A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine analogue in persons with lipoatrophy

Moyle, Graeme; Sabin, Caroline; Cartledge, J; Johnson, Margaret; Wilkins, E.G.L.; Churchill, Duncan; Hay, P; Fakoya, Ade; Murphy, Michael; Scullard, George; Leen, Clifford; Reilly, Geraldine

doi:10.1097/01.aids.0000247574.33998.03

Cited by 248 publications

(196 citation statements)

References 19 publications

Supporting

Mentioning

173

Contrasting

Unclassified

Order By: Relevance

“…So far, only switching away from thymidine analogues (namely stavudine) has been shown to be effective in reversing lipoatrophy (McComsey et al, 2004;Moyle et al, 2006). The effects in these studies were small and only detected by sensitive objective fat measurements (Martin et al, 2004;McComsey et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Uridine supplementation in HIV lipoatrophy: pilot trial on safety and effect on mitochondrial indices

et al. 2007

View full text Add to dashboard Cite

Objectives-Uridine abrogates mitochondrial toxicities of nucleoside reverse transcriptase inhibitor in adipocyte cell culture. We aim to study the effect of uridine supplementation on human adipocyte mitochondrial DNA (mtDNA) levels in subjects with human immunodeficiency (HIV) lipoatrophy.Methods-Sixteen patients with lipoatrophy on stavudine-containing antiretroviral therapy were enrolled, and received NucleomaxX, a dietary supplement with a high bioavailability of uridine (36 g TID every other day for 16 weeks). Patients were then followed off-uridine for another 16 weeks. Highly active antiretroviral therapy remained unchanged during the trial.Results-Fourteen patients completed the study. Two subjects dropped out before week 4 for study-unrelated reasons. No adverse events were noted throughout the study. HIV-1 RNA, CD4 counts, liver enzymes and hemoglobin remained unchanged. Body mass index, lactate, lipids, insulin and homeostasis model assessment of insulin resistance were unaltered. Fat and peripheral blood and mononuclear cell mtDNA levels did not correlate with each other and exhibited no changes throughout the study. Lipoatrophy scores by patients and physician improved significantly at weeks 16 and 32 compared to study entry.Conclusion-In this pilot study, NucleomaxX was safe, well tolerated without apparent deleterious effect on HIV indices. In contrast to in vitro data, NucleomaxX did not lead to changes in fat or blood mtDNA levels.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Lipoatrophy can be partially reversed by substituting stavudine with abacavir or tenofovir or by switching to NRTI-sparing regimens (McComsey et al, 2004;Tebas et al, 2005;Moyle et al, 2006). Unfortunately, the reversal of lipoatrophy in these switch studies has been slow and only partial.…”

Section: Introductionmentioning

confidence: 99%

Uridine supplementation in HIV lipoatrophy: pilot trial on safety and effect on mitochondrial indices

et al. 2007

View full text Add to dashboard Cite

show abstract

“…The RAVE study was a multicentre, open-label, randomized study conducted in a group of 105 individuals with moderate to severe lipodystrophy who were receiving effective ART including either stavudine or zidovudine [23].…”

Section: Methodsmentioning

confidence: 99%

“…We postulated that switching from a thymidine NRTI to either tenofovir DF (TDF) or abacavir (ABC) would result in improvements in facial lipoatrophy. We therefore undertook a substudy of the RAVE Study [23] to determine the effect on facial lipoatrophy of switching ART using 3D surface laser assessment scans.…”

Section: Introductionmentioning

confidence: 99%

Improvements in cheek volume in lipoatrophic individuals switching away from thymidine nucleoside reverse transcriptase inhibitors

et al. 2009

View full text Add to dashboard Cite

Thymidine nucleoside reverse transcriptase inhibitors (NRTIs) are associated with subcutaneous fat loss. Facial changes cannot be assessed by dual-energy X-ray absorptiometry (DEXA) scans. There are limited objective data on the reversibility of facial lipoatrophy. MethodsWe performed a facial volume substudy of a randomized thymidine NRTI replacement study carried out in HIV-infected subjects with moderate to severe lipoatrophy. Facial volume changes were assessed using validated 3D laser imaging. Changes in body composition were measured using DEXA scans. The association between changes in facial volume and body composition parameters at 48 weeks was measured using Spearman's rank correlation. ResultsForty-seven individuals (46 male), 11 receiving zidovudine and 36 receiving stavudine, switched to either tenofovir disoproxil fumarate (DF) (n 5 23) or abacavir (ABC) (n 5 24). Thirty-nine of these 47 patients (84.8%) reported facial lipoatrophy at baseline. The median volume increase in both cheeks from baseline was 1857.3 mm 3 . These volume changes and increases in limb fat at 48 weeks were similar in the two groups and correlated significantly (Spearman's r 5 0.41, P 5 0.004). ConclusionsFacial volume in lipoatrophic individuals was found to increase after thymidine NRTI replacement. We demonstrated a significant correlation between improvements in facial and limb fat parameters. Switching from thymidine NRTIs in patients with facial lipoatrophy could potentially reduce the need for cosmetic interventions.

show abstract

“…Tale modifica della cART, ovviamente, può essere effettuata solo se il nuovo regime farmacologico è sempre in grado di garantire la piena efficacia virologica. Nell'ambito degli inibitori nucleosidici/nucleotidici della transcriptasi inversa (NRTI), i dati della letteratura hanno evidenziato generalmente una riduzione dei valori di trigliceridi, colesterolo totale ed LDL sostituendo stavudina, didanosina o zidovudina con tenofovir (preferibile) o abacavir (in alternativa, se il test HLA B*5701 è negativo) (24,25). Tra gli inibitori non nucleosidici della transcriptasi inversa (NNRTI), efavirenz è associato più spesso a dislipidemia e può essere sostituito, con effetti favorevoli sui parametri lipidici, da altri NNRTI (quali nevirapina, etravirina o rilpivirina) o da un inibitore dell'integrasi (raltegravir) (26)(27)(28)(29)(30).…”

Section: Gestione Del Rischio Cardiovascolare: Stile DI Vita E Terapiunclassified

Gestione del rischio cardiovascolare nel paziente HIV positivo

Calza¹

2017

JHA

View full text Add to dashboard Cite

RiassuntoDopo l'introduzione della moderna terapia antiretrovirale di combinazione (cART), l'infezione da HIV è divenuta una malattia cronica con un notevole prolungamento dell'attesa media di vita dei pazienti HIV-positivi. Di conseguenza le comorbosità tra cui le malattie cardiovascolari, hanno acquisito un'importanza via via crescente in questa popolazione. Nei pazienti con infezione da HIV si osserva infatti un rischio di infarto miocardico acuto significativamente più elevato rispetto alla popolazione generale, ma il meccanismo patogenetico di questa malattia aterosclerotica accelerata è complesso e certamente multifattoriale. La comparsa più frequente della malattia coronarica può essere la conseguenza di una maggiore prevalenza dei fattori di rischio tradizionali (che sono più frequenti tra i soggetti HIV-positivi), ma anche della replicazione diretta del virus e dell'effetto cardiotossico a lungo termine di alcuni farmaci antiretrovirali. Inoltre, nonostante la persistente soppressione della viremia indotta dalla cART generalmente si associ ad una riduzione del rischio cardiovascolare, numerosi studi hanno evidenziato in questi pazienti una condizione di infiammazione e di immunoattivazione cronica, che può condurre al danno endoteliale ed alla malattia aterosclerotica. La corretta gestione del rischio cardiovascolare e la prevenzione della malattia coronarica rappresentano oggi una sfida di primaria importanza per tutti i clinici coinvolti nella cura dei pazienti con infezione da HIV.

show abstract

A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine analogue in persons with lipoatrophy

Cited by 248 publications

References 19 publications

Uridine supplementation in HIV lipoatrophy: pilot trial on safety and effect on mitochondrial indices

Uridine supplementation in HIV lipoatrophy: pilot trial on safety and effect on mitochondrial indices

Improvements in cheek volume in lipoatrophic individuals switching away from thymidine nucleoside reverse transcriptase inhibitors

Gestione del rischio cardiovascolare nel paziente HIV positivo

Contact Info

Product

Resources

About