Rates of switching antiretroviral drugs in a primary care service in South Africa before and after introduction of tenofovir.
Rates of switching antiretroviral drugs in a primary care service in South Africa before and after introduction of tenofovir.
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DOI：
10.1371/journal.pone.0063596
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lawn SD
中科院分区：
文献类型：
--
作者：
Njuguna C;Orrell C;Kaplan R;Bekker LG;Wood R;Lawn SD
抗逆转录病毒药物的变化（单一药物替代和方案转换）限制了治疗选择，并带来了诸如费用增加、监测和坚持困难等挑战。司他夫定（d4 T）和齐多夫定（AZT）方案的药物替代和方案转换模式已得到很好的描述，但替诺福韦（TDF）的数据更为有限。本研究描述了这些抗逆转录病毒药物在成人中的药物变化的模式和风险因素。这项回顾性队列研究纳入了HIV阳性、抗逆转录病毒治疗（ART）初治、年龄≥18岁、开始ART治疗时使用两种核苷类逆转录酶抑制剂（NRTI）和一种非核苷类逆转录酶抑制剂的成人。在首次药物变更时删失随访，分析仅关注NRTI变更。2002年9月至2011年4月，5 095名成年人在Gugulethu开始了抗逆转录病毒疗法。这包括948例接受TDF的受试者，3438例接受d4 T的受试者和709例接受AZT的受试者。三组患者1年时的病毒学抑制率、因病毒学失败而转换治疗方案以及总体方案损失相似。TDF的药物替代发生率最低（2.6/100 P/Y），而d4 T为17.9/100 P/Y，AZT为8.5/100 P/Y。药物不良反应（ADR）占d4 T药物替代的大多数。多因素分析显示，年龄增加、女性和d4 T暴露与ADR导致的药物替代风险增加相关。相反，TDF暴露与替代风险显著降低相关（调整后的风险比为0.38; 95%CI为0.20-0.72）。暴露于TDF、d4 T和AZT的患者的方案转换和病毒学抑制相似，表明所有方案均同样有效。然而，TDF的耐受性更好，由于ADR而导致的药物替代率显著降低。
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.
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DOI：
10.1097/qai.0b013e3181f5bd03
发表时间：
2011-01-01
影响因子：
3.6
作者：
Castelnuovo, Barbara;Kiragga, Agnes;Manabe, Yukari
通讯作者：
Manabe, Yukari
影响因子：
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作者：
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作者：
Cassetti, Isabel;Madruga, Jose Valdez R.;Enejosa, Jeffrey
通讯作者：
Enejosa, Jeffrey
影响因子：
3.7
作者：
Prosperi, Mattia C. F.;Fabbiani, Massimiliano;Di Giambenedetto, Simona
通讯作者：
Di Giambenedetto, Simona