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August 5th, 2009

Just Out: Primary Care HIV Guidelines

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?

July 25th, 2009

IAS Cape Town 2009: Some Greatest Hits

Below is a highly-subjective list of some of the highlights from the Cape Town IAS meeting. I’m sure I missed something — it’s impossible to see everything at these large conferences.  Corrections/additions welcome!

My miss-rate might be particularly high since the international AIDS meetings are appropriately focused on HIV treatment in resource-limited settings (especially Africa) whereas my perspective is as a US treater/researcher.  That said, studies from these countries often have important take-home points for all of HIV medicine.

Apologies over, on to the content:

Immediate therapy increases survival for asymptomatic patients in Haiti (WESY201). This landmark study (CIPRAHT001) randomized asymptomatic patients with CD4 cell counts between 200 and 350 to start treatment immediately with ZDV/3TC + EFV or to wait until CD4 fell to 200.  An independent DSMB stopped the study early after finding 23 deaths in the “standard” therapy arm vs only 6 in the early treatment group.  The difference in the risk of infection-related deaths was particularly striking–  1 vs17 — and the standard therapy group also required greater intensity of lab follow-up and had higher treatment-related toxicity.  The results are a strong challenge to the WHO treatment guidelines (essentially to start rx with cd4 at 200), and can be added to the growing list of studies that find early ART is better than waiting.

Incidentally, the presentation was kind of hidden since apparently the study was submitted after the late-breaker deadline.  Too bad — I hope it gets a larger venue at CROI.

Treating pregnant women with ART for at least 6 months post-partum reduces breast-feeding transmission (WELBB101). Women in Botswana with higher CD4 cell counts were randomized to either ZDV/3TC/ABC or ZDV/3TC + LPV/r, and those with lower counts got standard ZDV/3TC/NVP. The individual regimens are less important than the fact that they continued treatment for 6 months post-partum, and were instructed to breast feed (switching to formula feeding in developing countries might avert some HIV infections, but the overall outcome for the infants is worse — even when clean water can be provided).  The results showed a transmission rate of only 1%, which is the lowest ever reported for a transmission study that includes breastfeeding — and not dissimilar to what is observed in industrialized countries.

Implications?  Seems to me that the myriad byzantine regimens being tested in this setting — including various single-dose NVP strategies, giving the babies prolonged “post-exposure” prophylaxis even though they are not infected, prescribing a “tail” of NRTIs to the moms to reduce resistance with the NVP — can all be replaced just treating the mom with standard antiretroviral therapy.  Of course easier said than done, but since when shouldn’t we try to do what’s best for pregnant women, which in general is the same thing as for non-pregnant women?  Let the controversies ensue, I know they are heated.

July 20th, 2009

Cape Town IAS Meeting — A Quick Look Back at Durban 2000

The international AIDS meeting finds its way today to South Africa, the country with arguably the greatest needs for HIV prevention and treatment.

This is not the first time the meeting was in this country, of course — in 2000, the World AIDS Conference took place in Durban, a truly landmark event in the history of the epidemic.

Aside from the obvious fact that HIV/AIDS was at that time largely ignored by the South African government, so that having the conference here was a major symbolic step forward, what else transpired?

  • President Mbeki, in his opening speech, continued to focus on poverty — not HIV — as the cause of AIDS, with no concrete mention of antiretroviral therapy as either treatment of HIV nor as a way of preventing perinatal transmission.
  • By contrast, Judge Edwin Cameron — openly HIV positive — stood up in front of thousands as the picture of health, describing how this was all due to his taking two pills twice a day.  (His regimen:  ZDV/3TC + NVP.)  He pleaded to make treatment more widely available.  It was riveting.
  • Tony Fauci introduced us to the idea of “STI’s” — structured treatment interruptions — with several purported benefits, including decreased toxicity of treatment, “auto-immunization”, and lower cost.  No, it didn’t work out so well, but it became a major research agenda for the next 5-plus years. The paradox of STI was perfectly encapsulated by my colleague Abie Zuger, who noted that while Aftricans were desperate for treatment, her patients in the US were almost as desperate to stop, so bad were the side effects of therapy at that time.
  • There was yet another study comparing ZDV/3TC plus either ABC or indinavir; ATLANTIC compared d4T/ddI plus one of either IDV, 3TC, or NVP; lopinavr/r was still called “ABT-378”; and the “next frontier” in antiretroviral therapy was correctly identified as entry inhibitors, with enfuvirtide right around the corner, and CCR5 antagonists already in development.
  • The whole issue of mitochondrial toxicity, and its link to lipoatrophy and lactic acidosis, was coming into clearer focus.  Although many studies had begun to target d4T as a main culprit, there was still some debate.
  • Nelson Mandella closed the conference with a beautiful speech — there was a general sense of hopefulness that contrasted markedly with the opening ceremony.

I also remember that the conference was superbly run from the technical perspective, and that the Durban beaches were gorgeous.  I purchased a pair of plastic flip-flops that my son still wears, and a cute bowl for my wife that has a giraffe handle.  The sun set very early in July way down here in the southern hemisphere.

Oh, and I learned then that South Africa is a long long way from Boston, and I was just reminded of that fact after a 24 hour trip here.  I am in awe of the stamina of my colleagues who make this trip on a regular basis.

Updates on interesting stuff here to come.

July 10th, 2009

Time for a Switch? What Actually Happened

A couple of months ago, I presented these three clinically stable, virologically suppressed patients — and asked if they should switch treatment:

  1. 50 year old man on ABC/3TC, EFV since 2000.  No renal disease.  Hyperlipidemia, on atorvastatin 80 mg a day.  Father died of an MI age 48.
  2. 63 year old man, on EFV + LPV/r for years; past history of neuropathy on d4T and 3TC.  Needs to go on inhaled steroids (preferably fluticasone) to help manage increasingly refractory asthma.
  3. 35 year old woman, on ABC/FTC, FPV/r BID — doing ok but missing some PM doses.

We also published them in AIDS Clinical Care, inviting both reader and and formal “expert” opinion.

Not surprisingly, there was disagreement from both the readers and the experts — some electing to change, some to switch, with various suggested new regimens.  It makes interesting reading, as all perspectives are defensible.

So what actually happened?  I switched them all:  Patient 1 is now on TDF/FTC/EFV, and Patient 3 on ABC/3TC, DRV/r.  They are both doing great.

Patient 2, um, not so much:  After switching to TDF/FTC/EFV, he almost immediately noted marked worsening in neuropathic symptoms — reminding me that in the bad old days of d4T and ddI, some patients did seem to experience worsening on 3TC.  So he went back on EFV + LPV/r, and the neuropathy returned to baseline over a month or so.

But — since he still needed the inhaled steroids for asthma treatment, and the fluticasone/PI interaction can be troublesome, I tried the combination of etravirine and raltegravir as a novel “NRTI- and PI-sparing” approach.  Almost immediately after this switch, he developed fevers, rigors, and malaise, and actually needed to be hospitalized overnight.

His current regimen?  Back to EFV + LPV/r — again doing well from the HIV perspective.  The pulmonologist managing his asthma is trying to get by with low dose beclomethasone, with some success.

Humbled, I’m reminded that this antiretroviral business can be tricky — and that sometimes, it’s better to do nothing than something.

July 4th, 2009

Progress on Consent for HIV Testing?

As I’ve noted here several times (some might say ad nauseum), I am convinced that Massachusetts’ arcane law requiring written informed consent prior to HIV testing is a barrier to more widespread screening — an opinion that is shared by virtually every clinician I’ve asked about this issue.

Last week, there was an announcement about progress (of sorts):

Clearing the way for HIV testing to become almost as routine as checking for cholesterol, state public health officials issued an advisory yesterday saying that the written consent required by law can be included in general permission forms patients sign for medical care.

Until now, Massachusetts doctors have typically given patients separate consent forms to authorize HIV testing, but yesterday’s directive makes clear that one form is sufficient, as long as the general consent form explicitly mentions HIV testing. Separate permission forms pose a barrier to testing for patients and healthcare providers alike, health officials said.

I’m of two minds about this.  On the one hand, we could simply do away with the law — something that most other states have already done, with Connecticut’s pending legislation providing a wonderfully common-sense approach on how to do this.

In addition, putting HIV in with the general consent for medical care seems both 1) kind of sneaky (does anyone actually read all that paperwork?) and 2) perpetuating HIV exceptionalism, since no other specific diseases are mentioned.

These concerns notwithstanding, I’m all for anything that makes it easier for people to find out their HIV status.  As noted in this article, 31% of people in MA find out they have HIV within 2 months of an AIDS diagnosis.

And that’s 31% too high.

June 24th, 2009

An Irrational Fear of IRIS?

One of the most important recent studies in HIV has just been “published” in (on?) PLoS ONE.  It’s ACTG 5164, led by Andrew Zolopa, which compared “early” versus “deferred” antiretroviral therapy in 282 patients presenting with acute opportunistic infections.

(Full disclosure: I am on the protocol study team — but am not an author on this paper.)

Take home message:  Starting antiretroviral therapy within 2 weeks of the OI diagnosis significantly reduced the risk of further AIDS complications or death, compared to the group that started 6-12 weeks later.  (For additional details of the study, here’s a nice summary in AIDS Clinical Care.)

When I discussed 5164 with some of my less clinically-inclined colleagues, they wonder why the study was even done — of course starting these severely immunocompromised patients on ART as soon as possible would be better than waiting.

But the clinicians, they were not so sure, and raised appropriate concerns about drug-drug interactions, pill burden, overlapping toxicities, reduced adherence, and — drum roll — the immune reconstitution inflammatory syndrome, or IRIS.

Some of us are terrified of IRIS, and I’m not quite sure why.  Yes, it can be difficult to manage (my sense is that we’re too reluctant to use steroids), and sometimes it’s very confusing exactly what is going on.  And of course there are occasional case reports of severe IRIS, some even leading to death — but always with such cases, I wonder whether the outcome would have been just as poor without ART, just with a different clinical manifestation.

So that’s why it’s particularly gratifying to see this finding in 5164:

IRIS was reported in 23 cases and confirmed in 20: 8 subjects in the immediate arm and 12 in the deferred arm.

June 20th, 2009

More HIV in the Adult Film Industry (Maybe)

From the New York Times last week:

Health officials in Los Angeles said Friday that 22 actors in adult sex movies had contracted HIV since 2004, when a previous outbreak led to efforts to protect pornography industry employees.

(snip)

Occupational health officials have long argued that failing to require that performers wear condoms during intercourse and other acts is a violation of safe-workplace regulations.

But Deborah Gold, a senior safety engineer with the California occupational health department, said violations in the pornography industry were so widespread that the state had a difficult time cracking down.

My first response on reading this was amazement that the number was so small — and, remarkably, that number turned out to be even smaller (1 case) when further details emerged in the LA Times:

Los Angeles County public health officials backtracked Tuesday on their statements last week that at least 16 unpublicized cases of HIV in adult film performers had been reported to them since 2004.

Despite their release of data to The Times describing the cases as “adult film performers,” the county’s top health official acknowledged that the agency does not know whether any of those people were actively working as porn performers at the time of their positive test.

(snip)

The county lacks sufficient information to delve deeply into the cases and still has received no formal report on the most recent case.

“The system we have and the laws we have do not facilitate the kind of contact tracing and verification that we’d like to see,” [LA County Health Officer] Fielding said. “AIDS has been treated separately from other STDs.”

Bottom line here:  Aside from this well-researched cluster of cases reported in 2004 in the MMWR, we likely only have a vague idea how many cases of HIV are in, or linked, to this “industry” — which in addition to these semi-regulated companies undoubtedly has a huge underground as well.

And until we get rid of this bit of HIV exceptionalism cited above by Dr Fielding, appropriate contact tracing and partner notification are going to be very difficult indeed.

June 16th, 2009

Q: What is the Purpose of a Note in the Patient Chart?

A:  Depends who you’re asking.

The best guidance I ever received on how to write a good note came from my residency program director, who told us that a note needn’t be encyclopedic to be excellent; in fact, he urged us to get away from the “second-year medical student” style, which typically includes absolutely everything.

Instead, he urged us to write, as concisely as possible, notes that included the following:

  1. What is going on with the patient
  2. Why we think so
  3. What we’re going to do about it

All this gets thrown on its head, however, when you get an email like this one:

Hello Dr. Sax,
Just a reminder that I will be meeting with you to discuss your billing audit results on Thursday 5:30 pm, right after your outpatient session is completed.
Judy

In this meeting, I predict Judy will tell me that the occasional visit I coded as “Level 5” really should have been “Level 4”, or even “Level 3” — since even though the case was incredibly complicated and involved reviewing years of treatment history, lab results, and prolonged communication with outside providers and the patient and his family members, I somehow neglected to include the requisite # of “Review of Systems” (10 required), with explicit mention of past, family, and social history, as well as a 9-system physical exam.  Oh, and the sentence:  “Time spent reviewing impression and plan with patient and family:  — minutes.”

Yes, abuses by MDs and hospitals on billing have been well documented.  Cases like this one are obviously serious, and cannot be condoned.  It could be argued that these periodic “compliance reviews” (my session this week with Judy) are merely the just rewards of a previously unpoliced system.

But does anyone think that the current rules we have in place — with these explicit guidelines for what constitutes a complex case based on who knows what (“Review of Systems?”  c’mon!) — is anything other than an invitation to game the system with fancy software, macros, templates, lots of copy-and-paste, and other such tricks?

And what happened to what should be the primary purpose of the note — which is to communicate the critical items of the medical encounter?

That’s the saddest part — it’s gone.

June 13th, 2009

Occupational Exposures and HIV Testing

A couple of years ago, an ID-colleague of mine told me about a tough case:  While working in the ICU, an anesthesiologist sustained a pretty severe needle stick.  Approached for HIV testing, the source of the exposure felt threatened by the providers in the ICU, and refused to sign the consent.

The patient then deteriorated and required intubation.  The intensivist, understandably in something of a panic, contacted my colleague for advice.

We’re about to post this case — actual details of which are slightly changed to protect anonymity — in AIDS Clinical Care.   We’ve asked some experts (MD, lawyer, ethicist) on the matter a few key questions, including:

  • How would you manage the intensivist who sustained the injury?
  • Would you give post-exposure prophylaxis? If so, what specifically would you give, and for how long?
  • How would you determine if the source patient has HIV? Would you perform surrogate testing (for example, obtain a CD4-cell count) to assess this? Would you consider testing him without written informed consent?
  • If he is tested, would you give him the results after he recovers if the test is negative? If the test is positive?

This case is different from the this one, but many of the issues are related.  (Different from this one too, obviously.)

And it’s a reminder that amidst all the controversy over “opt-out” testing and HIV screening, there’s another big issue out there regarding HIV testing that’s hardly been settled.

June 8th, 2009

H1N1: A Tale of Two Practices

As an adult ID/HIV doctor, I must say the clinical impact of H1N1 thus far has been underwhelming, notable more for the calls about prophylaxis or suspected cases than the real thing.

(Last week, one patient with fever and “suspected swine” — hard for people to shake that name — turned out to have … Lyme disease.  Ah, New England in June.)

But for my wife, the pediatrician? There’s a full-blown epidemic out there, with outpatient visit volumes way up, and nearly continuous oseltamivir prophylaxis among her staff.  As in mid-winter, she and her practice partners are routinely making the influenza diagnosis based on symptoms alone.

And while this report suggests the age cut-off for partial immunity to H1N1 is 60, I suspect strongly — based on our highly-anecdotal, two-doctor-family, completely non-scientific observation — that it’s going to turn out to be quite a bit younger.

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

NEJM Journal Watch
Infectious Diseases

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