Results of a large study released this week indicate that starting antiretroviral treatment earlier (at a CD4 count of 500 cells per microliter of blood) decreases the risk of getting AIDS-related illnesses. However, it does not improve survival relative to starting treatment later, once CD4 counts have dropped further.

“If the goal is to prevent AIDS or death, then initiation when CD4 cell count first drops below 500 is beneficial. However, this same benefit is not seen for mortality: the 5-year survival was similar for those initiating combination antiretroviral therapy when CD4 cell count first dropped below 500 and 350 cells per microliter,” said Dr. Lauren Cain, a research fellow at the Harvard School of Public Health and lead author of the study.

“Most importantly, our findings stress the need for early initiation. To fully benefit from early initiation, patients must present for medical care while their CD4 cell counts are still above 500 cells per microliter,” she added.

The study authors stated that their findings support treatment guidelines that recommend treatment starting at 500 cells per microliter.

“In the most recent Department of Health and Human Services guidelines, there were disagreements among panel members as to the strength of the recommendation to initiate [treatment] with CD4 cell counts between 350 and 500 and whether to recommend initiation at CD4 cell counts greater than 500. We hope that our results will help to settle these disagreements,” said Dr. Cain.

The researchers noted that their findings may not be applicable to people in developing countries, who may face different health challenges. Their study also did not examine the role of non-AIDS-related illnesses, which could still be higher in people who start treatment later.

In addition, large study populations and longer follow-up times may be needed to determine whether the timing of treatment initiation has an overall impact on survival. Forty-seven percent of participants never reached the 350 cells per microliter CD4 count threshold and had no AIDS-related illnesses during the study; 82 percent never reached 200 cells per microliter and had no AIDS-related illnesses.

The question of when to initiate antiretroviral treatment is still controversial. In the United States, treatment guidelines recommend starting treatment when a person’s CD4 (white blood cell) count drops to 500 cells per microliter or less. However, many international guidelines still use a lower threshold of 350 cells per microliter.

Several studies have indicated that starting treatment earlier can help prevent immune system damage caused by HIV. However, starting early also exposes patients to drug side effects sooner, may increase the risk of developing drug resistance, and is more expensive (see related AIDS Beacon news).

In this study, researchers attempted to determine whether starting treatment at a CD4 count threshold of 500 cells per microliter conferred any benefits over starting at 350 or 200 cells per microliter.

The study included approximately 21,000 previously untreated HIV-positive adults who participated in studies from five European countries and the U.S. during the period from 1996 to 2009. All participants began with CD4 counts of 500 cells per microliter or more.

Researchers measured participants’ CD4 counts and noted when they started combination antiretroviral therapy. The researchers also recorded any AIDS-related illnesses or deaths.

Results showed that starting treatment earlier did not appreciably affect the chances of surviving five years. Participants who started treatment within six months after reaching a CD4 count of 500 cells per microliter had a 98 percent chance of survival over the following five years, compared to 98 percent for those who initiated therapy within six months of reaching 350 cells per microliter and 97 percent for a CD4 threshold of 200 cells per microliter.

The researchers did find a small difference in the proportion of participants who experienced AIDS-related illnesses, depending on when the participants started treatment. Participants in the 500 cells per microliter group had a 94 percent chance of five-year AIDS-free survival, compared to 92 percent in the 350 cells per microliter group and 88 percent in the 200 cells per microliter group.

The results were not affected when the researchers excluded participants who started treatment before 1999 (before newer antiretrovirals were available), participants who were infected via injection drug use (which is associated with poorer outcomes), or participants who were female.

Dr. Cain stated that follow-up studies will examine the effects of early treatment initiation in older HIV-positive adults. The researchers will also continue to follow participants from this study to examine longer-term effects.

For more information, please see the study in the Annals of Internal Medicine (abstract).