Improvements in Subcutaneous Fat, Lipid Profile, and Parameters of Mitochondrial Toxicity in Patients with Peripheral Lipoatrophy When Stavudine is Switched to Tenofovir (LIPOTEST Study)

Ribera, Esteban; Paradiñeiro, J. C.; Curran, Adrían; Sauleda, Sílvia; Garcı́a-Arumı́, Elena; Castellà, Eva; Puiggròs, C.; Crespo, Manuel; Feijoo, Maria Augusta Córdoba; Díaz, M. Medina; Saz, Sara Villar del; Planas, M.; Sureda, D.; Falcó, Vicenç; Ocaña, Imma; Pahissa, Albert

doi:10.1310/hct0906-407

Cited by 55 publications

(48 citation statements)

References 35 publications

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“…[53][54][55][56] Other studies have reported a lowering of mitochondrial dysfunction when drug regimens were changed and NRTIs were replaced with tenofovir. [57][58][59] A recent study in rats found that very high doses (ie, 100 mg/kg/day) of tenofovir reduced mitochondrial DNA and gene expression in kidney cells. 60 The relevance of this observation given the very high dosing used is unclear.…”

Section: Mechanisms Of Tenofovir-associated Bone Lossmentioning

confidence: 99%

Tenofovir-associated bone density loss

Mansky¹

2009

TCRM

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Section: Mechanisms Of Tenofovir-associated Bone Lossmentioning

confidence: 99%

Tenofovir-associated bone density loss

Mansky¹

2009

TCRM

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“…Although few studies relating exclusively to facial lipoatrophy, a study conducted in Spain involving sixty-two patients with this type of Lipoatrophy, showed a similar distribution, with 71% of male patients [20].…”

Section: Discussionmentioning

confidence: 91%

“…Several studies have associated the use of Stavudine to the occurrence of lipodystrophy and more specifically to Facial Lipoatrophy [10,20,31,32,33]. Recent studies have demonstrated that Efavirenz is also associated with the onset and progression of lipoatrophy [5].…”

Section: Discussionmentioning

confidence: 99%

Oral sensorimotor system in AIDS patients with facial lipodystrophy

Pessôa¹,

Martins²,

Martins³

et al. 2015

Int Arch Med

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“…Several recent studies have confirmed the metabolically beneficial effects of d4T switching [15][16][17]. Although most of these studies focussed on fat distribution and adipocyte function, it is reasonable to assume that mitochondrial liver function would also be improved by switching to a less toxic NRTI backbone.…”

Section: Discussionmentioning

confidence: 99%

Impact of antiretroviral treatment on 13C-methionine metabolism as a marker of hepatic mitochondrial function: a longitudinal study

et al. 2010

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ObjectivesUncontrolled viral replication and antiretroviral treatment (ART) may independently contribute to hepatic mitochondrial toxicity. The present study was designed to explore the longitudinal effects of treatment modifications on hepatic mitochondrial function by means of noninvasive 13 C-methionine breath test (MeBT) diagnostics. MethodsA total of 113 HIV-infected patients underwent two consecutive MeBTs over an interval of 11.8 AE 3.5 months. Forty-nine patients remained on stable ART or no therapy; 28 participants switched ART; 27 patients (re)initiated ART, and nine individuals underwent a structured treatment interruption (STI) of ART between MeBTs 1 and 2. Breath test results were expressed as cumulative percentage dose of 13 CO 2 recovered after 1.5 h test time (cPDR 1.5h ). ResultsInitiation of ART in treatment-naïve individuals and patients on STI was associated with a significant improvement of hepatic mitochondrial function (Po0.05). Cessation of ART or a prolonged delay in initiating therapy in treatment-naïve patients in turn led to a significant decline of 13 C-exhalation compared with baseline (Po0.05). A marked increase in 13 C-exhalation was observed in individuals who switched from stavudine or ddI to tenofovir or abacavir ( 1 170%; Po0.001), while no differences between MeBTs 1 and 2 were found in individuals on ART who had remained on stable regimens or in those who changed a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) component. ConclusionThe present data suggest that hepatic mitochondrial function in HIV disease is a dynamic process with a high regenerative capacity and highlight the pathogenic relevance of HIV replication. Our findings suggest that modern ART per se does not negatively impact hepatic mitochondrial function. Keywords:13 C-methionine breath test, drug toxicity, HIV, mitochondrial toxicity IntroductionIncreasingly, deaths among HIV-infected persons are caused by hepatic complications [1,2]. Indeed, the majority of liver-related morbidity within the D:A:D cohort has been attributed to viral hepatitis coinfection. In the next few decades, a shift of morbidity to metabolic liver diseases is likely, analogous to the rising prevalence of the metabolic syndrome within the HIV-negative population [3]. The putative pathogenic role of antiretroviral therapy (ART) in this context is contested. Although the introduction of combination ART (cART) has reduced overall hepatic morbidity in both HIV-monoinfected and HIV/hepatitis C virus (HCV)-coinfected individuals, data on the long-term hepatotoxic effects of ART are absent. Two recently published cross-sectional trials showed a prevalence of DOI: 10.1111/j.1468-1293.2010.00847.x HIV Medicine (2011 r 2010 British HIV Association 40 nonalcoholic fatty liver disease in HIV-monoinfected patients of about 30%, which seems to be higher than calculated for the age-adjusted HIV-negative population [4,5]. Mitochondrial toxicity plays a major role in the pathogenesis of fatty liver disease irrespective...

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Improvements in Subcutaneous Fat, Lipid Profile, and Parameters of Mitochondrial Toxicity in Patients with Peripheral Lipoatrophy When Stavudine is Switched to Tenofovir (LIPOTEST Study)

Cited by 55 publications

References 35 publications

Tenofovir-associated bone density loss

Tenofovir-associated bone density loss

Oral sensorimotor system in AIDS patients with facial lipodystrophy

Impact of antiretroviral treatment on 13C-methionine metabolism as a marker of hepatic mitochondrial function: a longitudinal study

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