University of Southern California School of Medicine, Los Angeles, CA, USA.
Department of Medicine, McCord Hospital, Durban, South Africa.
J Acquir Immune Defic Syndr. 2012 Oct 1;61(2):158-163. doi: 10.1097/QAI.0b013e3182615ad1.
Currently, boosted protease inhibitor-containing regimens are the only option after first-line regimen failure available for patients in most resource-limited settings, yet little is known about long-term adherence and outcomes.
We enrolled patients with virologic failure (VF) who initiated lopinavir/ritonavir-containing second-line antiretroviral therapy (ART). Medication possession ratios were calculated using pharmacy refill dates. Factors associated with 12-month second-line virologic suppression [viral load (VL) <50 copies/mL] and adherence were determined.
One hundred six patients (median CD4 count and VL at failure: 153 cells/mm(3) and 28,548 copies/mL, respectively) were enrolled. Adherence improved after second-line ART switch (median adherence 6 months prior, 67%; median adherence during initial 6 months of second-line ART, 100%; P = 0.001). Higher levels of adherence during second-line ART was associated with virologic suppression at month 12 of ART (odds ratio 2.5 per 10% adherence increase, 95% CI 1.3 to 4.8, P = 0.01). Time to virologic suppression was most rapid among patients with 91%-100% adherence compared with patients with 80%-90% and <80% adherence (log rank test, P = 0.01). VF during 24 months of second-line ART was moderate (month 12: 25%, n = 32/126; month 18: 21%, n = 23/112; and month 24: 25%, n = 25/99).
The switch to second-line ART in South Africa was associated with an improvement in adherence, however, a moderate ongoing rate of VF--among approximately 25% of patients receiving second-line ART patients at each follow-up interval--was a cause for concern. Adherence level was associated with second-line ART virologic outcome, helping explain why some patients achieved virologic suppression after switch and others did not.
目前，在大多数资源有限的环境下，对于一线方案治疗失败的患者，唯一的选择是使用强化蛋白酶抑制剂方案。然而，对于长期的服药依从性和结果，我们知之甚少。
我们纳入了那些发生病毒学失败（VF）并开始使用洛匹那韦/利托那韦方案的二线抗逆转录病毒治疗（ART）患者。利用药物补充日期计算药物持有率。确定与 12 个月时二线病毒学抑制（VL<50 拷贝/mL）和依从性相关的因素。
共有 106 例患者（中位 CD4 计数和失败时的病毒载量分别为 153 个细胞/mm3 和 28548 拷贝/mL）被纳入研究。二线 ART 转换后依从性得到改善（二线 ART 前 6 个月的中位依从性为 67%，前 6 个月的中位依从性为 100%，P=0.001）。二线 ART 期间更高的依从性与第 12 个月时的病毒学抑制相关（每增加 10%的依从性，比值比为 2.5，95%置信区间为 1.3 至 4.8，P=0.01）。与依从性为 80%-90%和<80%的患者相比，依从性为 91%-100%的患者病毒学抑制更快（对数秩检验，P=0.01）。二线 ART 治疗 24 个月时的 VF 发生率中等（第 12 个月：25%，n=32/126；第 18 个月：21%，n=23/112；第 24 个月：25%，n=25/99）。
在南非二线 ART 的转换与依从性的改善相关，但在每个随访间隔内，约 25%的接受二线 ART 的患者仍然出现中度的 VF，这令人担忧。依从性水平与二线 ART 的病毒学结果相关，这有助于解释为什么有些患者在转换后达到了病毒学抑制，而有些患者没有。
