Are new antiretroviral treatments increasing the risks of clinical obesity?

Andrew Hill, Laura Waters, Anton Pozniak, Andrew Hill, Laura Waters, Anton Pozniak

Abstract

There is growing evidence that the use of integrase inhibitors could lead to statistically significant increases in body weight and even clinical obesity, although it is unclear whether these changes are clinically significant. The effects of integrase inhibitors on body weight need to be analysed for women and by race, because current evidence suggests different effects. Potential additional effects of NRTIs on body weight need to be evaluated. Combined, standardised analyses of Phase 3 and independent clinical trials, with endpoints following the US Food and Drug Administration (FDA) guidelines where feasible, should be conducted to answer this question definitively. Analyses should also include a range of laboratory markers of cardiovascular risk, as proposed by the FDA.

Keywords: antiretroviral therapy; bictegravir; dolutegravir; integrase inhibitors; obesity; raltegravir.

References

    1. Koethe J, Jenkins C, Lau B et al. . Rising obesity prevalence and weight gain among adults starting antiretroviral therapy in the United States and Canada. AIDS Res Hum Retroviruses 2016; 32: 50– 58.
    1. Bhaskaran K, Santos-Silva I, Leon D et al. . Association of BMI with overall and cause-specific mortality: a population-based cohort study of 3.6 million adults in the UK. Lancet Diabetes Endocrinol 2018; 6: 944– 995.
    1. Yuh B, Tate J, Butt AA et al. . Weight change after antiretroviral therapy and mortality. Clin Infect Dis 2015; 60: 1852– 1859.
    1. World Health Organization Overweight and obesity, key facts. Available at: ( accessed January 2019).
    1. Menard A, Meddeb L, Tissot-Dupont H et al. . Dolutegravir and weight gain: an unexpected bothering side-effect. AIDS 2017; 31: 1499– 1500.
    1. Norwood J, Turner C, Bofill C et al. . Brief report: weight gain in persons with HIV switched from efavirenz-based to integrase strand transfer inhibitor-based regimens. J Acquir Immune Defic Syndr 2017, 15: 527– 531.
    1. Bakal D, Coelho L, Luz P et al. . Obesity following ART initiation is common and influenced by both traditional and HIV-/ART-specific risk factors. J Antimicrob Chemother 2018; 73: 2177– 2185.
    1. Bedimo R, Adams-Huet B, Xilong L et al. . Integrase inhibitors-based HAART is associated with greater BMI gains in Blacks and Hispanics ID Week . November 2018. San Francisco, CA, USA: Abstract 538.
    1. Sculier D, Doco-Lecompte T, Yerly S et al. . Stable HIV-1 reservoirs on dolutegravir maintenance monotherapy: the MONODO study. HIV Med 2018; epub ahead of print.
    1. Bhagwat P, Ofotokun I, MComsey G et al. . Predictors of severe weight/body mass index gain following antiretroviral therapy initiation Conference on Retroviruses and Opportunistic Infections. February 2017. Seattle, WA, USA: Abstract 695.
    1. Bhagwat P, Ofotokun I, McComsey G et al. . Raltegravir is associated with greater abdominal fat increases after antiretroviral therapy initiation compared protease inhibitors 18th International Workshop on Comorbidities and Adverse Drug Reactions in HIV. September 2016. New York, NY, USA: Abstract 007.
    1. Bernadino J, Mocroft A, Wallet C et al. . Body composition and adipokines changes after initial treatment with darunavir-ritonavir plus either raltegravir or tenofovir disoproxil fumarate-emtricitabine: a sub-study of the NEAT 001/ANRS 143 randomised trial. PLoS Med 2019; in press.
    1. Waters L, Assoumou L, Rusconi S et al. . Switch to dolutegravir from a boosted protease inhibitor associated with a significant weight gain over 48 weeks in NEAT-022, a randomised 96-week trial HIV Glasgow. October 2018. Glasgow, UK: Abstract P102.
    1. Martinez E, Assoumou L. Moyle G et al. . 48-week changes in biomarkers in subjects with high cardiovascular risk switching from ritonavir-boosted protease inhibitors ro dolutegravir in the NEAT -022 study HIV Glasgow. October 2018. Glasgow, UK: Abstract O113.
    1. Stellbrink H, Arribas J, Stephens J et al. . Phase III randomised, controlled clinical trial of bictegravir coformulated with FTC/TAF in a fixed dose combination (B/F/TAF) versus dolutegravir (DTG) + FTC/TAF in treatment-naïve HIV-1 positive adults HIV Glasgow. October 2018. Glasgow, UK: Abstract O211.
    1. Orkin C, Eron J, Rockstroh J et al. . Efficacy and safety of the once-daily, darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) single-tablet regimen (STG) in ART-naïve, HIV-1 infected adults: AMBER 96 week results HIV Glasgow. October 2018. Glasgow, UK: Abstract O212.
    1. Martin A, Bloch M, Amin J et al. . Simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir-lamivudine: a randomised, 96-week trial. Clin Infect Dis 2009; 49: 1591– 1601.
    1. Gomez M, Seybold U, Roider J et al. . A retrospective analysis of weight changes in HIV-positive patients switching from a tenofovir disoproxil fumarate (TDF)- to a tenofovir alafenamide fumarate (TAF)-containing treatment regimen in one German university hospital in 2015–2017. Infection 2018; epub ahead of print.
    1. European Medicines Agency Assessment report. Dolutegravir (Tivicay) Available at: ( accessed January 2019).
    1. Vitoria M, Hill A, Ford N et al. . The transition to dolutegravir and other new antiretrovirals in low-income and middle-income countries: what are the issues? AIDS 2018; 32: 1551– 1561.
    1. Food and Drug Administration (USA) Guidance for Industry. Development of products for weight management. February 2007. Available at: ( accessed January 2019).

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever