Correlates of HIV-1 control after combination immunotherapy

The identification of therapeutic strategies to induce sustained antiretroviral therapy (ART)-free control of HIV infection is a major priority<sup>1</sup>. Combination immunotherapy including HIV vaccination, immune stimulation, latency reversal and passive transfer of broadly neutralizing antibodies (bNAbs) has shown promise in non-human primate models<sup>2-6</sup>, but few studies have translated such approaches into people. Here we performed a single-arm, proof-of-concept study in ten people living with HIV on ART, combining the following three approaches: (1) therapeutic vaccination with an HIV Gag conserved element-targeted DNA + IL-12 prime/modified vaccinia Ankara (MVA) boost regimen followed by (2) administration of two bNAbs (10-1074, VRC07-523LS) and a toll-like receptor 9 agonist (lefitolimod) during ART suppression, followed by (3) repeat bNAb administration at the time of ART interruption (Clinicaltrials.gov: NCT04357821 ). Seven out of the ten participants exhibited post-intervention control after pausing ART, independent of residual bNAb plasma levels. Robust expansion of activated CD8<sup>+</sup> T cells early in response to rebounding virus correlated with a lower median viral load after peak viraemia off ART. These data suggest that combination immunotherapy approaches might prove effective in inducing sustained control of HIV by slowing rebound and improving CD8<sup>+</sup> T cell responses, and that these approaches should continue to be optimized.

Authors

Institutions

Publication Details

Journal
Nature
Published
2025-12-01
DOI
https://doi.org/10.1038/s41586-025-09929-5
Citations
12
Primary Topic
HIV Research and Treatment
Type
article
Field-Weighted Citation Impact
12.44

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Correlates of HIV-1 control after combination immunotherapy

Steven A. Yukl, Michel C. Nussenzweig, M. Coburn Williams, Timothy J. Henrich et al.
12 citations
Nature
HIV Research and Treatment
12.44
article

Correlates of HIV-1 control after combination immunotherapy

Steven A. Yukl, Michel C. Nussenzweig, M. Coburn Williams, Timothy J. Henrich, Matthew H. Spitzer, Kara W Chew, Hari Prabhath Tummala, David V. Glidden, Thomas Dalhuisen, Rafael Tibúrcio, Marina Caskey, James I. Mullins, Gina M. Borgo, Leanne S. Whitmore, Michael Gale, R. A. Koup, Rebecca Hoh, Devi SenGupta, Lillian B. Cohn, Amelia N. Deitchman, R. L. Rutishauser, Christos J. Petropoulos, Lily Zemelko, Michael J. Peluso, J. D. Reeves, Demi Sandel, Leonid Serebryannyy, Elena Vendrame, Steven G. Deeks, George N. Pavlakis, Lúcio Gama, Barbara K. Felber, Mohit Deswal, Mandana Khalili, Michiko Shimoda, Jennifer Tisoncik-Go, S. Narpala, Sang‐In Kim, Kent Schwartz, Sompal Singh
article en
12 citations

Abstract

The identification of therapeutic strategies to induce sustained antiretroviral therapy (ART)-free control of HIV infection is a major priority<sup>1</sup>. Combination immunotherapy including HIV vaccination, immune stimulation, latency reversal and passive transfer of broadly neutralizing antibodies (bNAbs) has shown promise in non-human primate models<sup>2-6</sup>, but few studies have translated such approaches into people. Here we performed a single-arm, proof-of-concept study in ten people living with HIV on ART, combining the following three approaches: (1) therapeutic vaccination with an HIV Gag conserved element-targeted DNA + IL-12 prime/modified vaccinia Ankara (MVA) boost regimen followed by (2) administration of two bNAbs (10-1074, VRC07-523LS) and a toll-like receptor 9 agonist (lefitolimod) during ART suppression, followed by (3) repeat bNAb administration at the time of ART interruption (Clinicaltrials.gov: NCT04357821 ). Seven out of the ten participants exhibited post-intervention control after pausing ART, independent of residual bNAb plasma levels. Robust expansion of activated CD8<sup>+</sup> T cells early in response to rebounding virus correlated with a lower median viral load after peak viraemia off ART. These data suggest that combination immunotherapy approaches might prove effective in inducing sustained control of HIV by slowing rebound and improving CD8<sup>+</sup> T cell responses, and that these approaches should continue to be optimized.

NatureVol. 650(8100)
National Institutes of Health (US), University of Minnesota (US), San Francisco VA Medical Center (US), Howard Hughes Medical Institute (US), University of California, Los Angeles (US), University of California, San Francisco (US), University of Washington (US), Instituto Butantan (BR), LabCorp (United States) (US), Fred Hutch Cancer Center (US), Parker Institute for Cancer Immunotherapy (US), Frederick National Laboratory for Cancer Research (US), National Institute of Allergy and Infectious Diseases (US), Gilead Sciences (United States) (US), National Cancer Institute (US), Immune Regulation (United Kingdom) (GB), Center for Cancer Research (US), UCSF Helen Diller Family Comprehensive Cancer Center (US), University of San Francisco (US), Rockefeller University (US)
Bill and Melinda Gates Foundation, Cancer Research Institute, amfAR, The Foundation for AIDS Research, National Institutes of Health, University of California, San Francisco
Openalex Percentile: Top 1%
HIV Research and Treatment
12.44
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.