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The XVII International AIDS Conference (AIDS 2008)
  
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AIDS 2008 Conference Highlights: An Interview With Paul Sax, M.D.

August 7, 2008

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In this interview, Paul Sax, M.D., clinical director of the HIV program at Brigham and Women's Hospital in Boston, Mass., and associate professor of medicine at Harvard Medical School, offers his perspective on the most significant take-home messages from the XVII International AIDS Conference.

One of the highlights of this conference included a very interesting analysis evaluating cardiovascular risk in the SMART study.1 The SMART study looked at people both on and off treatment, and collected data on both AIDS-related and non-AIDS-related events.2 We already know that the people stopping treatment had more non-AIDS-related events.

Paul E. Sax, M.D.
Paul Sax, M.D.
This study followed up on the results of the D:A:D study3 and tried to evaluate whether receiving abacavir [ABC, Ziagen] was associated with an increased risk of cardiovascular events. It was presented by Jens Lundgren, who presented the D:A:D study4 as well.

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There were two important findings. One is that, yes, there was an increased risk of cardiovascular events in people who were receiving abacavir in the SMART study.1

The second important point is that stored specimens from the SMART study were able to be used to show that patients who were receiving abacavir had a higher level of C-reactive protein and IL-6 [interleukin-6] -- which are both markers of inflammation. Researchers such as Jens are currently postulating that the way in which abacavir might induce cardiovascular events is by inducing a state of inflammation; and if people already have underlying atherosclerosis, that inflammation might provide a sort of tipping point that would make them have a cardiovascular event.

It's interesting because lipids tend to cause atherosclerosis gradually over time, and in fact that's what was seen in the protease inhibitor analysis from the D:A:D study.3 But in this study, it's not like that at all. Abacavir seems to be a switch that can be turned on and off. Once people stop the abacavir, it looks like their cardiovascular risk goes down.

The take-home message from that analysis is that the people who don't have underlying cardiovascular risk factors are probably very safe on abacavir, because this effect is not going to cause cardiovascular disease [CVD]. But for people who have other cardiovascular risk factors, it's something to consider when selecting a regimen, and one might want to choose an alternative drug that does not have this link to CVD.

Basically, it confirms the D:A:D data?

It was very much confirmative of the D:A:D data, and to their credit, they ended up publishing the D:A:D data in Lancet3 very shortly after the retrovirus conference [Conference on Retroviruses and Opportunistic Infections].4 Also to their credit, they're going to publish these data in AIDS in September. They are really doing a thorough job with the analyses, and doing their best to control for all confounders. Even though it is an observational study -- with all the caveats associated with that -- the fact that there have been two studies with this effect is fairly persuasive.

Anything else that you found interesting?

This is slightly off the beaten track, but I was interested to see a Brazilian study looking at the administration of antiviral therapy for patients in intensive care units [ICUs].5

We have this debate all the time about when to start therapy. This year's ACTG 5164 study suggested that we should start therapy fairly early, even in people who are acutely ill with opportunistic infections.6

This study, which had to be retrospective, took it one step further and looked at the most acutely ill patients -- patients in intensive care units -- to see whether receiving antiviral therapy improved outcome.5 While the study did not find that it improved in-ICU mortality, it did find that receiving antiviral therapy improved six-month post-ICU survival. Once again, it provides a little bit of supportive data for getting our patients on antiviral therapy as soon as possible, if we can. Obviously, there are going to be numerous extenuating circumstances in the ICU, but it still does come up where you see someone in the ICU and he or she is taking other medications, either by a gastric tube or by mouth. And we think, well, should we start antiviral therapy now? It's certainly going to make me think that perhaps we should.

This transcript has been lightly edited for clarity.


References

  1. Lundgren J, Neuhaus J, Babiker A, et al, and the SMART/INSIGHT and D:A:D Study Groups. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the SMART study. In: Program and abstracts of the XVII International AIDS Conference; August 3-8, 2008; Mexico City, Mexico. Abstract THAB0305.

  2. Strategies for Management of Antiretroviral Therapy (SMART) Study Group, El-Sadr WM, Lundgren JD, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. November 30, 2006;355(22):2283-2296.

  3. D:A:D Study Group, Sabin CA, Worm SW, et al. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration. Lancet. April 26, 2008;371(9622):1417-1426.

  4. Sabin C, Worm S, Weber R, et al, and the D:A:D Study Group. Do thymidine analogues, abacavir, didanosine and lamivudine contribute to the risk of myocardial infarction? The D:A:D study. In: Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Mass. Abstract 957c.

  5. Croda J, Croda M, Neves A, Santos SDS. Impact of antiretroviral therapy in survival of HIV-infected patients admitted to intensive care unit. In: Program and abstracts of the XVII International AIDS Conference; August 3-8, 2008; Mexico City, Mexico. Abstract TUPE0105.

  6. Zolopa A, Andersen J, Komarow L, et al, and the ACTG A5164 Study Team. Immediate vs deferred ART in the setting of acute AIDS-related opportunistic infection: final results of a randomized strategy trial, ACTG A5164. In: Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Mass. Abstract 142.

  
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Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.

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