AUTHOR=Leal Lorna , Couto Elvira , Sánchez-Palomino Sonsoles , Climent Núria , Fernández Irene , Miralles Laia , Romero Yolanda , González Tania , Maleno Maria José , Paño Blanca , Pich Judit , Nicolau Carlos , Gatell José Maria , Plana Montserrat , García Felipe ,  the DCV3-RISVAC04 Study Group , Leal Lorna , Fernández Irene , Couto Elvira , Romero Yolanda , Miralles Laia , Hurtado Carmen , Climent Núria , González Tania , Maleno Maria José , Pich Judit , Burunat Laura , Arnaiz Joan Albert , Paño Blanca , Nicolau Carlos , Salvador Rafael , Farré Elisabet , Sánchez-Palomino Sonsoles , Gatell José Maria , Plana Montserrat , García Felipe , Torres Berta , Lucero Constanza , Laguno Montserrat , Martínez-Rebollar María , González-Cordón Ana , Rojas John , Inciarte Alexy , Mora Lorena de la , Mallolas Josep , Martínez Esteban , Blanco José Luis , Perpiñá Unai , Canals Josep , Martín Raquel , Echeverry Florencia , Xufré Cristina , Rovira Cristina , Sala Marta , Tricas Amparo 

TITLE=Effect of Intranodally Administered Dendritic Cell-Based HIV Vaccine in Combination With Pegylated Interferon α-2a on Viral Control Following ART Discontinuation: A Phase 2A Randomized Clinical Trial

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.767370

DOI=10.3389/fimmu.2021.767370

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>Functional cure has been proposed as an alternative to lifelong antiretroviral therapy and therapeutic vaccines represent one of the most promising approaches.</p></sec><sec><title>Materials and Methods</title><p>We conducted a double-blind randomized placebo-controlled clinical trial to evaluate the safety, immunogenicity, and effect on viral dynamics of a therapeutic vaccine produced with monocyte-derived dendritic cells (MD-DC) loaded with a high dose of heat-inactivated autologous (HIA) HIV-1 in combination with pegylated interferon alpha 2a (IFNα-2a) in people with chronic HIV-1.</p></sec><sec><title>Results</title><p>Twenty-nine male individuals on successful ART and with CD4+ ≥450 cells/mm<sup>3</sup> were randomized 1:1:1:1 to receive three ultrasound-guided inguinal intranodal immunizations, one every 2 weeks: (1) vaccine ~10<sup>7</sup> MD-DC pulsed with HIA-HIV-1 (10<sup>10</sup> HIV RNA copies) (<italic>n</italic> = 8); (2) vaccine plus three doses of 180 mcg IFNα-2a at weeks 4–6 (<italic>n</italic> = 6); (3) placebo = saline (<italic>n</italic> = 7); and (4) placebo plus three doses of 180 mcg IFNα-2a (<italic>n</italic> = 8). Thereafter, treatment was interrupted (ATI). Vaccines, IFNα-2a, and the administration procedures were safe and well tolerated. All patients’ viral load rebounded during the 12-week ATI period. According to groups, changes in viral set-point between pre-ART and during ATI were not significant. When comparing all groups, there was a tendency in changes in viral set-point between the vaccine group vs. vaccine + IFNα-2a group (&gt;0.5log<sub>10</sub><italic>p</italic> = 0.05). HIV-1-specific T-cell responses (IFN-ƴ Elispot) were higher at baseline in placebo than in the vaccine group (2,259 ± 535 vs. 900 ± 200 SFC/10<sup>6</sup> PBMC, <italic>p</italic> = 0.028). A significant difference in the change of specific T-cell responses was only observed at week 4 between vaccine and placebo groups (694 ± 327 vs. 1,718 ± 282 SFC/10<sup>6</sup> PBMC, <italic>p</italic> = 0.04). No effect on T-cell responses or changes in viral reservoir were observed after INFα-2a administration.</p></sec><sec><title>Discussion</title><p>Results from this study show that intranodally administered DC therapeutic vaccine in combination with IFNα-2a was safe and well-tolerated but had a minimal impact on viral dynamics in HIV-1 chronic infected participants.</p></sec><sec><title>Clinical Trial Registration</title><p>(<uri xlink:href="http://www.ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">www.ClinicalTrials.gov</uri>), identifier NCT02767193</p></sec>