The INSIGHT START Study Group conducted a large, randomized trial to evaluate the benefits and risks of starting antiretroviral therapy (ART) immediately in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter, compared to deferring therapy until the CD4+ count drops to 350 cells per cubic millimeter or until an AIDS-related event occurs. The study enrolled 4685 patients from 35 countries and followed them for a mean of 3.0 years. The primary endpoint was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause. The results showed that starting ART immediately reduced the risk of these events by 43% compared to deferring therapy. The hazard ratios for serious AIDS-related and non-AIDS-related events were 0.28 and 0.61, respectively. The study found that starting ART earlier provided net benefits, as more than two-thirds of the primary endpoints occurred in patients with a CD4+ count above 500 cells per cubic millimeter. The risks of grade 4 events and unscheduled hospitalizations were similar in both groups. The study concluded that initiating ART in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting therapy after the CD4+ count had declined to 350 cells per cubic millimeter. The findings support the recommendation to start ART earlier in HIV-positive individuals, regardless of CD4+ count, to reduce the risk of AIDS-related and non-AIDS-related events and to improve public health outcomes. The study was funded by the National Institute of Allergy and Infectious Diseases and others.The INSIGHT START Study Group conducted a large, randomized trial to evaluate the benefits and risks of starting antiretroviral therapy (ART) immediately in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter, compared to deferring therapy until the CD4+ count drops to 350 cells per cubic millimeter or until an AIDS-related event occurs. The study enrolled 4685 patients from 35 countries and followed them for a mean of 3.0 years. The primary endpoint was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause. The results showed that starting ART immediately reduced the risk of these events by 43% compared to deferring therapy. The hazard ratios for serious AIDS-related and non-AIDS-related events were 0.28 and 0.61, respectively. The study found that starting ART earlier provided net benefits, as more than two-thirds of the primary endpoints occurred in patients with a CD4+ count above 500 cells per cubic millimeter. The risks of grade 4 events and unscheduled hospitalizations were similar in both groups. The study concluded that initiating ART in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting therapy after the CD4+ count had declined to 350 cells per cubic millimeter. The findings support the recommendation to start ART earlier in HIV-positive individuals, regardless of CD4+ count, to reduce the risk of AIDS-related and non-AIDS-related events and to improve public health outcomes. The study was funded by the National Institute of Allergy and Infectious Diseases and others.