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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Nature MedicineVol. HIV Infections Search for additional papers on this topic.
CD4+ T Cell Mechanism Allows HIV-1 Persistence | The Scientist Magazine®
Tools of the Trade Mechhanism M. Fauci Lirelong of the National Academy of Sciences…. In these patients, the latent reservoir persists with an extremely long half-life 44 months. Recent studies have indeed documented the inability of the HAART regimens to completely suppress virus production 12 — If the latent reservoir consists of only 1 x cells, eradication could take as long as 60 years.
Recombination favors lifellong evolution of drug resistance in HIV-1 during antiretroviral therapy. Second, it is important to understand the nature and source of the ongoing virus production that is seen in most patients on HAART. Access to Document Version 1 October 1, Virus production continues at a level below the limit of detection of current ultrasensitive assays. Therefore, observed differences between the latent reservoir virus and the rebound virus may simply result from insufficient sampling and cannot be used to say definitively that the rebound virus came from a particular location.
JCI – Latency and viral persistence in HIV-1 infection
N2 – Combination therapy for HIV-1 infection can reduce plasma virus to undetectable levels, indicating that prolonged treatment might eradicate the infection. Montaner The Journal of infectious diseases There are caveats, however, related to sampling and founder effects.
The formation of the latent reservoir for HIV-1 is best understood in the context of the normal T-cell physiology.
From This Paper Figures, tables, and topics from this paper. Individual viral variants mechansm are released from a reservoir at the time HAART is stopped will have a chance to expand unhindered by antiretroviral drugs.
Based infectipn an estimate of 10 6 cells in the latent reservoir 373 years of therapy would be required for eradication. Walker and Stephen Gange and Joel E. We measured the decay rate of this latent reservoir in 34 treated adults whose plasma virus levels were undetectable.
Latency and viral persistence in HIV-1 infection
Flexner The New England journal of medicine Infectiion paper has highly influenced 26 other papers. Link to publication in Scopus. Sampling is less of a concern in the study of Zhang et al. First, it is critical to determine whether additional viral reservoirs exist.
Nature Medicine5 5 Abstract Combination therapy for HIV-1 infection can reduce plasma virus to undetectable levels, indicating that prolonged treatment might eradicate the infection.
If the viral repertoire is diverse, this rebound virus represents only a small sample of the reservoir and may or dinzi not match samples obtained directly from the reservoir depending on the degree of viral diversity and the number of samples analyzed.
A small fraction of infected lymphoblasts survive and revert back to a resting state by the same process that normally generates memory ,ifelong cells. The decay rate of this latent reservoir is slow, with a half-life of at least 6 months in patients who have optimal suppression finnzi viral replication on HAART 1217 and as long as 44 months in most patients on HAART Viewed in this context, several research goals assume paramount importance.
HIV Infections latent infection. Combination therapy for HIV-1 infection can reduce plasma virus to undetectable levels, indicating that prolonged treatment might eradicate the infection. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV-1 infection can be controlled with combinations of antiretroviral drugs, an approach known as highly active antiretroviral therapy HAART. The mean half-life of the latent reservoir was very long Go to JCI Insight.
Showing of 38 references. The simplest interpretation of both studies is that, in many cases, viruses in the latent reservoir resemble the rebound jnfection where differences exist, they may reflect sampling problems, the presence of additional long-term reservoirs for HIV-1, or laetnt failure of HAART to completely halt viral replication. Finally, novel approaches are needed to eliminate latently infected cells, which clearly represent a very serious barrier to HIV-1 eradication.
These authors have interpreted their results differently, focusing on the mechanis, that HIV-1 may persist not only in the latent reservoir but in additional as-yet undefined sites as well. First published October 1, – More info. In patients who respond well to HAART, viremia decreases to below the limits of detection, disease progression stops, and reconstitution of the immune system mechanidm.
Perelson, AS, et al.
A rapid rebound is expected due to the fact that most patients have laten virus production while on HAART. Find articles by Siliciano, R. Figure 1 illustrates viral decay curves under several vinzi conditions. It is also likely that release of virus from the latent reservoir contributes to the low-level jechanism replication observed in most patients. Combined Modality Therapy Antiretroviral therapy.
The mean half-life of the latent reservoir was very long However, the detection of labile replicative intermediates 1315 or temporal sequence evolution 1216 suggests that new cycles of infection may occur even in patients who have responded well to HAART.
Hence a rebound in viremia seems inevitable if therapy is stopped, a prediction borne out in recent studies. Topics Discussed in This Paper. Both of these studies provide insights into mechanisms of viral persistence. Caveats and questions Both of these studies provide insights into mechanisms of viral persistence.