CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Methods: In a sub-cohort of HIV-infected individuals participating in the Hawaii Aging with HIV Cohort (≥40 years of age and on stable antiretroviral therapy for > 3 months) without diagnosis of DM at baseline and with availability of two year longitudinal data, we analyzed the correlation between various plasma biomarkers including TNF-α, VEGF, MCP-1, IL-8, IL-6, PAI-1, IFN-y, CRP, SAA, MPO, MMP-9, sVCAM-1, sICAM-1, and sE-Selectin at baseline and whole body insulin sensitivity as measured by the Matsuda Index at baseline and at the two-year follow-up visit. Matsuda Index utilizes the mean plasma glucose and insulin concentration during a two-hour oral glucose tolerance test and provides a dynamic assessment of whole body insulin sensitivity rather than a static assessment such as homeostatic model assessment-2 (HOMA2) utilizing fasting glucose and insulin. Results: 62 subjects: 90.3%male, median age 51 (Q1, Q3; 46,56) years, median glucose and insulin during OGTT 117.81(99.75,141.91) mg/dl and 53.77(38.58,71.44) mg/dl, median BMI 26.07 (24046, 27.81) kg/m2, median CD4 count 513 (362,713) cells/mm3, and 69%with HIV RNA<50 copies/mL. We found a negative correlation between PAI-1 and baseline Matsuda Index (r = -.435 , p = .001) and a negative correlation with PAI-1 and Matsuda Index at two-year follow-up (r = -.377 , p = .005). In a linear regression model that included age, total body fat mass percentage, serum amyloid A (SAA) and family history of diabetes mellitus, PAI-1 still remained associated with Matsuda Index at two-year follow-up (r = -.409, p = .002). Conclusion: Plasminogen activator inhibitor type 1 (PAI-1), a key negative regulator of fibrinolysis, has been widely investigated to be a potential predictor of the development of IR and DM in non-HIV-infected individuals. Our results suggest that PAI-1 may be a particularly strong predictor of insulin resistance among chronically stable HIV-infected individuals, which is independent of age and body fat composition, 2 major traditional risk factors for IR.

Poster and Themed Discussion Abstracts

693 BODY MASS INDEX AND THE RISK OF SERIOUS NON-AIDS EVENTS: THE D:A:D STUDY Amit C. Achhra 1 , Caroline Sabin 2 , Lene Ryom 3 , Antonella d’Arminio Monforte 4 , Stephane de Wit 5 , Andrew Phillips 2 , Christian Pradier 6 , Jens D. Lundgren 7 , Matthew Law 1 , for the DAD Study Group 1 Kirby Inst, Sydney, Australia, 2 Univ Coll London, London, UK, 3 CHIP, Copenhagen, Denmark, 4 Univ of Milan, Milan, Italy, 5 Univ Libre de Bruxelles, Brussels, Belgium, 6 Nice Univ Hosp, Nice, France, 7 Univ of Copenhagen, Copenhagen, Denmark Background: Body mass index (BMI) (weight (kg)/ height(m2)) is a potentially modifiable risk factor for several serious non-AIDS events (SNAEs). However the relationship between BMI and SNAEs in HIV-positive individuals in not well understood. Methods: We followed D:A:D study participants on antiretroviral therapy from their first BMI measurement to the first occurrence of a SNAE or 1/2/2014. The SNAEs of interest, all well-adjudicated, were cardiovascular disease (CVD- composite of myocardial infarction/stroke/invasive cardiovascular procedures); diabetes; non-AIDS-defining malignancies (NADM); BMI-associated cancers (composite of malignancies known to be associated with BMI in general population, including esophagus, pancreas, colon, rectum, breast, endometrium, kidney, thyroid and gallbladder); and all-cause mortality. BMI was time-updated and lagged by 1 year (i.e. there was at least 1 year time-gap between last BMI measurement and a SNAE, so as to minimize bias from reverse causation) and categorised at clinical cut-offs: 18.5, 23, 25, 27.5 and 30 kg/m2. Poisson regression models adjusted for key confounders for each SNAE were used. Results: During 295,147 person-years of follow-up (PYFU) in 41,149 included individuals, incidence/1000 PYFU of outcomes were: CVD (n=1398): 4.8; diabetes (n=3025): 10.2; NADM (n=1143): 3.9; BMI-cancers (n=184): 0.6 and all-cause mortality (n=3025): 10.2. Participants were largely male (73%) with baseline mean age of 40 years and baseline median BMI of 23.3 (IQR: 21.2- 25.7). A majority of follow-up was in BMI categories of 18.5-23 (41%), 23-25 (22%) and 25-27.5 (17%). Overall, BMI showed a statistically significant J-shaped relationship with the risk of all outcomes except diabetes (Table). There was a higher risk of CVD, NADM, and all-cause mortality at BMI levels <18.5 and at 18.5-23 (especially for NADM and all-cause mortality), compared to the BMI at 23-25. High BMI (>30), compared to that at 23-25, was associated with the higher relative risk of CVD, diabetes, BMI-cancers and possibly all-cause mortality. For diabetes, there was a linear increase in risk with increasing BMI. Results were not sensitive to lagging latest BMI by 2 years (data not shown). Conclusion: We found that the low BMI, even at the levels of 18-23 and after being lagged by 1 year, was associated with higher short-term risk of CVD, NADM and all-cause mortality in this population. High BMI (>30) was a risk factor for CVD, diabetes, NADM and BMI-cancers. 694 RANDOMIZED TRIAL OF BEHAVIORAL WEIGHT LOSS FOR HIV-INFECTED PATIENTS Katie Becofsky 1 , Edward J. Wing 2 , Jeanne McCaffery 3 , Matthew Boudreau 3 , Rena R. Wing 3 1 Univ of Massachusetts Amherst, Amherst, MA, USA, 2 Brown Univ, Providence, RI, USA, 3 The Miriam Hosp, Providence, RI, USA Background: Obesity is increasingly prevalent in HIV-infected patients and compounds their cardiovascular disease (CVD) risk. Behavioral weight loss programs are recommended for overweight and obese individuals, but have not been systematically studied in people living with HIV. We conducted the first randomized trial testing the efficacy of an empirically validated behavioral weight loss program in HIV-infected patients.

CROI 2017 303