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Longitudinal study reveals HIV-1–infected CD4+ T cell dynamics during long-term antiretroviral therapy
Annukka A.R. Antar, … , Ya-Chi Ho, Robert F. Siliciano
Annukka A.R. Antar, … , Ya-Chi Ho, Robert F. Siliciano
Published March 19, 2020
Citation Information: J Clin Invest. 2020;130(7):3543-3559. https://doi.org/10.1172/JCI135953.
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Research Article AIDS/HIV

Longitudinal study reveals HIV-1–infected CD4+ T cell dynamics during long-term antiretroviral therapy

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Abstract

Proliferation of CD4+ T cells harboring HIV-1 proviruses is a major contributor to viral persistence in people on antiretroviral therapy (ART). To determine whether differential rates of clonal proliferation or HIV-1–specific cytotoxic T lymphocyte (CTL) pressure shape the provirus landscape, we performed an intact proviral DNA assay (IPDA) and obtained 661 near–full-length provirus sequences from 8 individuals with suppressed viral loads on ART at time points 7 years apart. We observed slow decay of intact proviruses but no changes in the proportions of various types of defective proviruses. The proportion of intact proviruses in expanded clones was similar to that of defective proviruses in clones. Intact proviruses observed in clones did not have more escaped CTL epitopes than intact proviruses observed as singlets. Concordantly, total proviruses at later time points or observed in clones were not enriched in escaped or unrecognized epitopes. Three individuals with natural control of HIV-1 infection (controllers) on ART, included because controllers have strong HIV-1–specific CTL responses, had a smaller proportion of intact proviruses but a distribution of defective provirus types and escaped or unrecognized epitopes similar to that of the other individuals. This work suggests that CTL selection does not significantly check clonal proliferation of infected cells or greatly alter the provirus landscape in people on ART.

Authors

Annukka A.R. Antar, Katharine M. Jenike, Sunyoung Jang, Danielle N. Rigau, Daniel B. Reeves, Rebecca Hoh, Melissa R. Krone, Jeanne C. Keruly, Richard D. Moore, Joshua T. Schiffer, Bareng A.S. Nonyane, Frederick M. Hecht, Steven G. Deeks, Janet D. Siliciano, Ya-Chi Ho, Robert F. Siliciano

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Figure 4

Percentages of unrecognized CTL epitopes in Gag, Pol, and Nef from HIV-1 proviruses do not change dramatically over long periods of time on suppressive ART.

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Percentages of unrecognized CTL epitopes in Gag, Pol, and Nef from HIV-1...
Percentages of wild-type, unrecognized (deleted, escaped, frameshifted, or preceding stop codon), and uncharacterized epitope sequences at each dominant epitope in 5 chronic progressors on suppressive ART at 2 widely spaced time points. Provirus epitope sequences that lay in an area with unavailable sequence information were discarded from the analysis. The average number of total available epitope sequences per participant time point is shown at right. Predicted dominant epitopes in Gag, Pol, and Nef given each participant’s HLA type are shown and labeled. Epitope information can be found in Supplemental Table 2. Del, epitope lay within a mapped deletion; FS, a frameshift mutation precedes the epitope; SC, a stop codon precedes the epitope.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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