Ongubo Dennis Miyoge, Lim Robertino, Tweya Hannock, Stanley Christopher Chikhosi, Tembo Petros, Broadhurst Richard, Gugsa Salem, Ngongondo McNeil, Speight Colin, Heller Tom, Phiri Sam, Hosseinipour Mina C
Tulane University School of Public Health and Tropical Medicine, New Orleans, USA.
Tufts University School of Medicine, Boston, USA.
BMC Infect Dis. 2017 Jul 3;17(1):461. doi: 10.1186/s12879-017-2528-0.
Malawi's national antiretroviral therapy program provides atazanavir/ritonavir-based second line regimens which cause concentration-dependent rise in indirect bilirubin. We sought to determine if elevated bilirubin, as a surrogate of atazanavir/ritonavir adherence, can aid in the evaluation of second line virological failure in Malawi.
We conducted a cross-sectional study of HIV-infected patients ≥15 years who were on boosted protease inhibitor-based second line antiretroviral therapy for at least 6 months in two urban HIV clinics in Lilongwe, Malawi. Antiretroviral therapy history and adherence data were extracted from the electronic medical records and blood was drawn for viral load, complete blood count, total bilirubin, and CD4 cell count at a clinic visit. Factors associated with virological failure were assessed using multivariate logistic regression model.
Out of 376 patients on second line antiretroviral therapy evaluated, 372 (98.9%) were on atazanavir/ritonavir-based therapy and 142 (37.8%) were male. Mean age was 40.9 years (SD ± 10.1), mean duration on second line antiretroviral therapy was 41.9 months (SD ± 27.6) and 256 patients (68.1%) had elevated bilirubin >1.3 mg/dL. Overall, 35 (9.3%) patients had viral load >1000 copies/ml (virological failure). Among the virologically failing vs. non-failing patients, bilirubin was elevated in 34.3% vs. 72.0% respectively (p < 0.001), although adherence by pill count was similar (62.9% vs. 60.7%, p = 0.804). The odds of virological failure were higher for adults aged 25-40 years (adjusted odds ratio (aOR) 2.5, p = 0.048), those with CD4 cell count <100 (aOR 17.5, p < 0.001), and those with normal bilirubin levels (aOR 5.4, p < 0.001); but were lower for the overweight/obese patients (aOR 0.3, p = 0.026). Poor pill count adherence (aOR 0.7, p = 0.4) and male gender (aOR 1.2, p = 0.698) were not associated with second line virological failure.
Among patients receiving atazanavir/ritonavir-based second line antiretroviral therapy, bilirubin levels better predicted virological failure than pill count adherence. Therefore, strategic use of bilirubin and viral load testing to target adherence counseling and support may be cost-effective in monitoring second line antiretroviral therapy adherence and virological failure. Drug resistance testing targeted for patients with virological failure despite elevated bilirubin levels would facilitate timely switch to third line antiretroviral regimens whenever available.
马拉维的国家抗逆转录病毒治疗项目提供基于阿扎那韦/利托那韦的二线治疗方案，该方案会导致间接胆红素浓度依赖性升高。我们试图确定胆红素升高作为阿扎那韦/利托那韦依从性的替代指标，是否有助于评估马拉维二线治疗的病毒学失败情况。
我们在马拉维利隆圭的两家城市艾滋病诊所，对年龄≥15岁、接受基于蛋白酶抑制剂强化治疗的二线抗逆转录病毒治疗至少6个月的HIV感染患者进行了一项横断面研究。从电子病历中提取抗逆转录病毒治疗史和依从性数据，并在门诊就诊时采集血液进行病毒载量、全血细胞计数、总胆红素和CD4细胞计数检测。使用多变量逻辑回归模型评估与病毒学失败相关的因素。
在接受评估的376例二线抗逆转录病毒治疗患者中，372例（98.9%）接受基于阿扎那韦/利托那韦的治疗，142例（37.8%）为男性。平均年龄为40.9岁（标准差±10.1），二线抗逆转录病毒治疗的平均疗程为41.9个月（标准差±27.6），256例患者（68.1%）胆红素升高>1.3mg/dL。总体而言，35例（9.3%）患者病毒载量>1000拷贝/ml（病毒学失败）。在病毒学失败与未失败的患者中，胆红素升高的比例分别为34.3%和72.0%（p<0.001），尽管通过药丸计数法得出的依从性相似（62.9%对60.7%，p=0.804）。25 - 40岁的成年人（调整后的优势比（aOR）2.5，p=0.048）、CD4细胞计数<100的患者（aOR 17.5，p<0.001）以及胆红素水平正常的患者（aOR 5.4，p<0.001）发生病毒学失败的几率更高；但超重/肥胖患者的几率较低（aOR 0.3，p=0.026）。药丸计数法依从性差（aOR 0.7，p=0.4）和男性（aOR 1.2，p=0.698）与二线病毒学失败无关。
在接受基于阿扎那韦/利托那韦的二线抗逆转录病毒治疗的患者中，胆红素水平比药丸计数法依从性更能预测病毒学失败。因此，战略性地使用胆红素和病毒载量检测来指导依从性咨询和支持，在监测二线抗逆转录病毒治疗的依从性和病毒学失败方面可能具有成本效益。针对胆红素水平升高但仍发生病毒学失败的患者进行耐药性检测，将有助于在有可用的三线抗逆转录病毒方案时及时进行转换。
