Start HIV Antiretroviral Therapy ASAP, Experts Urge

WASHINGTON -- Early initiation of antiretroviral therapy (ART) in patients with HIV can lead to better outcomes, especially for those ages 35 and younger, a follow-up analysis of the START trial showed.

For patients who had deferred ART until their CD4 counts were below 350 cells/mm³, there was a 21% higher risk of death or serious AIDS-related and non-AIDS-related health consequences in the 5-year period following initiation of therapy compared with patients who started ART immediately (P=0.09), reported Abdel G. Babiker, PhD, of University College London, during his presentation at IDWeek.

Even for patients who had CD4 counts over 500 cells/mm³ at diagnosis, "it's better not to delay therapy," Babiker told MedPage Today. "It's a gradient; the earlier you start, the better."

Of the patients who previously deferred ART, 27 progressed to AIDS and 57 died compared with 15 and 47 in the immediate group. Non-AIDS-related serious health issues, including cardiovascular disease, end-stage renal disease, decompensated liver disease, and non-AIDS-defining cancer, occurred in 88 patients in the delayed group versus 76 in the immediate group.

"These are critically important findings; we have to diagnose people earlier," Carlos del Rio, MD, of Emory University School of Medicine in Atlanta, told MedPage Today.

"Whenever you do a blood test in someone who is at risk, you should test for HIV," he urged. "People don't realize they have it until it's too late."

While the risk was worse for those who deferred therapy, Babiker noted that the risk was there for everyone. "The risk of AIDS was not zero among patients receiving antiretroviral therapy, even among those who had full viral suppression while receiving antiretroviral drugs. This finding indicates that damage to the immune system may occur early in the course of HIV infection."

However, one finding surprised the researchers: the dire results with delayed treatment were even more amplified in patients ages 35 and younger.

In this younger age group, 44 patients in the delayed group experienced primary endpoint events compared with 19 in the immediate group (HR 0.42, 95% CI 0.24-0.71), while these numbers were 69 and 70 in patients over 35 (HR 1.04, 95% CI 0.75-1.45; P=0.004).

"The risk seemed to be completely eliminated" in the older age group, Babiker said. His team could not figure out why. "The uptake of antiviral therapy and suppression of viral load was very similar; these did not vary by age -- we are still going to do some more investigation for this difference by age."

The START trial was first initiated in 2009, enrolling 4,684 HIV-positive patients (median age 36, 27% women), who had a CD4 count of ≥500 cells/mm³ (median 651 cells/mm³ ) at least 2 weeks apart within the 60 days before enrollment. Of these patients, 2,325 were randomized to start ART right away, and 2,359 were randomized to defer treatment until their CD4 count was ≤350 cells/mm³.

In 2015, results were published in the New England Journal of Medicine, showing that early treatment reduced the risk of serious AIDS-related events, serious non-AIDS-related health outcomes, and death by 57%.

At that point, participants who had been on delayed ART recorded significantly lower CD4 counts (median 460 cells/mm³, range 345-601) compared with participants who started ART immediately (median 648 cells/mm³, range 580-764).

Subsequently, all participants in START were treated with ART.

The current analysis included 4,436 patients, and spanned from January 2016 through December 2021.

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