Mapping Pathways is a multi-national project to develop and nurture a research-driven, community-led global understanding of the emerging evidence base around the adoption of antiretroviral-based prevention strategies to end the HIV/AIDS epidemic. The evidence base is more than results from clinical trials - it must include stakeholder and community perspectives as well.

12 October 2011

No Benefit to HAART in Patients With a CD4 Cell Count Over 500


Starting highly active antiretroviral therapy (HAART) in patients with HIV whose CD4 cell counts are above 500/μL does not slow the progress of the disease, according to results from the Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) study.

The study's findings were published by a writing committee for the CASCADE collaboration in the September 26 issue of the Archives of Internal Medicine.

The article lends weight to the argument that treating patients too early in the course of their infections can do more harm than good, Jay Levy, MD, a professor of medicine at the University of California, San Francisco, and codiscoverer of HIV, told Medscape Medical News. Many of the drugs used in HAART have strong adverse effects.

"Above 500, as far as I'm concerned, you have a long way to wait," he said. "I have been telling people, 'Be careful of treating too early.' You get resistance, and you get patients who are not going to stay on therapy."

At this time, the US Department of Health and Human Services guidelines say that antiretroviral therapy is indicated in all patients whose CD4 cell count is below 500/μL. The guidelines suggest considering the therapy for all patients from the time of HIV diagnosis.

For the observational cohort study, researchers from multiple institutions enrolled 9455 patients between the years 1996 and 2009, all of whom had not had HAART or developed AIDS at the time they were enrolled and had CD4 cell counts below 800/μL. The scientists enrolled new patients once every month, creating 161 sequential nested subcohorts.

The researchers then followed up the patients, noting the number of days until these patients either died or developed AIDS. If the patients initiated HAART, as nearly all did, the researchers noted the patients' CD4 counts at that point. The median follow-up time was 4.7 years (interquartile range, 2.0 - 9.1 years).

The authors found that patients who started HAART with CD4 cell counts from 0 to 49/μL were 68% less likely to die or develop AIDS. The advantage decreased to 52% in patients who started HARRT when their cell counts were from 50 to 199/μL, 41% in patients with cell counts from 200 to 349/μL, 25% in patients with cell counts from 350 to 499/μL, and −10% in patients with cell counts from 500 to 799/μL.

The research confirmed earlier findings on the benefits of the therapy in patients with cell counts below 500/μL, but conflicted with a 2009 study published in the New England Journal of Medicine by the North American AIDS Cohort Collaboration on Research and Design, which found benefits for patients with cell counts above 500/μL.

The CASCADE researchers acknowledged that their study is only observational, and a more definitive study would randomly assign patients with various cell counts to begin or defer HAART. Such trials are underway, but the results are not yet available.

Because the patients were not randomly assigned, there were differences between those who deferred HAART and those who started it. At baseline, those who started had higher viral loads, shorter duration of infection, and slightly lower CD4 cell counts compared with those who started HAART within each subcohort. However, they were also less likely to have a history of intravenous drug use and less likely to be coinfected with hepatitis.

In a commentary that accompanied the study, Harvard retrovirus researcher Daniel R. Kuritzkes, MD, lamented that the researchers were unable to study directly the effects of HAART on non-AIDS-defining HIV-1 complications such as cardiovascular disease, neurological disease, and other end-organ damage. "These complications may cause significant morbidity without contributing to mortality over the relatively short time frame considered herein," he writes. In addition, Dr. Kuritzkes explains, the CASCADE study did not measure the potential benefits of HAART on prevention of HIV-1 transmission.

However, he said the study provides important information that clinicians can use while awaiting the results of prospective randomized trials. "While awaiting more definitive data," Dr. Kuritzkes writes, "the pros and cons of starting HAART at CD4 cell counts above 500/μL should be weighed carefully by clinicians and patients."

Read the Abstract of the study here.

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

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