4.1 Article

Short-term weight gain after antiretroviral therapy initiation and subsequent risk of cardiovascular disease and diabetes: the D:A:D study

Journal

HIV MEDICINE
Volume 17, Issue 4, Pages 255-268

Publisher

WILEY-BLACKWELL
DOI: 10.1111/hiv.12294

Keywords

body mass index; cardiovascular diseases; diabetes; highly active antiretroviral therapy; HIV; inflammation; myocardial infarction; weight gain

Funding

  1. Highly Active Antiretroviral Therapy Oversight Committee (HAART-OC)
  2. European Agency for the Evaluation of Medicinal Products
  3. United States Food and Drug Administration
  4. Health Insurance Fund Council, Amstelveen, the Netherlands [CURE/97-46486]
  5. Agence Nationale de Recherches sur le SIDA [7]
  6. Foundation for AIDS Research, amfAR
  7. US National Institutes of Health's National Institute of Allergy and Infectious Diseases (NIAID) [U01-AI069907]
  8. Merck Sharp Dohme
  9. Gilead Sciences
  10. Bristol-Myers Squibb
  11. Boehringer Ingelheim
  12. Roche
  13. Pfizer
  14. GlaxoSmithKline
  15. Janssen Pharmaceuticals
  16. Australian Government Department of Health and Ageing
  17. Fondo de Investigacion Sanitaria [FIS 99/0887]
  18. Fundacion para la Investigacion y la Prevencion del SIDA en Espana [FIPSE 3171/00]
  19. National Institute of Allergy and Infectious Diseases, National Institutes of Health [5U01AI042170-10, 5U01AI046362-03]
  20. BIOMED 1 programme [CT94-1637]
  21. BIOMED 2 programme [CT97-2713]
  22. European Commission [QLK2-2000-00773]
  23. AbbVie
  24. Swiss National Science Foundation [148522]

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ObjectivesThe aim of the study was to assess the impact of the gain in body mass index (BMI) observed immediately after antiretroviral therapy (ART) initiation on the subsequent risk of cardiovascular disease (CVD) and diabetes. MethodsWe analysed data from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cohort study. Outcomes were development of (i) CVD (composite of myocardial infarction/stroke/coronary procedure) and (ii) diabetes. The main exposure variable was change in BMI from ART initiation (pre-ART) to 1 year after initiation (continuous variable) in treatment-naive individuals initiating ART with no history of CVD or diabetes (for respective outcomes). BMI [weight (kg)/(height (m))(2)] was categorized as underweight (<18.5), normal (18.5-25), overweight (25-30) and obese (>30). Poisson regression models were fitted stratified for each pre-ART BMI category to allow for category-specific estimates of incidence rate ratio (IRR). Models were adjusted for pre-ART BMI and CD4 count, key known risk factors (time-updated where possible) and calendar year. ResultsA total of 97 CVD events occurred in 43982 person-years (n=9321) and 125 diabetes events in 43278 person-years (n=9193). In fully adjusted analyses for CVD, the IRR/unit gain in BMI (95% confidence interval) in the first year of ART, by pre-ART BMI category, was: underweight, 0.90 (0.60-1.37); normal, 1.18 (1.05-1.33); overweight, 0.87 (0.70-1.10), and obese, 0.95 (0.71-1.28) (P for interaction=0.04). For diabetes, the IRR/unit gain in BMI was 1.11 (95% confidence interval 1.03 to 1.21), regardless of pre-ART BMI (P for interaction>0.05). ConclusionsShort-term gain in BMI following ART initiation appeared to increase the longer term risk of CVD, but only in those with pre-ART BMI in the normal range. It was also associated with increased risk of diabetes regardless of pre-ART BMI.

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