Recent data on adipose tissue, insulin resistance, diabetes and dyslipidaemia in antiretroviral therapy controlled HIV-infected persons

Abstract

Purpose of review: Increased total body fat with truncal redistribution is common in antiretroviral-treatment(ART)-controlled persons living with-HIV(PLWH), leading to insulin resistance, prediabetes/diabetes and dyslipidemia. We address these topics here.Recent findings: Most antiretrovirals are associated with gain in trunk fat, including visceral adipose tissue(VAT). Protease-inhibitors(PI) could inhibit white fat ability to dissipate energy (i.e. beiging) favoring fat gain. Expansion of VAT is associated with a pro-inflammatory profile linked to the tryptophan-kynurenine pathway and CD4 subtypes. ART-associated increased AT quantity leads to decreased AT density, insulin resistance and dyslipidemia that could be improved by lifestyle modifications.PLWH present high level of insulin resistance, regardless of their treatment, and a higher prevalence of prediabetes, but not diabetes, than non-infected persons. Otherwise, HbA1c values appear inaccurate to diagnose prediabetes/diabetes in PLWH.ART-related-dyslipidemia is characterized by elevated LDL-C and/or high triglycerides and reduced HDL-C. Whereas treatment with PIs generally results in worsened lipid values, treatment with integrase-strand-transfer-inhibitors is associated with a better profile.Tenofovir-alafenamide is associated with higher lipid levels than tenofovir-disoproxilfumarate. Treatment of LDL-C-dyslipidemia could benefit, in statin-insufficiently controlled patients, from the class of proprotein-convertase-subtilsin-kenin-type-9(PCSK-9) inhibitors.

Inhibition of Adipose Tissue Beiging by HIV Integrase Inhibitors, Dolutegravir and Bictegravir, Is Associated with Adipocyte Hypertrophy, Hypoxia, Elevated Fibrosis, and Insulin Resistance in Simian Adipose Tissue and Human Adipocytes

“…Among PLWH, overweight and obesity are of concern, given the worldwide increase in the prevalence of obesity. Indeed, weight gain is associated with a higher risk of cardiovascular and metabolic diseases [ 9 , 10 ]. Risk factors for this weight gain include age, ethnicity, body mass index (BMI), and female sex [ 11 ].…”

Weight and antiretrovirals: a new episode in a long series

“…In ART-controlled patients switched to an INSTI and/or TAF, it is too early to evaluate atherosclerotic risk. Data regarding diabetes are conflictual 10 . Taken as a whole, I think that an increased risk is associated with weight gain, as expected, but that an additional effect of INSTI and/or TAF is not proven.…”

Alterações metabólicas em pessoas que vivem com HIV: estudo de coorte retrospectivo

“…Entre as classes dos ARV descritas na literatura que podem contribuir na alteração do metabolismo da glicose, estão os Inibidores de Proteases (IP), os inibidores da transcriptase reversa análogos de nucleosídeos (ITRN) e os Inibidores da Integrase (INI) (CAPEAU et al, 2021;HSU et al, 2021). Ressaltase que, ainda que os efeitos da TARV possam conter a progressão da doença e a proliferação viral maciça, ocorre multiplicação do HIV em diferentes sítios, o que favorece ao estabelecimento de um estado inflamatório crônico.…”

“…Ressaltase que, ainda que os efeitos da TARV possam conter a progressão da doença e a proliferação viral maciça, ocorre multiplicação do HIV em diferentes sítios, o que favorece ao estabelecimento de um estado inflamatório crônico. Esses locais são considerados "santuários" de replicação viral, são eles: o sistema gastrintestinal, o sistema nervoso central e o tecido adiposo (CAPEAU et al, 2021;COBAS et al, 2022;HSU et al, 2021).…”

“…A infecção dos macrófagos e adipóticos (considerados reservatórios para a replicação viral), favorece a liberação de proteínas virais, modificando o fenótipo adipocitário. Do mesmo modo, os macrografo ao serem infectados pelo HIV, modificam seu fenótipo de um padrão anti-inflamatório (M2) para um pró-inflamatório (M1), com a secreção de citocinas pró-inflamatórias, resultando na indução de RI e alteração da produção de adipocinas (CAPEAU et al, 2021;COBAS et al, 2022;HSU et al,2021;TASCA et al, 2021).…”