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Treating HIV Very Early Enhances Immunity
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ART in..... primary HIV infection.....provide compelling support for early treatment on the basis of CD4+ T-cell restoration in peripheral blood:........ "A total of 64% of those treated within 4 months after the start of infection reached the primary CD4+ end point of 900 or more cells per cubic millimeter in peripheral blood within 48 months, whereas only 34% of those whose initial treatment was delayed beyond 4 months recovered CD4+ cell numbers to a similar degree."
Enhanced CD4+ T-Cell Recovery with Earlier HIV-1 Antiretroviral Therapy - (01/17/13)
N Engl J Med Jan 17 2013
"Starting ART soon after infection is likely to attenuate factors that are known to impair immune recovery (e.g., microbial translocation, immune activation,14 and lymphoid-tissue damage),14-20 promote development of HIV-specific T-helper responses, and limit the establishment and expansion of latent HIV reservoirs......This is mirrored by our observation that each additional month after the estimated date of infection that elapsed before ART was initiated was associated, on average, with about a 10% reduction in the likelihood of CD4+ T-cell recovery and a 10% slower rate of recovery"
[after acute infection] "In summary, after an acute decline, CD4+ T-cell counts have a transient spontaneous recovery. The initiation of ART within this early restorative time window, when the host immune system is poised for recovery, greatly accelerates the pace and augments the extent of CD4+ T-cell recovery. Even a fairly short deferral of ART after closure of this time window may come at the expense of compromised CD4+ T-cell recovery, irrespective of the CD4+ count at the time of treatment initiation. Further studies are needed to determine whether starting ART within the restorative time window promotes strategies that are designed to reduce latent HIV reservoirs."
"participants who initiated ART 4 months or less after the estimated date of infection had the highest likelihood and the fastest rate of primary and secondary recovery of CD4+ counts (defined as attainment of at least one CD4+ count of 900 or 800 cells per cubic millimeter, respectively) ......In addition, among patients receiving viral-load-suppressive ART, there is an inverse relationship between higher CD4+ counts during ART and the risk of complications not related to the acquired immunodeficiency syndrome (AIDS),27,28 the risk of AIDS, and the risk of death.29,30.......participants who initiated ART more than 4 months to 12 months after the estimated date of infection had an intermediate likelihood and rate of recovery, and participants who initiated ART more than 12 months after the estimated date of infection had the least likelihood and the slowest rate of recovery. However, even among participants who started ART earlier, those who initiated ART with lower CD4+ counts, as compared with those who initiated ART with higher CD4+ counts, had a reduced likelihood and rate of CD4+ T-cell recovery. This is reflective of our finding that initiation of ART at lower CD4+ counts, as compared with higher CD4+ counts, is in itself associated with a likelihood of CD4+ T-cell recovery that is reduced by about 90% and with a slower rate of recovery. These findings underscore the dual effect on CD4+ T-cell recovery of the timing of ART and of the CD4+ count at the initiation of ART....."
Antiretroviral Therapy in Early HIV Infection - - (01/17/13)
In this issue of the Journal, two studies address the timing of ART in relation to primary HIV infection and provide compelling support for early treatment on the basis of CD4+ T-cell restoration in peripheral blood.5,6 The two studies assess the effect of early treatment quite differently, and both rely on surrogate measures of disease progression rather than on clinical outcomes.
Le et al.5 investigated the effect of continuous therapy from the time of acute or early HIV infection on CD4+ T-cell recovery at 48 months in a prospective, nonrandomized observational study of a cohort of mostly white men in the United States who were infected with clade B virus and treated with standard-of-care combination ART regimens over a period from 1996 to 2010. They found that there was a transient and partial restoration of CD4+ counts during the first 4 months after the estimated date of HIV infection in untreated controls and that treatment initiated during this early period enhanced CD4+ T-cell recovery. A total of 64% of those treated within 4 months after the start of infection reached the primary CD4+ end point of 900 or more cells per cubic millimeter in peripheral blood within 48 months, whereas only 34% of those whose initial treatment was delayed beyond 4 months recovered CD4+ cell numbers to a similar degree. The likelihood of reaching the primary end point was lower and the rate of recovery was slower in those who initiated treatment more than 4 months after the estimated date of infection.
Short-Course Antiretroviral Therapy in Primary HIV Infection - (01/17/13)
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