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Published in: BMC Infectious Diseases 1/2024

Open Access 01-12-2024 | Dolutegravir | Research

The effect of a treatment switch to integrase Strand transfer inhibitor–based regimens on weight gain and other metabolic syndrome-related conditions

Authors: Omer Maman, Wiessam Abu Ahmad, Ofer Perzon, Keren Mahlab-Guri, Daniel Elbirt, Hila Elinav

Published in: BMC Infectious Diseases | Issue 1/2024

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Abstract

Objective

This study aimed to assess weight gain associated with treatment switching to INSTI-based regimens in people living with HIV (PLWH) and to determine whether it is accompanied by worsening features of hypertension, dyslipidemia, or hyperglycemia.

Methods

In this two-center retrospective observational study, we assessed weight gain and metabolic features in PLWH who switched to an INSTI-based regimen (study group) as compared to patients who remained on a non-INSTI regimen (control group) over a 24-month follow-up period.

Results

One-hundred seventy-four PLWH were included in the study group, and 175 were included in the control group. The study group gained 2.51 kg ± 0.31 (mean ± standard deviation) over the 2 years of follow-up, while the control group gained 1.1 ± 0.31 kg over the same time course (p < 0.001). INSTI treatment, Caucasian origin, and lower BMI were risk factors associated with excessive weight gain during the 2 years of follow-up. Among metabolic parameters, only glucose levels increased after initiating INSTI-based regimens, although limited to males of African origin (p = 0.009).

Conclusions

We observed a mild weight gain after switching to INSTI-based regimens, with no major impact on metabolic parameters over 2 years of follow-up. Longer follow-up might be needed to observe the adverse metabolic effects of INSTI-based regimens. The impact on weight gain should be discussed with every patient before the treatment switch to ensure a balanced diet and physical activity to prevent excessive weight gain that might hamper compliance with ART.
Literature
3.
go back to reference Arribas J MJ, Buckely RDM,Antinori A,Bracchi M,Calmy A,Dedes N,Horban A, Katlama C,Latysheva I,Lundgren JD, McCormack S,Mussini C,Pozniak A,Pulido F,Raffi F,Stelbrink HJ,Van der Vallk M, Vasylyev M. European AIDS clinical Society Guidlines 2021 [updated 10.2021; cited 2021 20.11.2021]. 11:[Available from: https://www.eacsociety.org/guidelines/eacs-guidelines/. Arribas J MJ, Buckely RDM,Antinori A,Bracchi M,Calmy A,Dedes N,Horban A, Katlama C,Latysheva I,Lundgren JD, McCormack S,Mussini C,Pozniak A,Pulido F,Raffi F,Stelbrink HJ,Van der Vallk M, Vasylyev M. European AIDS clinical Society Guidlines 2021 [updated 10.2021; cited 2021 20.11.2021]. 11:[Available from: https://​www.​eacsociety.​org/​guidelines/​eacs-guidelines/​.
7.
go back to reference McComsey GAEJ, Santiago S, Mounzer K, Moyle G, Vantig T, Sax PE, et al. Weight gain during treatment among 3,468 treatment-experienced adults with HIV. Seattle, Washington: Conference on retroviruses and opportunistic infections; 2019. McComsey GAEJ, Santiago S, Mounzer K, Moyle G, Vantig T, Sax PE, et al. Weight gain during treatment among 3,468 treatment-experienced adults with HIV. Seattle, Washington: Conference on retroviruses and opportunistic infections; 2019.
9.
go back to reference Bourgi K, Rebeiro PF, Turner M, Castilho JL, Hulgan T, Raffanti SP, et al. Greater Weight Gain in Treatment-naive Persons Starting Dolutegravir-based Antiretroviral Therapy. Clin Infect Dis. 2020;70(7):1267–74. https://doi.org/10.1093/cid/ciz407. PubMed PMID: 31100116; PubMed Central PMCID: PMCPMC8205610CrossRefPubMed Bourgi K, Rebeiro PF, Turner M, Castilho JL, Hulgan T, Raffanti SP, et al. Greater Weight Gain in Treatment-naive Persons Starting Dolutegravir-based Antiretroviral Therapy. Clin Infect Dis. 2020;70(7):1267–74. https://​doi.​org/​10.​1093/​cid/​ciz407. PubMed PMID: 31100116; PubMed Central PMCID: PMCPMC8205610CrossRefPubMed
11.
go back to reference Hill AVF, Delaporte E, Sokhela S, Kouanfack C, Moorhouse M, McCann K, et al. Progressive rises in weight and clinical obesity for TAF/FTC+DTG and TDF/FTC+DTG versus TDF/FTC/EFV: ADVANCE and NAMSAL trials. Mexico City: IAS 2019: conference on HIV pathogenesis; 2019. Hill AVF, Delaporte E, Sokhela S, Kouanfack C, Moorhouse M, McCann K, et al. Progressive rises in weight and clinical obesity for TAF/FTC+DTG and TDF/FTC+DTG versus TDF/FTC/EFV: ADVANCE and NAMSAL trials. Mexico City: IAS 2019: conference on HIV pathogenesis; 2019.
15.
go back to reference Erlandson KM, Carter CC, Melbourne K, Brown TT, Cohen C, Das M, et al. Weight change following antiretroviral therapy switch in people with viral suppression: pooled data from randomized clinical trials. Clin Infect Dis. 2021; https://doi.org/10.1093/cid/ciab444. PubMed PMID: 33987636 Erlandson KM, Carter CC, Melbourne K, Brown TT, Cohen C, Das M, et al. Weight change following antiretroviral therapy switch in people with viral suppression: pooled data from randomized clinical trials. Clin Infect Dis. 2021; https://​doi.​org/​10.​1093/​cid/​ciab444. PubMed PMID: 33987636
18.
go back to reference Samaras KWH, Law M, Emery S, Cooper D, Carr A. Prevalence of metabolic syndrome in HIV-infected patients receiving highly active antiretroviral therapy using international Diabetes Foundation and adult treatment panel III criteria: associations with insulin resistance, disturbed body fat compartmentalization, elevated C-reactive protein, and [corrected] hypoadiponectinemia. Diabetes Care. 2007;30(1):113–9. https://doi.org/10.2337/dc06-1075.CrossRefPubMed Samaras KWH, Law M, Emery S, Cooper D, Carr A. Prevalence of metabolic syndrome in HIV-infected patients receiving highly active antiretroviral therapy using international Diabetes Foundation and adult treatment panel III criteria: associations with insulin resistance, disturbed body fat compartmentalization, elevated C-reactive protein, and [corrected] hypoadiponectinemia. Diabetes Care. 2007;30(1):113–9. https://​doi.​org/​10.​2337/​dc06-1075.CrossRefPubMed
26.
go back to reference JC RRF, Bian A, Lake JE, Bourgi K, Moore RD, Horberg MA, et al. Risk of Incident Diabetes Mellitus, Weight Gain, and Their Relationships With Integrase Inhibitor-Based Initial Antiretroviral Therapy Among Persons With Human Immunodeficiency Virus in the United States and Canada. Clin Infect Dis. 2021;73(7):e2234–e42. https://doi.org/10.1093/cid/ciaa1403.CrossRef JC RRF, Bian A, Lake JE, Bourgi K, Moore RD, Horberg MA, et al. Risk of Incident Diabetes Mellitus, Weight Gain, and Their Relationships With Integrase Inhibitor-Based Initial Antiretroviral Therapy Among Persons With Human Immunodeficiency Virus in the United States and Canada. Clin Infect Dis. 2021;73(7):e2234–e42. https://​doi.​org/​10.​1093/​cid/​ciaa1403.CrossRef
30.
go back to reference Aldredge ALC, Summers NA, Mehta CC, Angert CD, Kerchberger AM, Sheri Weiser S, et al. Effects of Integrase Strand-Transfer Inhibitor Use on Lipids, Glycemic Control, and Insulin Resistance in the Women’s Interagency HIV Study (WIHS). Open Forum Infect Dis. 2019;supp 2:S38. https://doi.org/10.1093/ofid/ofz359.082.CrossRef Aldredge ALC, Summers NA, Mehta CC, Angert CD, Kerchberger AM, Sheri Weiser S, et al. Effects of Integrase Strand-Transfer Inhibitor Use on Lipids, Glycemic Control, and Insulin Resistance in the Women’s Interagency HIV Study (WIHS). Open Forum Infect Dis. 2019;supp 2:S38. https://​doi.​org/​10.​1093/​ofid/​ofz359.​082.CrossRef
33.
go back to reference Gorwood J, Bourgeois C, Pourcher V, Pourcher G, Charlotte F, Mantecon M, et al. The integrase inhibitors Dolutegravir and Raltegravir exert Proadipogenic and Profibrotic effects and induce insulin resistance in human/simian adipose tissue and human adipocytes. Clin Infect Dis. 2020;71(10):e549–e60. Epub 2020/03/14. https://doi.org/10.1093/cid/ciaa259.CrossRefPubMed Gorwood J, Bourgeois C, Pourcher V, Pourcher G, Charlotte F, Mantecon M, et al. The integrase inhibitors Dolutegravir and Raltegravir exert Proadipogenic and Profibrotic effects and induce insulin resistance in human/simian adipose tissue and human adipocytes. Clin Infect Dis. 2020;71(10):e549–e60. Epub 2020/03/14. https://​doi.​org/​10.​1093/​cid/​ciaa259.CrossRefPubMed
35.
go back to reference Domingo PVF, Giralt M, Domingo JC. Potential role of the melanocortin signaling system interference in the excess weight gain associated to some antiretroviral drugs in people living with HIV. Int J Obes. 2020;44:1970–3.CrossRef Domingo PVF, Giralt M, Domingo JC. Potential role of the melanocortin signaling system interference in the excess weight gain associated to some antiretroviral drugs in people living with HIV. Int J Obes. 2020;44:1970–3.CrossRef
36.
go back to reference Raffi F, Esser S, Nunnari G, Perez-Valero I, Waters L. Switching regimens in virologically suppressed HIV-1-infected patients: evidence base and rationale for integrase strand transfer inhibitor (INSTI)-containing regimens. HIV Med. 2016;17(Suppl 5):3–16. Epub 2016/10/08. https://doi.org/10.1111/hiv.12440.CrossRefPubMed Raffi F, Esser S, Nunnari G, Perez-Valero I, Waters L. Switching regimens in virologically suppressed HIV-1-infected patients: evidence base and rationale for integrase strand transfer inhibitor (INSTI)-containing regimens. HIV Med. 2016;17(Suppl 5):3–16. Epub 2016/10/08. https://​doi.​org/​10.​1111/​hiv.​12440.CrossRefPubMed
38.
go back to reference Munoz-Moreno JA, Fumaz CR, Ferrer MJ, Gonzalez-Garcia M, Molto J, Negredo E, et al. Neuropsychiatric symptoms associated with efavirenz: prevalence, correlates, and management. A neurobehavioral review AIDS Rev. 2009;11(2):103–9.PubMed Munoz-Moreno JA, Fumaz CR, Ferrer MJ, Gonzalez-Garcia M, Molto J, Negredo E, et al. Neuropsychiatric symptoms associated with efavirenz: prevalence, correlates, and management. A neurobehavioral review AIDS Rev. 2009;11(2):103–9.PubMed
39.
go back to reference Lennox JL, DeJesus E, Lazzarin A, Pollard RB, Madruga JV, Berger DS, et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. Lancet. 2009;374(9692):796–806. Epub 2009/08/04. https://doi.org/10.1016/S0140-6736(09)60918-1.CrossRefPubMed Lennox JL, DeJesus E, Lazzarin A, Pollard RB, Madruga JV, Berger DS, et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. Lancet. 2009;374(9692):796–806. Epub 2009/08/04. https://​doi.​org/​10.​1016/​S0140-6736(09)60918-1.CrossRefPubMed
Metadata
Title
The effect of a treatment switch to integrase Strand transfer inhibitor–based regimens on weight gain and other metabolic syndrome-related conditions
Authors
Omer Maman
Wiessam Abu Ahmad
Ofer Perzon
Keren Mahlab-Guri
Daniel Elbirt
Hila Elinav
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2024
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-024-09120-7

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