Research Department of Infection and Population Health, University College London, London, United Kingdom.
PLoS One. 2012;7(8):e42834. doi: 10.1371/journal.pone.0042834. Epub 2012 Aug 8.
BACKGROUND: The most recent World Health Organization (WHO) antiretroviral treatment guidelines recommend the inclusion of zidovudine (ZDV) or tenofovir (TDF) in first-line therapy. We conducted a cost-effectiveness analysis with emphasis on emerging patterns of drug resistance upon treatment failure and their impact on second-line therapy. METHODS: We used a stochastic simulation of a generalized HIV-1 epidemic in sub-Saharan Africa to compare two strategies for first-line combination antiretroviral treatment including lamivudine, nevirapine and either ZDV or TDF. Model input parameters were derived from literature and, for the simulation of resistance pathways, estimated from drug resistance data obtained after first-line treatment failure in settings without virological monitoring. Treatment failure and cost effectiveness were determined based on WHO definitions. Two scenarios with optimistic (no emergence; base) and pessimistic (extensive emergence) assumptions regarding occurrence of multidrug resistance patterns were tested. RESULTS: In the base scenario, cumulative proportions of treatment failure according to WHO criteria were higher among first-line ZDV users (median after six years 36% [95% simulation interval 32%; 39%]) compared with first-line TDF users (31% [29%; 33%]). Consequently, a higher proportion initiated second-line therapy (including lamivudine, boosted protease inhibitors and either ZDV or TDF) in the first-line ZDV user group 34% [31%; 37%] relative to first-line TDF users (30% [27%; 32%]). At the time of second-line initiation, a higher proportion (16%) of first-line ZDV users harboured TDF-resistant HIV compared with ZDV-resistant viruses among first-line TDF users (0% and 6% in base and pessimistic scenarios, respectively). In the base scenario, the incremental cost effectiveness ratio with respect to quality adjusted life years (QALY) was US$83 when TDF instead of ZDV was used in first-line therapy (pessimistic scenario: US$ 315), which was below the WHO threshold for high cost effectiveness (US$ 2154). CONCLUSIONS: Using TDF instead of ZDV in first-line treatment in resource-limited settings is very cost-effective and likely to better preserve future treatment options in absence of virological monitoring.
背景：世界卫生组织（WHO）最近的抗逆转录病毒治疗指南建议将齐多夫定（ZDV）或替诺福韦（TDF）纳入一线治疗。我们进行了一项成本效益分析，重点关注治疗失败时出现的耐药模式及其对二线治疗的影响。
方法：我们使用撒哈拉以南非洲地区艾滋病毒 1 型广义流行的随机模拟来比较两种一线联合抗逆转录病毒治疗策略，包括拉米夫定、奈韦拉平以及 ZDV 或 TDF。模型输入参数来自文献，对于耐药途径的模拟，根据无病毒学监测情况下一线治疗失败后的耐药数据进行估计。根据世界卫生组织的定义，确定治疗失败和成本效益。测试了两种关于多药耐药模式发生的假设情况（乐观情况，即没有出现；基础情况）和悲观情况（广泛出现）。
结果：在基础情况下，根据世界卫生组织标准，一线 ZDV 使用者的治疗失败累积比例高于一线 TDF 使用者（中位数为六年后 36%[95%模拟区间 32%；39%]）。因此，一线 ZDV 使用者中启动二线治疗（包括拉米夫定、增效蛋白酶抑制剂以及 ZDV 或 TDF）的比例更高，为 34%[31%；37%]，而一线 TDF 使用者为 30%[27%；32%]。在二线治疗开始时，一线 ZDV 使用者中携带 TDF 耐药 HIV 的比例（16%）高于一线 TDF 使用者中 ZDV 耐药病毒的比例（基础情况和悲观情况分别为 0%和 6%）。在基础情况下，与一线使用 TDF 相比，一线使用 ZDV 的增量成本效益比（以质量调整生命年[QALY]表示）为 83 美元（悲观情况下为 315 美元），低于世界卫生组织的高成本效益阈值（2154 美元）。
结论：在资源有限的情况下，在一线治疗中使用 TDF 代替 ZDV 非常具有成本效益，并且可能在没有病毒学监测的情况下更好地保留未来的治疗选择。
J Acquir Immune Defic Syndr. 2011-12-15
J Acquir Immune Defic Syndr. 2011-11-1
Clin Infect Dis. 2010-2-1
Trop Med Int Health. 2015-7
J Acquir Immune Defic Syndr. 2008-7-1
Curr Opin HIV AIDS. 2013-11
J Acquir Immune Defic Syndr. 2012-2-1
J Acquir Immune Defic Syndr. 2011-11-1
J Acquir Immune Defic Syndr. 2011-3-1
J Acquir Immune Defic Syndr. 2010-10
Zotero 插件
