Prakit Riyaten1, Nicolas Salvadori, Patrinee Traisathit, Nicole Ngo-Giang-Huong, Tim R Cressey, Prattana Leenasirimakul, Malee Techapornroong, Chureeratana Bowonwatanuwong, Pacharee Kantipong, Ampaipith Nilmanat, Naruepon Yutthakasemsunt, Apichat Chutanunta, Suchart Thongpaen, Virat Klinbuayaem, Luc Decker, Sophie Le Cœur, Marc Lallemant, Jacqueline Capeau, Jean-Yves Mary, Gonzague Jourdain. 1. *Department of Statistics, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand; †Institut de recherche pour le développement (IRD) UMI 174-PHPT, Chiang Mai, Thailand; ‡Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; §Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA; ‖Nakornping Hospital, Chiang Mai, Thailand; ¶Prapokklao Hospital, Chantaburi, Thailand; #Chonburi Hospital, Chonburi, Thailand; **Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand; ††Hat Yai Hospital, Songkla, Thailand; ‡‡Nong Khai Hospital, Nong Khai, Thailand; §§Samutsakhon Hospital, Samutsakhon, Thailand; ‖‖Mahasarakham Hospital, Mahasarakham, Thailand; ¶¶Sanpatong Hospital, Chiang Mai, Thailand; ##Institut National d'Etudes Démographiques, Paris, France; ***Sorbonne Universités, INSERM UPMC UMR_S938, APHP, Univ Paris 06, Paris, France; and †††INSERM U1153, Team ECSTRA, Université Paris Diderot-Paris 7, Hôpital Saint-Louis, Paris, France.
Abstract
BACKGROUND: Use of several antiretrovirals (ARVs) has been shown to be associated with a higher risk of diabetes in HIV-infected adults. We estimated the incidence of new-onset diabetes and assessed the association between individual ARVs and ARV combinations, and diabetes in a large cohort in Thailand. METHODS: We selected all HIV-1-infected, nondiabetic, antiretroviral-naive adults enrolled in the Program for HIV Prevention and Treatment cohort (NCT00433030) between January 2000 and December 2011. Diabetes was defined as confirmed fasting plasma glucose ≥ 126 mg/dL or random plasma glucose ≥ 2 00 mg/dL. Incidence was the number of cases divided by the total number of person-years of follow-up. Association between ARVs and ARV combinations, and new-onset diabetes was assessed using Cox proportional hazards models. RESULTS: Overall, 1594 HIV-infected patients (76% female) were included. Median age at antiretroviral therapy initiation was 32.5 years. The incidence rate of diabetes was 5.0 per 1000 person-years of follow-up (95% confidence interval: 3.8 to 6.6) (53 cases). In analyses adjusted for potential confounders, exposure to stavudine + didanosine [adjusted hazard ratio (aHR) = 3.9; P = 0.001] and cumulative exposure ≥ 1 year to zidovudine (aHR = 2.3 vs. no exposure; P = 0.009) were associated with a higher risk of diabetes. Conversely, cumulative exposure ≥ 1 year to tenofovir (aHR = 0.4 vs. no exposure; P = 0.02) and emtricitabine (aHR = 0.4 vs. no exposure; P = 0.03) were associated with a lower risk. CONCLUSIONS: The incidence of diabetes in this predominantly female, young, lean population was relatively low. Although stavudine and didanosine have now been phased out in most antiretroviral therapy programs, our analysis suggests a higher risk of diabetes with zidovudine, frequently prescribed today in resource-limited settings.
BACKGROUND: Use of several antiretrovirals (ARVs) has been shown to be associated with a higher risk of diabetes in HIV-infected adults. We estimated the incidence of new-onset diabetes and assessed the association between individual ARVs and ARV combinations, and diabetes in a large cohort in Thailand. METHODS: We selected all HIV-1-infected, nondiabetic, antiretroviral-naive adults enrolled in the Program for HIV Prevention and Treatment cohort (NCT00433030) between January 2000 and December 2011. Diabetes was defined as confirmed fasting plasma glucose ≥ 126 mg/dL or random plasma glucose ≥ 2 00 mg/dL. Incidence was the number of cases divided by the total number of person-years of follow-up. Association between ARVs and ARV combinations, and new-onset diabetes was assessed using Cox proportional hazards models. RESULTS: Overall, 1594 HIV-infectedpatients (76% female) were included. Median age at antiretroviral therapy initiation was 32.5 years. The incidence rate of diabetes was 5.0 per 1000 person-years of follow-up (95% confidence interval: 3.8 to 6.6) (53 cases). In analyses adjusted for potential confounders, exposure to stavudine + didanosine [adjusted hazard ratio (aHR) = 3.9; P = 0.001] and cumulative exposure ≥ 1 year to zidovudine (aHR = 2.3 vs. no exposure; P = 0.009) were associated with a higher risk of diabetes. Conversely, cumulative exposure ≥ 1 year to tenofovir (aHR = 0.4 vs. no exposure; P = 0.02) and emtricitabine (aHR = 0.4 vs. no exposure; P = 0.03) were associated with a lower risk. CONCLUSIONS: The incidence of diabetes in this predominantly female, young, lean population was relatively low. Although stavudine and didanosine have now been phased out in most antiretroviral therapy programs, our analysis suggests a higher risk of diabetes with zidovudine, frequently prescribed today in resource-limited settings.
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