The Fat of the Matter: Obesity and Visceral Adiposity in Treated HIV Infection

Lake, Jordan E.

doi:10.1007/s11904-017-0368-6

Cited by 84 publications

(74 citation statements)

References 107 publications

(101 reference statements)

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“…The association between dolutegravir or raltegravir vs elvitegravir use and weight gain was confirmed in observational cohorts of PLWH initiated with ART [9,10,11]. Weight gain following ART initiation could be attributable in part to a "return to health" phenomenon, but is also clearly associated with individual INSTI and with personal factors as sex and ethnicity [12].…”

Section: Role Of Instimentioning

confidence: 83%

Metabolic complications affecting adipose tissue, lipid and glucose metabolism associated with HIV antiretroviral treatment

Lagathu

Béréziat

Gorwood

et al. 2019

Expert Opinion on Drug Safety

112

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Introduction: Efficient antiretroviral-treatment(ART) generally allows control of HIV infection. However, persons-living-with-HIV(PLWH), when ageing, present a high prevalence of metabolic diseases. Area covered: Altered adiposity, dyslipidemias, insulin resistance, diabetes and their consequences are prevalent in PLWH and could be partly related to ART. Expert opinion: At first, personal and lifestyle factors are involved in the onset of these complications. The persistence of HIV in tissue reservoirs could synergize with some ART and enhance metabolic disorders. Altered fat repartition, diagnosed as lipodystrophy, has been related to first-generation nucleoside-reverse-transcriptase-inhibitors(NRTIs) (stavudine zidovudine) and some protease inhibitors(PIs). Recently, use of some integraseinhibitors(INSTI) resulted in weight/fat gain, which represents a worrisome unresolved situation.Lipid parameters were affected by some first-generation NRTIs, non-NRTIs(efavirenz) but also PIs boosted by ritonavir, with increased total and LDL-cholesterol and triglycerides.Insulin resistance is common in aging PLWH, often associated with abdominal obesity.Diabetes incidence, high with first-generation-ART (zidovudine, stavudine, didanosine, indinavir) has declined with contemporary ART close to that of the general population.Metabolic syndrome, a dysmetabolic situation with central obesity and insulin resistance, and liver steatosis are common in PLWH and could indirectly result from ART-associated fat gain and insulin resistance. All these dysmetabolic situations increase the atherogenic cardiovascular risk.Before 2000, PLWH received first-generation ART, as nucleoside analogue reverse transcriptase inhibitors (thymidine NRTIs, stavudine, zidovudine, didanosine) and protease inhibitors (PI, indinavir, ritonavir, nelfinavir) responsible for marked adverse events on lipid and glucose metabolism and on adipose tissue. These ART were replaced by newer molecules presenting a markedly lower metabolic toxicity.However, some PLWH, previously treated with first-generation NRTIs, present long-lasting fat alterations with metabolic consequences [1]. Some contemporary ART as integrase inhibitors (INSTI), considered as metabolic-friendly, were recently associated with weight/fat gain. Therefore, there are remaining and evolving concerns regarding the effect of ART on metabolism and adipose tissue in PLWH.As a consequence of the metabolic effects of some ART, increased prevalence of cardiovascular diseases (CVD), particularly atherosclerotic CVD[2] and diabetes, has been reported, but differ according to the calendar years and the geographic area. It is important to consider the metabolic profile of each patients to adapt ART. If required, classical lipid and glucose-lowering medications are prescribed.

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Section: Role Of Instimentioning

confidence: 83%

Metabolic complications affecting adipose tissue, lipid and glucose metabolism associated with HIV antiretroviral treatment

Lagathu

Béréziat

Gorwood

et al. 2019

Expert Opinion on Drug Safety

112

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“…Weight gain following ART initiation could be attributable in part to a "return to health" phenomenon in patients with severe HIV infection, but this is not the case for switched patients. Weight gain is also associated with personal factors as sex, age and ethnicity [4,49]. This increased weight has been associated, for DTG and raltegravir, with a decreased circulating level of the adipokine adiponectin [13,50], an insulin-sensitizing and anti-inflammatory adipokine, suggesting a deleterious impact of these INSTIs on adipose tissue.…”

Section: Discussionmentioning

confidence: 99%

HIV antiretroviral drugs, dolutegravir, maraviroc and ritonavir-boosted atazanavir use different pathways to affect inflammation, senescence and insulin sensitivity in human coronary endothelial cells

et al. 2020

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Objectives Aging HIV-infected antiretroviral-treatment (ART)-controlled patients often present cardiovascular and metabolic comorbidities. Thus, it is mandatory that lifelong used ART has no cardiometabolic toxicity. Protease inhibitors have been associated with cardiometabolic risk, integrase-strand-transfer-inhibitors (INSTI) with weight gain and the CCR5 inhibitor maraviroc with improved vascular function. We have previously reported that the INSTI dolutegravir and maraviroc improved, and ritonavir-boosted atazanavir(atazanavir/r) worsened, inflammation and senescence in human coronary artery endothelial cells (HCAEC)s from adult controls. Here, we analyzed the pathways involved in the drugs' effects on inflammation, senescence and also insulin resistance. Methods We analyzed the involvement of the anti-inflammatory SIRT-1 pathway in HCAECs. Then, we performed a transcriptomic analysis of the effect of dolutegravir, maraviroc and atazanavir/r and used siRNA-silencing to address ubiquitin-specific-peptidase-18 (USP18) involvement into ART effects. Results Dolutegravir reduced inflammation by decreasing NFκB activation and IL-6/IL-8/sICAM-1/ sVCAM-1 secretion, as did maraviroc with a milder effect. However, when SIRT-1 was inhibited by splitomicin, the drugs anti-inflammatory effects were maintained, indicating that they were SIRT-1-independant.

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“…In the past, the development of lipodystrophy was partially related to drugs (i.e., stavudine and zidovudine) included in the treatment regimen, but it is also influenced by age, CD4 levels, viral load, therapy duration, and race (especially caucasians). Remarkably, the new classes of cART and inhibitors (fusion, integrase, and entry) do not alter the metabolic parameters of fat distribution ( 1 , 50 ).…”

Section: Consequences Of Immune Activation and Insulin Resistance Inmentioning

confidence: 99%

Insulin Resistance in HIV-Patients: Causes and Consequences

et al. 2018

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Here we review how immune activation and insulin resistance contribute to the metabolic alterations observed in HIV-infected patients, and how these alterations increase the risk of developing CVD. The introduction and evolution of antiretroviral drugs over the past 25 years has completely changed the clinical prognosis of HIV-infected patients. The deaths of these individuals are now related to atherosclerotic CVDs, rather than from the viral infection itself. However, HIV infection, cART, and intestinal microbiota are associated with immune activation and insulin resistance, which can lead to the development of a variety of diseases and disorders, especially with regards to CVDs. The increase in LPS and proinflammatory cytokines circulating levels and intracellular mechanisms activate serine kinases, resulting in insulin receptor substrate-1 (IRS-1) serine phosphorylation and consequently a down regulation in insulin signaling. While lifestyle modifications and pharmaceutical interventions can be employed to treat these altered metabolic functions, the mechanisms involved in the development of these chronic complications remain largely unresolved. The elucidation and understanding of these mechanisms will give rise to new classes of drugs that will further improve the quality of life of HIV-infected patients, over the age of 50.

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The Fat of the Matter: Obesity and Visceral Adiposity in Treated HIV Infection

Cited by 84 publications

References 107 publications

Metabolic complications affecting adipose tissue, lipid and glucose metabolism associated with HIV antiretroviral treatment

Metabolic complications affecting adipose tissue, lipid and glucose metabolism associated with HIV antiretroviral treatment

HIV antiretroviral drugs, dolutegravir, maraviroc and ritonavir-boosted atazanavir use different pathways to affect inflammation, senescence and insulin sensitivity in human coronary endothelial cells

Insulin Resistance in HIV-Patients: Causes and Consequences

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