A stable latent reservoir for HIV-1 in resting CD4+ T lymphocytes in infected children
Deborah Persaud, … , Stuart Ray, Robert F. Siliciano
Deborah Persaud, … , Stuart Ray, Robert F. Siliciano
Published April 1, 2000
Citation Information: J Clin Invest. 2000;105(7):995-1003. https://doi.org/10.1172/JCI9006.
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Article

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

Abstract

HIV-1 persists in a latent state in resting CD4+ T lymphocytes of infected adults despite prolonged highly active antiretroviral therapy (HAART). To determine whether a latent reservoir for HIV-1 exists in infected children, we performed a quantitative viral culture assay on highly purified resting CD4+ T cells from 21 children with perinatally acquired infection. Replication-competent HIV-1 was recovered from all 18 children from whom sufficient cells were obtained. The frequency of latently infected resting CD4+ T cells directly correlated with plasma virus levels, suggesting that in children with ongoing viral replication, most latently infected cells are in the labile preintegration state of latency. However, in each of 7 children who had suppression of viral replication to undetectable levels for 1–3 years on HAART, latent replication-competent HIV-1 persisted with little decay, owing to a stable reservoir of infected cells in the postintegration stage of latency. Drug-resistance mutations generated by previous nonsuppressive regimens persisted in this compartment despite more than 1 year of fully suppressive HAART, rendering untenable the idea of recycling drugs that were part of failed regimens. Thus the latent reservoir for HIV-1 in resting CD4+ T cells will be a major obstacle to HIV-1 eradication in children.

Authors

Deborah Persaud, Theodore Pierson, Christian Ruff, Diana Finzi, Karen R. Chadwick, Joseph B. Margolick, Andrea Ruff, Nancy Hutton, Stuart Ray, Robert F. Siliciano

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HIV-1 RT and protease sequences from viral isolates cultured from the re...
HIV-1 RT and protease sequences from viral isolates cultured from the resting CD4+ T lymphocytes. Dashes represent amino acids that are unchanged from the reference sequence HXB2R. Blanks represent codons not determined. Numbers in the top row indicate RT codons associated with drug resistance and protease codons associated with drug resistance, common polymorphisms, or polymorphism and accessory substitutions to protease inhibitors. Mutations associated with resistance to antiretroviral drugs are shown in blocks of the appropriate color. Positions in protease at which polymorphisms occur are shown in black type. Known polymorphisms that are also seen as accessory substitutions contributing to resistance to ritonavir (RTV) or nelfinavir (NFV) are shown in colored type.