Nachega Jean B, Hislop Michael, Dowdy David W, Gallant Joel E, Chaisson Richard E, Regensberg Leon, Maartens Gary
Department of Internal Medicine and Center for Infectious Disease, Stellenbosch University, Cape Town, South Africa.
AIDS. 2008 Oct 18;22(16):2117-25. doi: 10.1097/QAD.0b013e328310407e.
To determine the effectiveness of efavirenz versus nevirapine in initial antiretroviral therapy regimens for adults in sub-Saharan Africa.
Observational cohort study.
Study participants were 2817 HIV-infected, highly active antiretroviral therapy-naive adults who began nevirapine-based or efavirenz-based highly active antiretroviral therapy between January 1998 and September 2004 via a private-sector HIV/AIDS program in nine countries of southern Africa. The primary outcome was time to virologic failure (two measurements of viral loads >or=400 copies/ml). Secondary outcomes included all-cause mortality, time to viral load less than 400 copies/ml, pharmacy-claim adherence, and discontinuation of nevirapine or efavirenz without virologic failure.
The median follow-up period was 2.0 years (interquartile range 1.2-2.6). Patients started on nevirapine were significantly less likely than those started on efavirenz to achieve high adherence, whether defined as 100% (30.2 versus 38.1%, P < 0.002) or more than 90% (44.8 versus 49.4%, P < 0.02) pharmacy-claim adherence. In a multivariate analysis, patients on nevirapine had greater risk of virologic failure [hazard ratio (HR 1.52; 95% confidence interval (CI) 1.24-1.86)], death (2.17; 1.31-3.60), and regimen discontinuation (1.67; 1.32-2.11). Switching from nevirapine to efavirenz had no significant virologic effect, whereas switching from efavirenz to nevirapine resulted in significantly slower time to suppression (hazard ratio 0.58, 95% confidence interval 0.35-0.93) and faster time to failure (hazard ratio 3.92; 95% confidence interval 1.61-9.55) than remaining on efavirenz.
In initial highly active antiretroviral therapy regimens, efavirenz was associated with superior virologic and clinical outcomes than nevirapine, suggesting that efavirenz might be the preferred nonnucleoside reverse transcriptase inhibitor in resource-limited settings. However, its higher cost and potential teratogenicity are important barriers to implementation.
确定依法韦仑与奈韦拉平在撒哈拉以南非洲地区成人初始抗逆转录病毒治疗方案中的疗效。
观察性队列研究。
研究参与者为2817名未接受过高效抗逆转录病毒治疗的HIV感染成人，他们于1998年1月至2004年9月期间，通过南部非洲九个国家的一个私营部门HIV/艾滋病项目，开始接受以奈韦拉平或依法韦仑为基础的高效抗逆转录病毒治疗。主要结局是病毒学失败时间（两次测量的病毒载量≥400拷贝/毫升）。次要结局包括全因死亡率、病毒载量降至低于400拷贝/毫升的时间、药房报销依从性，以及在无病毒学失败的情况下停用奈韦拉平或依法韦仑。
中位随访期为2.0年（四分位间距1.2 - 2.6年）。开始使用奈韦拉平的患者实现高依从性的可能性显著低于开始使用依法韦仑的患者，无论依从性定义为100%（30.2%对38.1%，P < 0.002）还是超过90%（44.8%对49.4%，P < 0.02）的药房报销依从性。在多变量分析中，使用奈韦拉平的患者发生病毒学失败的风险更高[风险比（HR）1.52；95%置信区间（CI）1.24 - 1.86]、死亡风险更高（2.17；1.31 - 3.60）以及治疗方案停用风险更高（1.67；1.32 - 2.11）。从奈韦拉平换用依法韦仑没有显著的病毒学影响，而从依法韦仑换用奈韦拉平导致达到病毒抑制的时间显著延长（风险比0.58，95%置信区间0.35 - 0.93），且失败时间比继续使用依法韦仑更快（风险比3.92；95%置信区间1.61 - 9.55）。
在初始高效抗逆转录病毒治疗方案中，依法韦仑与优于奈韦拉平的病毒学和临床结局相关，这表明在资源有限的环境中，依法韦仑可能是首选的非核苷类逆转录酶抑制剂。然而，其较高的成本和潜在的致畸性是实施过程中的重要障碍。
