Treating HIV in the first weeks and months of infection is associated with slower disease progression and better recovery of the immune system, according to two studies in the Jan. 17 issue of the New England Journal of Medicine.
In the so-called SPARTAC trial, researchers found that 48 weeks of antiretroviral therapy started within 6 months of infection significantly slowed HIV progression compared with no treatment.
In a second study, investigators found that starting therapy during a transient immune system rebound, usually seen about 4 months after infection, was associated with a more robust recovery of the immune system than delayed treatment.
Taken together, the studies add "more fuel to the fire" of increased interest in early treatment, commented Michael Saag, MD, the director of the division of infectious diseases at the University of Alabama at Birmingham.
The bottom line, he told MedPage Today in a video interview, is that "these studies underscore that by starting (treatment) early, especially in the setting of acute or recent infection, you can get a lot of clinical benefit."
The question of when to start therapy has long vexed HIV clinicians and patients, especially in the early years of highly active antiretroviral therapy (HAART), when drug treatment was often associated with serious adverse events.
The most recent recommendations of the International Antiviral Society–USA, issued last July, urge that anyone with HIV get treatment, regardless of the state of his or her immune system.
In that context, the SPARTAC trial showed that early treatment of HIV had a clear impact on two important markers of HIV, according to Jonathan Weber, FRCP, of Imperial College in London, and colleagues.
They were looking at the possible long-term effects of a short burst of anti-HIV therapy soon after infection – the trial's acronym stands for Short Pulse Antiretroviral Therapy at Seroconversion.
The 366 participants, whose median count of CD4-positive T cells was 599 per cubic millimeter of blood, were randomly assigned to 12 or 48 weeks of triple-drug treatment or to no therapy, which was the standard of care.
The primary endpoint of the trial was a composite of reaching a CD4 count of 350 or having to begin anti-HIV therapy if it had been stopped or never started.
Weber and colleagues found that, after an average follow-up of 4.2 years, half of those who got 48 weeks of treatment had reached the primary endpoint, compared with 61% in each of the other two groups.
That yielded a hazard ratio for the primary endpoint with 48-week treatment of 0.63 compared with standard care (95% CI 0.45 to 0.90, P=0.01). The hazard ratio with 12-week treatment compared with standard care was not significant.
The median time for those on 48-week treatment to reach the primary endpoint was longer by 65 weeks than with standard care, Weber and colleagues reported.
They also found a benefit in terms of the level of HIV – 36 weeks after stopping therapy, plasma viral loads in the 48-week group were lower by 0.44 log10 copies/mL than were viral loads in the standard care group 36 weeks after they were randomized.
The other study, by Sunil Ahuja, MD, of the South Texas Veterans Health Care System in San Antonio, and colleagues, looked at the "trajectory" of CD4 cell counts over a 48-week period in 468 patients with acute or early HIV infection.
The primary endpoint of the study was the likelihood of reaching a plasma CD4 cell count of 900 cells per cubic millimeter within 48 months of starting HAART.
In the absence of therapy, they found a transient increase in the CD4 count from the level at study entry at about 4 months after infection – from a median of 495 cells per cubic millimeter to a median peak of 763 cells before resuming a decline.
When patients started triple-drug therapy during that period, Ahuja and colleagues reported, their CD4 counts rebounded to a much higher point than if treatment were delayed.
Specifically, 64% of those treated within 4 months after infection reached 900 or more CD4 cells per cubic millimeter within 48 months, compared with 34% of those whose initial treatment was delayed beyond 4 months.
Taken together, both studies offer evidence of a greater CD4 cell recovery associated with earlier initiation of therapy, according to Bruce Walker, MD, and Martin Hirsch, MD, both of Massachusetts General Hospital in Boston.
However, they noted in an accompanying editorial, "both fall short of defining a clear clinical benefit for such early treatment."
The studies support current recommendations for immediate treatment but do not "provide ironclad proof" that such treatment offers health benefits for patients, they wrote.
Saag, for his part, told that evidence of clinical benefit is unlikely to be observed in such short-term studies. "For that benefit to be seen," he said, "you're going to have to follow patients for 10, 15, 20 years."