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Brief Report

HIV Antibodies Decline During Antiretroviral Therapy but Remain Correlated With HIV DNA and HIV-Specific T-Cell Responses

Keating, Sheila M. PhDa,b; Jones, Richard Brad PhDc; Lalama, Christina M. MSd; Bosch, Ronald J. PhDd; McMahon, Deborah MDe; Hampton, Dylan BSa; Cyktor, Joshua PhDe; Eron, Joseph J. MDf; Mellors, John W. MDe; Busch, Michael P. MD, PhDa,b; Gandhi, Rajesh T. MDg the ACTG 5321 Team

JAIDS Journal of Acquired Immune Deficiency Syndromes: August 15, 2019 - Volume 81 - Issue 5 - p 594–599
doi: 10.1097/QAI.0000000000002080
Translational Research
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Background: In people with HIV on antiretroviral therapy (ART), the relationship between HIV-specific immune responses and measures of HIV persistence is uncertain.

Methods: We evaluated 101 individuals on suppressive ART in the AIDS Clinical Trials Group A5321 cohort. Cell-associated (CA) HIV DNA and RNA levels and HIV antibody concentrations and avidity to Env/p24 were measured longitudinally at years 1, 4, and 6–15 after ART initiation. Plasma HIV RNA by single copy assay and T-cell responses (IFN-γ ELISPOT) against multiple HIV antigens were measured at the last time point.

Results: HIV antibody levels declined significantly with increasing time on ART (19%/year between year 1 and 4). HIV antibody levels correlated with T-cell responses to HIV Pol (r = 0.28, P = 0.014) and to Nef/Tat/Rev (r = 0.34; P = 0.002). HIV antibody and T-cell responses were positively associated with HIV DNA levels; for example, at the last time point (median 7 years on ART), r = 0.35 for antibody levels and HIV DNA (P < 0.001); r = 0.23 for Nef/Tat/Rev-specific T-cell responses and HIV DNA (P = 0.03). Neither antibody nor T-cell responses correlated with cell-associated HIV RNA or plasma RNA by single copy assay.

Conclusions: In individuals on long-term ART, HIV-specific antibody and T-cell responses correlate with each other and with HIV DNA levels. The positive correlation between HIV immune responses and HIV DNA implies that the immune system is sensing, but not clearing, infected cells, perhaps because of immune dysfunction. Measuring immune responses to HIV antigens may provide insight into the impact of reservoir-reducing strategies.

aBlood Systems Research Institute, San Francisco, CA;

bDepartment of Laboratory Medicine, University of California, San Francisco, CA;

cDivision of Infectious Diseases, Weill Cornell Medicine, New York;

dHarvard T.H. Chan School of PH, Boston, MA;

eDivision of Infectious Diseases, University of Pittsburgh, Pittsburgh, PA;

fDivision of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC; and

gDivision of Infectious Diseases, Massachusetts General Hospital, Boston, MA.

Correspondence to: Rajesh T. Gandhi, MD, Massachusetts General Hospital, GRJ 504, Boston, MA 02114 (e-mail: rgandhi@mgh.harvard.edu).

M.P.B. receives ongoing funding from Ortho Clinical Diagnostics, Inc., provided to Blood Systems Research Institute, to enable ongoing evaluations of their respective assays. R.T.G.'s institution has received educational grants from Gilead, Viiv, Janssen, Theratechnologies and Merck; R.T.G. has served on scientific advisory boards for Merck, Gilead and Theratechnologies. J.J.E. is an ad hoc consultant to Merck, Gilead Sciences, Janssen and ViiV Healthcare and receives contract support from Gilead Sciences, Janssen and ViiV Healthcare for work unrelated to this study. R.B.J. serves on the scientific advisory board of Abbvie Inc. For the remaining authors, none were declared. This study received grant support from AI–68634 (Statistical and Data Management Center), UM1–A1–26617, AI–131798,AI–68636 (ACTG), and R01- AI–144994. Research was also supported as part of the amfAR Institute for HIV Cure Research, with funding from amfAR grant number 109301.

Presented at Conference on Retroviruses and Opportunistic Infections (CROI); Seattle, WA; February 13–16, 2017 and Boston, MA; March 4–7, 2018.

The authors have no conflicts of interest to disclose.

S.M.K., R.B.J., M.P.B., and R.T.G. contributed equally.

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Received November 27, 2018

Accepted April 08, 2019

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

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