amfAR, The Foundation for AIDS Research

When to Start?

New Study examines Best time to Start treatment


March 2009—A question that has plagued the HIV community for years is when to start treatment to achieve the best outcomes. In the mid-1990s, Dr. David Ho recommended "hitting early and hitting hard," meaning that antiretroviral therapy (ART) should be started as soon as HIV infection is diagnosed, and a multi-drug regimen should be used. Because treatment of HIV is life-long, however, side effects from ART can make it difficult to tolerate prolonged treatment and maintain adequate adherence to therapy.

These findings highlight the need for people to get tested earlier so they can receive greater benefit from ART.
The medications used to treat people living with HIV are effective at suppressing HIV and improving the body's natural defense system and are now being made in forms that are well tolerated. However, 12 years after the advent of highly-active ART there are still concerns about drug side effects, adherence to daily dosing, development of HIV strains that do not respond to medications, and the high costs of the drugs over the course of life-long treatment. These factors have typically led doctors to delay starting ART until a patient's immune system is weakened, as measured by lower CD4+ cell counts.

The most recent HIV treatment guidelines issued by the World Health Organization (WHO) in 2006 recommend starting ART for people without symptoms of disease when their CD4+ count is less than 200 cells/mL3, and less than 350 cells/mL3 in persons who have advanced HIV disease. But the 2008 US treatment guidelines recommend starting those without symptoms at a CD4+ count of less than 350 cells/mL3. This translates to starting ART before the immune system becomes severely compromised (CD4+ less than 200 cells/mL3) but not too early to risk fatigue from ART (greater than 350 cells/mL3).

Results of a recent study, however, suggest that starting ART even earlier may lower the risk of death. These recent findings were from a large study involving 22 research groups in North America and included data from 8,374 patients. The study examined patients with CD4+ counts of 351-500 cells/mL3 who were being actively followed between 1996 and 2006. Their results showed a 70 percent improvement in survival for people starting ART with CD4+ counts above 350 cells/mL3 over those patients who waited until their CD4+ counts dropped below 350 cells/mL3.

This means that these patients from North America had a lower risk of dying when they were started on ART at a higher CD4+ count. In many parts of the world, however, people are often not diagnosed with HIV infection or started on ART until their CD4+ cells have dropped below 200 cells/mL3. These findings highlight the need for people to get tested earlier so they can receive greater benefit from ART, and they also raise questions about whether international guidelines should be revised to encourage earlier treatment initiation.