980. Effects of Integrase Strand-Transfer Inhibitor Use on Lipids, Glycemic Control, and Insulin Resistance in the Women’s Interagency HIV Study (WIHS)

Abstract

BackgroundIntegrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) is recommended first-line HIV treatment. We recently demonstrated increased weight gain associated with INSTI use among women living with HIV (WLH) enrolled in the Women’s Interagency HIV Study (WIHS), raising concern for cardiometabolic consequences. We, therefore, evaluated the effects of INSTI use on lipids, insulin resistance, and glycemic control in WLH.MethodsData from 2008 to 2017 were analyzed from WLH enrolled in WIHS. Women who switched to or added an INSTI to ART (SWAD group) were compared with women who remained on non-INSTI ART (STAY group). Outcomes included changes in fasting total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), and glucose; hemoglobin A1c; and incident insulin resistance (defined as homeostatic model assessment of insulin resistance [HOMA] score ≥2). Outcomes were measured 6–12 months before and 6–18 months after INSTI switch/add in the SWAD group with comparable time points in the STAY group. Linear regression models compared change over time in each outcome by SWAD/STAY group, adjusted for age, race, WIHS site, income, smoking status, statin use, and ART regimen at baseline.ResultsIn total, 881 WIHS participants (182 SWAD and 699 STAY) were followed for a mean 1.8 (±1.1) years. Mean age was 49 (±8.8) years, BMI was 31 (±8.2) kg/m2, and 49% were Black. At baseline, SWAD vs. STAY was more likely to report NNRTI (vs. PI)-based ART and statin use (both P < 0.0001), but all baseline lipid and glucose variables were similar. Compared with STAY, the SWAD group experienced significantly greater decreases in HDL (−2.4 vs. +0.09 mg/dL, P = 0.03) and trended toward greater decreases in TC (−2.6 vs. −2.4 mg/dL, P = 0.07) at follow-up, without significant differences in TG or LDL. The SWAD group had significantly greater increases in A1c (+0.08% vs. −0.05%, P = 0.01) but trended toward lower incidence of insulin resistance (19% vs. 32%, P = 0.05).ConclusionDespite reported increases in weight, INSTI use was associated with only modest changes in lipid measurements and glycemic control during short-term follow-up of WLH compared with non-INSTI ART. Research is needed to elucidate long-term cardiometabolic effects. DisclosuresAnandi N. Sheth, MD, MS, Gilead Sciences, Inc.: Research Grant.

Blood glucose level and serum lipid profiles among people living with HIV on dolutegravir-based versus efavirenz-based cART; a comparative cross-sectional study

“…In addition, this study revealed that there were statistically insignificant differences in the mean values of LDL-C and median values of TG between two groups. This is supported by the result of the previous study [ 39 ]. Furthermore, a statistically insignificant difference between the two groups was also observed in the median TC/HDL-C ratios.…”

The effect of a treatment switch to integrase Strand transfer inhibitor–based regimens on weight gain and other metabolic syndrome-related conditions

“…The only metabolic effect observed in our cohort other than weight gain was an increase in glucose levels following a switch from NNRTIs or PIs to INSTI, solely in the subgroup of African descendant males. Similarly to others [ 30 ], we did not identify a worsening of other metabolic parameters such as hypertension or dyslipidemia, following the treatment switch.…”

Implications of weight gain with newer anti-retrovirals: 10-year predictions of cardiovascular disease and diabetes

“…Emerging evidence links weight gain with INSTIs and T2DM. When switching to INSTIs, HbA1c has been found to be raised in the INSTI group vs. the non-INSTI group [44,45]. In another cohort study, participants initiating INSTIs (in particular raltegravir) were more likely to develop T2DM compared with NNRTIs [46].…”