Proviral Quasispecies Diversity Is Not Associated With Virologic Breakthrough or CD4 T Cell Loss in HIV-1 Elite Controllers.

Authors:
Edson Delatorre
Edson Delatorre
North Fluminense State University (UENF)
Brazil
Marcelo Ribeiro-Alves
Marcelo Ribeiro-Alves
Centro de Citricultura Sylvio Moreira
Brazil
Brenda Hoagland
Brenda Hoagland
Laboratório de Pesquisa Clinica em DST/AIDS
Beatriz Grinsztejn
Beatriz Grinsztejn
HIV/AIDS Clinical Research Center
Brazil
Valdilea G Veloso
Valdilea G Veloso
University of California
United States
Mariza G Morgado
Mariza G Morgado
Oswaldo Cruz Institute
Brazil

Front Microbiol 2019 2;10:673. Epub 2019 Apr 2.

Laboratório de AIDS & Imunologia Molecular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.

Elite controllers (EC) are able to control HIV-1 replication to extremely low levels (<50 HIV-1 RNA copies/mL) in the absence of antiretroviral therapy. However, some EC experience CD4 T cell loss and/or lose their ability to control HIV-1 over the course of infection. High levels of HIV-1 proviral diversity, activated T cells and proinflammatory cytokines were pointed out as relevant biomarkers for detection of EC at risk of virologic/immunologic progression. The aim of this study was to assess the importance of proviral diversity as a prognostic marker of virologic and/or immunologic progression in EC. To this end, we analyzed plasma viremia, total HIV DNA levels, T cells dynamics, and activation/inflammatory biomarkers in EC with low (EC = 4) and high (EC = 6) HIV-1 diversity. None of EC and EC subjects displayed evidence of immunologic progression (decrease in absolute and percentage of CD4 T cells) and only one EC subject presented virologic progression (≥2 consecutive viral loads measurements above the detection limit) 2-5 years after determination of proviral diversity. Despite differences in proviral genetic diversity, the EC and EC subgroups displayed comparable levels of total cell-associated HIV DNA, activated CD8 T (CD38HLA-DR) cells and plasmatic inflammatory biomarkers (IP-10, IL-18, RANTES, PDGF-AA, and CTACK). These results indicate that the genetic diversity of the HIV-1 proviral reservoir is not a surrogate marker of residual viral replication, immune activation or inflammation, nor an accurate biomarker for the prediction of virologic breakthrough or CD4 T cells loss in EC.

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Source
https://www.frontiersin.org/article/10.3389/fmicb.2019.00673
Publisher Site
http://dx.doi.org/10.3389/fmicb.2019.00673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454058PMC
April 2019
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References

(Supplied by CrossRef)
Disease progression in HIV-1-infected viremic controllers.
Groves et al.
J. Acquir. Immune Defic. Syndr. 2012

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