Vaccination of people with HIV with BG505 SOSIP.v4.1-GT1.1: An interim safety analysis of the investigator-initiated RENEW-SHCS Phase I trial
- 1Institute of Medical Virology, University of Zurich, Zurich, Switzerland
Abstract
BackgroundVaccination of people with HIV (PWH) on suppressive antiretroviral therapy (ART) represents a novel approach for evaluating candidate broadly neutralizing antibody (bnAb) immunogens for preventive and therapeutic HIV vaccines. Given pre-existing immunity in PWH, the safety of this approach requires careful assessment prior to broader application. Here, we report on the design and safety of the RENEW-SHCS study which evaluates the immunization of PWH with BG505 SOSIP.v4.1-GT1.1, an immunogen engineered to induce precursors of CD4 binding site (CD4bs)- and V2-apex targeting bnAbs.
MethodsRENEW-SHCS is a phase I, open-label, non-randomized vaccination trial evaluating a single dose of the recombinant germline-targeting envelope trimer BG505 SOSIP.v4.1-GT1.1 (GT1.1), adjuvanted with 3M052-AF and Aluminum hydroxide (alum), in PWH on suppressive ART enrolled from the Swiss HIV Cohort Study. Participants were previously classified as bnAb or non-neutralizing antibody (nnAb) inducers, with a target enrollment of 15 per group, and were monitored for safety and immunogenicity for 24 weeks while continuing standard ART. Due to an out-of-specification stability measurement of adjuvant 3M052-AF the trial was paused after 23 immunizations and subjected to an unscheduled interim safety and reactogenicity assessment comprising protocol defined outcome measures (adverse events, clinical laboratory measurements and HIV-1 viral load).
ResultsTwenty-three participants (10 bnAb and 13 nnAb inducers, median age 59 years, 17 male / 6 female) were vaccinated between March and August 2025 before interruption of the trial. All participants completed follow-up with full protocol adherence. The interim-safety analysis confirmed that no vaccine-related serious adverse events occurred. Solicited local (96%) and systemic (83%) reactions were common, predominantly grade 1-2, transient, and self-limited. Transient laboratory changes occurred but mostly remained within the normal range, with no vaccine-related grade 3 abnormalities. We observed predominantly transient local and systemic reactions, which were similar or milder to the reactogenicity profile reported for immunization of adult people without HIV (PWOH) with GT1.1 adjuvanted with AS01b reported in the IAVI C101 trial. No viral rebound under ART occurred. One participant experienced two viral blips (>50 HIV-1 RNA copies/ml), one before and one 16 weeks after vaccination with subsequent re-suppression. All others maintained viral suppression (<50 copies/ml) throughout follow-up.
ConclusionRENEW-SHCS demonstrated a favorable safety and reactogenicity profile of single dose immunization with GT1.1 in PWH, comparable to that observed in PWOH. The findings of this phase I study support the feasibility of vaccinating ART-treated PWH in trials of preventive and therapeutic HIV vaccine strategies.
Trial registrationSNCTP000006192 | BASEC2024-01623. ClinicalTrials.gov NCT07769983
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BibTeX
@misc{poulose2026vaccination,
title = {{Vaccination of people with HIV with BG505 SOSIP.v4.1-GT1.1: An interim safety analysis of the investigator-initiated RENEW-SHCS Phase I trial}},
author = {R. Poulose and K. Kusejko and A. Eichenberger and A. Manrique and J. Nemeth and D. L. Braun and I. C. Caringi and S. Mahomed and N. Garrett and L. Aceto and H. Kovari and M. Huber and M. Schanz and R. D. Kouyos and M. Caskey and R. W. Sanders and P. L. Moore and A. Rauch and H. F. Guenthard and A. Trkola},
howpublished = {medRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.24.26360985},
url = {https://www.medrxiv.org/content/10.64898/2026.08.24.26360985v2},
note = {CC BY},
}
RIS
TY - UNPB
TI - Vaccination of people with HIV with BG505 SOSIP.v4.1-GT1.1: An interim safety analysis of the investigator-initiated RENEW-SHCS Phase I trial
AU - R. Poulose
AU - K. Kusejko
AU - A. Eichenberger
AU - A. Manrique
AU - J. Nemeth
AU - D. L. Braun
AU - I. C. Caringi
AU - S. Mahomed
AU - N. Garrett
AU - L. Aceto
AU - H. Kovari
AU - M. Huber
AU - M. Schanz
AU - R. D. Kouyos
AU - M. Caskey
AU - R. W. Sanders
AU - P. L. Moore
AU - A. Rauch
AU - H. F. Guenthard
AU - A. Trkola
PY - 2026
DA - 2026/08/24
PB - medRxiv
DO - 10.64898/2026.08.24.26360985
UR - https://www.medrxiv.org/content/10.64898/2026.08.24.26360985v2
AB - BackgroundVaccination of people with HIV (PWH) on suppressive antiretroviral therapy (ART) represents a novel approach for evaluating candidate broadly neutralizing antibody (bnAb) immunogens for preventive and therapeutic HIV vaccines. Given pre-existing immunity in PWH, the safety of this approach requires careful assessment prior to broader application. Here, we report on the design and safety of the RENEW-SHCS study which evaluates the immunization of PWH with BG505 SOSIP.v4.1-GT1.1, an immunogen engineered to induce precursors of CD4 binding site (CD4bs)- and V2-apex targeting bnAbs. MethodsRENEW-SHCS is a phase I, open-label, non-randomized vaccination trial evaluating a single dose of the recombinant germline-targeting envelope trimer BG505 SOSIP.v4.1-GT1.1 (GT1.1), adjuvanted with 3M052-AF and Aluminum hydroxide (alum), in PWH on suppressive ART enrolled from the Swiss HIV Cohort Study. Participants were previously classified as bnAb or non-neutralizing antibody (nnAb) inducers, with a target enrollment of 15 per group, and were monitored for safety and immunogenicity for 24 weeks while continuing standard ART. Due to an out-of-specification stability measurement of adjuvant 3M052-AF the trial was paused after 23 immunizations and subjected to an unscheduled interim safety and reactogenicity assessment comprising protocol defined outcome measures (adverse events, clinical laboratory measurements and HIV-1 viral load). ResultsTwenty-three participants (10 bnAb and 13 nnAb inducers, median age 59 years, 17 male / 6 female) were vaccinated between March and August 2025 before interruption of the trial. All participants completed follow-up with full protocol adherence. The interim-safety analysis confirmed that no vaccine-related serious adverse events occurred. Solicited local (96%) and systemic (83%) reactions were common, predominantly grade 1-2, transient, and self-limited. Transient laboratory changes occurred but mostly remained within the normal range, with no vaccine-related grade 3 abnormalities. We observed predominantly transient local and systemic reactions, which were similar or milder to the reactogenicity profile reported for immunization of adult people without HIV (PWOH) with GT1.1 adjuvanted with AS01b reported in the IAVI C101 trial. No viral rebound under ART occurred. One participant experienced two viral blips (>50 HIV-1 RNA copies/ml), one before and one 16 weeks after vaccination with subsequent re-suppression. All others maintained viral suppression (<50 copies/ml) throughout follow-up. ConclusionRENEW-SHCS demonstrated a favorable safety and reactogenicity profile of single dose immunization with GT1.1 in PWH, comparable to that observed in PWOH. The findings of this phase I study support the feasibility of vaccinating ART-treated PWH in trials of preventive and therapeutic HIV vaccine strategies. Trial registrationSNCTP000006192 | BASEC2024-01623. ClinicalTrials.gov NCT07769983
ER -