Mitochondrial Effects of HIV Infection on the Peripheral Blood Mononuclear Cells of HIV-Infected Patients Who Were Never Treated with Antiretrovirals

Miró, Òscar; López, Sònia; Martínez, Estebán; Pedrol, Enric; Milinkovic, Ana; Deig, Elisabeth; Garrabou, Glòria; Casademont, Jordi; Gatell, Josep M.; Cardellach, Francesc

doi:10.1086/423176

Cited by 134 publications

(109 citation statements)

References 35 publications

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“…Clinically, female gender, advanced immunosuppression, and possibly ethnicity have been cited as factors that play a role in increasing an individual's risk for hyperlactatemia/lactic acidosis [64]. To further emphasize the complexity and multifactorial nature of this problem, mitochondrial dysfunction has also been reported in HIV-infected individuals who are naïve to ARVs [65].…”

Section: Hyperlactatemia and Lactic Acidosismentioning

confidence: 99%

A Review of the Toxicity of HIV Medications

et al. 2013

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Antiretroviral therapy has changed human immunodeficiency virus (HIV) infection from a near-certainly fatal illness to one that can be managed chronically. More patients are taking antiretroviral drugs (ARVs) for longer periods of time, which naturally results in more observed toxicity. Overdose with ARVs is not commonly reported. The most serious overdose outcomes have been reported in neonates who were inadvertently administered supratherapeutic doses of HIV prophylaxis medications. Typical ARV regimens include a "backbone" of two nucleoside reverse transcriptase inhibitors (NRTI) and a "base" of either a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor. New classes of drugs called entry inhibitors and integrase inhibitors have also emerged. Older NRTIs were associated with mitochondrial toxicity, but this is less common in the newer drugs, emtricitabine, lamivudine, and tenofovir. Mitochondrial toxicity results from NRTI inhibition of a mitochondrial DNA polymerase. Mitochondrial toxicity manifests as myopathy, neuropathy, hepatic failure, and lactic acidosis. Routine lactate assessment in asymptomatic patients is not indicated. Lactate concentration should be obtained in patients taking NRTIs who have fatigue, nausea, vomiting, or vague abdominal pain. Mitochondrial toxicity can be fatal and is treated by supportive care and discontinuing NRTIs. Metabolic cofactors like thiamine, carnitine, and riboflavin may be helpful in managing mitochondrial toxicity. Lipodystrophy describes changes in fat distribution and lipid metabolism that have been attributed to both PIs and NRTIs. Lipodystrophy consists of loss of fat around the face (lipoatrophy), increase in truncal fat, and hypertriglyceridemia. There is no specific treatment of lipodystrophy. Clinicians should be able to recognize effects of chronic toxicity of ARVs, especially mitochondrial toxicity.

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Section: Hyperlactatemia and Lactic Acidosismentioning

confidence: 99%

A Review of the Toxicity of HIV Medications

et al. 2013

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“…Considering all these results, our findings suggest that these cell models may at least partially reproduce in vitro the alterations observed in vivo in HIV‐infected patients 4, 8, 9, 12, 13 that should be further characterized in depth.…”

Section: Discussionmentioning

confidence: 58%

HIV‐1 promonocytic and lymphoid cell lines: an in vitro model of in vivo mitochondrial and apoptotic lesion

Morén

González‐Casacuberta

Álvarez-Fernández

et al. 2016

J Cellular Molecular Medi

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To characterize mitochondrial/apoptotic parameters in chronically human immunodeficiency virus (HIV‐1)‐infected promonocytic and lymphoid cells which could be further used as therapeutic targets to test pro‐mitochondrial or anti‐apoptotic strategies as in vitro cell platforms to deal with HIV‐infection. Mitochondrial/apoptotic parameters of U1 promonocytic and ACH2 lymphoid cell lines were compared to those of their uninfected U937 and CEM counterparts. Mitochondrial DNA (mtDNA) was quantified by rt‐PCR while mitochondrial complex IV (CIV) function was measured by spectrophotometry. Mitochondrial‐nuclear encoded subunits II–IV of cytochrome‐c‐oxidase (COXII‐COXIV), respectively, as well as mitochondrial apoptotic events [voltage‐dependent‐anion‐channel‐1(VDAC‐1)‐content and caspase‐9 levels] were quantified by western blot, with mitochondrial mass being assessed by spectrophotometry (citrate synthase) and flow cytometry (mitotracker green assay). Mitochondrial membrane potential (JC1‐assay) and advanced apoptotic/necrotic events (AnexinV/propidium iodide) were measured by flow cytometry. Significant mtDNA depletion spanning 57.67% (P < 0.01) was found in the U1 promonocytic cells further reflected by a significant 77.43% decrease of mitochondrial CIV activity (P < 0.01). These changes were not significant for the ACH2 lymphoid cell line. COXII and COXIV subunits as well as VDAC‐1 and caspase‐9 content were sharply decreased in both chronic HIV‐1‐infected promonocytic and lymphoid cell lines (<0.005 in most cases). In addition, U1 and ACH2 cells showed a trend (moderate in case of ACH2), albeit not significant, to lower levels of depolarized mitochondrial membranes. The present in vitro lymphoid and especially promonocytic HIV model show marked mitochondrial lesion but apoptotic resistance phenotype that has been only partially demonstrated in patients. This model may provide a platform for the characterization of HIV‐chronicity, to test novel therapeutic options or to study HIV reservoirs.

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“…HIV itself may also cause mitochondrial toxicity and OS contributing to lipoatrophy also during natural infection [45][46][47][48].…”

Section: Oxidative Stress In Hiv Natural Infectionmentioning

confidence: 99%

“…Also mitochondrial dysfunction and its impact on chronic inflammation during HIV natural evolution have been suggested [45][46][47].…”

Section: Oxidative Stress In Hiv Natural Infectionmentioning

confidence: 99%

Altered Redox Regulation as Cofactor in Comorbidities and Accelerated Aging in HIV Infection Evolution and Antiretroviral Treatment

Valle¹

2014

Epidemiol

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Metabolic issues persist in HIV patients who are otherwise stable with and without antiretroviral treatment. Metabolic alterations are associated to chronic inflammation, severe mitochondrial toxicity and oxidative stress as critical factors influencing HIV disease outcomes even during antiretroviral treatment. These aspects could also be involved in comorbidities and premature aging. Both factors should be managed during therapy and they should be focus of intense ongoing investigation.The aim of this mini-review is to describe essential mechanisms of in vivo reactive oxygen species generation, antioxidants pathways, and oxidative stress involved in HIV disease. Potential impact on reactive oxygen species, oxidative damage, cellular function, and how these responses change could mediate aging in pathophysiological situations are discussed. Accrual experimental and clinical reports analyses allow us a better understanding of various inter-related contributing factors. In addition, oxidative stress as an often-overlooked link between HIVinfection and the progression of aids, during antiretroviral treatment, is analyzed. Potential long-term consequences of antioxidant treatment require on-going investigation in order to obtain important clinical issues that have recently been reported. Currently, the most practical advice is to start antiretroviral therapy early and to manage traditional risk factors of non-aids-related conditions.

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Mitochondrial Effects of HIV Infection on the Peripheral Blood Mononuclear Cells of HIV-Infected Patients Who Were Never Treated with Antiretrovirals

Cited by 134 publications

References 35 publications

A Review of the Toxicity of HIV Medications

A Review of the Toxicity of HIV Medications

HIV‐1 promonocytic and lymphoid cell lines: an in vitro model of in vivo mitochondrial and apoptotic lesion

Altered Redox Regulation as Cofactor in Comorbidities and Accelerated Aging in HIV Infection Evolution and Antiretroviral Treatment

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