An ongoing dialogue on HIV/AIDS, infectious diseases,
December 24th, 2011
Making a List and Checking it Twice, Then Making Sure 052 is On It
How big a news story was HPTN 052, which demonstrated that HIV treatment reduced transmission by at least 96%?
(I like to emphasize that “at least” bit, since it’s likely that none of the study subjects with undetectable HIV RNA levels transmitted to their partners — the one case that did transmit did so before virologic suppression.)
Well, sources as disparate as Science and Time magazine both chose 052 for their “Top 10” in this year’s review of scientific breakthroughs. Science even put 052 as #1, something that you can bet we’ll have in common with this august periodical when Journal Watch AIDS Clinical Care publishes its own “Top Stories” next week.
But a Bronx Cheer out to Scientific American, which not only excluded 052, but then mentioned the following as a runner up:
…the report of a new target against HIV, in which a doorway to infection (the so-called CCR5-receptor on immune cells) is blocked.
CCR5 blockade a “new target”? That news is so 2002.
December 18th, 2011
Let’s Just Say I’m Glad the Grades Don’t Count
A friend alerted me to this test of scientific literacy.
Give it a try — no google cheating — and let me know how you do.
And even though I got the first 5 questions right, my final score (to be disclosed in the comments, eventually) left little doubt that I was an English major in college.
Yeah, that’s my excuse.
December 14th, 2011
No HIV in Pepsi? Now THAT’S a Relief
How reassuring to be treated with the following news:
An SMS has been circulating that Pepsi products are contaminated with HIV but Permanis Sandilands Sdn Bhd has clarified that this is a hoax. Its marketing vice-president Hemalatha Ragavan said there was no truth to it. She urged people not to believe such claims.
I have a couple of thoughts about this breaking story.
First, we all know that texting — without other confirmation — is now the preferred current medium for obtaining important health information. And you can see how the text reads like the work of a highly-respected public health official:
for d next few days, do not drink any product from pepsi company like pepsi, tropicana juice, slice, 7up, coca cola, etc,,as a worker from the company has added his blood contaminated with HIV. watch NDtv …please 4ward this 2 every 1 u care about…..ok. Please note seriously
Second, the company issuing the denial — “Permanis Sandilands Sdn Bhd” — should think up a new slogan. “Come on board, it’s time to be COOL, have FUN and DARE FOR MORE!” is not not going to cut it among hip Malaysians.
December 11th, 2011
An Unlikely Interviewee Discusses “Six-Class” HIV Drug Resistance
He’d never acknowledge it, but in our field, it’s no secret this guy is something of a rock star.
I can think of several key principles in HIV pathogenesis and treatment that he and his research group have discovered, or elucidated most clearly, or simply explained the best — largely through his unique ability to link smart clinicians and laboratory scientists.
In other words, translational research at its finest.
Note I’m not using his name, since he’d definitely not approve of of any of this. Which is why I was particularly lucky to get him to agree to this interview, where we discuss those patients who, despite our numerous treatment options, are unfortunate enough to have HIV that is resistant to everything. “Six class” antiviral resistance.
No, he didn’t agree because I have incriminating photos or other dirt. But he owed me, since I was able to give him the correct date for his lecture at IDSA — the date was changed, and no one told him. (A recurrent nightmare of mine, by the way.)
Thanks again, SD.
December 8th, 2011
Big TB Prevention Study Important, Highly Relevant — Even Here
As I’ve noted before, tuberculosis is disappearing from the United States — which means that the bulk of cutting-edge research in TB (both clinical and basic science) has little relevance to US-based practitioners.
But over in NEJM, a much-anticipated TB study is published today that is highly relevant:
We conducted an open-label, randomized noninferiority trial comparing 3 months of directly observed once-weekly therapy with rifapentine (900 mg) plus isoniazid (900 mg) (combination-therapy group) with 9 months of self-administered daily isoniazid (300 mg) (isoniazid-only group) in subjects at high risk for tuberculosis. Subjects were enrolled from the United States, Canada, Brazil, and Spain … Tuberculosis developed in 7 of 3986 subjects in the combination-therapy group (cumulative rate, 0.19%) and in 15 of 3745 subjects in the isoniazid-only group (cumulative rate, 0.43%), for a difference of 0.24 percentage points.
Just how relevant is this study?
At the risk of over sharing, I would have been eligible to participate: Back in medical school, I cared for an elderly man with cough, weight loss, and lung cancer — only he didn’t have lung cancer, he had TB (oops). My next TB skin test was positive when I started internship, and I was advised to take 9 months of preventive therapy with INH.
Only I didn’t — not initially. For whatever reason, I somehow deluded myself into thinking it was a false-positive (just a little redness … right) and continued blithely on this path through both residency and ID fellowship.
Not smart, I know. Selfish, foolish youth.
Only when I became an actual ID specialist did it finally click. Needing another skin test before starting my job, I could no longer ignore the 15 mm welt on my arm. Nor could I bear the thought of harming my patients, never mind the painful irony and public health nightmare that would ensue if an ID specialist got active TB — headline: “ID Doc Infects Dozens; Ignored Advice He Gave Others.”
I finally took the INH. Oh, and it was no big deal.
But if I had the choice back then of 12 doses, taken once a week? Somehow this seems just so much easier, and I suspect I would have accepted treatment sooner had this option been available.
And as this short-course regimen enters formal treatment guidelines, I have a hunch it will be widely adopted — without the recommended directly observed component.
Do you agree?
December 4th, 2011
Images are Back
This site has been looking awfully plain the last couple of weeks. No pictures!
The reason? You figure it out.
But now we’ve got an exciting new treasure-trove of images, and I’m going to take advantage of this resource and provide some very exciting visuals for your enjoyment.
Like this one, if you’re feeling cold:
And this one too, if you’re hungry:
And finally, this one if you want to look at slugs again:
Some fun, eh?
You’re welcome.
December 1st, 2011
World AIDS Day Wanderings
Some quick HIV and ID Observations (better blog title anyone?) for this 2011 World AIDS Day:
- Through meticulous, painstaking research that took me all of 10 seconds, I’ve learned that the first World AIDS Day was in 1988. What ever did we do before the internet?
- Looks like New York City’s health department is following San Francisco’s lead in recommending that all people with HIV get treated — for personal and public health benefit. Important for many reasons, but these two in particular: 1) New York has by far the largest number of people living with HIV of any US city, and 2) It doesn’t appear that this policy change means an infusion of new funding. Not surprised, but let’s face it — more people on treatment is initially going to cost more (meds, providers, outreach). Well worth it, in my opinion.
- Of course people can’t get treated if they’re not in care, and this MMWR report paints a pretty bleak picture of what proportion of all HIV patients in the United States are virologically suppressed — only 28%! Here’s the key finding: “Of the estimated 942,000 persons with HIV who were aware of their infection [out of an estimated 1.2 million with HIV total], approximately 77% were linked to care, and 51% remained in care.” In other words, those diagnosed and not in care greatly exceed those undiagnosed — and saying it’s important to get them back into care and on treatment is kind of like saying that people who smoke should quit. Everyone agrees, but how do we make it happen?
- As a card-carrying member of the AIDS Clinical Trials Group (ACTG — the cards they give us are really nice), I must point out that 25 years ago tomorrow — December 2, 1986 — Margaret Fischl enrolled the first patient in the first-ever ACTG study, Study 002. Lots accomplished since then by the ACTG, and there have been lots of study numbers. But here’s something you might find reassuring — no one can keep them all straight!
- Speaking of Margaret, here’s a terrific interview she did a few years back about the early days of the HIV epidemic — highly recommended.
- Finally, is anyone else bothered by the fact that coformulated medications are increasingly being written in alphabetical order? That is, “emtricitabine-tenofovir” instead of “tenofovir-emtricitabine” (as it has been for years) or, very strangely, “emtricitabine-rilpivirine-tenofovir”, which splits the NRTIs with the NNRTI in the middle. The first time I saw it was in the iPrEx study, and now it’s happening more and more. What’s up with that?
Sorry I haven’t been able to post images recently — I was quite fond of this one — but at least I can still link to them. And though it has absolutely nothing to do with World AIDS Day, here’s a personal favorite.
November 29th, 2011
HIV Cure Makes the NY Times — Anything New to Report?
It’s right there, on page 1 of today’s Science Times:
Medical researchers are again in pursuit of a goal they had all but abandoned: curing AIDS. Until recently, the possibility seemed little more than wishful thinking. But the experiences of two patients now suggest to many scientists that it may be achievable.
Two patients? What, did I miss something?
- Case One is the famous Berlin patient, Timothy Brown, who underwent a bone marrow transplant for leukemia from a CCR5-negative donor (homozygous for the delta-32 mutation). He’s been much discussed, much studied, and now much photographed. (Reminder: he’s really the second “Berlin Patient” — here’s the first — and he now lives in San Francisco; his interviews have been fascinating.)
He’s a bona fide cure, with no evidence of HIV in blood by the most sensitive techniques or in various biopsies where the virus could potentially hide out (brain, bone marrow, rectal mucosa). Plus, his HIV antibody test is fading.To date, we don’t know what exactly led to his cure — if it was the ablation procedure that precedes the transplant, the CCR5-negative donor, the beneficial effects of graft-vs-host, or some combination of these factors.
As I’ve mentioned before, we also don’t know why there hasn’t been another case yet, given that the cure was first reported in 2008 — seems likely that by now someone else with HIV would have required a bone marrow transplant and had the good fortune to have a CCR5-negative donor, though maybe that’s just the non-oncologist’s view (what do I know).
- Case Two? This case was reported at ICAAC in September, using the “zinc finger nuclease modification of CD4 cells” approach championed by Sangamo and first reported at CROI earlier this year.
(Sangamo — it’s a biotech company, not a maker of 1980s video games.)
The patient’s cells are removed from the body by pheresis, treated with the magic zinc finger nuclease which alters the surface CCR5 receptor on the CD4 cell, making these cells less susceptible to infection, then they are reinfused.
We heard at CROI that such modified cells can engraft, and at ICAAC, researchers reported that one of the patients in a small clinical study (n=6) maintained (after a brief viral rebound) undetectable HIV RNA in the blood after stopping HIV treatment.An important detail — he was heterozygous for the delta-32 mutation, meaning that already he had partial resistance to HIV, and a greater likelihood of slow HIV progression.
The reason this case is being viewed with such caution — and not trumpeted as a cure — is that the duration of follow-up has been only 12 weeks. The HIV literature includes other cases of “spontaneous” control of the virus (including the original Berlin patient!), most of which ultimately turned out to be transient. Experienced HIV clinicians probably have a few cases in their own practices who seemed to be on this exciting path back during the heyday of treatment interruption.
In other words, these were not cures.
So in fact, nothing new here in the Times on the HIV cure scorecard. One cure, and one tantalizing case that was reported two months ago.
But what is new is the level of excitement surrounding the effort. Whether it’s something analogous to the zinc finger nuclease approach, or the use of drugs to stimulate and then eradicate the latent viral reservoir, or something completely novel being dreamt up by the field’s boldest thinkers (here’s my vote for one potential candidate), we can now say to our patients that a cure for HIV infection is potentially achievable in their lifetime.
And that’s a wonderful thing to say.
November 28th, 2011
Tenofovir Gel Disappointing in VOICE Trial
From the Microbicide Trials Network:
VOICE, an HIV prevention trial that has been evaluating two antiretroviral (ARV)-based approaches for preventing the sexual transmission of HIV in women – daily use of one of two different ARV tablets or of a vaginal gel – will be dropping the vaginal gel from the study … The DSMB recommended that VOICE discontinue the tenofovir gel and placebo gel arms, because there was no difference in effect between them in preventing HIV infection.
This leaves only the TDF/FTC intervention arm still open in VOICE, as the TDF alone arm was stopped for futility by a similar DSMB action in September.
We’ll be covering these new data in greater detail in Journal Watch AIDS Clinical Care (including some speculation on why tenofovir gel here failed), but on first pass, this news comes as a big disappointment — especially in light of the CAPRISA 004 study, results of which triggered a standing ovation at the International AIDS Conference in Vienna in 2010.
In fact, HIV prevention research has been on quite a roll the past few years, so much so that maybe we’re unrealistically expecting the data equivalent of a home run with each study.
If it were that easy, however, we wouldn’t have to do the research — in other words (to continue the metaphor), that’s why they play the games on the field.