Evaluation of HIV-1 reservoir size and broadly neutralizing antibody susceptibility in acute antiretroviral therapy-treated individuals

Brian Moldt; Huldrych F. Gunthard; Kimberly A. Workowski; Susan J. Little; Joseph J. Eron; Edgar T. Overton; Clara Lehmann; Casper Rokx; Michael J. Kozal; Rajesh T. Gandhi; Dominique L. Braun; Aiyappa Parvangada; Jiani Li; Ross Martin; Lisa Selzer; Stephanie Cox; Nicolas Margot; Hui Liu; Debbie Slamowitz; Tariro Makadzange; Sean E. Collins; Romas Geleziunas; Christian Callebaut

doi:10.1097/qad.0000000000003088

Evaluation of HIV-1 reservoir size and broadly neutralizing antibody susceptibility in acute antiretroviral therapy-treated individuals

Brian Moldt^*
, Huldrych F. Gunthard
, Kimberly A. Workowski
, Susan J. Little
, Joseph J. Eron
, Edgar T. Overton
, Clara Lehmann
, Casper Rokx
, Michael J. Kozal
, Rajesh T. Gandhi
, Dominique L. Braun
, Aiyappa Parvangada
, Jiani Li
, Ross Martin
, Lisa Selzer
, Stephanie Cox
, Nicolas Margot
, Hui Liu
, Debbie Slamowitz
, Tariro Makadzange

Sean E. Collins, Romas Geleziunas, Christian Callebaut

^*Corresponding author for this work

Gilead Sciences, Inc.
University Hospital Zürich
University of Zurich
Emory University
University of California at San Diego
University of North Carolina School of Medicine
University of Alabama at Birmingham
University Hospital Cologne
German Center for Infection Research; Partner Site Bonn
University of Cologne
Yale University
Massachusetts General Hospital

Research output: Contribution to journal › Article › Academic › peer-review

15 Citations (Scopus)

Abstract

Objective: Persistence of the viral reservoir is the main barrier to curing HIV. Initiation of ART during acute HIV infection can limit the size and diversity of the reservoir. In depth characterization of the reservoir in individuals who initiate ART during acute infection will be critical for clinical trial design and cure strategies. Methods: Four cohortswith participantswhoinitiatedARTduring acute infection or during chronic infectionwere enrolled in a cross-sectional, noninterventional study.Viral reservoir was evaluated by the Intact Proviral DNA Assay (IPDA), the Total HIVDNA Assay (THDA) and the Quantitative Viral Outgrowth Assay (QVOA). Viral diversity and susceptibility to V3-glycan bNAbs were determined by genotyping of the viral envelope gene. Results: Participants who initiated ART during the acute Fiebig I-IV stages had lower level of total HIV DNA than participants who initiated ART during chronic infection whereas no difference was observed in intact HIV DNA or outgrowth virus. Participants who initiated ART during Fiebig I-IV also had lower viral diversity and appeared to have higher susceptibility to bNAbs than participants initiating ART during chronic infection. Conclusion: Individuals initiating ART during Fiebig I-IV had small viral reservoirs, low viral diversity, and high susceptibility to bNAbs, and would be an optimal target population for proof-of-concept HIV cure trials.

Original language	English
Pages (from-to)	205-214
Number of pages	10
Journal	AIDS
Volume	36
Issue number	2
DOIs	https://doi.org/10.1097/qad.0000000000003088
Publication status	Published - 1 Feb 2022

Bibliographical note

Funding Information:
B.M., A.P., J.L., R.M., L.S., S.C., N.M., H.L., D.S., T.M., S.E.C., R.G., and C.C. are employees and stockholders of Gilead Sciences, Inc. H.F.G. has received unrestricted research grants from Gilead Sciences and Roche; fees for data and safety monitoring board membership from Merck; consulting/advisory board membership fees from Gilead Sciences, Merck and ViiV Healthcare; and grants from SystemsX, and the National Institutes of Health. The institution of H.F.G. received educational grants form Gilead Sciences, ViiV, MSD, Abbvie, and Sandoz. S.J.L. received grants for investigator initiated studies from Gilead outside of the submitted work. E.T.O. received honoraria from ViiV, Merck, and Theratechnologies outside of the submitted work. C.L. received honoraria and travel grants from Janssen, Gilead, ViiV, and Merck outside of the submitted work. C.R. received honoraria and travel grants and grants for investigator-initiated studies from Gilead, ViiV, Janssen-Cilag, and Merck outside the context of the submitted work. M.J.K. received research support from Gilead and ViiV Healthcare. R.T.G. receives grant funding from the Harvard University Center for AIDS Research (NIH P30 AI060354) and the AIDS Clinical Trials Group (NIH/NIAID 2 UMAI069412-09). D.L.B. received honoraria and travel grants from Gilead, ViiV, and Merck outside of the submitted work.

Funding Information:
Funding: this study was funded by Gilead Sciences, Inc.

Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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Moldt, B., Gunthard, H. F., Workowski, K. A., Little, S. J., Eron, J. J., Overton, E. T., Lehmann, C., Rokx, C., Kozal, M. J., Gandhi, R. T., Braun, D. L., Parvangada, A., Li, J., Martin, R., Selzer, L., Cox, S., Margot, N., Liu, H., Slamowitz, D., ... Callebaut, C. (2022). Evaluation of HIV-1 reservoir size and broadly neutralizing antibody susceptibility in acute antiretroviral therapy-treated individuals. AIDS, 36(2), 205-214. https://doi.org/10.1097/qad.0000000000003088

@article{b6cf52c09e6a48cabcd85d819466368c,

title = "Evaluation of HIV-1 reservoir size and broadly neutralizing antibody susceptibility in acute antiretroviral therapy-treated individuals",

abstract = "Objective: Persistence of the viral reservoir is the main barrier to curing HIV. Initiation of ART during acute HIV infection can limit the size and diversity of the reservoir. In depth characterization of the reservoir in individuals who initiate ART during acute infection will be critical for clinical trial design and cure strategies. Methods: Four cohortswith participantswhoinitiatedARTduring acute infection or during chronic infectionwere enrolled in a cross-sectional, noninterventional study.Viral reservoir was evaluated by the Intact Proviral DNA Assay (IPDA), the Total HIVDNA Assay (THDA) and the Quantitative Viral Outgrowth Assay (QVOA). Viral diversity and susceptibility to V3-glycan bNAbs were determined by genotyping of the viral envelope gene. Results: Participants who initiated ART during the acute Fiebig I-IV stages had lower level of total HIV DNA than participants who initiated ART during chronic infection whereas no difference was observed in intact HIV DNA or outgrowth virus. Participants who initiated ART during Fiebig I-IV also had lower viral diversity and appeared to have higher susceptibility to bNAbs than participants initiating ART during chronic infection. Conclusion: Individuals initiating ART during Fiebig I-IV had small viral reservoirs, low viral diversity, and high susceptibility to bNAbs, and would be an optimal target population for proof-of-concept HIV cure trials.",

author = "Brian Moldt and Gunthard, \{Huldrych F.\} and Workowski, \{Kimberly A.\} and Little, \{Susan J.\} and Eron, \{Joseph J.\} and Overton, \{Edgar T.\} and Clara Lehmann and Casper Rokx and Kozal, \{Michael J.\} and Gandhi, \{Rajesh T.\} and Braun, \{Dominique L.\} and Aiyappa Parvangada and Jiani Li and Ross Martin and Lisa Selzer and Stephanie Cox and Nicolas Margot and Hui Liu and Debbie Slamowitz and Tariro Makadzange and Collins, \{Sean E.\} and Romas Geleziunas and Christian Callebaut",

note = "Funding Information: B.M., A.P., J.L., R.M., L.S., S.C., N.M., H.L., D.S., T.M., S.E.C., R.G., and C.C. are employees and stockholders of Gilead Sciences, Inc. H.F.G. has received unrestricted research grants from Gilead Sciences and Roche; fees for data and safety monitoring board membership from Merck; consulting/advisory board membership fees from Gilead Sciences, Merck and ViiV Healthcare; and grants from SystemsX, and the National Institutes of Health. The institution of H.F.G. received educational grants form Gilead Sciences, ViiV, MSD, Abbvie, and Sandoz. S.J.L. received grants for investigator initiated studies from Gilead outside of the submitted work. E.T.O. received honoraria from ViiV, Merck, and Theratechnologies outside of the submitted work. C.L. received honoraria and travel grants from Janssen, Gilead, ViiV, and Merck outside of the submitted work. C.R. received honoraria and travel grants and grants for investigator-initiated studies from Gilead, ViiV, Janssen-Cilag, and Merck outside the context of the submitted work. M.J.K. received research support from Gilead and ViiV Healthcare. R.T.G. receives grant funding from the Harvard University Center for AIDS Research (NIH P30 AI060354) and the AIDS Clinical Trials Group (NIH/NIAID 2 UMAI069412-09). D.L.B. received honoraria and travel grants from Gilead, ViiV, and Merck outside of the submitted work. Funding Information: Funding: this study was funded by Gilead Sciences, Inc. Publisher Copyright: {\textcopyright} 2022 Lippincott Williams and Wilkins. All rights reserved.",

year = "2022",

month = feb,

day = "1",

doi = "10.1097/qad.0000000000003088",

language = "English",

volume = "36",

pages = "205--214",

journal = "AIDS",

issn = "0269-9370",

publisher = "Lippincott Williams \& Wilkins",

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Moldt, B, Gunthard, HF, Workowski, KA, Little, SJ, Eron, JJ, Overton, ET, Lehmann, C, Rokx, C, Kozal, MJ, Gandhi, RT, Braun, DL, Parvangada, A, Li, J, Martin, R, Selzer, L, Cox, S, Margot, N, Liu, H, Slamowitz, D, Makadzange, T, Collins, SE, Geleziunas, R & Callebaut, C 2022, 'Evaluation of HIV-1 reservoir size and broadly neutralizing antibody susceptibility in acute antiretroviral therapy-treated individuals', AIDS, vol. 36, no. 2, pp. 205-214. https://doi.org/10.1097/qad.0000000000003088

TY - JOUR

T1 - Evaluation of HIV-1 reservoir size and broadly neutralizing antibody susceptibility in acute antiretroviral therapy-treated individuals

AU - Moldt, Brian

AU - Gunthard, Huldrych F.

AU - Workowski, Kimberly A.

AU - Little, Susan J.

AU - Eron, Joseph J.

AU - Overton, Edgar T.

AU - Lehmann, Clara

AU - Rokx, Casper

AU - Kozal, Michael J.

AU - Gandhi, Rajesh T.

AU - Braun, Dominique L.

AU - Parvangada, Aiyappa

AU - Li, Jiani

AU - Martin, Ross

AU - Selzer, Lisa

AU - Cox, Stephanie

AU - Margot, Nicolas

AU - Liu, Hui

AU - Slamowitz, Debbie

AU - Makadzange, Tariro

AU - Collins, Sean E.

AU - Geleziunas, Romas

AU - Callebaut, Christian

N1 - Funding Information: B.M., A.P., J.L., R.M., L.S., S.C., N.M., H.L., D.S., T.M., S.E.C., R.G., and C.C. are employees and stockholders of Gilead Sciences, Inc. H.F.G. has received unrestricted research grants from Gilead Sciences and Roche; fees for data and safety monitoring board membership from Merck; consulting/advisory board membership fees from Gilead Sciences, Merck and ViiV Healthcare; and grants from SystemsX, and the National Institutes of Health. The institution of H.F.G. received educational grants form Gilead Sciences, ViiV, MSD, Abbvie, and Sandoz. S.J.L. received grants for investigator initiated studies from Gilead outside of the submitted work. E.T.O. received honoraria from ViiV, Merck, and Theratechnologies outside of the submitted work. C.L. received honoraria and travel grants from Janssen, Gilead, ViiV, and Merck outside of the submitted work. C.R. received honoraria and travel grants and grants for investigator-initiated studies from Gilead, ViiV, Janssen-Cilag, and Merck outside the context of the submitted work. M.J.K. received research support from Gilead and ViiV Healthcare. R.T.G. receives grant funding from the Harvard University Center for AIDS Research (NIH P30 AI060354) and the AIDS Clinical Trials Group (NIH/NIAID 2 UMAI069412-09). D.L.B. received honoraria and travel grants from Gilead, ViiV, and Merck outside of the submitted work. Funding Information: Funding: this study was funded by Gilead Sciences, Inc. Publisher Copyright: © 2022 Lippincott Williams and Wilkins. All rights reserved.

PY - 2022/2/1

Y1 - 2022/2/1

N2 - Objective: Persistence of the viral reservoir is the main barrier to curing HIV. Initiation of ART during acute HIV infection can limit the size and diversity of the reservoir. In depth characterization of the reservoir in individuals who initiate ART during acute infection will be critical for clinical trial design and cure strategies. Methods: Four cohortswith participantswhoinitiatedARTduring acute infection or during chronic infectionwere enrolled in a cross-sectional, noninterventional study.Viral reservoir was evaluated by the Intact Proviral DNA Assay (IPDA), the Total HIVDNA Assay (THDA) and the Quantitative Viral Outgrowth Assay (QVOA). Viral diversity and susceptibility to V3-glycan bNAbs were determined by genotyping of the viral envelope gene. Results: Participants who initiated ART during the acute Fiebig I-IV stages had lower level of total HIV DNA than participants who initiated ART during chronic infection whereas no difference was observed in intact HIV DNA or outgrowth virus. Participants who initiated ART during Fiebig I-IV also had lower viral diversity and appeared to have higher susceptibility to bNAbs than participants initiating ART during chronic infection. Conclusion: Individuals initiating ART during Fiebig I-IV had small viral reservoirs, low viral diversity, and high susceptibility to bNAbs, and would be an optimal target population for proof-of-concept HIV cure trials.

AB - Objective: Persistence of the viral reservoir is the main barrier to curing HIV. Initiation of ART during acute HIV infection can limit the size and diversity of the reservoir. In depth characterization of the reservoir in individuals who initiate ART during acute infection will be critical for clinical trial design and cure strategies. Methods: Four cohortswith participantswhoinitiatedARTduring acute infection or during chronic infectionwere enrolled in a cross-sectional, noninterventional study.Viral reservoir was evaluated by the Intact Proviral DNA Assay (IPDA), the Total HIVDNA Assay (THDA) and the Quantitative Viral Outgrowth Assay (QVOA). Viral diversity and susceptibility to V3-glycan bNAbs were determined by genotyping of the viral envelope gene. Results: Participants who initiated ART during the acute Fiebig I-IV stages had lower level of total HIV DNA than participants who initiated ART during chronic infection whereas no difference was observed in intact HIV DNA or outgrowth virus. Participants who initiated ART during Fiebig I-IV also had lower viral diversity and appeared to have higher susceptibility to bNAbs than participants initiating ART during chronic infection. Conclusion: Individuals initiating ART during Fiebig I-IV had small viral reservoirs, low viral diversity, and high susceptibility to bNAbs, and would be an optimal target population for proof-of-concept HIV cure trials.

UR - https://www.scopus.com/pages/publications/85122333306

U2 - 10.1097/qad.0000000000003088

DO - 10.1097/qad.0000000000003088

M3 - Article

C2 - 34586088

AN - SCOPUS:85122333306

SN - 0269-9370

VL - 36

SP - 205

EP - 214

JO - AIDS

JF - AIDS

IS - 2

ER -

Evaluation of HIV-1 reservoir size and broadly neutralizing antibody susceptibility in acute antiretroviral therapy-treated individuals

Abstract

Bibliographical note

UN SDGs

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