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April 4th, 2010

San Francisco Public Health: Treatment Recommended for All with HIV

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Could there be anything more interesting than the start of the baseball season?

Maybe, because this is quite something:

In a major shift of HIV treatment policy, San Francisco public health doctors have begun to advise patients to start taking antiviral medicines as soon as they are found to be infected, rather than waiting — sometimes years — for signs that their immune systems have started to fail.

Yes, the field is heading in this direction, but thus far no one has had the guts actually to recommend universal treatment as policy.

In the early 2000s, I often referred to this review by my friend and colleague Keith Henry for why we might want to hold off on starting treatment for as long as possible.  How did we get from there to a policy to treat everyone?  Selected highlights:

  • 2006:  SMART study stopped — intermittent therapy is worse than continuous treatment, including the risk of non-AIDS complications.  In other words, toxicity of ART notwithstanding, untreated HIV is worse.
  • 2006:  One-pill a day treatment (TDF/FTC/EFV) approved. It wasn’t and still isn’t for for everyone, but it definitely was the next chapter in making treatment much easier to take, a far cry from the handful of toxic pills we prescribed in the late 1990′s.
  • 2007:  SMART “naive” analysis is presented at the Sydney IAS meeting, (link is to published paper) showing that even for those starting SMART with high CD4′s but not on therapy, intermittent treatment was worse.
  • 2008:  The famous “Swiss Statement” proclaimed that patients with undetectable HIV RNA on treatment cannot transmit HIV to others.  (If you read French, here is the original.)  A series of studies — some in serodiscordant couples, some population-based, some just mathematical models — have followed, all essentially demonstrating that HIV treatment is more effective than any other preventive strategy we currently have.
  • 2009:  NA-ACCORD is presented at CROI, concluding that deferring therapy until the CD4 falls below 500 cells is associated with a nearly two-fold increased risk of death.  The paper is then published in the NEJM, adding credibility to the statistical gyrations required to do such an analysis.

That’s not a comprehensive list, of course, but these and other data led to a change in the latest HIV treatment guidelines, which despite raising the CD4 threshold for starting therapy, still do not go as far as the proposed San Francisco recommendations.

Is their room for uncertainty?  You bet:

James D. Neaton of the University of Minnesota School of Public Health, contends that a rigorous, randomized clinical trial is needed to show whether early intervention works. The risks of early treatment — giving powerful drugs to people at low risk of disease — – could outweigh the “modest predicted benefit,” Dr. Neaton wrote in an e-mail message. “That is why we do randomized trials.”

And more:

Dr. Lisa C. Capaldini, who runs an AIDS practice in the Castro district, also has strong reservations. “H.I.V. behaves differently in different people,” she said.  Although Dr. Capaldini recognizes that today’s drugs are a vast improvement over earlier therapies, the program, she said “is not ready for prime time.”

San Francisco has always had a distinctive role in the history of the HIV epidemic.

Why should now be any different?

6 Responses to “San Francisco Public Health: Treatment Recommended for All with HIV”

  1. Donald Blair says:

    Rigorous randomized trials are the sine qua non for adopting universal treatment.

    Further, from the start, Intent to treat is insufficient, as adherence and continued treatment, is the key point. Full analysis of why treatment was stopped should be an essential component of the research.

    Dblair

  2. Oren Hillel says:

    Can you please explain the rational in more detail? From what I read in NYTimes all sounds very philosophical and far from EBM. Is it ethical?

  3. Paul Sax says:

    Can you please explain the rational in more detail?

    I am not part of this specific discussion in SF (am based in SF-East, according to some!), but it seems to me that it’s not just one thing — it’s the multiple studies pointing in the direction of benefits of therapy, both on a personal and public health basis. We need to be humble about our limitations as clinicians, both in our inability to see long-term toxicities but also our not being able to see benefits of treatment when asymptomatic patients seem to be doing so well.

    But your point is well taken, and indeed is the one put forth by the START study investigators.

  4. Jon Li says:

    Despite the increasing evidence for early treatment, I always think of the estrogen replacement controversy as a cautionary tale for those all too enamored with observational studies. Sometimes these medication side-effects do not show up for years or decades. I’m not entirely sure the circumstantial evidence is strong enough yet to make it a clear risk-benefit decision. Until RCTs are complete, why not take it on a case-by-case basis with an emphasis on individual preference, as is normally the case when things are not clear cut?

  5. Paul Sax says:

    Jon, many good points.

    Some further comments:

    1) observational studies: Yes they were famously wrong on estrogen replacement, but they’ve been famously right too! (Smoking and lung cancer, Vioxx and CV disease, etc.)
    2) Tox of meds: No doubt it might take decades for these to show up, but one of the aspects of the NA-ACCORD study I found most interesting was that the benefit of starting with CD4 > 500 was seen even though most of the pts starting at that high count were using older regimens — the ones with the high toxicity and lower efficacy (think d4t, 3tc, nelfinavir, or azt, 3tc, indinavir). This either makes the findings either more impressive or, if you’re in a doubting mood, more likely to be wrong!

    Seems like individualizing is the way to go for now — which is ultimately what will probably happen, even after the SF “guidelines” get announced.

  6. Enrique Naveira-Abeigon says:

    Hoy por hoy, con el numero de existen de antirretrovirales, el tratamiento individualizado debe ser una realidad.
    Enrique

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HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

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