Desmond Tutu HIV Centre, Institute for Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
PLoS One. 2013 May 22;8(5):e63596. doi: 10.1371/journal.pone.0063596. Print 2013.
Antiretroviral changes (single drug substitutions and regimen switches) limit treatment options and introduce challenges such as increased cost, monitoring and adherence difficulties. Patterns of drug substitutions and regimen switches from stavudine (d4T) and zidovudine (AZT) regimens have been well described but data on tenofovir (TDF) are more limited. This study describes the patterns and risk factors for drug changes of these antiretroviral drugs in adults.
This retrospective cohort study included HIV positive, antiretroviral treatment (ART) naïve adults aged ≥18 years who started ART with two nucleoside reverse transcriptase inhibitors (NRTIs) and a non-nucleoside reverse transcriptase inhibitor. Follow-up was censored at first drug change and analysis focused on NRTI changes only.
Between September 2002 and April 2011, 5095 adults initiated ART in Gugulethu. This comprised 948 subjects on TDF, 3438 on d4T and 709 subjects on AZT. Virological suppression rates at 1 year, regimen switching due to virological failure and overall losses to the programme were similar across the three groups. TDF had the lowest incidence rate of drug substitutions (2.6 per 100 P/Ys) compared to 17.9 for d4T and 8.5 per 100 P/Ys for AZT. Adverse drug reactions (ADRs) accounted for the majority of drug substitutions of d4T. Multivariate analysis showed that increasing age, female sex and d4T exposure were associated with increased hazard of drug substitution due to ADRs. Conversely, TDF exposure was associated with a substantially lower risk of substitution (adjusted hazards ratio 0.38; 95% CI 0.20-0.72).
Regimen switches and virological suppression were similar for patients exposed to TDF, d4T and AZT, suggesting all regimens were equally effective. However, TDF was better tolerated with a substantially lower rate of drug substitutions due to ADRs.
抗逆转录病毒药物的改变（单一药物替换和方案转换）限制了治疗选择，并带来了增加成本、监测和依从性困难等挑战。 已充分描述了从司他夫定（d4T）和齐多夫定（AZT）方案中进行药物替换和方案转换的模式，但关于替诺福韦（TDF）的数据则更为有限。本研究描述了这些抗逆转录病毒药物在成人中的药物改变模式和风险因素。
这是一项回顾性队列研究，纳入了年龄≥18 岁、首次接受抗逆转录病毒治疗（ART）的 HIV 阳性成人，他们接受了两种核苷逆转录酶抑制剂（NRTIs）和一种非核苷逆转录酶抑制剂的治疗。随访截止于首次药物改变，并重点分析仅 NRTI 改变。
2002 年 9 月至 2011 年 4 月期间，5095 名成年人在 Gugulethu 开始接受 ART。其中，948 名接受 TDF，3438 名接受 d4T，709 名接受 AZT。三组的 1 年病毒学抑制率、因病毒学失败而进行方案转换以及总体方案损失率相似。与 d4T（17.9/100 人年）和 AZT（8.5/100 人年）相比，TDF 的药物替换发生率最低（2.6/100 人年）。药物替换的主要原因是不良反应（ADRs），多变量分析显示，年龄增长、女性和 d4T 暴露与因 ADR 导致的药物替换风险增加相关。相反，TDF 暴露与药物替换风险显著降低相关（调整后的危险比为 0.38；95%CI 0.20-0.72）。
接受 TDF、d4T 和 AZT 治疗的患者方案转换和病毒学抑制率相似，表明所有方案均同样有效。然而，TDF 的耐受性更好，因 ADR 导致的药物替换率显著降低。
