Two papers in The New England Journal of Medicine suggest that starting antiretroviral treatment (ART) early after HIV infection is diagnosed may improve patients' immune response, boosting the initial recovery of the immune system and delaying progression of the disease.
In the first, researchers led by Sunil Ahuja (University of Texas Health Science Center, San Antonio, USA) found that CD4+ T-cell counts in peripheral blood are transiently restored in the 4 months after HIV-1 infection, and that initiating ART during this period enhances T-cell recovery compared with starting treatment later.
And in the second paper, Jonathan Weber (Imperial College London, UK) and co-investigators of the SPARTAC trial report that 48 weeks of ART initiated upon primary HIV infection diagnosis significantly delays disease progression, compared with no ART, although only by the length of the initial treatment.
However, there did appear to be some lasting effects, with HIV RNA levels remaining lowered after the 48-week treatment period, and CD4+ recovery improved after initiation of long-term ART.
Commentators Bruce Walker and Martin Hirsch (Massachusetts General Hospital and Harvard Medical School, Boston, USA) write in an accompanying editorial that both studies "provide compelling support for early treatment," although both also "fall short of defining a clear clinical benefit for such early treatment."
As a result, they stress that the findings do not alter current US Department of Health and Human Services and International Antiviral Society-USA guidelines, which already recommend ART for "nearly everyone who is HIV-infected, regardless of the stage of infection" in resource-rich settings. Moreover, Walker and Hirsch add, where resources are severely constrained, "the bar for proving benefit deserves to be higher, and treatment emphasis should still be on saving lives by treating a greater number of patients at later stages of disease."
The study by Ahuja and team was an observational study of people with acute or early HIV-1 infection. Among 384 participants not receiving ART, peripheral blood CD4+ counts rose rapidly soon after infection, from a median of 495 cells/mm3 at study entry to a peak of 763 cells/mm3 within approximately 4 months after the estimated date of infection, before falling progressively thereafter.
Meanwhile, in a partially overlapping group of 213 participants who received ART soon after study entry or sometime thereafter, CD4+ counts recovered to at least 900 cells/mm3 within 48 months in 64% of those who initiated ART within the first 4 months of the estimated infection date, compared with just 34% who initiated ART later. This difference persisted after accounting for whether ART started when the CD4+ count was at or below 500 cells/mm3.
The SPARTAC (Short Pulse Anti-Retroviral Therapy at Seroconversion) trial showed that among 366 patients with primary HIV infection, 50% of patients randomized to receive 48 weeks of ART straight after diagnosis reached the primary endpoint of a CD4+ count of less than 350 cells/mm3 or long-term ART initiation over a median of 4.2 years of follow up. This compared with 61% of patients assigned directly to 12 weeks of ART, and 61% assigned to standard care.
The median time to the primary endpoint was 65 weeks longer in the 48-week ART group than in the standard care group, but this difference was not significantly longer than the duration of ART (48 weeks). However, further analysis suggested a trend toward a greater delay in disease progression the sooner after the estimated seroconversion date that ART was initiated.
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