Thalidomide is Associated With Increased T Cell Activation and Inflammation in Antiretroviral-naive HIV-infected Individuals in a Randomised Clinical Trial of Efficacy and Safety

• Autor(a) principal: Vergara, Tania R. C. [UNIFESP]
• Data de Publicação: 2017
• Outros Autores: Samer, Sadia [UNIFESP], Santos-Oliveira, Joanna R., Giron, Leila B. [UNIFESP], Arif, Muhammad Shoaib [UNIFESP], Silva-Freitas, Maria Luciana, Cherman, Lia A., Treitsman, Mauro S., Chebabo, Alberto, Sucupira, Maria Cecilia A. [UNIFESP], Da-Cruz, Aldam., Diaz, Ricardo Sobhie [UNIFESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://repositorio.unifesp.br/handle/11600/51310; http://dx.doi.org/10.1016/j.ebiom.2017.08.007
• topic: Thalidomide; T cell activation; Inflammation; Latency reversal agent; HIV

Trial Design: Open-label, randomised, controlled, pilot proof-of-concept clinical trial. Methods: Participants: Antiretroviral naive adult males with CD4 count >= 350 cells/mm(3). Interventions: Patients were randomised to receive thalidomide 200 mg QD for 3 weeks (Thalidomide group) or not (Control group) and followed for 48 weeks. Objective: We hypothesized that short-term Thalidomide use would reduce HIV related inflammation and HIV replication among antiretroviral naive HIV infected individuals. Outcome: Viral loads, CD4/CD8 counts, ultra-sensitive C-reactive protein (US-CRP), cell activation markers, and plasma lipopolysaccharide (LPS) were analyzed. Randomisation: Unrestricted randomisation. Blinding: No blinding was used. Results: Numbers randomised: Thirty recruited individuals were randomised to Thalidomide (16 patients) or Control (14 patients) groups. Recruitment: Patients were recruited from April 2011 to January 2013. Outcome: Viral loads remained stable in both groups. During thalidomide treatment, a decrease in CD4/CD8 ratio (p = 0.04), a decrease in CD4 count (p = 0.04), an increase in cell activation calculated by the percentage of CD38 (+)/HLA-DR+ CD8 cells (p < 0.05) and an increase in US-CRP (p < 0.01) were observed in the Thalidomide group, with all parameters returning to baseline levels after thalidomide interruption. We confirmed that thalidomide increased HIV replication in vitro of 6 of 7 samples from long-term antiretroviral suppressed individuals. Harms: No class 3/4 adverse events occurred. Conclusions: Short-termuse of thalidomide led to an intense transient increase in T cell activation and inflammation, with a decrease in the CD4(+) cell count without changes to the CD8(+) cell count. We confirmed that thalidomide acts in vitro as a latency reversal agent and speculate that the in vivo results obtained were due to an increase in HIV replication. (C) 2017 The Authors. Published by Elsevier B.V.