Bonnet Fabrice, Aurillac-Lavignolle Valerie, Breilh Dominique, Thiébaut Rodolphe, Peuchant Evelyne, Bernard Noëlle, Lacoste Denis, Dabis François, Beylot Jacques, Chêne Geneviève, Morlat Philippe
Service de Médecine Interne et Maladies Infectieuses, Hôpital Saint-André, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
HIV Clin Trials. 2007 Jan-Feb;8(1):53-60. doi: 10.1310/hct0801-53.
The objectives of the study were to assess the effects of pravastatin on plasma HIV RNA, lipid parameters, and protease inhibitor (PI) concentrations in patients treated with PI-containing regimens and with total cholesterol (TC) > or = 5.5 mmol/L.
A clinical trial including patients randomized to receive pravastatin or matching placebo for 12 weeks was implemented.
Twelve patients were included in the pravastatin group and 9 in the placebo group. At week 12 (W12), no patient had experienced virological failure. Between week 0 (W0) and W12, the median differences for TC were -1.4 mmol/L in the pravastatin group and +0.2 mmol/L in the placebo group (p = .005); for LDL, they were -1.0 mmol/L and +0.3 (p = .007), respectively. A significant decrease of the PI concentration (12 hours after administration) ratio W12 - W0/W0 was noticed in the pravastatin group (-0.2 [interquartile range, -0.3 to -0.1] as compared with the placebo group (0.1 [IQR, 0.0 to 0.3]) (p = .03). When the study was restricted to patients treated with lopinavir/ritonavir, a decrease from 3.8 microg/mL at baseline to 2.9 mug/mL at W12 was noticed in the pravastatin arm (p = .04) but not in the control arm (p = 1.00). No clinical adverse event reached a severity of grade 3.
We observed in this study that the use of pravastatin in PI-treated patients was not associated with major change in the plasma HIV RNA on 12 weeks of follow-up. However, we found a trend of decrease of the trough PI concentration at W12, suggesting a possible drug-drug interaction of pravastatin on PI metabolism.
本研究的目的是评估普伐他汀对接受含蛋白酶抑制剂（PI）方案治疗且总胆固醇（TC）≥5.5 mmol/L的患者血浆HIV RNA、脂质参数和PI浓度的影响。
开展一项临床试验，将患者随机分为接受普伐他汀或匹配安慰剂治疗12周。
普伐他汀组纳入12例患者，安慰剂组纳入9例患者。在第12周（W12）时，无患者出现病毒学失败。在第0周（W0）和W12之间，普伐他汀组TC的中位数差异为-1.4 mmol/L，安慰剂组为+0.2 mmol/L（p = 0.005）；低密度脂蛋白（LDL）的中位数差异分别为-1.0 mmol/L和+0.3（p = 0.007）。普伐他汀组PI浓度（给药后12小时）的W12 - W0/W0比值显著下降（-0.2[四分位间距，-0.3至-0.1]），而安慰剂组为0.1[四分位间距，0.0至0.3]（p = 0.03）。当研究仅限于接受洛匹那韦/利托那韦治疗的患者时，普伐他汀组从基线时的3.8μg/mL降至W12时的2.9μg/mL（p = 0.04），而对照组未出现下降（p = 1.00）。无临床不良事件达到3级严重程度。
我们在本研究中观察到，在接受PI治疗的患者中使用普伐他汀在12周的随访期内与血浆HIV RNA的重大变化无关。然而，我们发现W12时PI谷浓度有下降趋势，提示普伐他汀可能对PI代谢存在药物相互作用。
