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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
Author(s) -
Nakanjako Damalie,
Ssinabulya Isaac,
Nabatanzi Rose,
Bayigga Lois,
Kiragga Agnes,
Joloba Moses,
Kaleebu Pontiano,
Kambugu Andrew D.,
Kamya Moses R.,
Sekaly Rafick,
Elliott Alison,
MayanjaKizza Harriet
Publication year - 2015
Publication title -
tropical medicine and international health
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.056
H-Index - 114
eISSN - 1365-3156
pISSN - 1360-2276
DOI - 10.1111/tmi.12442
Subject(s) - atorvastatin , medicine , placebo , immune system , t cell , adverse effect , immunology , crossover study , gastroenterology , pathology , alternative medicine
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.