南非农村高流行地区基于二线蛋白酶抑制剂的人类免疫缺陷病毒1型治疗的病毒学转归：一项竞争风险前瞻性队列分析
Virological Outcomes of Second-line Protease Inhibitor-Based Treatment for Human Immunodeficiency Virus Type 1 in a High-Prevalence Rural South African Setting: A Competing-Risks Prospective Cohort Analysis.
作者信息
Collier Dami, Iwuji Collins, Derache Anne, de Oliveira Tulio, Okesola Nonhlanhla, Calmy Alexandra, Dabis Francois, Pillay Deenan, Gupta Ravindra K
机构信息
Department of Infection and Immunity, University College London, United Kingdom.
Africa Health Research Institute, Durban, KwaZulu-Natal, South Africa.
出版信息
Clin Infect Dis. 2017 Apr 15;64(8):1006-1016. doi: 10.1093/cid/cix015.
BACKGROUND
Second-line antiretroviral therapy (ART) based on ritonavir-boosted protease inhibitors (bPIs) represents the only available option after first-line failure for the majority of individuals living with human immunodeficiency virus (HIV) worldwide. Maximizing their effectiveness is imperative.
METHODS
This cohort study was nested within the French National Agency for AIDS and Viral Hepatitis Research (ANRS) 12249 Treatment as Prevention (TasP) cluster-randomized trial in rural KwaZulu-Natal, South Africa. We prospectively investigated risk factors for virological failure (VF) of bPI-based ART in the combined study arms. VF was defined by a plasma viral load >1000 copies/mL ≥6 months after initiating bPI-based ART. Cumulative incidence of VF was estimated and competing risk regression was used to derive the subdistribution hazard ratio (SHR) of the associations between VF and patient clinical and demographic factors, taking into account death and loss to follow-up.
RESULTS
One hundred one participants contributed 178.7 person-years of follow-up. Sixty-five percent were female; the median age was 37.4 years. Second-line ART regimens were based on ritonavir-boosted lopinavir, combined with zidovudine or tenofovir plus lamivudine or emtricitabine. The incidence of VF on second-line ART was 12.9 per 100 person-years (n = 23), and prevalence of VF at censoring was 17.8%. Thirteen of these 23 (56.5%) virologic failures resuppressed after a median of 8.0 months (interquartile range, 2.8-16.8 months) in this setting where viral load monitoring was available. Tuberculosis treatment was associated with VF (SHR, 11.50 [95% confidence interval, 3.92-33.74]; P < .001).
CONCLUSIONS
Second-line VF was frequent in this setting. Resuppression occurred in more than half of failures, highlighting the value of viral load monitoring of second-line ART. Tuberculosis was associated with VF; therefore, novel approaches to optimize the effectiveness of PI-based ART in high-tuberculosis-burden settings are needed.
CLINICAL TRIALS REGISTRATION
NCT01509508.
背景
对于全球大多数感染人类免疫缺陷病毒（HIV）的个体而言，基于利托那韦增强型蛋白酶抑制剂（bPIs）的二线抗逆转录病毒疗法（ART）是一线治疗失败后的唯一可用选择。最大化其疗效至关重要。
方法
这项队列研究嵌套于法国国家艾滋病和病毒性肝炎研究机构（ANRS）在南非夸祖鲁 - 纳塔尔农村地区开展的12249号治疗即预防（TasP）整群随机试验中。我们前瞻性地调查了联合研究组中基于bPI的ART发生病毒学失败（VF）的危险因素。VF定义为在开始基于bPI的ART后≥6个月，血浆病毒载量>1000拷贝/mL。估计VF的累积发病率，并使用竞争风险回归来推导VF与患者临床和人口统计学因素之间关联的亚分布风险比（SHR），同时考虑死亡和失访情况。
结果
101名参与者提供了178.7人年的随访数据。65%为女性；中位年龄为37.4岁。二线ART方案基于利托那韦增强型洛匹那韦，联合齐多夫定或替诺福韦加拉米夫定或恩曲他滨。二线ART的VF发病率为每100人年12.9例（n = 23），审查时VF的患病率为17.8%。在这个可进行病毒载量监测的环境中，这23例（56.5%）病毒学失败中有13例在中位8.0个月（四分位间距，2.8 - 16.8个月）后病毒载量再次被抑制。结核病治疗与VF相关（SHR，11.50 [95%置信区间，3.92 - 33.74]；P <.001）。
结论
在这种情况下二线VF很常见。超过一半的失败病例出现了病毒载量再次抑制，突出了二线ART病毒载量监测的价值。结核病与VF相关；因此，需要新的方法来优化在高结核病负担环境中基于PI的ART的疗效。
临床试验注册
NCT01509508。
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