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.

Trajectories of objectively measured physical activity and childhood overweight: longitudinal analysis of the IDEFICS/I.Family cohort

Background Since only few longitudinal studies with appropriate study designs investigated the relationship between objectively measured physical activity (PA) and overweight, the degree PA can prevent excess weight gain in children, remains unclear. Moreover, evidence is limited on how childhood overweight determines PA during childhood. Therefore, we analyzed longitudinal trajectories of objectively measured PA and their bi-directional association with weight trajectories of children at 2- and 6-year follow-ups. Methods Longitudinal data of three subsequent measurements from the IDEFICS/I.Family cohort study were used to analyze the bi-directional association between moderate-to-vigorous PA (MVPA) and weight status by means of multilevel regression models. Analyses comprised 3393 (2-year follow-up) and 1899 (6-year follow-up) children aged 2–15.9 years from eight European countries with valid accelerometer data and body mass index (BMI) measurements. For categorized analyses, children’s weight status was categorized as normal weight or overweight (cutoff: 90th percentile of BMI) and children’s PA as (in-) sufficiently active (cutoffs: 30, 45 and 60 min of MVPA per day). Results Children engaging in at least 60 min MVPA daily at baseline and follow-ups had a lower odds of becoming overweight (odds ratio [OR] at 2-year follow-up: 0.546, 95% CI: 0.378, 0.789 and 6-year follow-up: 0.393, 95% CI: 0.242, 0.638), compared to less active children. Similar associations were found for 45 min MVPA daily. On the other side, children who became overweight had the lowest odds to achieve 45 or 60 min MVPA daily (ORs: 0.459 to 0.634), compared to normal weight children. Conclusions Bi-directional associations between MVPA and weight status were observed. In summary, at least 60 min MVPA are still recommended for the prevention of childhood overweight. To prevent excess weight gain, 45 min MVPA per day also showed preventive effects.

REVIEW ON MEDOVAHASROTAS AND ITS MOOLSTHANA WITH REFERENCE TO OBESITY INDUCED HYPERTENSION

Excess weight gain, especially when associated with increased visceral adiposity, is a major cause of hypertension accounting 65-75% of total cases of hypertension. Increased renal tubular sodium reabsorption by the impairment in renal pressure natriuresis plays an important role in initiating obesity induced hypertension. The present study conceptually tries to substantiate the relation between moolasthana described for medovahasrotas with reference to the pathology of obesity induced hypertension. The moola explained for medovahasrotas are Kati, Vrikka, Vapavahana and Mamsa (Kidney, Suprarenal gland, Lumbosacral region, Superficial fat) which are the general regions of deposition of visceral fat or meda. The increased meda will hamper the renal pressure natriuresis in mainly three ways: 1)Physical compression of the kidneys by fat in and around kidney. 2)Increased activation of RAAS. 3)Increased SNS activity. Thus, medovaha srotodushti further enhances medodhatudushti (Obesity or Sthoulyata) itself, which in turn destroys the srotomoola. Hence, evidence of inherent relation among medovaha srotas and its respective srotomoola is established. Keywords: Medovahasrotas, Srotomoola, obesity induced hypertension

Prevalence of excess weight gain and associated risk factors among postmenopausal women: a population-based study in Ghana.

Background: Excess weight (obesity and overweight) is a pervasive condition that is considered a global epidemic and a threat to public health. Furthermore, numerous changes in fat deposits occur with the advent of menopause, leading to a change in the distribution of body fat. Therefore this study determined the prevalence of excess weight gain and associated risk factors among postmenopausal women (PW) in Ghana.Methods: This is a descriptive cross-sectional study conducted over five months at Bono-East regional capital, Techiman in Ghana. A total of 378 postmenopausal women were recruited for this study. Structured questionnaires were administered to obtain the socio-demographic data from each study participant. Anthropometrics such as body mass index (BMI), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) among participants were also determined. Data were inputted into excel, and analysis was done using IBM SPSS 25.Results: BMI, WHtR and WHR recorded participants with the excess weight of 73.2%, 91.8%, and 91.0% respectively out of the total study participants and there was no significant difference among the stratified study participants. Participants age ≤50 years were at a high risk of been obese even though it was not significant. Study participants with > 15 years of the postmenopausal stage have a high chance of been obese for BMI and WHtR but not WHR. The mean age of study participants was 60.09±6.24 years with the 51-60 years age group having the highest frequency (48.8%). Out of the total study participants, 26.8%, 8.2% and 9.0% with desirable weight were recorded using BMI, WHtR, and WHR respectively. And there was no significant difference (P=0.999) between the proportions for WHtR and WHR. However, the distribution of study participants with desirable weight by BMI was significantly higher than that of WHtR (P=0.0031) and WHR (P=0.0063). Conclusions: The prevalence rates of obesity and overweight were higher among postmenopausal women using the WHR than BMI and WHtR. Participants age ≤ 50 years, parity and those from the Ga tribe were also at a higher risk of having abdominal obesity.

A Pilot Feasibility Study of Interpersonal Psychotherapy for the Prevention of Excess Weight Gain Among Adolescent Military-dependent Girls

ABSTRACT Introduction Adolescent military-dependents face unique psychosocial stressors due to their parents’ careers, suggesting they may be particularly vulnerable to excess weight gain and symptoms of depression and anxiety. Despite these risk factors, there is a lack of tested preventative interventions for these youths. Given the transient nature of military family deployments, research may be hindered due to difficulty in collecting long-term prospective outcome data, particularly measured height and weight. The primary aim of this study was to examine the feasibility and acceptability of collecting body mass index (BMI, kg/m2) outcome data up to 2 years following a randomized controlled pilot trial of an adapted interpersonal psychotherapy (IPT) program aimed at preventing excess weight gain and improving psychological functioning for adolescent military-dependents. In exploratory analyses, patterns in body composition over time were examined. Materials and Methods Twenty-seven adolescent military-dependent girls (baseline: Mage: 14.4 ± 1.6 years; MBMI: 30.7 ± 4.9 kg/m2; MBMI-z: 1.9 ± 0.4) participated in this study. After a baseline assessment, utilizing a computerized program to create a randomization string, girls were assigned to either an IPT or a health education (HE) program. Participants completed three follow-up visits (posttreatment, 1-year follow-up, and 2-year follow-up). Girls completed a Treatment Acceptability Questionnaire at posttreatment; at all time points, height and fasting weight were collected. For the primary aim, Fisher’s exact tests examined the rate of obtained follow-up data and lost to follow-up status between the two groups, Mann-Whitney U tests examined the session attendance between groups, and treatment acceptability ratings were compared between the two groups at posttreatment using an independent samples t-test. For the exploratory aim, one-way analyses of covariance (ANCOVAs) examined the group differences in BMI at each time point, adjusting for baseline values, and paired samples t-tests examined the within-group differences at each time point relative to baseline. Using imputed data in the full intent-to-treat sample, mixed model ANCOVAs were conducted to examine the group differences over time. Results Across both groups, girls attended an average of 72.0% of sessions. At least partial data were collected at posttreatment, 1-year follow-up, and 2-year follow-up for 96.3%, 85.2%, and 74.1% of the participants, respectively. There were no significant group differences in follow-up data collection rates, follow-up status, number of sessions attended, or treatment acceptability. BMI-z stabilized across groups, and there were no group differences in BMI-z. In adjusted ANCOVA models with imputed data, no significant group-by-time effects emerged. Conclusions For this randomized controlled prevention trial, long-term outcome data collection of measured BMI was possible in adolescent military-dependents and IPT was an acceptable and feasible intervention. An adequately powered trial is required to assess the efficacy of this intervention among military-dependents for obesity prevention and improvements in BMI.