Study population and demographics:
The Copenhagen Comorbidity in HIV Infection (COCOMO) Study is a non-interventional cohort studythat included PLWH from the greater Copenhagen area. Inclusion criteria were a positive HIV test and age > 18 years. The procedures for recruitment and data collection have been described in detail elsewhere(13). Inclusion and baseline examinations took place from March 2015 to December 2016 where 1099 participants were included. Of these, 949 participants participated in the 2-year-follow-up examination which took place from April 2017 to April 2019. In the present study, we included well-treated participants at the 2-year-follow-up examinations with available fasting serum insulin and plasma glucose, current treatment with ART and HIV RNA < 50 copies/mL, and absence of co-infection with hepatitis B and C. In total 643 participants were included in the present study.
Hepatitis B virus co-infection was defined as positive hepatitis B virus surface antigen. Hepatitis C virus co-infection was defined as positive hepatitis C virus RNA.
Ethical approval was obtained by the Regional Ethics Committee of Copenhagen (H-8-2014-004). Written informed consent was obtained from all participants.
At the 2-year-follow-up, a physical exam including anthropometrics and blood pressure was performed by trained clinical staff and questionnaires were used to collect information regarding smoking, medical history, and medication. Fasting blood samples were collected and serum insulin, plasma glucose, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total cholesterol were measured. Fasting blood samples were collected after ≥8 hours of fasting. Data regarding HIV infection were obtained from a review of medical charts. Exposure to old generation ART was defined as ever use of thymidine analogues (zidovudine and stavudine) and/or didanosine.
Definition of clinical outcomes:
In accordance with the original homeostasis model assessment (HOMA), insulin resistance was calculated using the equation: fasting plasma glucose (mmol/L) x fasting serum insulin (mU/L)/ 22.5(14). Due to the lack of standardized cut-off value for insulin resistance(15), we defined high insulin resistance (high HOMA-IR) as the upper quartile of the HOMA insulin resistance index.
According to WHO guidelines, abdominal obesity was defined as waist-to-hip ratio (WHR) ≥0.9 for men and ≥0.85 for women and BMI was classified as <18.5 underweight, 18.5–24.99 normal weight, 25–29.99 overweight, and ≥30 kg/m2 obese(16).
We reported frequency counts and percentages for categorical data and continuous data with means and standard deviations for normal deviates and medians with interquartile ranges (IQR) for variables not normally distributed. Furthermore, we used χ2 test or Fisher’s test was used to compare categorical data between groups, and T-test or Mann–Whitney U test to compare continuous data between groups.
We investigated the association between high HOMA-IR and traditional and HIV-specific risk factors using a logistic regression model adjusted for age, sex, BMI category, smoking status (previous/current/never smoker), and origin. Traditional risk factors were included in the adjusted model. Additionally, we tested the association between abdominal obesity and insulin resistance by adding abdominal obesity to the predefined model. Furthermore, HIV-specific risk factors (CD4+, CD4+/CD8+-ratio, CD4+ nadir < 200, prior exposure to old generation ART and previous AIDS-defining conditions) were investigated by adding them to the model one at a time. When including exposure to old generation ART in the model, we also adjusted for time with HIV.
A possible effect modification by prior exposure to old generation ART on the association between significant risk factors and high HOMA-IR was explored by adding an interaction term to the model.