Modelling body mass index trajectory in HIV-infected individuals
Catalina Barceló (1), Monia Guidi (1,2), Thierry Buclin (1), Philip Tarr (3), Chantal Csajka (1,2) and the Swiss HIV Cohort Study
(1) University Hospital Centre of Lausanne, Switzerland, (2) School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Switzerland, (3) Infectious Diseases Service, Kantonsspital Baselland, University of Basel, Switzerland
Objectives: Weight gain is common following antiretroviral therapy (ART) initiation, especially during the first years, and might be associated with an increased risk of diabetes and cardiovascular disease1,2. The aims of this study were to develop a population model characterizing body mass index (BMI) evolution before and after ART initiation, and to quantify the relative contribution of demographic and clinical factors.
Methods: We included 1303 participants of the Swiss HIV Cohort Study who initiated ART after 2005. A piecewise-linear mixed-effects model was developed based on longitudinal BMI data covering a median of 10 (range 5 to 31) years of follow-up (NONMEM 7.3). The impact of different individual characteristics (age, gender, ethnicity, CD4 nadir, smoking and physical activity habits, educational degree and diabetes and HCV diagnostic) was tested using the linearized stepwise covariate model building combined with cross-validation (PsN 4.2).
Results: Baseline BMI (BMI0) with between-subject variability (BSV %CV) was 23.6 kg/m2 (13.7%). The final model included a pre-ART slope (SL0) of 0.1 kg/m2year (275%), a first post-ART slope for the first 2.5 years (SL1) of 0.2 kg/m2year (316%), and a second post-ART slope (SL2) of 0.1 kg/m2year (304%). A proportional error model with autocorrelation was used to describe residual variability. BMI0 was higher by 6% in Africans and 16% in diabetics, increasing by 0.03 kg/m2 per 10 additional years, while Asians had 9% lower BMI0. CD4 nadir <100 cells/μL decreased SL0, resulting in weight loss or stability, while a nadir <200 cells/μL increased SL1 by 1-fold. SL1 was zero in Hispanics and 84% higher in Africans compared to other ethnicities. HCV co-infection decreased SL2 by 74%.
Conclusions: Individual factors such as CD4 nadir and ethnicity have an important effect on weight gain following ART initiation. After a relatively steep slope during the first 2.5 years of ART, weight gain returns to an average level comparable with the general population, being lessened by HCV co-infection3. Such a model, further refined according to genetic markers and type of ART regimens, might inform metabolic risk factor management in the HIV-infected population.
References:
[1] Achhra AC, Mocroft A, Reiss P et al. Short-term weight gain after antiretroviral therapy initiation and subsequent risk of cardiovascular disease and diabetes: the D:A:D study. HIV Med 2016; 17: 255-68.
[2] Hasse B, Iff M, Ledergerber B et al. Obesity Trends and Body Mass Index Changes After Starting Antiretroviral Treatment: The Swiss HIV Cohort Study. Open Forum Infect Dis 2014; 1: ofu040.
[3] Collaboration NCDRF. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet 2016; 387: 1377-96.
