Antiretroviral therapy and the human immunodeficiency virus – improved survival but at what cost?

Bradbury, R. A.; Samaras, Katherine

doi:10.1111/j.1463-1326.2007.00760.x

Cited by 26 publications

(23 citation statements)

References 90 publications

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“…27 , 28 It is currently thought that PIs act synergically with NRTIs through means that are still not totally understood, modifying the function of adipose tissue. 29 One unexpected fi nding was that the chance of lipodystrophy was smaller for those using lopinavir/ritonavir for up to 3 years, even after adjusting for the length of time of use of the other drugs. Prospective studies should go some way to clarifying these fi ndings.…”

Section: Variable Related To Hiv Infectionmentioning

confidence: 97%

Risk Factors in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Patients Undergoing Antiretroviral Therapy in the State of Pernambuco, Brazil: A Case–Control Study

Gelenske

Farias

Ximenes

et al. 2010

Metabolic Syndrome and Related Disorders

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In this study, factors related to antiretroviral therapy were the main risk factors for lipodystrophy, corroborating the literature, but the findings also point to the need for further exploration into some of these associations, especially with the use of didanosine and lopinavir/ritonavir, which are less frequently reported. Future studies with a larger number of patients and a prospective design could provide valuable information for understanding this disorder.

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Section: Variable Related To Hiv Infectionmentioning

confidence: 97%

Risk Factors in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Patients Undergoing Antiretroviral Therapy in the State of Pernambuco, Brazil: A Case–Control Study

Gelenske

Farias

Ximenes

et al. 2010

Metabolic Syndrome and Related Disorders

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“…Long-term treatment with the HIV-PIs is associated with adverse effects such as hyperlipidemia or hypolipidemia, body fat redistribution, osteopenia and osteoporosis (47), as well as insulin resistance and susceptibility to type II diabetes (48)(49)(50)(51). Interestingly, loss-of-function mutation in CReP protein leading to decreased PP1 binding and sustained eIF2α phosphorylation has recently been shown to drive β-cell dysfunction and metabolic defects that can lead to diabetes in human (52).…”

Section: Discussionmentioning

confidence: 99%

An inhibitor of HIV-1 protease modulates constitutive eIF2α dephosphorylation to trigger a specific integrated stress response

Gassart

Bujisic

Zaffalon

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Inhibitors of the HIV aspartyl protease [HIV protease inhibitors (HIV-PIs)] are the cornerstone of treatment for HIV. Beyond their well-defined antiretroviral activity, these drugs have additional effects that modulate cell viability and homeostasis. However, little is known about the virus-independent pathways engaged by these molecules. Here we show that the HIV-PI Nelfinavir decreases translation rates and promotes a transcriptional program characteristic of the integrated stress response (ISR). Mice treated with Nelfinavir display hallmarks of this stress response in the liver, including α subunit of translation initiation factor 2 (eIF2α) phosphorylation, activating transcription factor-4 (ATF4) induction, and increased expression of known downstream targets. Mechanistically, Nelfinavir-mediated ISR bypassed direct activation of the eIF2α stress kinases and instead relied on the inhibition of the constitutive eIF2α dephosphorylation and down-regulation of the phophatase cofactor CReP (Constitutive Repressor of eIF2α Phosphorylation; also known as PPP1R15B). These findings demonstrate that the modulation of eIF2α-specific phosphatase cofactor activity can be a rheostat of cellular homeostasis that initiates a functional ISR and suggest that the HIV-PIs could be repositioned as therapeutics in human diseases to modulate translation rates and stress responses.

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“…In recent years, therefore, research has begun to focus on the deleterious effects of ART on risk of CVD (135) . Early reports of CVD appeared in peer-reviewed literature shortly after the introduction of PI (164,165) .…”

Section: Cvdmentioning

confidence: 99%

“…Before the ART era, the development of T2DM in HIVinfected individuals was attributed to the anti-microbial medication pentamidine (134) and was relatively uncommon (135) . Following the introduction of PI, however, a greater number of reported glucose disorders began to emerge in HIV-infected individuals (15,136,137) .…”

Section: Glucose Abnormalitiesmentioning

confidence: 99%

Nutrition and the HIV-associated lipodystrophy syndrome

Loonam

Mullen

2012

Nutr. Res. Rev.

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HIV-associated lipodystrophy syndrome (HALS), comprising metabolic and morphological alterations, is a known side effect of highly active antiretroviral therapy (HAART). Evidence for the role of nutrition in the management of the systemic parameters of HALS is currently limited. In the present paper we review the current knowledge base surrounding HALS, focusing particularly on the role of nutrition in mitigating the systemic parameters of the syndrome. Reported prevalence of HALS was found to vary from 9 to 83 % due to lack of a standardised definition, as well as variations in assessment methods and in the study population used. HALS is associated with both morphological (lipoatrophy, lipohypertrophy) and metabolic (dyslipidaemia, glucose intolerance, diabetes, hypertension, endothelial dysfunction and atherosclerosis) alterations, which may occur singly or in combination, and are associated with an increased risk of CVD. HAART-induced adipocyte inflammation, oxidative stress and macrophage infiltration, as well as altered adipocyte function and mitochondrial toxicity, have been shown to be central to the development of HALS. The adipocyte, therefore, represents a plausible target for treatment. Pharmacological and surgical treatment interventions have shown effect. However, their use is associated with numerous adverse effects and complications. Targeted lifestyle interventions may provide a useful alternative for managing HALS owing to their safety and tolerability. A Mediterranean-style diet has been found to be effective in improving the systemic parameters of HALS. Furthermore, the effects of n-3 PUFA supplementation are encouraging and future randomised controlled trials investigating the beneficial effects of n-3 PUFA in HALS are justified.

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Antiretroviral therapy and the human immunodeficiency virus – improved survival but at what cost?

Cited by 26 publications

References 90 publications

Risk Factors in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Patients Undergoing Antiretroviral Therapy in the State of Pernambuco, Brazil: A Case–Control Study

Risk Factors in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Patients Undergoing Antiretroviral Therapy in the State of Pernambuco, Brazil: A Case–Control Study

An inhibitor of HIV-1 protease modulates constitutive eIF2α dephosphorylation to trigger a specific integrated stress response

Nutrition and the HIV-associated lipodystrophy syndrome

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