Hoffman Risa M, Umeh Obiamiwe C, Garris Cindy, Givens Naomi, Currier Judith S
Division of Infectious Diseases and Center for Clinical AIDS Research Education, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
HIV Clin Trials. 2007 Nov-Dec;8(6):371-80. doi: 10.1310/hct0806-371.
Recent studies focusing on HIV-1-infected women have suggested the existence of sex-related differences in natural history, antiretroviral pharmacokinetics, efficacy, and tolerability. This article analyzes three pivotal trials of the protease inhibitor (PI) fosamprenavir (FPV) with a view to providing a better understanding of potential sex differences in efficacy and safety.
A post hoc, descriptive analysis was performed on data from 700 subjects (26% women) in three trials of FPV to evaluate sex differences with regard to efficacy, rates of discontinuation, and treatment-related adverse events.
No major sex differences were found. Men and women had similarly good antiviral responses, with greater than 60% of treatment-naïve subjects achieving virologic suppression (<400 copies/mL) at 48 weeks. PI-experienced women in CONTEXT receiving once-daily FPV/r experienced the highest rates of discontinuations due to virologic failure (29% in women vs. 8% in men). Women generally had slightly lower rates of liver enzyme elevations and fewer abnormalities of total cholesterol and triglycerides.
The absence of major sex differences provides reassurance, but the small number of women in these trials limited the ability to draw conclusions. Future trials should be specifically powered to detect sex differences in safety and efficacy.
近期针对感染HIV-1的女性的研究表明，在疾病自然史、抗逆转录病毒药物的药代动力学、疗效和耐受性方面存在性别差异。本文分析了三项蛋白酶抑制剂（PI）福沙那韦（FPV）的关键试验，以期更好地了解疗效和安全性方面可能存在的性别差异。
对FPV三项试验中700名受试者（26%为女性）的数据进行事后描述性分析，以评估疗效、停药率和治疗相关不良事件方面的性别差异。
未发现重大性别差异。男性和女性的抗病毒反应同样良好，超过60%未经治疗的受试者在48周时实现了病毒学抑制（<400拷贝/毫升）。在CONTEXT试验中，有PI治疗经验且接受每日一次FPV/r治疗的女性因病毒学失败导致停药的比例最高（女性为29%，男性为8%）。女性肝酶升高的发生率通常略低，总胆固醇和甘油三酯异常的情况也较少。
未发现重大性别差异，这让人放心，但这些试验中女性数量较少，限制了得出结论的能力。未来的试验应专门设计以检测安全性和疗效方面的性别差异。
