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

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.

• Authors: Emmanouil Papasavvas, Steven M Lada, Jocelin Joseph, Xiangfan Yin, Qin Liu, Livio Azzoni, Karam Mounzer, Jay R Kostman, Douglas Richman, Luis J Montaner
• Journal: AIDS (London, England) (AIDS) Vol. 32 Issue 13 Pg. 1763-1772 (08 24 2018) ISSN: 1473-5571 [Electronic] England
• PMID: 30045057 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Anti-Retroviral Agents

Topics

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