An ongoing dialogue on HIV/AIDS, infectious diseases,
October 3rd, 2011
CASCADE: When to Start, (Yet) Another Take
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 E. Sax, MD
Associate Editor
NEJM Clinician
Biography | Disclosures & Summaries
Learn more about HIV and ID Observations.
FROM NEJM — Recent Infectious Disease Articles- The Invisible Load of Cognitive Symptoms July 2, 2026Patients with shrinking cognitive bandwidth may feel their disability keenly in daily life, even if they can pass a controlled test of cognitive capacity. How should clinicians approach and care for them?
- Cat Scratch Disease July 2, 2026A 40-year-old woman presented with a 1-month of history of fevers and 3-week history of swelling in her right armpit. Ultrasonography showed enlarged lymph nodes with an adjacent fluid collection.
- Operative versus Nonoperative Management for Appendicitis July 2, 2026This feature about treatment of appendicitis offers a case vignette accompanied by two essays, one recommending operative management and the other supporting a nonoperative approach.
- Advances in Multiple Sclerosis July 2, 2026This review summarizes advances in the treatment of multiple sclerosis, with emphasis on effective disease-modifying therapies for relapsing disease and the need for better treatments to prevent progression and rebuild myelin.
- Ebola at 50 — Lessons for Outbreak Response and Preparedness July 1, 2026An accurate history of Ebola begins with partnerships, including those between responders and the populations they serve. One of its key lessons is that equity must be integral to outbreak preparedness.
- The Invisible Load of Cognitive Symptoms July 2, 2026