Karamchand Sumanth, Leisegang Rory, Schomaker Michael, Maartens Gary, Walters Lourens, Hislop Michael, Dave Joel A, Levitt Naomi S, Cohen Karen
From the Division of Clinical Pharmacology (SK, RL, GM, KC), Division of Endocrinology, Department of Medicine (JAD, NSL), Center for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town (MS), Aid for AIDS Management (Pty) Limited (MH), Health Intelligence Unit, Medscheme (Pty) Limited (LW), Chronic Disease Initiative for Africa, Cape Town (JAD, NSL), South Africa.
Medicine (Baltimore). 2016 Mar;95(9):e2844. doi: 10.1097/MD.0000000000002844.
Efavirenz is the preferred nonnucleoside reverse transcriptase inhibitor (NNRTI) in first-line antiretroviral therapy (ART) regimens in low- and middle-income countries, where the prevalence of diabetes is increasing. Randomized control trials have shown mild increases in plasma glucose in participants in the efavirenz arms, but no association has been reported with overt diabetes. We explored the association between efavirenz exposure and incident diabetes in a large Southern African cohort commencing NNRTI-based first-line ART. Our cohort included HIV-infected adults starting NNRTI-based ART in a private sector HIV disease management program from January 2002 to December 2011. Incident diabetes was identified by the initiation of diabetes treatment. Patients with prevalent diabetes were excluded. We included 56,298 patients with 113,297 patient-years of follow-up (PYFU) on first-line ART. The crude incidence of diabetes was 13.24 per 1000 PYFU. Treatment with efavirenz rather than nevirapine was associated with increased risk of developing diabetes (hazard ratio 1.27 (95% confidence interval (CI): 1.10-1.46)) in a multivariate analysis adjusting for age, sex, body mass index, baseline CD4 count, viral load, NRTI backbone, and exposure to other diabetogenic medicines. Zidovudine and stavudine exposure were also associated with an increased risk of developing diabetes. We found that treatment with efavirenz, as well as stavudine and zidovudine, increased the risk of incident diabetes. Interventions to detect and prevent diabetes should be implemented in ART programs, and use of antiretrovirals with lower risk of metabolic complications should be encouraged.
在糖尿病患病率不断上升的低收入和中等收入国家，依法韦仑是一线抗逆转录病毒疗法（ART）方案中首选的非核苷类逆转录酶抑制剂（NNRTI）。随机对照试验表明，使用依法韦仑治疗的参与者血浆葡萄糖水平有轻度升高，但未报告与显性糖尿病有关联。我们在一个开始基于NNRTI的一线ART治疗的大型南部非洲队列中，探讨了依法韦仑暴露与新发糖尿病之间的关联。我们的队列包括2002年1月至2011年12月期间在一个私营部门HIV疾病管理项目中开始基于NNRTI的ART治疗的HIV感染成年人。新发糖尿病通过开始糖尿病治疗来确定。患有糖尿病的患者被排除。我们纳入了56298名患者，对一线ART治疗进行了113297人年的随访（PYFU）。糖尿病的粗发病率为每1000 PYFU 13.24例。在对年龄、性别、体重指数、基线CD4细胞计数、病毒载量、核苷类逆转录酶抑制剂主干以及其他致糖尿病药物暴露进行多变量分析时，使用依法韦仑而非奈韦拉平与患糖尿病风险增加相关（风险比1.27（95%置信区间（CI）：1.10 - 1.46））。齐多夫定和司他夫定暴露也与患糖尿病风险增加相关。我们发现，使用依法韦仑以及司他夫定和齐多夫定治疗会增加新发糖尿病的风险。应在ART项目中实施检测和预防糖尿病的干预措施，并鼓励使用代谢并发症风险较低的抗逆转录病毒药物。
