Background:
T cell-based therapeutic vaccination is a potential approach to achieving durable control of HIV. We previously reported immunogenicity data from a randomized clinical trial (“PENNVAX”, NCT03606213) of Gag+Pol+IL-12 DNA (G/P), Gag+Pol+Env+IL-12 DNA (G/P/E), or placebo (PBO) vaccination in 45 participants with HIV on suppressive antiretroviral therapy, and found that vaccination induced de novo and boosted Gag-specific T-cell responses, with the most robust responses with G/P. We now present virologic outcomes from the trial.
Methods:
Participants (median 8.4 years virologically suppressed) were vaccinated Weeks 0, 4, 8, and 12. The HIV-1 reservoir was assessed serially pre- and post-vaccination by LTR-gag HIV-1 DNA (total DNA), cell-associated LTR-gag RNA (caRNA) and intact proviral DNA assay (IPDA) on isolated CD4+ T cells from cryopreserved PBMCs, as well as plasma HIV-1 RNA (vRNA) by automated single-copy assay (SCA). Longitudinal changes from baseline to week 64 (W64) were compared between arms by linear mixed effects models, parametric model accommodating left censoring at limit of detection for change in SCA, and Fisher exact tests. Two participants with known ART interruptions were excluded from analyses.
Results:
Across all reservoir measurements, G/P recipients had numerically greater reductions in total HIV-1 DNA, defective genomes, caRNA, and plasma vRNA and increases in the proportion who achieved an undetectable plasma vRNA over time, but no change in intact proviruses by IPDA (Table). The effects were modest and significant compared to placebo only for total DNA and quantitative plasma vRNA.
Conclusions:
We found modest but consistent signals of reductions in reservoir markers with G/P vaccination, the arm that induced the greatest Gag-specific T-cell responses by IFNg ELISPOT. Further work to characterize correlates of favorable vaccine-elicited immunologic and virologic responses is ongoing, and may inform future therapeutic vaccine design.
Table. Change in reservoir measures from baseline to week 64 by treatment arm. 