title: Risk Factors for Incident Diabetes in a Cohort Taking First-Line Nonnucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy.
abstract: 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.
authors.affiliation: 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.
authors.forename: Sumanth
authors.initials: S
authors.lastname: Karamchand
authors.forename: Rory
authors.initials: R
authors.lastname: Leisegang
authors.forename: Michael
authors.initials: M
authors.lastname: Schomaker
authors.forename: Gary
authors.initials: G
authors.lastname: Maartens
authors.forename: Lourens
authors.initials: L
authors.lastname: Walters
authors.forename: Michael
authors.initials: M
authors.lastname: Hislop
authors.forename: Joel A
authors.initials: JA
authors.lastname: Dave
authors.forename: Naomi S
authors.initials: NS
authors.lastname: Levitt
authors.forename: Karen
authors.initials: K
authors.lastname: Cohen
mesh_terms: D000328:Adult; D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects*; D003521:Cyclopropanes; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D013223:Statistics as Topic
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; C098320:efavirenz