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

AIDS. 2018 Aug 24;32(13):1763-1772. doi: 10.1097/QAD.0000000000001909.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Anti-Retroviral Agents / administration & dosage*
  • Female
  • Flow Cytometry
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV-1 / isolation & purification*
  • Humans
  • Leukocytes, Mononuclear / virology
  • Male
  • Middle Aged
  • Plasma / virology
  • Viral Load*
  • Withholding Treatment*
  • Young Adult


  • Anti-Retroviral Agents