Achhra Amit C, Boyd Mark A, Law Matthew G, Matthews Gail V, Kelleher Anthony D, Cooper David A
The Kirby Institute, UNSW Australia, Sydney, New South Wales, Australia.
PLoS One. 2014 Jun 26;9(6):e99530. doi: 10.1371/journal.pone.0099530. eCollection 2014.
Regimens sparing RATE (ritonavir, abacavir, tenofovir, efavirienz) agents might have better long-term safety. We conducted a feasibility exercise to assess the potential for a randomised trial evaluating RATE-sparing regimens.
Observational.
We first calculated RATE-sparing options available to an average patient receiving RATE agents. We reviewed treatment history and all resistance assays from patients attending the St. Vincent's Hospital (Sydney) clinic and receiving ≥2 RATE agents (n = 120). A viable RATE-sparing regimen with 2 or 3 fully-active agents was constructed from the following six 'safer' agents: rilpivirine or etravirine; atazanavir; raltegravir; maraviroc; and lamivudine. Activity for each drug was predicted as 1 (full-activity), 0.5 or 0 (no activity) using the Stanford mutation database. The utility of maraviroc was calculated assuming both maraviroc activity and inactivity where unknown. The analysis was restricted to regimens for which supporting evidence was identified in the literature or conference proceedings. Finally, we calculated the proportion of patients in the nationally representative Australian HIV Observational Database (AHOD) cohort receiving ≥2 RATE agents (n = 1473) to measure the potential population-level uptake of RATE-sparing agents.
Assuming full maraviroc activity, 117(97.5%) and 107(89.2%) individuals had at least one option with 2 or 3 active RATE-sparing agents, respectively. Assuming no maraviroc activity this decreased to 113(94.2%) and 104(86.7%), respectively. In AHOD, 837(56.8%) patients were receiving ≥2 RATE agents.
Feasible treatment switch options sparing RATE agents exist for the majority of patients. Understanding the pros and cons of switching stable patients onto new RATE-sparing regimens requires evidence derived from randomised controlled trials.
保留RATE（利托那韦、阿巴卡韦、替诺福韦、依非韦伦）药物的治疗方案可能具有更好的长期安全性。我们开展了一项可行性研究，以评估进行一项评价保留RATE方案的随机试验的可能性。
观察性研究。
我们首先计算了接受RATE药物的普通患者可选择的保留RATE方案。我们回顾了悉尼圣文森特医院诊所中接受≥2种RATE药物（n = 120）的患者的治疗史和所有耐药检测结果。从以下六种“更安全”的药物中构建了一种含有2种或3种全效药物的可行的保留RATE方案：利匹韦林或依曲韦林；阿扎那韦；拉替拉韦；马拉维罗；以及拉米夫定。使用斯坦福突变数据库将每种药物的活性预测为1（全效）、0.5或0（无活性）。在马拉维罗活性未知和无活性的情况下分别计算其效用。分析仅限于在文献或会议记录中找到支持证据的方案。最后，我们计算了在具有全国代表性的澳大利亚HIV观察数据库（AHOD）队列中接受≥2种RATE药物（n = 1473）的患者比例，以衡量保留RATE药物在人群层面的潜在接受程度。
假设马拉维罗具有全效活性，分别有117名（97.5%）和107名（89.2%）个体至少有一种含有2种或3种活性保留RATE药物的方案。假设马拉维罗无活性，这一比例分别降至113名（94.2%）和104名（86.7%）。在AHOD中，837名（56.8%）患者正在接受≥2种RATE药物。
对于大多数患者而言，存在可行的保留RATE药物的治疗转换方案。要了解将病情稳定的患者转换到新的保留RATE方案的利弊，需要来自随机对照试验的证据。
