When highly active antiretroviral therapy (HAART) first became available, some scientists expressed the opinion that long term suppression of HIV replication might lead to the virus being eradicated from the body. But because HIV can integrate into cellular DNA and persist in a latent (inactive) state, the majority of the scientific community were skeptical of these claims. This skepticism was borne out by subsequent studies demonstrating the long term persistence of latent HIV in resting memory CD4 T cells. A new study from Anthony Fauci's laboratory at the National Institute of Allergy and Infectious Diseases (NIAID) now once again attempts to resurrect the possibility of eradication by claiming that, in people treated early in infection, infected resting memory CD4 T cell numbers decline with a half-life of 4.6 months. The authors extrapolate from their data that HIV could theoretically be eradicated by 7.7 years of HAART. Given the many potential sanctuaries for latent HIV in the human body (which include not just CD4 T cells but also macrophages and potentially other cell types), this claim is severely lacking in biological plausibility.
In an accompanying commentary, David Margolis and Nancie Archin politely highlight the study's limitations:
"...although Chun et al.'s study finds that the half-life of latently infected resting CD4+ T cells in this cohort is the shortest ever reported (4.6 months), a close examination of the data suggests that, at least in 4 of the patients studied, a second, slower phase of decay appears to exist. If so, the frequency of infection may not diminish to much less than 1 cell per billion after years of therapy. In this case, given the 110 billion resting CD4+ T cells carried by the average human, the few infected cells remaining may be enough to reignite infection. And, of course, the possibility exists that HIV may rarely persist in cells other than resting CD4+ T cells or that circulating resting cells somehow underrepresent infection in resting cells in the tissue."
The Journal of Infectious Diseases 2007;195:000
EDITORIAL COMMENTARY
Eliminating Persistent HIV Infection: Getting to the End of the Rainbow
David M. Margolis1,2,3 and Nancie M. Archin1
Departments of 1Medicine, 2Microbiology and Immunology, and 3Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill
The Journal of Infectious Diseases 2007;195:000
Brief Report
Tae-Wook Chun,1 J. Shawn Justement,1 Susan Moir,1 Claire W. Hallahan,2 Janine Maenza,3 James I. Mullins,3,4,5 Ann C. Collier,3 Lawrence Corey,3,5 and Anthony S. Fauci1
1Laboratory of Immunoregulation and 2Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Departments of 3Medicine, 4Microbiology, and 5Laboratory Medicine, University of Washington School of Medicine, Seattle
(See the editorial commentary by Margolis and Archin, on pages XXX–XX.)
The persistence of latently infected resting CD4+ T cells has been clearly demonstrated in human immunodeficiency virus (HIV)–infected individuals receiving effective antiviral therapy. However, estimates of the half-life of this viral reservoir have been quite divergent. We demonstrate clear evidence for decay of this HIV reservoir in patients who initiated antiviral therapy early in infection. The half-life of this latent viral reservoir was estimated to be 4.6 months. It is projected that it will take up to 7.7 years of continuous therapy to completely eliminate latently infected resting CD4+ T cells in infected individuals who initiate antiviral therapy early in HIV infection.
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