Getaneh Yimam, Lejissa Tadesse, Getahun Tigist, Khairunisa Siti Qamariyah, Husada Dominicus, Kuntaman Kuntaman, Lusida Maria Inge
Doctoral Program, Faculty of Medicine, Universitas Airlangga, Indonesia.
Ethiopian Public Health Institute, Indonesia.
Heliyon. 2023 Apr 28;9(5):e15779. doi: 10.1016/j.heliyon.2023.e15779. eCollection 2023 May.
Highly Active Antiretroviral therapy (HAART) plays significant role in reduction of mortality among children infected with HIV. Despite the inevitable impact of HAART on inflammation and toxicity, there is limited evidence on its impact among children in Ethiopia. Moreover, evidence on contributing factors to toxicity has been poorly described. Hence, we evaluated HAART induced inflammation and toxicity among children taking HAART in Ethiopia.
This cross-sectional study was conducted among children (<15 years old) taking HAART in Ethiopia. Stored plasma samples and secondary data from a previous study on HIV-1 treatment failure were used for this analysis. By 2018, a total of 554 children were recruited from randomly selected 43 health facilities in Ethiopia. The different levels of liver (SGPT), renal (Creatinine) and hematologic toxicity (Hemoglobin) toxicity were assessed using established cut-off value. Inflammatory biomarkers (CRP and vitamin-D) were also determined. Laboratory tests were done at the national clinical chemistry laboratory. Clinical and baseline laboratory data were retrieved from the participant's medical record. Questionnaire was also administered to study guardians to assess individual factors to inflammation and toxicity. Descriptive statistics was used to summarize the characteristics of the study participants. Multivariable analysis was conducted and considered significant at P < 0.05.
Overall 363 (65.6%) and 199 (36%) of children taking HAART in Ethiopia developed some level of inflammation and vitamin-D in-sufficiency, respectively. A quarter of the children 140 (25.3%) were at Grade-4 liver toxicity while renal toxicity were 16 (2.9%). A third 275 (29.6%) of the children also developed anemia. Children who were on TDF+3 TC + EFV, those who were not virally suppressed and children with liver toxicity were at 17.84 (95%CI = 16.98, 18.82), 2.2 (95%CI = 1.67, 2.88) and 1.20 (95%CI = 1.14, 1.93) times risk of inflammation, respectively. Children on TDF+3 TC + EFV, those with CD4 count of <200 cells/mm and with renal toxicity were at 4.10 (95%CI = 1.64, 6.89), 2.16(95%CI = 1.31, 4.26) and 5.94 (95%CI = 1.18, 29.89) times risk of vitamin-D in-sufficiency, respectively. Predictors of liver toxicity were history of HAART substitution (AOR = 4.66; 95%CI = 1.84, 6.04) and being bedridden (AOR = 3.56; 95%CI = 2.01, 4.71). Children from HIV positive mother were at 4.07 (95%CI = 2.30, 6.09) times risk of renal toxicity while the different type of HAARTs had different level of risk for renal toxicity AZT+3 TC + EFV (AOR = 17.63; 95%CI = 18.25, 27.54); AZT+3 TC + NVP (AOR = 22.48; 95%CI = 13.93, 29.31); d4t+3 TC + EFV (AOR = 4.34; 95%CI = 2.51, 6.80) and d4t+3 TC + NVP (AOR = 18.91; 95%CI = 4.87, 27.74) compared to those who were on TDF+3 TC + NVP. Similarly, children who were on AZT+3 TC + EFV were at 4.92 (95%CI = 1.86, 12.70) times risk of anemia compared to those who were on TDF+ 3 TC + EFZ.
The high level of HAART induced inflammation and liver toxicity among children calls for the program to consider safer regimens for pediatric patients. Moreover, the high proportion of vitamin-D in-sufficiency requires program level supplement. The impact of TDF+3 TC + EFV on inflammation and vitamin-D deficiency calls for the program to revise this regimen.
高效抗逆转录病毒疗法（HAART）在降低感染艾滋病毒儿童的死亡率方面发挥着重要作用。尽管HAART对炎症和毒性有不可避免的影响，但在埃塞俄比亚儿童中，关于其影响的证据有限。此外，关于毒性促成因素的证据也很少被描述。因此，我们评估了埃塞俄比亚接受HAART治疗的儿童中HAART引起的炎症和毒性。
这项横断面研究是在埃塞俄比亚接受HAART治疗的儿童（<15岁）中进行的。本分析使用了储存的血浆样本和先前关于HIV-1治疗失败研究的二次数据。到2018年，从埃塞俄比亚随机选择的43个卫生设施中总共招募了554名儿童。使用既定的临界值评估不同水平的肝脏（SGPT）、肾脏（肌酐）和血液学毒性（血红蛋白）毒性。还测定了炎症生物标志物（CRP和维生素D）。实验室检测在国家临床化学实验室进行。临床和基线实验室数据从参与者的病历中获取。还向研究监护人发放了问卷，以评估炎症和毒性的个体因素。描述性统计用于总结研究参与者的特征。进行了多变量分析，P<0.05时被认为具有统计学意义。
总体而言，埃塞俄比亚接受HAART治疗的儿童中，分别有363名（65.6%）和199名（36%）出现了一定程度的炎症和维生素D不足。四分之一的儿童140名（25.3%）处于4级肝脏毒性，而肾脏毒性为16名（2.9%）。三分之一的儿童275名（29.6%）也出现了贫血。接受替诺福韦酯（TDF）+拉米夫定（3TC）+依非韦伦（EFV）治疗的儿童、病毒未得到抑制的儿童以及有肝脏毒性的儿童发生炎症的风险分别是17.84（95%置信区间=16.98，18.82）、2.2（95%置信区间=1.67，2.88）和1.20（95%置信区间=1.14，1.93）倍。接受TDF+3TC+EFV治疗的儿童、CD4细胞计数<200个/mm且有肾脏毒性的儿童发生维生素D不足的风险分别是4.10（95%置信区间=1.64，6.89）、2.16（95%置信区间=1.31，4.26）和5.94（95%置信区间=1.18，29.89）倍。肝脏毒性的预测因素是HAART替换史（调整后比值比[AOR]=4.66；95%置信区间=1.84，6.04）和卧床不起（AOR=3.56；95%置信区间=2.01，4.71）。来自艾滋病毒阳性母亲的儿童发生肾脏毒性的风险是4.07（95%置信区间=2.30，6.09）倍，而不同类型的HAART对肾脏毒性有不同程度的风险，与接受TDF+3TC+奈韦拉平（NVP）治疗的儿童相比，齐多夫定（AZT）+3TC+EFV（AOR=17.63；95%置信区间=18.25，27.54）；AZT+3TC+NVP（AOR=22.48；95%置信区间=13.93，29.31）；司他夫定（d4t）+3TC+EFV（AOR=4.34；95%置信区间=2.51，6.80）和d4t+3TC+NVP（AOR=18.91；95%置信区间=4.87，27.74）。同样，与接受TDF+3TC+依法韦仑（EFZ）治疗的儿童相比，接受AZT+3TC+EFV治疗的儿童发生贫血的风险是4.92（95%置信区间=1.86，12.70）倍。
儿童中HAART引起的炎症和肝脏毒性水平较高，这要求该项目考虑为儿科患者采用更安全有效的治疗方案。此外，维生素D不足的比例较高，需要在项目层面进行补充。TDF+3TC+EFV对炎症和维生素D缺乏的影响要求该项目修订这一治疗方案。
