Continued Decay of HIV Proviral DNA Upon Vaccination With HIV-1 Tat of Subjects on Long-Term ART: An 8-Year Follow-Up Study

Frontiers in Immunology
Cecilia SgadariBarbara Ensoli

Abstract

Introduction: Tat, a key HIV virulence protein, has been targeted for the development of a therapeutic vaccine aimed at cART intensification. Results from phase II clinical trials in Italy (ISS T-002) and South Africa (ISS T-003) indicated that Tat vaccination promotes increases of CD4+ T-cells and return to immune homeostasis while reducing the virus reservoir in chronically cART-treated patients. Here we present data of 92 vaccinees (59% of total vaccinees) enrolled in the ISS T-002 8-year extended follow-up study (ISS T-002 EF-UP, ClinicalTrials.gov NCT02118168). Results: Anti-Tat antibodies (Abs) induced upon vaccination persisted for the entire follow-up in 34/92 (37%) vaccinees, particularly when all 3 Ab classes (A/G/M) were present (66% of vaccinees), as most frequently observed with Tat 30 μg regimens. CD4+ T cells increased above study-entry levels reaching a stable plateau at year 5 post-vaccination, with the highest increase (165 cells/μL) in the Tat 30 μg, 3 × regimen. CD4+ T-cell increase occurred even in subjects with CD4+ nadir ≤ 250 cells/uL and in poor immunological responders and was associated with a concomitant increase of the CD4+/CD8+ T-cell ratio, a prognostic marker of morbidity/mortality inversely rela...Continue Reading

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Citations

Apr 12, 2020·Viruses·Hongping JinDavid Harrich
Jan 21, 2020·Expert Review of Vaccines·Sonia MorettiBarbara Ensoli
Apr 23, 2020·Frontiers in Cellular and Infection Microbiology·Jordan ThomasGeorgios Pollakis
Feb 5, 2021·European Journal of Medicinal Chemistry·Juliana Romano LopesJean Leandro Dos Santos
Jan 6, 2021·International Journal of Molecular Sciences·Aurelio CafaroBarbara Ensoli
Apr 12, 2021·EBioMedicine·Antonella TripicianoBarbara Ensoli
Aug 15, 2021·Archives of Virology·Barbara EnsoliAurelio Cafaro
Aug 21, 2020·Current HIV Research·Edward K MainaRaphael M Lwembe
Nov 28, 2020·Current HIV Research·Narges Farahani KhojastehAzam Bolhassani

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Methods Mentioned

BETA
ISS
flow cytometry
enzyme-linked immunosorbent assay
PCR
ELISA

Clinical Trials Mentioned

NCT00751595
NCT01024556
NCT02118168

Software Mentioned

STATA
BLAST
Amplilink
SAS®

Related Concepts