Metabolic Changes Associated With the Use of Integrase Strand Transfer Inhibitors Among Virally Controlled Women

Abstract

Background: Integrase strand transfer inhibitors (INSTIs) have been associated with weight gain among women living with HIV. We aimed to investigate the association between INSTIs and change in cardiometabolic risk indicators. Setting: Retrospective cohort. Methods: Data from 2006 to 2017 were analyzed from women living with HIV enrolled in the longitudinal Women's Interagency HIV Study who were virally controlled on antiretroviral therapy (ART) for ≥5 consecutive semiannual visits. Women who switched/added an INSTI to ART (INSTI group) were compared with women who remained on non-INSTI ART (non-INSTI group). Outcomes included changes in fasting lipids and glucose, hemoglobin A1c (HbA1c), blood pressure (BP), and incident diabetes, hypertension, and insulin resistance. Outcomes were measured 6–12 months before and 6–18 months after INSTI switch/add in the INSTI group with comparable visits in the non-INSTI group. Longitudinal linear regression models compared change over time in each outcome by the study group. Results: One thousand one hundred eighteen participants (234 INSTI, 884 non-INSTI) were followed for a median 2.0 (Q1 1.9, Q3 2.0) years. Participants were median age 49 years, 61% Black, and 73% overweight or obese (body mass index ≥25 kg/m2). Compared with non-INSTI, the INSTI group experienced greater increases in HbA1c (+0.05 vs. −0.06 mg/dL, P = 0.0318), systolic BP (+3.84 vs. +0.84 mm Hg, P = 0.0191), and diastolic BP (+1.62 vs. −0.14 mm Hg, P = 0.0121), with greatest change in HbA1c among women on INSTIs with ≥5% weight gain. Conclusions: INSTI use was associated with unfavorable changes in HbA1c and systolic and diastolic BP during short-term follow-up. Further research is needed to understand long-term cardiometabolic effects of INSTI use.

Assessment of Obesity and Cardiometabolic Status by Integrase Inhibitor Use in REPRIEVE: A Propensity-Weighted Analysis of a Multinational Primary Cardiovascular Prevention Cohort of People With Human Immunodeficiency Virus

“…However, this prior analysis did not have a non-INSTI comparator group and was restricted to sub-Saharan Africa where obesity and diabetes rates are on the rise among the general population [ 6 , 22 ]; therefore, one cannot attribute the increased risk seen in this population solely to INSTI use. An analysis of the WIHS cohort showed slight increases in HbA1c (+0.05 vs −0.06) and blood pressure compared with non-INSTI users [ 23 ]. More importantly, however, the WIHS study enrolled only women in the United States and included a significant percentage of PWH with diabetes, all of whom were studied before 2017.…”

Antiretroviral Therapy Switch Rates and Switching Patterns in 16,069 People Living With HIV: A Nationwide, Population-Based Study in Japan

“…22 Switching regimens appears to be more stable in virologically suppressed HIV-1-infected patients who receive INSTI-based regimens initially. 21,24 Other possible explanations suggested for increased switching include the expansion of HIV/AIDS treatment programs in middle-income or resource-limited areas. 25 In addition, HIV-infected patients are more likely to be younger, less educated, and to have detectable HIV-1 DNA when switching to a secondline cART regimen, which may predispose to worse outcomes.…”

Recent data on adipose tissue, insulin resistance, diabetes and dyslipidaemia in antiretroviral therapy controlled HIV-infected persons

“…Over 48 weeks, DTG/3TC treatment decreased TC, LDL-C and TG levels as compared to the TAF arm(30). The difference between the two arms could result from the INSTI, cobicistat or TAF use.In the WIHS, comparing women switched or not to an INSTI, HDL-C level was decreased only in those INSTI-treated and gaining ≥5% weight, stressing weight-related rather than INSTIrelated changes(38).…”