Berenguer Juan, Bellón José M, Miralles Pilar, Alvarez Emilio, Castillo Isabel, Cosín Jaime, López Juan Carlos, Sánchez Conde Matilde, Padilla Belén, Resino Salvador
HIV Infectious Diseases Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Clin Infect Dis. 2008 Jan 1;46(1):137-43. doi: 10.1086/524080.
We analyzed the effect of exposure to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) on the progression of liver fibrosis in patients with human immunodeficiency virus (HIV) and hepatitis C virus coinfection.
We analyzed data and liver biopsy findings for 201 coinfected patients. Fibrosis was scored following the French METAVIR Cooperative Study Group. We used multinomial logistic regression analysis and the fibrosis progression rate to assess the association between cumulative exposure to antiretroviral drugs and stage of fibrosis.
The adjusted odds ratio (AOR) and 95% confidence interval (CI) of having a fibrosis stage score of 0 or 1, compared with 3 or 4, increased with each additional year of exposure to HAART (AOR, 1.32; 95% CI, 1.04-1,67), to NNRTIs as a class (AOR, 1.64; 95% CI, 1.18-2.27), to efavirenz (AOR, 1.54; 95% CI, 1.03-2.30), and to nevirapine (AOR, 1.72; 95% CI, 1.15-2.78). This effect was not found with PIs as a class. The AOR (95% CI) of having a fibrosis stage score of 2 versus 3 or 4 increased with each additional year of exposure to NNRTIs (AOR, 1.51; 95% CI, 1.08-2.10) and nevirapine (AOR, 1.58; 95% CI, 1.06-2.37). This effect was not found with highly active antiretroviral therapy, PIs, or efavirenz. The AOR (95% CI) of having a fibrosis progression rate < or = 0.1 versus > 0.1 increased with each additional year of exposure to highly active antiretroviral therapy (AOR, 1.31; 95% CI, 1.07-1.60), to NNRTIs (AOR, 1.33; 95% CI, 1.03-1.70), and to nevirapine (AOR, 1.44; 95% CI, 1.07-1.95). This effect was not found with PIs or with efavirenz.
In contrast with previous studies, we found that exposure to NNRTIs was clearly associated with a reduction in fibrosis progression, whereas exposure to PIs was not. Of note, exposure to nevirapine was more consistently associated with a reduction in fibrosis progression than was exposure to efavirenz. Prospective work is needed in this area.
我们分析了接触非核苷类逆转录酶抑制剂（NNRTIs）和蛋白酶抑制剂（PIs）对人类免疫缺陷病毒（HIV）和丙型肝炎病毒合并感染患者肝纤维化进展的影响。
我们分析了201例合并感染患者的数据和肝活检结果。按照法国METAVIR协作研究组的标准对纤维化进行评分。我们使用多项逻辑回归分析和纤维化进展率来评估抗逆转录病毒药物的累积暴露与纤维化阶段之间的关联。
与纤维化阶段评分为3或4相比，纤维化阶段评分为0或1的校正比值比（AOR）和95%置信区间（CI）随着接受高效抗逆转录病毒治疗（HAART）时间每增加一年而升高（AOR，1.32；95%CI，1.04 - 1.67），作为一类药物的NNRTIs（AOR，1.64；95%CI，1.18 - 2.27），依非韦伦（AOR，1.54；95%CI，1.03 - 2.30），以及奈韦拉平（AOR，1.72；95%CI，1.15 - 2.78）。作为一类药物的PIs未发现此效应。与纤维化阶段评分为3或4相比，纤维化阶段评分为2的AOR（95%CI）随着接触NNRTIs时间每增加一年而升高（AOR，1.51；95%CI，1.08 - 2.10）以及奈韦拉平（AOR，1.58；95%CI，1.06 - 2.37）。高效抗逆转录病毒治疗、PIs或依非韦伦未发现此效应。与纤维化进展率>0.1相比，纤维化进展率≤0.1的AOR（95%CI）随着接受高效抗逆转录病毒治疗时间每增加一年而升高（AOR，1.31；95%CI，1.07 - 1.60），NNRTIs（AOR，1.33；95%CI，1.03 - 1.70），以及奈韦拉平（AOR，1.44；95%CI，1.07 - 1.95）。PIs或依非韦伦未发现此效应。
与先前的研究相反，我们发现接触NNRTIs与纤维化进展的降低明显相关，而接触PIs则不然。值得注意的是，与接触依非韦伦相比，接触奈韦拉平与纤维化进展降低的关联更一致。该领域需要进行前瞻性研究。
