Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Diana Finzi, Joel N. Combination therapy for HIV-1 infection can reduce plasma virus to Thus, latent infection of resting CD4+ T cells provides a mechanism for lifelong persistence Diana Finzi, Joel Blankson, +14 authors Robert F. Siliciano; Published in. Due to the importance of the latent reservoir in maintaining infection despite .. the long-term persistence of latent virus in HIV-infected individuals Finzi et al.

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Active nuclear import of human immunodeficiency virus type 1 pre-integration complexes. Numbers in the top row indicate RT codons associated with drug resistance and protease codons incection with drug resistance, common polymorphisms, or polymorphism and accessory substitutions to protease inhibitors. A rapid method knfection simultaneous detection of phenotypic resistance to inhibitors of protease and reverse transcriptase in recombinant human immunodeficiency virus type 1 isolates from patients treated with antiretroviral drugs.

In comparing the latent reservoir for HIV-1 in children and adults, the following conclusions can be drawn.

Kinetics of response in lymphoid tissues to antiretroviral therapy of HIV-1 infection. Showing of 38 references.

Infectiin in a separate latenr. CrandallDavid Posada Infection, genetics and evolution: Fauci Proceedings of the National Academy of Sciences…. A particularly dramatic illustration of the stability of the latent reservoir is provided by the case of the child who has had the longest duration 37 months of suppression of viral replication with HAART patient 8.

The precise mechanisms involved in the generation of this latent reservoir are unknown; the occasional reversion of HIV-1—infected, activated T lymphocytes to a resting memory state with integrated HIV-1 is one plausible mechanism. Sequencing was performed on viral isolates that represent distinct biological clones obtained with a limiting dilution culture technique.


Chadwick3 Joseph B.

Los Alamos National Laboratory. In vivo fate of HIVinfected T cells: Analysis of the viral isolates cultured from this compartment in a group of children who were pretreated with nonsuppressive antiretroviral regimens showed the persistence, for up to 2 years, of drug-resistant substitutions selected by previous nonsuppressive antiretroviral therapies.

This paper has highly influenced 26 other papers. Revised classification finzj for human immunodeficiency virus in children less than 13 years of age. Deficient human immunodeficiency virus type 1-specific cytotoxic T cell responses in vertically infected children.

A stable latent reservoir for HIV-1 in resting CD4+ T lymphocytes in infected children

In the former case, the composition of the latent reservoir should not change on therapy and should reflect the virologic status before HAART. Thus although children are establishing a pool of memory cells, the fraction of these cells that carry replication-competent HIV-1 does not appear to be significantly higher than in adults. After the rapid initial decay in the first 3 months of treatment, little subsequent decay is detected.

Highly active antiretroviral therapy. This reservoir has a biphasic decay pattern after the initiation of HAART, with a rapid initial drop in the first 3 months of therapy followed by a second phase in which there is minimal decay.

These results therefore establish the existence of this cellular reservoir in children. In these 4 children, within 1 to 8 months of therapy with HAART it became difficult to culture HIV-1 at 1 or more time points using the standard input of 2. Dashes represent amino acids that are unchanged from the reference sequence HXB2R. These results demonstrate persistence of latent HIV-1 near the limit of detection, with possible slow decay. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia.

Hertogs K, et al. In contrast, 5 of the 6 children who were treated previously with incompletely suppressive regimens of zidovudine and didanosine and who had suppression of viral replication for 12—30 months on HAART had persistence of replication-competent HIV-1 harboring mutations conferring resistance to zidovudine and didanosine. BartonSarah E. Because the MI mutation is associated with drug resistance to both didanosine and lamivudine and both children received previous nonsuppressive therapy with didanosine, then were subsequently treated with a suppressive regimen that contained lamivudine, it is not possible to determine to which drug this mutation should be attributed.


A subset of 9 children in the initial cohort achieved durable suppression of viral replication on HAART and were followed longitudinally to determine whether there was time-dependent decay in the latent reservoir.

Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection.

Observed resistance mutations were consistent with treatment history of individual patients. HIV-1 dynamics in children. Zhang L, et al.

However, the data presented here indicate that the latent reservoir for HIV-1 is fjnzi in infected children and will likely represent a major barrier to virus eradication that will have to be considered in all therapeutic strategies for the treatment of pediatric HIV-1 infection. Decay characteristics of HIVinfected compartments during combination therapy. Walker and Stephen Gange and Joel E. Included in this group were 6 children patients 7, 10, 11, 14, 15, and 21 who were started on HAART and followed longitudinally.

Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection.

Virus isolated from the latent reservoir at 19 and 21 months showed multiple mutations conferring resistance to zidovudine. Sequence validation was carried out by recommended methods Basic local alignment search tool BLAST searches of the Genbank revealed that none of the sequences incection laboratory or patient isolates published previously.

Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. HIV Infections Search for additional papers on this topic.