NEW YORK (Reuters Health) - For people infected with HIV, starting therapy before AIDS symptoms appear or before levels of a certain kind of white blood cell fall below a specific threshold can dramatically delay the development of AIDS-related events and death, according to two studies released by the New England Journal of Medicine.

Until now, evidence on when to begin the treatment of asymptomatic patients has not been clear, and there's been concern that giving antiretroviral therapy earlier might increase patients’ risk of cardiovascular and renal disease.

“It has been controversial for two decades over whether to start treatment” when levels of so-called CD4-positive white blood cells are above 350 cells per cubic millimeter, the coauthor of the larger of the two studies, Dr. Jens Lundgren of Rigshospitalet at the University of Copenhagen, told Reuters Health in a telephone interview.

"It's clear that with early treatment there's obviously a transmission benefit, a public health benefit, but that's not a benefit to individuals," he said. "This controversy has been going on for so many years, we thought it was important to settle it."

In his team’s study, known as START and reported Monday afternoon at the International AIDS Society 2015 Conference in Vancouver, 4,685 HIV-positive adults were followed for an average of three years. Half were randomly assigned to start taking antiretroviral drugs immediately, while their CD4-positive counts were still higher than 500. In the remaining volunteers, treatment was delayed until their counts dropped to 350.

The findings were so dramatic, the test was terminated prematurely and all patients were put on antiretroviral therapy.

While 1.8 percent of patients in the immediate-treatment group reached a composite end point of death from any cause, a serious AIDS-related event or a serious non-AIDS related event, 4.1 percent of people in the deferred-therapy group reached that end point. When treatment was delayed, it typically took three years for the counts to drop low enough to begin antiretroviral therapy.

Side effects from early therapy were not a major problem, the researchers said. The odds of having a grade 4 (serious) event or an unscheduled hospital admission were comparable in the two groups, and early treatment didn't seem to significantly increase the risk of cardiovascular or renal disease during the study.

"We are demonstrating a benefit from treatment with what we could consider to be a normal CD4-positive count," said Lundgren. "From that logic, everybody (who is HIV positive) should be treated because in any patient who is HIV infected but with a high CD4-positive count there is some immune deficiency that antiretroviral treatment can essentially repair."

The benefit for patients who received early treatment seemed to come from lower rates of tuberculosis and in lower rates of cancer, including types of cancer not associated with AIDS.

"It really opens up a whole new discussion around what are actually the factors driving cancer development in people with impaired immune systems, which is obviously an issue in HIV patients," said Lundgren.

The study, initiated in 2009, was done by the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) and involved volunteers treated at 215 sites in 35 countries.

The second study, by Xavier Anglaret of INSERM in Bordeaux, France and colleagues, reached a similar conclusion. It followed 2,056 infected patients at nine care centers in Abidjan, the economic capital of Ivory Coast. That research team looked at volunteers whose CD4-positive counts were above or below 500, the standard set by the World Health Organization.

Antiretroviral therapy "provides substantial clinical benefits in patients who have higher CD4+ counts at the time of initiation than those previously recommended for the initiation of ART," the researchers concluded.

"My sense is that this will galvanize the efforts to put more people on treatment and that most, if not all, guidelines will change to recommending treatment irrespective of CD4-positive count," said Lundgren. "That's our recommendation. We feel these results are definitive and it would be unethical to repeat the study. I think we have resolved the controversy that has persisted for the last two decades."

(Reporting by Gene Emery)