Moholisa Retsilisitsoe R, Schomaker Michael, Kuhn Louise, Castel Sandra, Wiesner Lubbe, Coovadia Ashraf, Strehlau Renate, Patel Faeezah, Pinillos Francoise, Abrams Elaine J, Maartens Gary, McIlleron Helen
From the *Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa; †Centre for Infectious Diseases Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa; ‡Gertrude H Sergievsky Center, College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY; §Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa; ¶ICAP, Mailman School of Public Health, and College of Physicians & Surgeons, Columbia University, New York, NY; and ‖Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Pediatr Infect Dis J. 2016 Dec;35(12):e378-e383. doi: 10.1097/INF.0000000000001319.
Adequate exposure to antiretroviral drugs is necessary to achieve and sustain viral suppression. However, the target antiretroviral concentrations associated with long-term viral suppression have not been adequately defined in children. We assessed the relationship between plasma lopinavir or nevirapine concentrations and the risk of subsequent viremia in children initially suppressed on antiretroviral therapy.
After an induction phase of antiretroviral treatment, 195 children with viral suppression (viral load ≤400 copies/mL) were randomized to continue a lopinavir/ritonavir-based regimen or to switch to a nevirapine-based regimen (together with lamivudine and stavudine). Viral load and lopinavir or nevirapine concentrations were measured at clinic visits 4, 8, 12, 16, 20, 24, 36, 52, 64 and 76 weeks post randomization. Cox multiple failure event models were used to estimate the effects of drug concentrations on the hazard of viremia (viral load >50 copies/mL) RESULTS:: At randomization, the median (interquartile range) age, CD4 T-Lymphocyte percentage, weight-for-age and weight-for-height z scores were 19 (16-24) months, 29% (23-37), -0.6 (-1.3 to 0.2) and -3.2 (-4.1 to -2.1), respectively. The proportion of children with viral load 51-400 copies/mL at randomization was 43%. The hazard of subsequent viremia during follow-up was increased for lopinavir concentrations <1 versus ≥1 mg/L [adjusted hazard ratio 0.62 (95% confidence interval, 0.40-0.94)] and for children with viral loads 51-400 copies/mL at randomization. Nevirapine concentrations were not significantly associated with subsequent viremia.
Plasma lopinavir concentrations predicted viral outcomes in children receiving lopinavir-based antiretroviral therapy. Our findings support a minimum target concentration of ≥1 mg/L of lopinavir to ensure sustained viral suppression.
充分暴露于抗逆转录病毒药物对于实现并维持病毒抑制是必要的。然而，与长期病毒抑制相关的目标抗逆转录病毒浓度在儿童中尚未得到充分界定。我们评估了血浆洛匹那韦或奈韦拉平浓度与最初接受抗逆转录病毒治疗且病毒得到抑制的儿童随后发生病毒血症风险之间的关系。
在抗逆转录病毒治疗的诱导期之后，195名病毒得到抑制（病毒载量≤400拷贝/毫升）的儿童被随机分为继续基于洛匹那韦/利托那韦的治疗方案或换用基于奈韦拉平的治疗方案（联合拉米夫定和司他夫定）。在随机分组后第4、8、12、16、20、24、36、52、64和76周的门诊就诊时测量病毒载量以及洛匹那韦或奈韦拉平浓度。使用Cox多失败事件模型来估计药物浓度对病毒血症（病毒载量>50拷贝/毫升）风险的影响。结果：随机分组时，年龄中位数（四分位间距）、CD4 T淋巴细胞百分比、年龄别体重和身高别体重Z评分分别为19（16 - 24）个月、29%（23 - 37）、-0.6（-1.3至0.2）和-3.2（-4.1至-2.1）。随机分组时病毒载量为51 - 400拷贝/毫升的儿童比例为43%。对于洛匹那韦浓度<1毫克/升与≥1毫克/升的情况以及随机分组时病毒载量为51 - 400拷贝/毫升的儿童，随访期间随后发生病毒血症的风险增加。奈韦拉平浓度与随后的病毒血症无显著关联。
血浆洛匹那韦浓度可预测接受基于洛匹那韦的抗逆转录病毒治疗儿童的病毒学结局。我们的研究结果支持洛匹那韦的最低目标浓度≥1毫克/升以确保持续的病毒抑制。
