Thus, latent infection of resting CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective anti-retroviral therapy. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of Diana Finzi;, Joel Blankson;, Janet D. Siliciano;, Joseph B. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence Finzi D, Blankson J, Siliciano JD, Margolick JB, Chadwick K, Pierson T, Smith K.
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This paper has highly influenced 26 other papers. HIV Infections latent infection. Gallant and Robert F. The contribution of monocyte infection and trafficking to viral persistence, and maintenance of the viral reservoir in HIV infection. BartonSarah E. The decay rate of this latent reservoir is slow, with a half-life of at least 6 months in patients who have optimal suppression of viral replication on HAART 1217 and as long as 44 months in most patients on HAART The second, slower phase of decay is still fast enough to allow eradication of residual infected cells in 2—3 years.
From This Paper Figures, tables, and topics from this paper. There are caveats, however, related to sampling and founder effects.
First published October 1, – More info. We measured the decay rate of this latent reservoir in 34 treated adults whose plasma virus levels were undetectable. However, env sequences amplified from initial rebound viruses from the other three patients were different in length from latent reservoir sequences.
This reservoir is extremely stable due to the fundamental biology of memory cells, which must survive for many years to provide protection against previously encountered antigens. Find articles by Siliciano, J. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Go to JCI Insight. If the latent reservoir consists of only 1 x 10 5 cells, eradication could take as long as 60 years.
N2 – Combination therapy for HIV-1 infection can reduce plasma virus to undetectable levels, indicating that prolonged treatment might eradicate the infection. The source of this rebound virus has not been determined. Caveats and questions Both of these studies provide insights into mechanisms of viral persistence.
Combined Modality Therapy Antiretroviral therapy. If HAART is interrupted, viruses that are actively replicating will expand quickly, producing a rebound of viremia to high levels in about 2 weeks. Combination therapy for HIV-1 infection can reduce plasma virus to undetectable levels, indicating that prolonged treatment might eradicate the infection. If the latent reservoir consists of only 1 x cells, eradication could take as long as 60 years. We measured the decay rate of this latent reservoir in 34 treated adults whose plasma virus levels were undetectable.
Recent studies have indeed documented the inability of the HAART regimens to completely suppress virus production 12 — An important study by David Ho and colleagues in this issue of JCI 7 suggests that the latent reservoir may be the source of this rebound virus.
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JCI – Latency and viral persistence in HIV-1 infection
Commentary Free access Hence a rebound in viremia seems inevitable if therapy is stopped, a prediction borne out in recent studies. Version 1 October 1, Virus production continues at a level below the limit of detection of current ultrasensitive assays. The simplest interpretation of both studies is that, in many cases, viruses in the latent reservoir resemble the rebound virus; where mechanim exist, they may reflect sampling problems, the presence of additional long-term reservoirs for HIV-1, or the failure of HAART to completely halt viral replication.
It is also likely that release of virus from the latent reservoir contributes to the low-level ongoing replication observed in most patients.
For the first time since the beginning of the epidemic, the possibility of curing HIV-1 infection has been seriously considered 1.
CD4+ T Cell Mechanism Allows HIV-1 Persistence
Link to citation list in Scopus. AB – Combination therapy for HIV-1 infection can reduce plasma virus to undetectable levels, indicating that prolonged treatment might eradicate the infection. A rapid rebound is expected due to the fact that most patients have continued virus production while on HAART.
Decay characteristics of HIVinfected compartments during combination therapy. Highly active antiretroviral therapy. How to Define the Latent Reservoir: Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. The rebound virus may therefore be derived from a small number of cells in the reservoir that happened to be activated when HAART was stopped. Nature MedicineVol. Access to Document Of course, continued low-level virus production could reflect release of virus from some stable reservoir without the generation of newly infected cells.
These authors have interpreted their results differently, focusing on the idea that HIV-1 may persist not only in the latent reservoir but in additional as-yet undefined sites as well.
Skip to search form Skip to main content. Topics Discussed in This Paper. View this article via: The mean half-life of the latent reservoir was very long MetcalfDouglas J.
CD4+ T Cell Mechanism Allows HIV-1 Persistence | The Scientist Magazine®
The formation of the latent reservoir for HIV-1 is best understood in the context of the normal T-cell physiology. In five patients, env sequences from rebound viruses were identical in length to sequences in the latent reservoir.
Second, it is important to understand the nature and source of the ongoing virus production that is seen in most patients latnt HAART.