Abstract
OBJECTIVET-cell activation independently predicts mortality, poor immune recovery and non-AIDS illnesses during combination antiretroviral therapy (cART). Atorvastatin showed anti-immune activation effects among HIV-infected cART-naïve individuals. We investigated whether adjunct atorvastatin therapy reduces T-cell activation among cART-treated adults with suboptimal immune recovery.METHODSA randomised double-blind placebo-controlled crossover trial, of atorvastatin 80 mg daily vs. placebo for 12 weeks, was conducted among individuals with CD4 increase <295 cells/μl after seven years of suppressive cART. Change in T-cell activation (CD3 + CD4 + /CD8 + CD38 + HLADR+) and in T-cell exhaustion (CD3 + CD4 + /CD8 + PD1 + ) was measured using flow cytometry.RESULTSThirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28% greater reduction in CD4 T-cell activation (60% reduction) than placebo (32% reduction); P = 0.001. Atorvastatin also resulted in a 35% greater reduction in CD8-T-cell activation than placebo (49% vs. 14%, P = 0.0009), CD4 T-cell exhaustion (27% vs. 17% in placebo), P = 0.001 and CD8 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.CONCLUSIONAtorvastatin reduced T-cell immune activation and exhaustion among cART-treated adults in a Ugandan cohort. Atorvastatin adjunct therapy should be explored as a strategy to improve HIV treatment outcomes among people living with HIV in sub-Saharan Africa.
Highlights
The HIV/AIDS pandemic remains a major challenge to global health with 34 million people living with HIV (PLHIV) worldwide
Atorvastatin resulted in a 28% greater reduction in CD4 T-cell activation (60% reduction) than placebo (32% reduction); P = 0.001
Atorvastatin adjunct therapy should be explored as a strategy to improve HIV treatment outcomes among people living with HIV in sub-Saharan Africa
Summary
The HIV/AIDS pandemic remains a major challenge to global health with 34 million people living with HIV (PLHIV) worldwide. Access to life-saving combination antiretroviral therapy (cART) has increased exponentially in the last 5 years, and up to 6 million people are receiving cART (WHO/UNAIDS/UNICEF 2011; UNAIDS 2012). The immune activation associated with chronic HIV infection interferes with immunological recovery during suppressive cART (Hunt et al 2011; Nakanjako et al 2011). Our team previously reported persistent T-cell activation and exhaustion associated with suboptimal immune recovery after 4 years of suppressive cART (Nakanjako et al 2011). Chronic persistent immune activation contributes to CD4 depletion in both untreated and successfully treated patients and increases the risk of non-AIDS-defining illnesses (NADIS), such as chronic kidney and coronary artery disease among PLHIV (Hunt et al 2003, 2008; Gupta et al 2009; Crowe et al 2010).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
