Dragovic G J, Smith C J, Jevtovic D J, Johnson M A, Ranin J, Salemovic D, Youle M S
Department of Pharmacology, Clinical Pharmacology, and Toxicology, School of Medicine, University of Belgrade, Belgrade, Serbia.
HIV Clin Trials. 2009 Sep-Oct;10(5):306-13. doi: 10.1310/hct1005-306.
Use of dideoxynucleoside reverse transcriptase inhibitors (dNRTIs) may lead to increased mitochondrial toxicity. We compared nucleoside reverse transcriptase inhibitor (NRTI) use as part of antiretroviral therapy (ART) in two HIV clinics: one in a low-middle income (HIV Centre Belgrade [HCB], Serbia) and one a high income (ICDC, Royal Free Hospital, London, UK) country.
Antiretroviral naïve patients starting ART from 2003 to 2005 were included. Specific NRTIs were compared between centers, focusing on dNRTI use. Kaplan-Meier estimates of the percentage of patients making changes to their NRTI backbone (a) for any reason or (b) for mitochondrial toxicity (peripheral neuropathy, pancreatitis, lactic acidosis) were calculated.
Of 287 HCB patients, 89 (31.0%) received didanosine (ddI)-containing, 39 (13.6%) stavudine (d4T)-containing, and 39 (13.6%) ddI+d4T-containing regimens; for 539 ICDC patients, these were 18 (3.3%), 66 (12.2%), and 0 (0.0%), respectively (p < .0001). After 12 months, 57.5% and 52.6% at HCB and ICDC had switched their NRTI backbone. This was reduced to 34.5% at HCB after excluding changes due to drug supply interruption and to 11.2% and 1.3% at HCB and ICDC after changes were made for mitochondrial-related reasons. At 6 months, 73/80 (91.3%) and 385/488 (78.9%) had viral load below 50 copies/mL at HCB and ICDC, respectively.
Patients treated at HCB faced higher levels of mitochondrial-related toxicity, likely due to greater dNRTI use.
使用双脱氧核苷逆转录酶抑制剂（dNRTIs）可能会增加线粒体毒性。我们比较了两家艾滋病诊所将核苷逆转录酶抑制剂（NRTIs）用作抗逆转录病毒疗法（ART）一部分的情况：一家位于中低收入国家（塞尔维亚贝尔格莱德艾滋病中心[HCB]），另一家位于高收入国家（英国伦敦皇家自由医院ICDC）。
纳入2003年至2005年开始接受抗逆转录病毒治疗的初治患者。比较各中心使用的特定NRTIs，重点关注dNRTIs的使用情况。计算Kaplan-Meier估计值，即患者因任何原因（a）或因线粒体毒性（周围神经病变、胰腺炎、乳酸酸中毒）（b）而改变其NRTI主干的百分比。
在287例HCB患者中，89例（31.0%）接受含去羟肌苷（ddI）方案，39例（13.6%）接受含司他夫定（d4T）方案，39例（13.6%）接受含ddI + d4T方案；对于539例ICDC患者，相应比例分别为18例（3.3%）、66例（12.2%）和0例（0.0%）（p <.0001）。12个月后，HCB和ICDC分别有57.5%和52.6%的患者更换了其NRTI主干。排除因药物供应中断导致的更换后，HCB的这一比例降至34.5%；因线粒体相关原因进行更换后，HCB和ICDC的比例分别降至11.2%和1.3%。6个月时，HCB和ICDC分别有73/80（91.3%）和385/488（78.9%）的患者病毒载量低于50拷贝/mL。
在HCB接受治疗的患者面临更高水平的线粒体相关毒性，可能是由于dNRTIs的使用更多。
