Print this page    •   Back to Web version of article

CASCADE: When to Start, (Yet) Another Take

By Paul E. Sax, M.D.

October 3, 2011

As we await the enrollment, analysis, and results of the START study -- which is randomizing patients with CD4>500 to start HIV therapy vs waiting until the CD4 falls to 350 -- much of the research on "when to start" ART in patients with high CD4's comes from observational studies. Several have already been published (NA-ACCORD, ART-CC, CAUSAL), but one limitation of each of them is that none could accurately assess duration of HIV infection.

Enter "CASCADE", or "Concerted Action on SeroConversion to AIDS and Death in Europe". CASCADE includes patients from Europe, Australia, and Canada only if they have a defined date of HIV acquisition, thereby limiting effects of lead-time bias. In order to get at the when-to-start question, the investigators constructed something called "nested subcohorts" between 1996 and 2009, comparing the outcomes of those who started ART vs. those who didn't.

The results? Out of 9,455 patients, starting ART (vs deferring) was associated with a lower risk of developing AIDS or death for those with a CD4 cell count < 500 -- but not for those who started between 500-799. An interesting aspect of this study is that they were able to calculate a "number needed to treat" (NNT) to prevent progression. Over 3 years of follow-up, 21 and 34 patients would need to start treatment to prevent one patient from progressing to AIDS or death in those with CD4s between 200-349 and 350-499 respectively.

Usual caveats of observational studies apply -- most notably that no such study can control for all factors between those who started ART vs those who didn't that would influence outcome -- but the results are helpful nonetheless, as the benefits of therapy before the CD4 cell count falls to < 350 shown here have been consistently seen in multiple studies. Furthermore, the NNT data to prevent AIDS or death -- 34 for CD4 between 350-499 -- place the benefits of treating these patients as even greater than what we accomplish with statin therapy for hypercholesterolemia to prevent MIs, which is estimated as 40-70.

Bottom line: Treating patients with CD4 350-500 and no symptoms may not be as exciting giving ART to someone with advanced HIV disease, but it sure makes good clinical sense.

Paul Sax is Clinical Director of Infectious Diseases at Brigham and Women's Hospital. His blog HIV and ID Observations is part of Journal Watch, where he is Editor-in-Chief of Journal Watch AIDS Clinical Care.




This article was provided by Journal Watch. You can find this article online by typing this address into your Web browser:
http://www.thebodypro.com/content/64241/cascade-when-to-start-yet-another-take.html

General Disclaimer: The Body PRO is designed for educational purposes only and is not engaged in rendering medical advice or professional services. The information provided through The Body PRO should not be used for diagnosing or treating a health problem or a disease. It is not a substitute for professional care. If you have or suspect you may have a health problem, consult your health care provider.