Atorvastatin reduces T ‐cell activation and exhaustion among HIV ‐infected c ART ‐treated suboptimal immune responders in U ganda: a randomised crossover placebo‐controlled trial

Objective T‐cell activation independently predicts mortality, poor immune recovery and non‐ AIDS illnesses during combination antiretroviral therapy (c ART ). Atorvastatin showed anti‐immune activation effects among HIV ‐infected c ART ‐naïve individuals. We investigated whether adjunct atorvastatin therapy reduces T ‐cell activation among c ART ‐treated adults with suboptimal immune recovery. Methods A randomised double‐blind placebo‐controlled crossover trial, of atorvastatin 80 mg daily vs . placebo for 12 weeks, was conducted among individuals with CD 4 increase <295 cells/μl after seven years of suppressive c ART . Change in T ‐cell activation ( CD 3 +  CD 4 + / CD 8 +  CD 38 +  HLADR +) and in T‐cell exhaustion ( CD 3 +  CD 4 + / CD 8 +  PD 1 + ) was measured using flow cytometry. Results Thirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28% greater reduction in CD 4 T ‐cell activation (60% reduction) than placebo (32% reduction); P  = 0.001. Atorvastatin also resulted in a 35% greater reduction in CD 8‐ T ‐cell activation than placebo (49% vs . 14%, P  = 0.0009), CD 4 T ‐cell exhaustion (27% vs . 17% in placebo), P  = 0.001 and CD 8 T ‐cell exhaustion (27% vs . 16%), P  = 0.004. There was no carry‐over/period effect. Expected adverse events were comparable in both groups, and no serious adverse events were reported. Conclusion Atorvastatin reduced T ‐cell immune activation and exhaustion among c ART ‐treated adults in a U gandan cohort. Atorvastatin adjunct therapy should be explored as a strategy to improve HIV treatment outcomes among people living with HIV in sub‐ S aharan A frica.