乌干达感染艾滋病毒的孕妇和哺乳期妇女头发中的抗逆转录病毒药物浓度可预测病毒抑制情况。
Hair concentrations of antiretrovirals predict viral suppression in HIV-infected pregnant and breastfeeding Ugandan women.
作者信息
Koss Catherine A, Natureeba Paul, Mwesigwa Julia, Cohan Deborah, Nzarubara Bridget, Bacchetti Peter, Horng Howard, Clark Tamara D, Plenty Albert, Ruel Theodore D, Achan Jane, Charlebois Edwin D, Kamya Moses R, Havlir Diane V, Gandhi Monica
机构信息
aHIV/AIDS Division, San Francisco General Hospital, University of California, San Francisco, San Francisco, California, USA bMakerere University-University of California, San Francisco Research Collaboration, Kampala, Uganda cMedical Research Council Unit, The Gambia dDepartment of Obstetrics, Gynecology and Reproductive Sciences eDepartment of Epidemiology and Biostatistics fHair Analysis Laboratory gCenter for AIDS Prevention Studies hDepartment of Pediatrics, University of California, San Francisco, San Francisco, California, USA iDepartment of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
出版信息
AIDS. 2015 Apr 24;29(7):825-30. doi: 10.1097/QAD.0000000000000619.
OBJECTIVE
Hair concentrations are a noninvasive measure of cumulative antiretroviral exposure and the strongest predictor of viral suppression in large cohorts of nonpregnant patients. We examined hair concentrations of antiretrovirals in relation to virologic outcomes in pregnant and breastfeeding women for the first time.
DESIGN AND METHODS
The Prevention of Malaria and HIV Disease in Tororo trial (NCT00993031) enrolled HIV-infected pregnant Ugandan women at 12-28 weeks gestation who were randomized to lopinavir or efavirenz-based antiretroviral therapy (ART). Small hair samples were collected at 30-34 weeks gestation and 10-25 weeks postpartum. Efavirenz and lopinavir hair concentrations were measured via liquid chromatography/tandem mass spectrometry. Multivariate logistic regression models examined predictors of viral suppression (HIV-1 RNA ≤400 copies/ml) at delivery and 24 weeks postpartum.
RESULTS
Among 325 women, median CD4 cell count was 366 cells/μl (interquartile range 270-488) at ART initiation. Mean self-reported 3-day adherence was greater than 97% in each arm. Viral suppression was achieved by 98.0% (efavirenz) and 87.4% (lopinavir) at delivery. At 24 weeks postpartum, 92.5% (efavirenz) and 90.6% (lopinavir) achieved viral suppression; 88% of women were breastfeeding. In multivariate models including self-reported adherence and pretreatment HIV-1 RNA, antiretroviral hair concentrations were the strongest predictor of viral suppression at delivery [efavirenz: adjusted odds ratio (aOR) 1.86 per doubling in concentration, 95% confidence interval (CI) 1.14-3.1, P = 0.013; lopinavir: aOR 1.90, 95% CI 1.33-2.7, P = 0.0004] and 24 weeks postpartum (efavirenz: aOR 1.81, 95% CI 1.22-2.7, P = 0.003; lopinavir: aOR 1.53, 95% CI 1.05-2.2, P = 0.026).
CONCLUSION
Antiretroviral hair concentrations represent an innovative tool that strongly predicts viral suppression among HIV-infected childbearing women during the critical periods of delivery and breastfeeding.
目的
头发中的抗逆转录病毒药物浓度是一种非侵入性的累积抗逆转录病毒暴露量测量方法，也是非妊娠患者大型队列中病毒抑制的最强预测指标。我们首次研究了妊娠和哺乳期妇女头发中的抗逆转录病毒药物浓度与病毒学结局的关系。
设计与方法
托罗罗预防疟疾和艾滋病试验（NCT00993031）纳入了妊娠12 - 28周的乌干达HIV感染孕妇，她们被随机分配接受基于洛匹那韦或依非韦伦的抗逆转录病毒治疗（ART）。在妊娠30 - 34周和产后10 - 25周收集少量头发样本。通过液相色谱/串联质谱法测量依非韦伦和洛匹那韦的头发浓度。多变量逻辑回归模型研究了分娩时和产后24周病毒抑制（HIV - 1 RNA≤400拷贝/ml）的预测因素。
结果
在325名妇女中，开始接受抗逆转录病毒治疗时CD4细胞计数中位数为366个/μl（四分位间距270 - 488）。每组中自我报告的3天依从性平均大于97%。分娩时，依非韦伦组病毒抑制率为98.0%，洛匹那韦组为87.4%。产后24周，依非韦伦组病毒抑制率为92.5%，洛匹那韦组为90.6%；88%的妇女进行母乳喂养。在包括自我报告的依从性和治疗前HIV - 1 RNA的多变量模型中，抗逆转录病毒药物头发浓度是分娩时病毒抑制的最强预测指标[依非韦伦：浓度每增加一倍，调整后的优势比（aOR）为1.86，95%置信区间（CI）为1.14 - 3.1，P = 0.013；洛匹那韦：aOR为1.90，95% CI为1.33 - 2.7，P = 0.0004]以及产后24周病毒抑制的最强预测指标（依非韦伦：aOR为1.81，95% CI为1.22 - 2.7，P = 0.003；洛匹那韦：aOR为1.53，95% CI为1.05 - 2.2，P = 0.026）。
结论
抗逆转录病毒药物头发浓度是一种创新工具，能有力预测HIV感染的育龄妇女在分娩和母乳喂养关键期的病毒抑制情况。
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