Weight Gain: A Possible Side Effect of All Antiretrovirals

Taramasso, Lucia; Ricci, Elena; Menzaghi, Barbara; Orofino, Giancarlo; Passerini, Simone; Madeddu, Giordano; Cv, Martinelli; Gv, De Socio; Squillace, Nicola; Rusconi, Stefano; Bonfanti, Paolo; Biagio, Antonio Di

doi:10.1093/ofid/ofx239

Cited by 79 publications

(63 citation statements)

References 14 publications

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“…Several studies have reported an increasing prevalence of being overweight and obese in PWH, and have demonstrated that weight gain occurs in many PWH after initiating antiretroviral therapy (ART) [1][2][3][4]. Factors associated with weight gain in PWH include demographic factors (such as sex and race), HIV disease-related factors (such as disease stage and viral load), and ART-associated factors (specific antiretroviral drugs) [2,3,[5][6][7][8][9]. These observations have led to several non-exclusive mechanistic hypotheses for ART-associated weight gain, including a mirroring of societal trends, a return-to-health effect of ART, improved tolerability of ART regimens, and off-target effects of antiretroviral drugs.…”

Section: Introductionmentioning

confidence: 99%

Lack of an association between clinical INSTI-related body weight gain and direct interference with MC4 receptor (MC4R), a key central regulator of body weight

et al. 2020

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An increasing prevalence of overweight and obesity in people living with HIV has been associated with initiation of antiretroviral therapy with integrase strand transfer inhibitors (INSTIs). An off-target inhibition of the endogenous ligand binding to the human melanocortin 4 receptor (MC4R) has been suggested as a potential mechanism for clinical body weight gain following initiation of dolutegravir, an INSTI. In this study, we interrogated several INSTIs for their capacity for antagonism or agonism of MC4R in an in vitro cell-based assays including at concentrations far exceeding plasma concentrations reached at the recommended dosages. Our results indicate that while INSTIs do exhibit the capacity to antagonize MC4R, this occurs at concentrations well above predicted clinical exposure and is thus an implausible explanation for INSTI-associated weight gain. OPEN ACCESS Citation: McMahon C, Trevaskis JL, Carter C, Holsapple K, White K, Das M, et al. (2020) Lack of an association between clinical INSTI-related body weight gain and direct interference with MC4 receptor (MC4R), a key central regulator of body weight. PLoS ONE 15(2): e0229617. https://doi.

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Section: Introductionmentioning

confidence: 99%

Lack of an association between clinical INSTI-related body weight gain and direct interference with MC4 receptor (MC4R), a key central regulator of body weight

et al. 2020

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“…Overweight/obesity has become more common [4,5]. Some experts considered this shi of HIV/AIDS clinical picture or the weight gain among PLWH as a side e ect of all ART regimens [6], while for others, it was considered to be an immunological response or a re ection of an increased CD4 cell count [7]. is is because of the substantial number of reports of associations between CD4 cell increase and weight gain [7,8].…”

Section: Introductionmentioning

confidence: 99%

Overweight and Obesity among Recipients of Antiretroviral Therapy at HIV Clinics in Gaborone, Botswana: Factors Associated with Change in Body Mass Index

Tshikuka

Magafu

Rankgoane-Pono

et al. 2020

AIDS Research and Treatment

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Background. Factors associated with overweight/obesity among antiretroviral therapy (ART) recipients have not been sufficiently studied in Botswana. Objectives. To: (i) estimate the prevalence and trends in overweight/obesity by duration of exposure to ART among recipients, (ii) assess changes in BMI categories among ART recipients between their first clinic visit (BMI-1) and their last clinic visit (BMI-2), (iii) identify ART regimen that predicts overweight/obesity better than the others and factors associated with BMI changes among ART recipients. Methods. A 12-year retrospective record-based review was conducted. Potential predictors of BMI change among patients after at least three years of ART exposure were examined using a multiple logistic regression model. Adjusted odds ratios (AOR) and their 95% confidence intervals (CIs) were computed. ART regimens, duration of exposure to ART, and recipients’ demographic and biomedical characteristics including the presence or absence of diabetes mellitus-related comorbidities (DRC), defined as any morbidity associated with type 2 diabetes as described in the international statistical classification of diseases and related health problems (ICD-10-CM) codebook index, were investigated as potential predictors of overweight/obesity. Results. Twenty-nine percent of recipients were overweight, 16.6% had obesity of whom 2.4% were morbidly-obese at the last clinic visit. Overweight/obese recipients were more likely to be female, to have DRC and less likely to have CD4 count between 201 and 249 cells/mm3. Neither the first-line nor the second-, third-line ART regimens predicted overweight/obesity better than the other and neither did the duration of exposure to ART. No significant linear trends were observed in the prevalence of overweight/obesity by the duration of exposure to ART. Conclusion. These results suggest that the ART regimens studied have a comparable effect on overweight/obesity and that the duration of exposure does not affect the outcome. This study calls for further research to elucidate the relative contribution of various factors to BMI change among recipients, including ART regimens.

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“…A discussion is currently ongoing about the role of integrase inhibitors in weight gain. Some authors report a significant weight gain in patients starting this class (15,16), although a similar effect could be observed in other classes (17), with differences existing between drugs from the same class. The effectiveness of cohort drugs in naïve patients, at least during the first year of treatment, was comparable.…”

Section: Discussionmentioning

confidence: 65%

I pazienti naive delle coorti SCOLTA: motivi di interruzione durante il primo anno di trattamento.

Ricci¹,

Al.²

2021

JHA

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Il progetto SCOLTA (Surveillance Cohort Long-term Toxicity Antiretrovirals) è un sistema di sorveglianza online degli eventi avversi dei farmaci antiretrovirali di recente commercializzazione. È uno studio di farmacovigilanza prospettico, multicentrico, che prevede una coorte di pazienti per ciascun nuovo farmaco. In questa analisi, sono stati inclusi tutti i pazienti naïve che hanno iniziato un trattamento di prima linea con lopinavir (LPV), atazanavir (ATZ), raltegravir (RTG), darunavir (DRV), rilpivirina (RPV), elvitegravir (EVG), e dolutegravir (DTG). Dal 2002, abbiamo incluso 697 pazienti naïve. Le caratteristiche basali dei pazienti erano diverse nelle diverse coorti, in termini sia epidemiologici che di variabili relative all’infezione. Utilizzando DTG come gruppo di riferimento, i pazienti in LPV avevano una probabilità maggiore di interrompere il trattamento durante il primo anno (HR 2.89, 95% CI 1.68-4.98, p=0.0001) e quelli in RPV una probabilità inferiore (HR 0.28, 95% CI 0.10-0.83, p=0.02). In tutte le coorti, i pazienti presentavano meno interruzioni rispetto a LPV, con differenza significativa per DRV, RPV, EVG e DTG. Colesterolo totale e HDL aumentavano in LPV, EVG e DTG, mentre in DRV oltre al colesterolo totale anche i trigliceridi presentavano un aumento significativo. La variazione del peso era positiva in tutte le coorti. I CD4 aumentavano significativamente in tutti i farmaci in studio, ma la soppressione virale a 6 mesi era meno frequente nelle coorti più vecchie. Questa analisi riflette la storia della terapia antiretrovirale di prima linea degli ultimi 20 anni. Nelle nostre coorti, abbiamo osservato che la durability aumenta nel tempo, in concomitanza con l’inizio del trattamento in pazienti con infezione meno avanzata e con la disponibilità di terapie antiretrovirali in combinazione più tollerabili.

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Weight Gain: A Possible Side Effect of All Antiretrovirals

Cited by 79 publications

References 14 publications

Lack of an association between clinical INSTI-related body weight gain and direct interference with MC4 receptor (MC4R), a key central regulator of body weight

Lack of an association between clinical INSTI-related body weight gain and direct interference with MC4 receptor (MC4R), a key central regulator of body weight

Overweight and Obesity among Recipients of Antiretroviral Therapy at HIV Clinics in Gaborone, Botswana: Factors Associated with Change in Body Mass Index

I pazienti naive delle coorti SCOLTA: motivi di interruzione durante il primo anno di trattamento.

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