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

TRIAL DESIGN: Open-label, randomised, controlled, pilot proof-of-concept clinical trial. METHODS: Participants: Antiretroviral naïve 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 naïve 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-term use 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.