Contemporary antiretrovirals and body-mass index: a prospective study of the RESPOND cohort consortium

Bansi‐Matharu, Loveleen; Phillips, Andrew; Oprea, Cristiana; Grabmeier‐Pfistershammer, Katharina; Günthard, Huldrych F.; Wit, Stéphane De; Guaraldi, Giovanni; Vehreschild, Jörg Janne; Wit, Ferdinand W. N. M.; Law, Matthew; Wasmuth, Jan‐Christian; Chkhartishvili, Nikoloz; Monforte, Antonella d’Arminio; Fontas, Éric; Vesterbacka, Jan; Miró, José M.; Castagna, Antonella; Stephan, Christoph; Llibre, Josep M; Neesgaard, Bastian; Greenberg, Lauren; Smith, Colette; Kirk, Ole; Duvivier, Claudine; Dragović, Gordana; Lundgren, Jens D; Dedes, Nikos; Knudsen, Andreas Dehlbæk; Gallant, Joel E.; Vannappagari, Vani; Peters, Lars; Elbirt, Daniel; Sarcletti, Mario; Braun, Dominique L; Necsoi, Coca; Mussini, Cristina; Muccini, Camilla; Bolokadze, Natalia; Hoy, Jennifer; Mocroft, Amanda; Ryom, Lene

doi:10.1016/s2352-3018(21)00163-6

Cited by 39 publications

(30 citation statements)

References 26 publications

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“…In line with results from a number of other studies [ 8 , 10 , 11 , 15 ], Western and sub-Saharan African females, those younger than 40 years, and those previously losing weight had a significantly higher risk of ≥10% weight gain after switch to either TAF, INSTI, or both. Moreover, those discontinuing EFV (which was the case for approximately one-third of participants starting an INSTI) were at increased risk of ≥10% weight gain after switch to INSTI or TAF + INSTI.…”

Section: Discussionsupporting

confidence: 87%

“…There may also be a subset of individuals prone to gaining more extreme amounts of weight when exposed to TAF and/or an INSTI, and who may possibly suffer greater metabolic consequences. Studies examining weight gains of more than 7% or 10%, for example, have not all been restricted to virally suppressed individuals [ 7 , 8 , 15 ] or to those being exposed to only TAF, only an INSTI and both simultaneously [ 10 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

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One in 10 Virally Suppressed Persons With HIV in The Netherlands Experiences ≥10% Weight Gain After Switching to Tenofovir Alafenamide and/or Integrase Strand Transfer Inhibitor

Verburgh

Wit

Boyd

et al. 2022

Open Forum Infectious Diseases

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Background We determined the frequency of and factors associated with ≥10% weight gain and its metabolic effects in virally suppressed people with HIV (PWH) from the Dutch national ATHENA cohort switching to TAF and/or INSTI. Methods We identified ART-experienced, but TAF/INSTI-naïve PWH, who switched to a TAF and/or INSTI-containing regimen whilst virally suppressed for >12 months. Individuals with comorbidities/co-medication associated with weight change were excluded. Analyses were stratified by switch to only TAF, only INSTI or combined TAF + INSTI. Factors associated with ≥10% weight gain were assessed using parametric survival models. Changes in glucose, lipids and blood pressure post-switch were modelled using mixed-effect linear regression and compared between those with and without ≥10% weight gain. Results Among 1,544 PWH who switched to only TAF, 2,629 to only INSTI and 918 to combined TAF + INSTI, ≥10% weight gain was observed in 8.8%, 10.6% and 14.4%, respectively. Across these groups, weight gain was more frequent in Western and Sub-Saharan African females than Western males. Weight gain was also more frequent in those with weight loss ≥1 kg/yr before switching, age < 40 years, and those discontinuing efavirenz. In those with ≥10% weight gain, 53.7% remained in the same BMI category, whilst a BMI change from normal/overweight at baseline to obesity at 24 months post-switch was seen in 13.9%, 11.7% and 15.2% of those switching to only TAF, only INSTI and combined TAF + INSTI respectively. PWH with ≥10% weight gain showed significantly larger, but small increases in glucose, blood pressure and lipid levels. Lipid increases were limited to those whose switch included TAF, whereas lipids decreased after switching to only INSTI. Conclusions Weight gain of ≥10% after switch to TAF and/or INSTI was common in virally suppressed PWH, particularly in females and those starting both drugs simultaneously. Consequent changes in metabolic parameters were however modest.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

One in 10 Virally Suppressed Persons With HIV in The Netherlands Experiences ≥10% Weight Gain After Switching to Tenofovir Alafenamide and/or Integrase Strand Transfer Inhibitor

Verburgh

Wit

Boyd

et al. 2022

Open Forum Infectious Diseases

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“…Prevalence of obesity has been increasing in PWH [5,6,32,33], and may be linked to high fat diets, limited exercise, changing demographics in an ageing population, and potentially an effect of newer antiretroviral agents [5][6][7][8][9][10][11][12][13][14][15][16]. Our data showed an overall increase of overweight individuals and obesity by 2019 of 8.2% and 4.8%, respectively.…”

Section: Discussionmentioning

confidence: 88%

Changes in body mass index and clinical outcomes after initiation of contemporary antiretroviral regimens

Mast

Wit

Gerstoft

et al. 2022

Aids

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Background: Weight gain is becoming increasingly prevalent amongst people with HIV (PWH) receiving contemporary antiretroviral treatment. We investigated BMI changes and clinical impact in a large prospective observational study.Methods: PWH aged !18 years were included who started a new antiretroviral (baseline) during 2010-2019 with baseline and !1 follow-up BMI assessment available. Rates of clinical outcomes (cardiovascular disease [CVD], malignancies, diabetes mellitus [DM] and all-cause mortality) were analysed using Poisson regression to assess effect of time-updated BMI changes (>1 kg/m 2 decrease, AE1 kg/m 2 stable, >1 kg/m 2 increase), lagged by 1-year to reduce reverse causality. Analyses were adjusted for baseline BMI plus key confounders including antiretroviral exposure.Results: 6721 PWH were included; 72.3% were male, median age 48 years (interquartile range [IQR] 40-55). At baseline, 8.4% were antiretroviral-naive, and 5.0% were underweight, 59.7% healthy weight, 27.5% overweight, and 7.8% were living with obesity. There was an 8.2% increase in proportion of overweight and 4.8% in obesity over the study period (median follow-up 4.4 years ).

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“…Over recent years there have been several analyses of observational cohorts and randomized controlled trials showing differential impact in weight gain with different combinations of antiretroviral therapy (ART). Integrase inhibitors, particularly DTG and bictegravir, and tenofovir alafenamide (TAF) have been particularly associated with higher weight increases and women, black individuals and older people appear to be particularly at risk of excessive weight gain (3)(4)(5). Because both excessive and insufficient body mass index (BMI) are associated with negative outcomes in the general (6) and HIV-infected (7) populations, understanding the real impact of different antiretrovirals on weight and the risk factors and possible mechanisms for ART-related weight change is of crucial importance.…”

Section: Introductionmentioning

confidence: 99%

Limited Weight Impact After Switching From Boosted Protease Inhibitors to Dolutegravir in Persons With Human Immunodeficiency Virus With High Cardiovascular Risk: A Post Hoc Analysis of the 96-Week NEAT-022 Randomized Trial

Waters

Assoumou

González-Cordón

et al. 2022

Clinical Infectious Diseases

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Background In the NEAT022 trial, virologically suppressed persons with HIV at high cardiovascular risk switching from protease inhibitors to dolutegravir either immediately (DTG-I) or after 48 weeks (DTG-D) showed non-inferior virological suppression and significant lipid and CVD risk reductions on switching to dolutegravir relative to continuing protease inhibitors. Methods Post-hoc analysis. Major endpoints were 48-week and 96-week weight and body mass index (BMI) changes. Factors associated with weight/BMI changes within the first 48 weeks of DTG exposure, proportion of participants by category of percent weight change, proportions of BMI categories over time, and impact on metabolic outcomes were also assessed. Results Between May/2014 and November/2015, 204 (DTG-I) and 208 (DTG-D) participants were included. Weight significantly increased (mean +0.810 kg DTG-I arm, and +0.979 kg DTG-D arm) in the first 48 weeks post-switch, but remained stable from 48 to 96 weeks in DTG-I arm. Switching from darunavir, white race, total-to-HDL cholesterol ratio <3.7, and normal/underweight BMI were independently associated with higher weight/BMI gains. The proportion of participants with ≥5% weight change increased similarly in both arms over time. The proportions of BMI categories, use of lipid-lowering drugs, diabetes and/or use of antidiabetic agents, and hypertension and/or use of antihypertensive agents did not change within or between arms at 48 and 96 weeks. Conclusions Switching from protease inhibitors to dolutegravir in persons with HIV with high cardiovascular risk led to modest weight gain limited to the first 48 weeks which involved preferentially normal-weight or underweight persons and was not associated with negative metabolic outcomes.

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Contemporary antiretrovirals and body-mass index: a prospective study of the RESPOND cohort consortium

Cited by 39 publications

References 26 publications

One in 10 Virally Suppressed Persons With HIV in The Netherlands Experiences ≥10% Weight Gain After Switching to Tenofovir Alafenamide and/or Integrase Strand Transfer Inhibitor

One in 10 Virally Suppressed Persons With HIV in The Netherlands Experiences ≥10% Weight Gain After Switching to Tenofovir Alafenamide and/or Integrase Strand Transfer Inhibitor

Changes in body mass index and clinical outcomes after initiation of contemporary antiretroviral regimens

Limited Weight Impact After Switching From Boosted Protease Inhibitors to Dolutegravir in Persons With Human Immunodeficiency Virus With High Cardiovascular Risk: A Post Hoc Analysis of the 96-Week NEAT-022 Randomized Trial

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