Dolling David I, Goodall Ruth L, Chirara Michael, Hakim James, Nkurunziza Peter, Munderi Paula, Eram David, Tumukunde Dinah, Spyer Moira J, Gilks Charles F, Kaleebu Pontiano, Dunn David T, Pillay Deenan
MRC Clinical Trials Unit at UCL, London, UK.
University of Zimbabwe, Harara, Zimbabwe.
BMC Infect Dis. 2017 Feb 21;17(1):160. doi: 10.1186/s12879-017-2266-3.
Few low-income countries have virological monitoring widely available. We estimated the virological durability of first-line antiretroviral therapy (ART) after five years of follow-up among adult Ugandan and Zimbabwean patients in the DART study, in which virological assays were conducted retrospectively.
DART compared clinically driven monitoring with/without routine CD4 measurement. Annual plasma viral load was measured on 1,762 patients. Analytical weights were calculated based on the inverse probability of sampling. Time to virological failure, defined as the first viral load measurement ≥200 copies/mL after 48 weeks of ART, was analysed using Kaplan-Meier plots and Cox regression models.
Overall, 65% of DART trial patients were female. Patients initiated first-line ART at a median (interquartile range; IQR) age of 37 (32-42) and with a median CD4 cell count of 86 (32-140). After 240 weeks of ART, patients initiating dual-class nucleoside reverse-transcriptase inhibitor (NRTI) -non-nucleoside reverse-transcriptase (NNRTI) regimens containing nevirapine + zidovudine + lamivudine had a lower incidence of virological failure than patients on triple-NRTI regimens containing tenofovir + zidovudine + lamivudine (21% vs 40%; hazard ratio (HR) =0.48, 95% CI:0.38-0.62; p < 0.0001). In multivariate analyses, female patients (HR = 0.79, 95% CI: 0.65-0.95; p = 0.02), older patients (HR = 0.73 per 10 years, 95% CI: 0.64-0.84; p < 0.0001) and patients with a higher pre-ART CD4 cell count (HR = 0.64 per 100 cells/mm, 95% CI: 0.54-0.75; p < 0.0001) had a lower incidence of virological failure after adjusting for adherence to ART. No difference in failure rate between the two randomised monitoring strategies was observed (p= 0.25).
The long-term durability of virological suppression on dual-class NRTI-NNRTI first-line ART without virological monitoring is remarkable and is enabled by high-quality clinical management and a consistent drug supply. To achieve higher rates of virological suppression viral-load-informed differentiated care may be required.
Prospectively registered on 18/10/2000 as ISRCTN13968779 .
很少有低收入国家能够广泛开展病毒学监测。在DART研究中，我们对乌干达和津巴布韦成年患者进行了为期五年的随访，以评估一线抗逆转录病毒疗法（ART）的病毒学持久性，该研究中的病毒学检测是回顾性进行的。
DART研究比较了有/无常规CD4测量的临床驱动监测。对1762例患者进行了年度血浆病毒载量检测。根据抽样的逆概率计算分析权重。使用Kaplan-Meier曲线和Cox回归模型分析病毒学失败时间，病毒学失败定义为ART治疗48周后首次病毒载量测量≥200拷贝/毫升。
总体而言，DART试验患者中65%为女性。患者开始一线ART治疗的中位（四分位间距；IQR）年龄为37岁（32 - 42岁），CD4细胞计数中位数为86（32 - 140）。ART治疗240周后，开始使用含奈韦拉平+齐多夫定+拉米夫定的双类核苷类逆转录酶抑制剂（NRTI）-非核苷类逆转录酶（NNRTI）方案的患者病毒学失败发生率低于使用含替诺福韦+齐多夫定+拉米夫定的三联NRTI方案的患者（21%对40%；风险比（HR）=0.48，95%置信区间：0.38 - 0.62；p＜0.0001）。在多变量分析中，女性患者（HR = 0.79，95%置信区间：0.65 - 0.95；p = 0.02）、年龄较大的患者（HR = 每10年0.73，95%置信区间：0.64 - 0.84；p＜0.0001）和ART治疗前CD4细胞计数较高的患者（HR = 每100个细胞/立方毫米0.64，95%置信区间：0.54 - 0.75；p＜0.0001）在调整ART依从性后病毒学失败发生率较低。两种随机监测策略之间的失败率没有差异（p = 0.25）。
在没有病毒学监测的情况下，双类NRTI - NNRTI一线ART的病毒学抑制长期持久性显著，这得益于高质量的临床管理和持续的药物供应。为实现更高的病毒学抑制率，可能需要基于病毒载量的差异化护理。
于2000年10月18日前瞻性注册为ISRCTN13968779 。
