In:
AIDS, Ovid Technologies (Wolters Kluwer Health), Vol. 36, No. 3 ( 2022-03-1), p. 363-372
Kurzfassung:
To assess the central nervous system (CNS) impact of a kick & kill HIV cure strategy using therapeutic vaccine MVA.HIVconsv and the histone deacetylase inhibitor (HDACi) romidepsin (RMD) as latency-reversing agent. Design: Neurological observational substudy of the BCN02 trial (NCT02616874), a proof-of-concept, open-label, single-arm, phase I clinical trial testing the safety and immunogenicity of the MVA.HIVconsv vaccine and RMD in early-treated HIV-1-infected individuals. A monitored antiretroviral pause (MAP) was performed, with cART resumption after 2 pVL more than 2000 copies/ml. Reinitiated participants were followed for 24 weeks. Methods: Substudy participation was offered to all BCN02 participants ( N = 15). Evaluations covered cognitive, functional, and brain imaging outcomes, performed before RMD administration (pre-RMD), after three RMD infusions (post-RMD), and at the end of the study (EoS). A group of early-treated HIV-1-infected individuals with matched clinical characteristics was additionally recruited ( n = 10). Primary endpoint was change in a global cognitive score (NPZ-6). Results: Eleven participants from BCN02 trial were enrolled. No significant changes were observed in cognitive, functional, or brain imaging outcomes from pre-RMD to post-RMD. No relevant alterations were detected from pre-RMD to EoS either. Scores at EoS were similar in participants off cART for 32 weeks ( n = 3) and those who resumed therapy for 24 weeks ( n = 7). Controls showed comparable punctuations in NPZ-6 across all timepoints. Conclusion: No detrimental effects on cognitive status, functional outcomes, or brain imaging parameters were observed after using the HDACi RMD as latency-reversing agent with the MVA.HIVconsv vaccine in early-treated HIV-1-infected individuals. CNS safety was also confirmed after completion of the MAP.
Materialart:
Online-Ressource
ISSN:
0269-9370
,
1473-5571
DOI:
10.1097/QAD.0000000000003121
Sprache:
Englisch
Verlag:
Ovid Technologies (Wolters Kluwer Health)
Publikationsdatum:
2022
ZDB Id:
2012212-3