Viganò Alessandra, Brambilla Paolo, Pattarino Giulia, Stucchi Sara, Fasan Silvia, Raimondi Chiara, Cerini Chiara, Giacomet Vania, Zuccotti Gian V, Bedogni Giorgio
Pediatric Clinic, L. Sacco Hospital, University of Milan, Milan, Italy.
Clin Drug Investig. 2009;29(2):101-9. doi: 10.2165/0044011-200929020-00004.
Few and mainly cross-sectional studies of glucose homeostasis are available in HIV-infected children treated with highly active antiretroviral therapy (HAART). The aim of the present study was to describe a 4-year course of glucose homeostasis in a cohort of HAART-treated children and adolescents, using glucose and insulin levels during an oral glucose tolerance test (OGTT) as outcome measures. In addition, we investigated possible risk factors, both related and unrelated to antiretroviral therapy, associated with insulin resistance.
We assessed glucose metabolism yearly for 4 consecutive years in 37 HIV-infected children receiving a protease inhibitor (PI)-based HAART regimen containing lamivudine/stavudine plus indinavir or ritonavir or nelfinavir or a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART regimen containing lamivudine/tenofovir/efavirenz. Generalized estimating equations were used to evaluate the relationship between the loge-transformed area under the serum concentration-time curve (AUC) of insulin during OGTT and antiretroviral therapy, controlling for time, sex, baseline age, puberty, body mass index and CD4+ T cells percentage.
Ritonavir-unboosted PI-based HAART regimens were administered to most children at baseline; however, their use decreased during follow-up in favour of an NNRTI-based regimen. The nelfinavir/lamivudine/stavudine (regression coefficient=-0.69, p<0.05) and efavirenz/lamivudine/tenofovir (regression coefficient=-0.93, p<0.05) regimens, but not the ritonavir/lamivudine/stavudine regimen, were negatively associated with loge-transformed insulin AUC compared with indinavir/lamivudine/stavudine. Puberty was positively associated with loge-transformed insulin AUC.
This 4-year prospective study of HAART-treated HIV-infected children shows that: (i) the nelfinavir/lamivudine/stavudine and the efavirenz/lamivudine/tenofovir regimens but not the ritonavir/lamivudine/stavudine regimen were associated with higher insulin sensivity, i.e. lower insulin AUC, compared with indinavir/lamivudine/stavudine; (ii) the treatment switched substantially in favour of NNRTI from the third year on and this change was associated with an improvement in insulin sensitivity compared with the previous HAART-based regimens; and (iii) puberty is a primary determinant of insulin sensitivity.
在接受高效抗逆转录病毒治疗（HAART）的HIV感染儿童中，关于葡萄糖稳态的研究较少，且主要为横断面研究。本研究的目的是，以口服葡萄糖耐量试验（OGTT）期间的葡萄糖和胰岛素水平作为观察指标，描述一组接受HAART治疗的儿童和青少年4年的葡萄糖稳态变化过程。此外，我们还调查了与胰岛素抵抗相关的、与抗逆转录病毒治疗相关和不相关的可能危险因素。
我们对37名接受含拉米夫定/司他夫定加茚地那韦或利托那韦或奈非那韦的基于蛋白酶抑制剂（PI）的HAART方案，或含拉米夫定/替诺福韦/依非韦伦的基于非核苷类逆转录酶抑制剂（NNRTI）的HAART方案治疗的HIV感染儿童，连续4年每年评估其葡萄糖代谢情况。采用广义估计方程来评估OGTT期间胰岛素血清浓度-时间曲线下面积（AUC）的对数转换值与抗逆转录病毒治疗之间的关系，并对时间、性别、基线年龄、青春期、体重指数和CD4+T细胞百分比进行校正。
大多数儿童在基线时接受不含利托那韦增强的基于PI的HAART方案；然而，在随访期间其使用减少，转而采用基于NNRTI的方案。与茚地那韦/拉米夫定/司他夫定相比，奈非那韦/拉米夫定/司他夫定方案（回归系数=-0.69，p<0.05）和依非韦伦/拉米夫定/替诺福韦方案（回归系数=-0.93，p<0.05），但不包括利托那韦/拉米夫定/司他夫定方案，与对数转换后的胰岛素AUC呈负相关。青春期与对数转换后的胰岛素AUC呈正相关。
这项对接受HAART治疗的HIV感染儿童进行的4年前瞻性研究表明：（i）与茚地那韦/拉米夫定/司他夫定相比，奈非那韦/拉米夫定/司他夫定和依非韦伦/拉米夫定/替诺福韦方案，但不包括利托那韦/拉米夫定/司他夫定方案，与更高的胰岛素敏感性相关，即更低的胰岛素AUC；（ii）从第三年起，治疗方案大幅转向支持NNRTI，与之前基于HAART的方案相比，这种变化与胰岛素敏感性的改善相关；（iii）青春期是胰岛素敏感性的主要决定因素。
