Monday, February 04, 2013

Recent Studies Show Concerns With The Use of Tenofovir (Viread), Popular Drug in HIV Treatment


By on 2:43 PM


Tenofovir impairs enzyme that stops cells aging


This study let us know that NRTI drugs, already known for causing the damage to mitochondrial DNA that leads to peripheral neuropathy, fat loss and some other side-effects, also exert an effect on cellular DNA, and that in this case tenofovir may be the drug to keep an eye on.

Telomerase shortening is, by definition, a side-effect that won’t start causing symptoms for many years, and the study does provide a cautionary note in discussions about the possibility of very long-term side-effects associated with the use of tenofovir, both in HIV treatment and in pre-exposure prophylaxis.

More information here


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Changes in Fat Mitochondrial DNA and Function in Subjects Randomized to Abacavir+Lamivudine or Tenofovir DF+ Emtricitabine With Atazanavir-Ritonavir or Efavirenz: AIDS Clinical Trials Group Study A5224s, Substudy of A5202


"In conclusion, we have shown significant perturbation in mitochondrial indices after 96 weeks of nonthymidine NRTI containing regimens which were assigned randomly. In the TDF/FTC group, changes in oxidative phosphorylation complex I and complex IV activity levels consistently were inversely correlated with changes in several objective measures of body fat, including in both subcutaneous and visceral compartments"


  Patients with human immunodeficiency virus type 1 (HIV-1) infection receiving thymidine nucleoside reverse-transcriptase inhibitors (NRTIs) experience a high rate of metabolic abnormalities, including lipoatrophy. Depletion of adipose tissue mitochondrial DNA (mtDNA) and impairment of the oxidative phosphorylation system are associated with lipoatrophy induced by thymidine NRTI containing regimens. Mitochondrial oxidative phosphorylation enzymes nicotinamide adenine dinucleotide (reduced; NADH) dehydrogenase (complex I) and cytochrome c oxidase (complex IV) contain polypeptides of mtDNA-encoded subunits and so are affected by mtDNA depletion.
In the current era of nonthymidine NRTI containing regimens, lipoatrophy incidence has significantly decreased but has not been completely prevented . In addition, subjects who have established lipoatrophy while taking thymidine NRTI containing regimens experience only a slow and incomplete resolution of lipoatrophy after switching to nonthymidine NRTI based therapy , putting into question the mitochondrial toxicity.

More information here

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Fortunately, 10 year observational data on the use of TDF show encouraging results in stabilization of reduced creatinine clearance


Association Between Tenofovir Exposure and Reduced Kidney Function in a Cohort of HIV-Positive Patients: Results From 10 Years of Follow-up


 "In this cohort, TDF exposure was associated with reduced kidney function, but the loss in eGFR attributable to TDF is relatively mild in a long-term perspective.

There has been debate about the association between TDF exposure and renal dysfunction and about the clinical impact of the loss in eGFR due to TDF exposure. Our study shows that the association was not of a high magnitude and that the quantified loss in eGFR attributable to TDF is relatively modest after many years of exposure. Importantly, the loss attributable to TDF seems to occur during the first year of exposure and stabilizes after that. Although the loss is maintained, it does not seem to further deteriorate with additional years of exposure. The clinical impact of this association need to be analyzed, taking into account the efficacy of TDF, but it is highly plausible that TDF exposure, although associated with reduced kidney function, has no severe adverse effects over the long term for most HIV-positive patients.”

More information here

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