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Analytical antiretroviral therapy interruption does not irreversibly change preinterruption levels of cellular HIV.

  • Author(s): Papasavvas, Emmanouil
  • Lada, Steven M
  • Joseph, Jocelin
  • Yin, Xiangfan
  • Liu, Qin
  • Azzoni, Livio
  • Mounzer, Karam
  • Kostman, Jay R
  • Richman, Douglas
  • Montaner, Luis J
  • et al.

Published Web Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289896/
No data is associated with this publication.
Abstract

Objective

The impact of short-term analytical treatment interruptions (ATI) on the levels of cellular HIV and of residual activation after subsequent antiretroviral therapy (ART)-mediated plasma HIV viral load re-suppression remains under active investigation.

Design

Peripheral blood mononuclear cells (PBMC) from 23 ART-suppressed, chronically HIV-1-infected patients were evaluated at the initiation of an ATI, during ATI, and following plasma re-suppression of HIV with ART.

Methods

T-cell activation was measured by flow cytometry. Total cellular HIV DNA, and episomal 2-long terminal repeat (2-LTR) circles were measured by droplet digital PCR (ddPCR). Cellular HIV multiply spliced RNA (tat/rev), unspliced (gag), and poly(A) tailed transcripts [poly(A)] were measured by reverse transcriptase-ddPCR. Analyses were performed using R version 2.5.1 or JMP Pro 11.

Results

ATI (median ATI duration, 4 weeks) resulted in a rise of plasma HIV RNA (median = 72900 copies/ml), decrease in CD4+ T cells/μl (median = 511.5 cells/μl; P = 0.0001), increase in T-cell activation, and increase in cellular HIV DNA and RNA. Mean fluorescence intensity of CD38 on CD4+HLA-DR+ T cells at baseline was positively associated with total HIV DNA levels during ATI (pol: P = 0.03, Rho = 0.44). Upon ART resumption, plasma HIV re-suppression occurred after a median of 13 weeks and resulted in restoration of pre-ATI CD4+ T cells/μl, T-cell activation, and levels of cellular HIV DNA and RNA.

Conclusion

Monitored viremia and immune activation during an ATI in ART-suppressed chronic HIV-infected patients does not change the amount of persistent cellular HIV RNA or total HIV DNA after ART-mediated re-suppression.

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