Excess weight gain with integrase inhibitors and tenofovir alafenamide: what is the mechanism and does it matter?

Numerous studies have detected a greater likelihood of excess weight gain with specific antiretrovirals (ARV’s), particularly tenofovir alafenamide and integrase inhibitors, as compared to other agents and classes. The long-term implications and potential reversibility for individuals who have experienced substantial ARV-associated weight accumulation remain poorly understood. Furthermore, the underlying mechanism remains controversial: is the explanation mitochondrial toxicity and weight suppression from the older agents or direct effects of the newer drugs on appetite, adipocytes, or other unintended targets? This review discusses proposed mechanisms and evidence to date and argues that the question about mechanism is highly clinically relevant because it carries significant implications for ARV management. The existing literature suggests that older ARV’s, such as tenofovir disoproxil fumarate and efavirenz, suppress weight gain, but also that integrase inhibitors may stimulate excess weight gain through several pausible biologic pathways. Confirming the mechanisms of ARV-associated excess weight gain should be high priority for future research.

Traditional versus developmental measures of weight suppression: Exploring their relationships with bulimic psychopathology

Objective: Weight suppression (WS) is related to a wide variety of eating disorder characteristics. However, individuals with eating disorders usually reach their highest premorbid weight while still developing physically. Therefore, a more sensitive index of individual differences in highest premorbid weight may be one that compares highest premorbid z-BMI to current z-BMI (called developmental weight suppression (DWS) here). Method: We compared the relationships between traditional weight suppression (TWS) and DWS and a wide variety of measures related to bulimic psychopathology in 91 females (M age, 25.2; 60.5% White), with clinical or sub-clinical bulimia nervosa. Results: TWS and DWS were correlated (r = .40). TWS was significantly related to only one of 23 outcome variables whereas DWS showed significant or near-significant relationships to 14 outcomes. DWS showed consistent positive relations with behavioral outcomes (e.g., binge eating) but consistent negative relations with cognitive/affective outcomes (e.g., weight concerns). Conclusions: Findings indicated a much more consistent relationship between the novel DWS measure and bulimic characteristics than with the traditional weight suppression measure. DWS showed both positive and negative relations with bulimic symptoms, though these findings require replication to confirm their validity. Consistent evidence indicated that the two WS measures served as mutual suppressor variables.

Lifetime Weight Characteristics of Adult Inpatients With Severe Anorexia Nervosa: Maximal Lifetime BMI Predicts Treatment Outcome

Background: The body mass index is a key predictor of treatment outcome in patients with anorexia nervosa. In adolescents, higher premorbid BMI is a strong predictor of a favorable treatment outcome. It is unclear whether this relationship holds true for adults with anorexia nervosa. Here, we examine adult patients with AN and investigate the lowest and highest lifetime BMI and weight suppression as predisposing factors for treatment outcome.Methods: We included 107 patients aged 17–56 with anorexia nervosa and tracked their BMI from admission to inpatient treatment, through discharge, to follow-up at 1–6 years. Illness history, including lowest and highest lifetime BMI were assessed prior to admission. We used multiple linear regression models with minimal or maximal lifetime BMI or weight suppression at admission as independent variables to predict BMI at admission, discharge and follow-up, while controlling for patients' age, sex, and duration of illness.Results: Low minimal BMI had a negative influence on the weight at admission, which in turn resulted in a lower BMI at discharge. Higher maximal BMI had a substantial positive influence on BMI at discharge and follow-up. Weight suppression was highly correlated with maximal BMI and showed similar effects to maximal BMI.Conclusion: Our findings strongly support a relationship between low minimal lifetime BMI and lower BMI at admission, and between higher maximal lifetime BMI or weight suppression and a positive treatment outcome, even years after discharge. Overall, maximal BMI emerged as the most important factor in predicting the weight course in adults with AN.

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Background: The body mass index is a key predictor of treatment outcome in patients with anorexia nervosa. In adolescents, higher premorbid BMI is a strong predictor of a favourable treatment outcome. It is unclear whether this relationship holds true for adults with anorexia nervosa. Here, we examine adult patients with AN and investigate the lowest and highest lifetime BMI and weight suppression as predisposing factors for treatment outcome.Methods: We included 107 patients aged 17-56 with anorexia nervosa and tracked their BMI from admission to inpatient treatment, through discharge, to follow-up at 1-6 years. Illness history, including lowest and highest lifetime BMI were assessed prior to admission. We used multiple linear regression models with minimal or maximal lifetime BMI or weight suppression at admission as independent variables to predict BMI at admission, discharge and follow-up, while controlling for patients’ age, sex, and duration of illness. Results: Low minimal BMI had a negative influence on the weight at admission, which in turn resulted in a lower BMI at discharge. Higher maximal BMI had a substantial positive influence on BMI at discharge and follow-up. Weight suppression was highly correlated with maximal BMI and showed similar effects to maximal BMI.Conclusion: Our findings strongly support a relationship between low minimal lifetime BMI and lower BMI at admission, and between higher maximal lifetime BMI or weight suppression and a positive treatment outcome, even years after discharge. Overall, maximal BMI emerged as the most important factor in predicting the weight course in adults with AN.

Can adolescents with eating disorders be treated in primary care? A retrospective clinical cohort study

Background Family-Based Treatment (FBT) is considered the first-line intervention for adolescent anorexia nervosa. However, access to this treatment is limited. Treatment programs for other pediatric mental health conditions have successfully overcome barriers to accessing evidence-based intervention by integrating mental health services into primary care. This study evaluated the proof-of-concept of a novel modification of FBT, Family-Based Treatment for Primary Care (FBT-PC) for adolescent restrictive eating disorders designed for delivery by primary care providers in their practices. Methods This retrospective clinical cohort study evaluated 15 adolescents with restrictive eating disorders receiving FBT-PC and 15 adolescents receiving standard FBT. We examined improvement in BMI percentile, reduction in weight suppression, and clinical benchmarks of eating disorder recovery including weight restoration to > 95% of expected body weight (EBW) and resolution of DSM-5 criteria for eating disorders. Results In both groups, effect sizes for increased BMI percentile exceeded Cohen’s convention for a large effect (FBT-PC: d = .94; standard FBT: d = 1.15) as did effect sizes for reduction in weight suppression (FBT-PC: d = 1.83; standard FBT: d = 1.21). At the end of treatment, 80% of the FBT-PC cohort and 87% in the standard FBT group achieved > 95%EBW and 67% in the FBT-PC group and 60% in the standard FBT group no longer met DSM-5 criteria for an eating disorder. There were no cohort differences in the number of treatment drop-outs or referrals to a more intensive level of eating disorder treatment. Conclusions Findings suggest that primary care providers have potential to improve weight and clinical status in adolescents with restrictive eating disorders. Based on these results, more rigorous testing of the FBT-PC model is warranted.