Trial Design: Open-label, randomised, controlled, pilot proof-of-concept clinical trial. Methods: Participants: Antiretroviral naïve adult males with CD4 count ≥350 cells/mm3. 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 b 0.05) and an increase in US-CRP (p b 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.