDS who are able to transmit the virus.

CDC English is a little difficult for native speakers to interpret, but I think that the translation of “likely not sustainable” is:  “we need more money or else the incidence is going to go up.”

Now, 50,000 new HIV infections each year is bad news for 50,000 Americans.  But on a population basis, it’s not a very high number.  The HIV prevention industry will wring its hands, and perhaps Mr. Kramer will, too.  They can all grumble that after 30 years of AIDS there should be no new infections at all.   But that’s ridiculous.  A pipe dream.  HIV is a sexually transmissible infection.  And STIs can’t be eradicated — because, well, people have sex.  No matter what.  And sometimes the kind of sex that isn’t recommended by the experts. With the wrong people.  And so forth.

Really, that there are only 50,000 new infections each year is a sign of (a) the low inherent infectiousness of HIV and (b) Americans’ sharp awareness of how to protect themselves from HIV infection.   It’s not really clear that any new prevention is needed.

What is needed:  get effective treatment into more HIV-infected people.   Obviously, to slow the progression of HIV-based impairment in the individual — but also as a public health measure, to reduce the HIV carrier’s infectivity and thereby reduce the probability of transmission.  It would have medical value and public health value.  But there’s not much policy on that.

CDC officials are bean counters, not policy makers.  That’s why, Mr. Kramer, your expectations are too high.  The CDC’s job is not to do anything about AIDS.  CDC’s job was never to do anything about AIDS.  CDC’s job was, and is, and presumably will always be:  to keep CDC in business.

They’re terrific bean counters, obsessive, scrupulous, punctilious, completely absorbed in their own assumption that their data are a source of truth, committed to deciphering the supposedly unequivocal message the data send.

The message, always, is “CDC needs to do more of what it’s been doing.”

I gave the CDC a hard time in August 2008, when the agency published its estimate that there are 56,000 new HIV infections in the U.S. each year.  That seemed too high, I told the NY Times at the time.  Of course, it was useful for the CDC’s rudderless AIDS division to claim that HIV incidence was higher than everyone thought:  suddenly, lots of people were urging that HIV  prevention programs be beefed up.

Now, the agency has backpedaled. The 2006 incidence wasn’t 56,000 after all, the CDC now figures, it was only 48,000.  And anyway 56,000 is the same as 48,000, the agency now says.

Let me summarize:  Back in 2008, the CDC’s estimate supposedly showed that prevention wasn’t working, so the agency needed to do more of it.  The new estimate, which is almost the same as the old estimate, shows that prevention does work, so the agency needs to do more of it.  All CDC calculations point to the same conclusion:  keep CDC in business.

If CDC were interested in the nation’s health, more so than maintaining its meager status quo, it would be advocating for more treatment (to Donald McNeil’s credit, he makes that point in today’s NYT article).

And if CDC were interested in HIV as a public health problem, and not just in bean counting for the purposes of keeping itself in business, it would stop putting its beans into 30-year-old jars.  What’s the point of the tired “race/ethnicity” breakdown?  Does anybody know anymore how to categorize people into the ancient non-Hispanic-black/Hispanic-including-black/non-Hispanic-white codification?  Does anybody know what it means?

And the famous transmission categories, the MSM-IDU-heterosexual-other breakdown:  that was useful early on, when we weren’t sure that the modes of communication of HIV were fully known.  But that era ended in 1985.

Dear CDC:  Could you please put your beans into some useful jars?

No, it’s asking too much.  Because CDC’s aim isn’t to be useful.  It’s to keep counting beans exactly the way it knows how to count them, and put them into the same jars as always, and keep on concluding that the data — the beans — show that CDC must keep on doing exactly what it has been doing.

 

 

 

 

USPHS Back in Bed with Big Pharma

Just in case you thought that the U.S. Public Health Service’s main interest is the public’s health:

Recently, Paul Sax reported at The Body on a plan to issue guidelines on the use of pre-exposure HIV prophylaxis (PrEP) using a combination of antiretroviral drugs, announced in the January 28 issue of CDC’s Morbidity and Mortality Weekly Report. The effect of issuing guidelines is to endorse the procedure, which will help enrich pharmaceutical companies — the first being Gilead, which makes Truvada (combination of tenofovir + emtricitabine).

Here’s the CDC’s rationale for issuing interim guidelines now, with formal guidelines to follow:

CDC and other U.S. Public Health Service (PHS) agencies have begun to develop PHS guidelines on the use of PrEP for MSM at high risk for HIV acquisition in the United States as part of a comprehensive set of HIV prevention services…  [W]ithout early guidance, various unsafe and potentially less effective PrEP-related practices could develop among health-care providers and MSM … [including]

1) use of other antiretrovirals than those so far proven safe for uninfected persons;

2) use of dosing schedules of unproven efficacy;

3) not screening for acute infection before beginning PrEP or long intervals without retesting for HIV infection; and

4) providing prescriptions without other HIV prevention support (e.g., condom access and risk-reduction counseling).

Translation:  if  CDC or another USPHS agency doesn’t do something now, homosexual men might not buy  as much medication as they could.

What’s the impetus for this guidance?   Results of the iPrEx study, which was supported by the National Institute of Allergy and Infectious Diseases at NIH, were published in the New England Journal of Medicine in December.  The study purported to show a 44% reduction in HIV incidence among men who had sex with men who were taking Truvada prior to sexual exposure.  But the study was so deeply flawed, and the authors so cagey about their methods, that it’s  impossible to conclude that Truvada makes any difference to the chances of acquiring HIV.

As the iPrEx trial’s logo implies

iPrEx

it was multinational, involving almost 2500 HIV-negative people who were male (at birth) and adjudged to be at high risk of acquiring HIV because of their pattern of sexual activity.  It involved sites in Peru, Brazil, Ecuador, South Africa, Thailand, and the U.S. The comparison was between subjects taking Truvada and subjects taking a placebo.

The famous 44% reduction, however, was clearly not obtained in each site — and the authors don’t state which sites showed more effect.  More importantly, the reduced HIV incidence among those taking Truvada occurred only for a small subset of subjects who stayed on the drug for more than a year without becoming infected.  And it only lasted for about one additional year.

In other words, in the iPrEx study, people who took Truvada and remained HIV-negative for a year were slightly less likely to acquire HIV in the following year than were those who took placebo and remained HIV-negative.

Finally, even the small, second-year-only effect of Truvada is of questionable use to men in the U.S.  Because the study was based on men living in places with extremely HIV prevalences — higher than those in much of the U.S. — and involved men having a large number of partners, it provided essentially no evidence for any utility in the U.S.

As other trials of pre-exposure chemoprophylaxis are going on now, other companies’ products are likely to be included in the final version of the CDC guidelines.  So more corporations can benefit from the largesse of the Public Health Service.

Condoms are very effective at interrupting HIV transmission.  Obviously, you have to use them (properly) in order to benefit from that effect.  Because people don’t like them very much, condom promotion is a poor public-health strategy.

But as a matter of guidance for men who have sex with men, in what way is it better for the USPHS to suggest Truvada, which has to be used consistently even when you’re not having sex, probably won’t take effect for a year or so, and even then will only give you a minor reduction in the chances of acquiring HIV — rather than condoms?

Answer:  it is if you’re trying to promote profits for the pharmaceutical industry.

NYC: Unethical Research by Bloomberg Administration

I had missed this story when the NY Daily News broke it in September, but  the front page of today’s NY Times made it impossible to ignore:  Mayor Mike Bloomberg’s administration is conducting unethical experimentation on human beings.

The News describes the experiment very simply:

[New York City's] Department of Homeless Services split 400 struggling families into haves and have-nots.

The “haves” get rental assistance, job training and other services through a program called Homebase.

The other half … were dubbed the “control group” and shut out of Homebase for two years. Instead, they were handed a list of 11 agencies and told to hunt for help on their own.

The aim of the experiment, allegedly, is to find out whether Homebase, a $23 million program, is effective.  The city’s Commissioner of Homeless Services told the Times that

When you’re making decisions about millions of dollars and thousands of people’s lives, you have to do this on data, and that is what this is about.

(If you thought that what it’s about, for a commissioner meant to deal with homelessness, is making sure that people have homes — you were so wrong.  Silly you.)

To make matters worse: what’s being tested is a program whose effectiveness the city has already asserted. As Mike, who blogs brilliantly on this and many related topics at SLO Homeless, notes:  the 2010 Mayor’s Management Report, issued in September, claimed that Homebase helped “ninety percent of clients in all populations receiving prevention services to stay in their communities and avoid shelter entry.”

So, to make sure this is clear:  New York City is deliberately denying a couple of hundred families access to an existing homelessness-prevention program that it has already declared to be highly effective.

The scenario is identical to one that kicked up storms of controversy in the medical-research world in the 1990s (neatly contextualized and summarized here):   experiments were conducted in Africa and southeast Asia supposedly to test the effectiveness  of an already-proven preventive regimen, AZT.  Administered during pregnancy, it reduced the likelihood of mother-to-fetus or mother-to-infant transmission of HIV.  In the poor-country experiments, half of the women enrolled got the effective regimen; the other half got placebo.

In other words, if you were pregnant and infected with HIV and you had had the wisdom to live in the U.S., you got a treatment that protected your infant from infection.  If you lived in a poor country you got:  studied.

There’s something about poor people, and especially about poor women with kids, that seems to make them smell like catnip to the always evidence-hungry technocrat cats.

Want to run a placebo-controlled trial?  Find something that already works (antiretrovirals, homelessness prevention, or, in other circumstances, syphilis treatment, TB prevention, etc.), then find a few women with kids who need it — then tell them you’ll flip a coin.  Heads, they get what they need; tails… well, too bad.

I’m a scientist.  I believe that evidence can be helpful.  Sometimes, it’s crucial.  When you’re truly unsure whether to pick prevention A or prevention B, data can help you to choose right and avoid harm.  That’s the great promise of science.

But sometimes the appeal to evidence is baleful — like here in Bloomberg’s New York, where evidence on homelessness is just a way of furthering the aims of the technocracy.  Which always means that some people will avoid harm.  Others will pay the price.

And the others are, so often, poor women with children.

AIDS Goes to Ground

This week, Donald McNeil, Jr. continues his praiseworthy efforts to highlight the sad reality of AIDS among the world’s poor.

In an article posted on the NY Times website Sunday (and published in the print edition Monday), McNeil reports on the inability of treatment programs in parts of Africa (this piece focuses on Uganda) to keep up with the need for AIDS medication as funding falls.   A very compelling video report accompanies the online version of the article.

An accompanying article explains the decline in funding, starting with the fall in the U.S. administration’s request on behalf of PEPFAR, as a Times graphic shows.

The number of new infections with the AIDS virus is estimated to be about 2 million per year now.  Some observers think annual incidence will rise as the population expands; even if not, the annual number of new AIDS virus infections is unlikely to fall in the near future, given present circumstances.

At the same time, the Times reports, anticipated PEPFAR funding is essentially flat to 2013, at $5 to $5.5 billion per year.  Financing for AIDS medications through the Global Fund to Fight AIDS, Tuberculosis and Malaria is in dire straits.

In terms of people, not dollars:  of the 33 million or so individuals who are infected with the AIDS virus worldwide, only about 4 million get regular antiretroviral therapy.

A few years ago, I wondered why,  after a quarter-century of AIDS and with the availability of effective treatment (at least in wealthy countries), Americans still didn’t see AIDS as an ordinary illness.

Now I have an answer:  we do see AIDS as ordinary… for poor countries.  To us, AIDS is no longer an epidemic problem worth our getting worked up over, or so it would seem judging by PEPFAR.  AIDS is like malaria, tuberculosis, or schistosomiasis.  It’s like diarrhea.  The Bill and Melinda Gates Foundation will put money into research or specific programs but we as a country will not need to care anymore.  We shift the funding away from the people in Africa, who are going to die young anyway, and put it into the hands of institutions (often, pharmaceutical companies) that can give us the promise of immunity from disaster.

The U.S. put less funding last year into PEPFAR than it did into preparations for H1N1 flu ($7.6 billion) or the school lunch program ($14.9 billion, according to the Robert Wood Johnson Foundation’s Center to Prevent Childhood Obesity), battleground in the war against childhood obesity.

Flu and obesity are epidemic.  They threaten American assumptions about ourselves.  “Epidemic” means:  crisis in our society.  Our epidemiologists say that malaria, diarrhea, and the other problems that collectively kill 20,000 or 25,000 people (mostly children) every day are endemic

“Endemic” means:  not our problem.

AIDS is endemic too, now.  It has gone to ground, gone the route of other once-dreaded infections that caused calamity in America and triggered heated debate (yellow fever, cholera, typhoid, TB) but have disappeared from our scene.  It’s their problem, now.