By Bob Roehr
Delaying the start of HIV therapy increases the risk of death by 70 percent, according to an analysis of data from all 22 HIV cohort studies in the United States and Canada.
The striking finding has been under-reported since its presentation in late October at the annual meeting of the Infectious Disease Society of America.
The North American AIDS Cohort Collaboration on Research and Design analysis focused on an intermediate group of patients, those with 351 to 500 CD4 T-cells. U.S. treatment guidelines strongly recommend that those with fewer than 350 T-cells start treatment while those above 500 have no need to do so.
It identified 2,473 patients who began treatment (8,358 person-years) and 5,901 (16,636 person-years) who deferred treatment during the period 1996 to 2006. It excluded those who had previously been on therapy or experienced an AIDS-defining illness.
The results were clear. Those who deferred starting HAART had a 70 percent greater risk of death than patients who began therapy. "These data strongly support the use of antiretroviral treatment for patients at a CD4 count of 500 and below, regardless of the presence of symptoms," said lead author Mari Kitahata, from the University of Washington Center for AIDS Research.
"These are really important data," says Harvard University professor of medicine Daniel Kuritzkes. Earlier studies have suggested similar trends but "they have lacked the power to find meaningful differences in strategies." Combining the data from these cohorts created sufficient statistical power to reach definitive conclusions.
Opinions on when to start treating HIV have swung back and forth. "Hit it early, hit it hard" became the mantra of the mid-1990s with the introduction of highly active antiretroviral therapy (HAART). Physicians and patients grew to be more cautious as the side effects of those drugs became more evident.
Then the pendulum began to swing back with the approval of newer drugs that were more tolerable and carried fewer long-term risks. The findings from this study are sure to nudge opinions back toward earlier intervention.
Kuritzkes said the study means that additional "hundreds of thousands of people" in the U.S. should be started on therapy. But the reality is, "At our center a quarter of the people get diagnosed with HIV for the first time because they got diagnosed with an AIDS-defining illness. They are being identified far too late."
Los Angeles physician Anthony Mills primarily treats gay men, a group that is more likely to test early for HIV as a regular part of medical care. He strongly advocates early intervention because "people who start early just do better; they suppress more quickly, their T-cells rebound better, they have fewer side effects. Now that the medications are so well tolerated, why would we wait?"
New York City physician Scott Hammer says he initiates the discussion on when to begin treatment at a patient's first visit. "I say to people, right now, the way the field is moving, is away from these arbitrary thresholds [of T-cell counts]. There are potential reasons to treat earlier and earlier, when you are ready."
The debate over when to start treatment is likely to intensify when Cohort Collaboration researchers present their analysis of patients with more than 500 T-cells. That may come as early as the retroviral conference in early February, 2009.
The cost of treating a single HIV patient in the U.S. with the most commonly used anti-HIV "cocktail" is about $15,000 a year. Adding tens of thousands of patients a year, for their lifetime, will further stress an already over-burdened healthcare system, particularly the AIDS Drug Assistance Program (ADAP).
