February 13th, 2009

CROI 2009: Greatest Hits

Fresh back from lovely Montreal, where the temperature (I’m glad to report) climbed into the balmy 40’s …

Here’s a rapid-fire listing of the Greatest Hits.  As I’m sure to be leaving something off this list, happy to accept other suggestions:

  1. Interleukin-2 does not work.  The ESPRIT and SILCAAT studies are over. Yes, the CD4’s increase, but compared to antiretroviral therapy alone, there’s absolutely no clinical benefit, and plenty of side effects.
  2. Should we be starting antiretroviral therapy at even higher CD4s? At ICAAC, the NA-ACCORD group said starting before 350 improved survival; here they said it was 500!  The ART-CC disagreed, slightly (their estimate was around 350).
  3. Switching from lopinavir/r to raltegravir increases the risk of virologic failure in suppressed patients. Likely explanation:  undetected NRTI resistance at baseline.  This study should have no bearing on the use of raltegravir in either treatment-naive or treatment-experienced patients — essentially, the drug must be used with at least one other fully active agent.  (Oh yeah, the lipids improved, not surprisingly.)
  4. Treating HIV during TB treatment increases survival compared with waiting until TB therapy is completed. One of the most interesting things about this study is that TB treatment outcomes were similar — but those who delayed therapy obviously had HIV disease progression.  By contrast, a small study of cryptococcal meningitis from Zambia suggested that early ART was harmful — the first time early ART has been associated with worse outcomes.
  5. Treating HIV significantly reduces the risk of HIV transmission to a seronegative partner. This study from Zambia and Uganda involved nearly 3000 discordant couples (!), and the effect was dramatic — especially when one considers that HIV therapy was only given if clinically indicated (i.e., not to prevent transmission).
  6. …But the risk of transmission is not zero. Some studies showed persistent HIV shedding in semen despite effective antiretroviral therapy.  No surprise — but this doesn’t diminish my enthusiasm for #5 above, as the reduction in risk from treatment is huge.
  7. Antivirals and cardiovascular disease. D:A:D is updated, and continues to implicate abacavir, and a French Hospital Database study does the same — and both now cite lopinavir/r as associated with increased risk as well.  An ACTG database study does not find an association with abacavir, but a prospective randomized switch trial (to ABC/3TC or TDF/FTC) does — in the updated analysis, the difference was statistically significant.  Regarding abacavir, pathogenesis studies were all over the place — split about evenly whether positive or negative.  Peter Reiss gave a sensational summary on this complex issue — web cast highly recommended if you have 15 minutes to spare.
  8. Lopinavir/r is better than nevirapine for women who previously received single-dose nevirapine. This might seem intuitively obvious, but it answers an important question that has generated enormous controversy over the years.  (Plus the first author is a beloved colleague.)
  9. Two non-ritonavir boosters are introduced. (Details here and here.)  Yes, data are early, but something without the GI and lipid effects would be welcome indeed.  Whether we really will need PK boosters at all remains an open question, but for now they clearly are needed for PIs and the investigational integrase inhibitor elvitegravir.
  10. A microbicide works.  Sort of.

So what’s missing?  Not a single phase III study of a novel agent, nor a phase IV comparative trial of existing drugs done in the developed world.

Yes, it’s a very “quiet” phase in HIV drug development — too quiet.  If this poster is a harbinger of what’s coming with integrase resistance, let’s hope it’s not quiet for long.

5 Responses to “CROI 2009: Greatest Hits”

  1. Jon says:

    I wonder if the IL-2 trial results bode poorly for the ongoing Maraviroc trial for those with suboptimal CD4 recovery. Thoughts?

  2. Paul Sax says:

    I’m no immunologist (this is an understatement), but I guess what I’ve learned from those who are is that a quantitative CD4 is not necessarily a qualitative one — so the IL-2-generated CD4s didn’t work so well. But this doesn’t mean the maraviroc ones won’t!
    That study will have plenty of sophisticated immunologic assays, so stay tuned!

  3. Charles Steinberg MD says:

    #5–Rx in serodiscordant couples of HIV Positive partner prevents seroconversion was done in Zambia and Rwanda. You say Uganda, and that is where I am and it is definitely needed here where up to 65 % of partners of HIV positives are negative (serodiscordant) .

  4. Paul Sax says:

    Charles, my bad — have corrected. Thank you for your note.

    p.s. this is an incredible study!

  5. Robert Nowinski says:

    Fantastic list, thank you for sharing!

    Robert Nowinski

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

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NEJM Journal Watch
Infectious Diseases

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