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Early ART initiation improved CD4 counts, delayed disease progression
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Results from two studies published in The New England Journal of Medicine suggest that patients who began antiretroviral therapy early after HIV seroconversion had improved CD4 cell counts and delayed disease progression.
Restorative time window
In the first study, researchers evaluated the relationship between timing of ART and the recovery of CD4 counts.
“This study identifies a narrow ‘restorative time window’ of approximately 4 months following infection with HIV, during which the immune system is able to recover to nearly normal function if ART is started within this time period,” Susan Little, MD, professor of medicine at the division of infectious diseases at the University of California, San Diego, told Infectious Disease News. “In the evolving discussion about when to start ART following HIV infection, these data showed that the probability of achieving a normal CD4 cell count on ART was greatest for those who started ART within 4 months of their estimated infection date. This was independent of the CD4 cell count at the start of ART.”
Little and colleagues conducted a prospective, observational cohort study that included 468 patients with HIV who had an estimated date of infection. The study had two overlapping sets. One set included 384 patients who did not receive ART during the restorative time window and the second set included 213 patients who received ART soon after infection and had suppressed plasma viral load. The researchers determined the trajectory of CD4 counts during a 48-month period.
Among patients who did not receive ART, CD4 counts peaked approximately 4 months after infection, at a median of 763 cells/mm3. After peaking, the CD4 counts declined progressively. Patients who received ART saw a rapid gain of approximately 200 CD4 counts, followed by a slower increase of CD4 counts. Among those who initiated ART within the 4-month window, 64% saw a recovery of CD4 counts to 900 cells/mm3 or more vs. 34% of patients who initiated ART more than 4 months after infection.
“These data support immediate treatment of all HIV-infected people and highlight the importance of diagnostic screening methods that allow identification of acute HIV infection,” Little said. “Further studies are needed to determine whether starting ART within the restorative time window demonstrates immunologic recovery that is associated with an improved response to ‘cure’ strategies.”
SPARTAC
For the second study, researchers with the Short Pulse Anti-Retroviral Therapy at Seroconversion (SPARTAC) trial evaluated whether early initiation of ART delayed disease progression.
“Treating patients with recent HIV infection with ART for 48 weeks delayed the time to needing long-term ART by an average of 65 weeks,” Jonathan Weber, MD, professor in the department of medicine at Imperial College London, told Infectious Disease News. “The delay appeared to be greater the closer treatment was commenced to the time of HIV infection. This study provides evidence from a randomized trial that greater CD4 cell recovery and preservation is achieved following immediate ART at primary infection.”
Jonathan Weber
Weber and colleagues evaluated 366 patients who were randomly assigned to receive ART for 48 weeks, ART for 12 weeks or no therapy.
The primary endpoint was a CD4 count of less than 350 cells/mm3. Among those who received 48 weeks of treatment, 50% reached the endpoint vs. 61% in both of the other groups. For those who received 48 weeks of treatment, the HR was 0.63 (95% CI, 0.45-0.9) compared with no treatment. For those who received 12 weeks of treatment, the HR was 0.93 (95% CI, 0.67-1.29).
Patients who received 48 weeks of treatment had a median time to primary endpoint that was 65 weeks longer compared with no treatment. Among patients who received 48 weeks of treatment, the proportion who reached the primary endpoint was 28% compared with 40% in both the 12-week group and the group that did not receive treatment. There was no difference in the rates of long-term ART initiation.
“Treatment during early infection may have additional benefits at a population level by reducing infectiousness, hence, reducing the likelihood of onward transmission,” Weber said. “The question of the optimal time to commence ART in chronic HIV infection remains uncertain, particularly in resource-limited settings, but this study provides strong evidence for a benefit of early therapy in primary infection.”
For more information:
Le T. N Engl J Med. 2013;doi:10.1056/NEJMoa1110187.
The SPARTAC Trial Investigators. N Engl J Med. 2013;doi:10.1056/NEJMoa1110039.
Disclosure: Weber and Little report no relevant financial disclosures.
Perspective
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Paul A. Volberding, MD
The case for immediate treatment of all HIV-infected persons at the time of diagnosis is continuing to strengthen. The recent large NIAID-sponsored trial in Africa showed that early treatment almost completely blocked subsequent HIV transmission, and that study and newer results show an advantage to the health of the treated person as well. The most recent papers in the New England Journal of Medicine add further light to the case for universal HIV therapy. The paper by Le et al. showed that earlier treatment was associated with improved CD4 cell recovery — a centrally important marker of immune health. The study by the SPARTAC investigators examined the immediate treatment of primary HIV infection in which therapy was discontinued after 48 weeks. In this trial, immediate treatment stopped disease progression. While there was no evidence that immediate treatment interrupted in this way was harmful, the study design leaves open the possibility that benefits might have continued had therapy not been stopped. Most clinicians rarely see acute, primary HIV infection, but more experts advocate for treatment that is not only immediate, but continuous and lifelong. These trials continue to remind us how potent current HIV therapy has become while simultaneously convenient and well tolerated. We've come a very long way, in a very short time.
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