Preserved central nervous system functioning after use of romidepsin as a latency-reversing agent in an HIV cure strategy
Por:
Munoz-Moreno, JA, Carrillo-Molina, S, Martinez-Zalacain, I, Miranda, C, Manzardo, C, Coll, P, Meulbroek, M, Hanke, T, Garolera, M, Miro, JM, Brander, C, Clotet, B, Soriano-Mas, C, Molto, J and Mothe, B
Publicada:
1 mar 2022
Resumen:
Objective: 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.
Filiaciones:
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Hosp Badalona Germans Trias & Pujol, Fundacio Lluita La SIDA FLS, Ctra Canyet SN, Badalona 08916, Catalonia, Spain
Univ Oberta Catalunya UOC, Fac Psychol & Educ Sci, Barcelona, Spain
Carrillo-Molina, S:
Hosp Badalona Germans Trias & Pujol, Fundacio Lluita La SIDA FLS, Ctra Canyet SN, Badalona 08916, Catalonia, Spain
Martinez-Zalacain, I:
Bellvitge Univ Hosp, Bellvitge Biomed Res Inst IDIBELL, Dept Psychiat, Lhospitalet De Llobregat, Spain
Univ Barcelona UB, Dept Clin Sci, Barcelona, Spain
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Hosp Badalona Germans Trias & Pujol, Fundacio Lluita La SIDA FLS, Ctra Canyet SN, Badalona 08916, Catalonia, Spain
Manzardo, C:
Hosp Clin IDIBAPS, Infect Dis Dept, Barcelona, Spain
Univ Barcelona UB, Barcelona, Spain
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Hosp Badalona Germans Trias & Pujol, Fundacio Lluita La SIDA FLS, Ctra Canyet SN, Badalona 08916, Catalonia, Spain
BCN Checkpoint, Projecte Dels NOMS Hispanosida, Barcelona, Spain
Hosp Badalona Germans Trias & Pujol, IrsiCaixa Aids Res Inst HIVACAT, Badalona, Catalonia, Spain
Meulbroek, M:
BCN Checkpoint, Projecte Dels NOMS Hispanosida, Barcelona, Spain
Hanke, T:
Univ Oxford, Jenner Inst, Oxford, England
Kumamoto Univ, Joint Res Ctr Human Retrovirus Infect, Kumamoto, Japan
Garolera, M:
Consorci Sanitari Hosp Terrassa CSHT, Neuropsychol Unit, Terrassa, Japan
Univ Barcelona UB, Grp Recerca Consolidat Neuropsicol, Barcelona, Spain
Miro, JM:
Hosp Clin IDIBAPS, Infect Dis Dept, Barcelona, Spain
Univ Barcelona UB, Barcelona, Spain
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Hosp Badalona Germans Trias & Pujol, IrsiCaixa Aids Res Inst HIVACAT, Badalona, Catalonia, Spain
Univ Vic, Fac Med, Univ Cent Catalunya UVic UCC, Vic, Spain
ICREA, Barcelona, Spain
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Hosp Badalona Germans Trias & Pujol, Fundacio Lluita La SIDA FLS, Ctra Canyet SN, Badalona 08916, Catalonia, Spain
Hosp Badalona Germans Trias & Pujol, IrsiCaixa Aids Res Inst HIVACAT, Badalona, Catalonia, Spain
Univ Vic, Fac Med, Univ Cent Catalunya UVic UCC, Vic, Spain
Hosp Badalona Germans Trias & Pujol, Infect Dis Dept, Badalona, Spain
Soriano-Mas, C:
Bellvitge Univ Hosp, Bellvitge Biomed Res Inst IDIBELL, Dept Psychiat, Lhospitalet De Llobregat, Spain
Carlos III Hlth Inst, CIBER Salud Mental CIBERSAM, Barcelona, Spain
Univ Autonoma Barcelona UAB, Dept Psychobiol & Methodol Hlth Sci, Cerdanyola Del Valles, Catalonia, Spain
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Hosp Badalona Germans Trias & Pujol, Fundacio Lluita La SIDA FLS, Ctra Canyet SN, Badalona 08916, Catalonia, Spain
Hosp Badalona Germans Trias & Pujol, Infect Dis Dept, Badalona, Spain
:
Hosp Badalona Germans Trias & Pujol, Fundacio Lluita La SIDA FLS, Ctra Canyet SN, Badalona 08916, Catalonia, Spain
Hosp Badalona Germans Trias & Pujol, IrsiCaixa Aids Res Inst HIVACAT, Badalona, Catalonia, Spain
Univ Vic, Fac Med, Univ Cent Catalunya UVic UCC, Vic, Spain
Hosp Badalona Germans Trias & Pujol, Infect Dis Dept, Badalona, Spain
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