Nakanjako Damalie, Ssinabulya Isaac, Nabatanzi Rose, Bayigga Lois, Kiragga Agnes, Joloba Moses, Kaleebu Pontiano, Kambugu Andrew D, Kamya Moses R, Sekaly Rafick, Elliott Alison, Mayanja-Kizza Harriet
Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda.
Trop Med Int Health. 2015 Mar;20(3):380-90. doi: 10.1111/tmi.12442. Epub 2015 Jan 6.
T-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.
A 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.
Thirty 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.
Atorvastatin 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.
在联合抗逆转录病毒疗法（cART）期间，T细胞活化可独立预测死亡率、免疫恢复不佳和非艾滋病相关疾病。阿托伐他汀在未接受cART治疗的HIV感染者中显示出抗免疫激活作用。我们研究了辅助使用阿托伐他汀治疗是否能降低免疫恢复欠佳的接受cART治疗的成年人的T细胞活化水平。
对接受了7年抑制性cART治疗后CD4细胞增加<295个/μl的个体进行了一项随机双盲安慰剂对照交叉试验，比较每日80mg阿托伐他汀与安慰剂治疗12周的效果。使用流式细胞术测量T细胞活化（CD3 + CD4 + /CD8 + CD38 + HLADR+）和T细胞耗竭（CD3 + CD4 + /CD8 + PD1 + ）的变化。
30名患者被随机分组，每组15人。阿托伐他汀导致CD4 T细胞活化的降低幅度比安慰剂大28%（60%对32%）；P = 0.001。阿托伐他汀还使CD8 - T细胞活化的降低幅度比安慰剂大35%（49%对14%，P = 0.0009），CD4 T细胞耗竭（27%对安慰剂组的17%），P = 0.001，以及CD8 T细胞耗竭（27%对16%），P = 0.004。没有残留/周期效应。两组预期不良事件相当，且未报告严重不良事件。
在乌干达队列中，阿托伐他汀降低了接受cART治疗的成年人的T细胞免疫活化和耗竭水平。应探索将阿托伐他汀辅助治疗作为改善撒哈拉以南非洲HIV感染者治疗效果的一种策略。
