Effects on Vitamin D, Bone and the Kidney of Switching from Fixed-Dose Tenofovir Disoproxil Fumarate/Emtricitabine/Efavirenz to Darunavir/ Ritonavir Monotherapy: A Randomized, Controlled Trial (MIDAS)

Hamzah, Lisa; Tiraboschi, Juan; Iveson, Helen; Toby, Martina; Mant, Christine; Cason, John; Burling, Keith; Wandolo, Emily; Jendrulek, Isabelle; Taylor, Chris; Ibrahim, Fowzia; Kulasegaram, Ranjababu; Teague, Alastair; Post, Frank A.; Fox, Julie

doi:10.3851/imp3000

Cited by 23 publications

(26 citation statements)

References 54 publications

(71 reference statements)

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“…Biomarkers of bone turnover were also significantly lower among patients receiving TAF at week 48 compared to patients receiving TDF . There have also been several case reports of improvement of proximal renal tubular function in CHB patients who were switched from TDF to TAF …”

Section: Discussionsupporting

confidence: 59%

“…This finding is clinically relevant given progressively ageing cohort of CHB patients worldwide and particularly the propensity of Asian CHB patients developing osteoporosis as a normal part of senescence . Similar increase in BMD was seen 48 weeks after switching from a TDF‐containing regimen to a TAF‐containing regimen or non–tenofovir‐based anti‐viral therapy among HIV‐infected patients . Taken together, these observations suggest that BMD caused by TDF is reversible.…”

Section: Discussionmentioning

confidence: 99%

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Improvement of bone mineral density and markers of proximal renal tubular function in chronic hepatitis B patients switched from tenofovir disoproxil fumarate to tenofovir alafenamide

Fong

Lee

Tien

et al. 2019

Journal of Viral Hepatitis

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Tenofovir alafenamide (TAF) is a novel prodrug that reduces tenofovir plasma levels by 90% compared to tenofovir disoproxil fumarate (TDF), resulting in decreased bone mineral density (BMD) loss and renal toxicity. We aimed to study changes in BMD and markers of renal function of chronic hepatitis B (CHB) patients previously treated with TDF who were switched to TAF in as early as 12 weeks. This was a prospective single‐arm open‐label study of 75 CHB patients treated with TDF 300 mg daily who were switched to TAF 25 mg daily and followed for 24 weeks. All patients had been treated with TDF for at least 12 months and had HBV DNA <21 IU/mL at the time of switch. BMD and markers of renal function were taken on the day of switch and repeated after 12 and 24 weeks of TAF treatment. Hip and spine bone mineral density significantly increased from baseline to week 12 (+12.9% and +2.4%, respectively, P < 0.01). There were significant decreases in urinary beta‐2‐microglobulin to creatinine and retinol‐binding protein to creatinine ratios by week 12 (P < 0.01 for both). Mean estimated glomerular filtration rate (GFR) did not change. Tubular reabsorption of phosphate was decreased at week 24 (P < 0.05). In conclusion, CHB patients previously treated with TDF experienced significant improvement in bone density and some markers of renal tubular function and as early as 12 weeks after switching to TAF. Bone density changes associated with TDF may not be entirely related to renal handling of phosphate.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Improvement of bone mineral density and markers of proximal renal tubular function in chronic hepatitis B patients switched from tenofovir disoproxil fumarate to tenofovir alafenamide

Fong

Lee

Tien

et al. 2019

Journal of Viral Hepatitis

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“…Table 2 displays switch studies that evaluated BMD change after switches from TDF to non-TDF containing regimens (37–39). Prior to the recently reported TAF switch study (40; described in a subsequent section in this review), the studies were small.…”

Section: Tenofovir Disoproxil Fumarate: Clinical Datamentioning

confidence: 99%

“…Forty-eight weeks after the switch, individuals had a significant increase in BMD from baseline of 3.0% and 2.5% at the lumbar spine and hip, respectively. Finally, the MIDAS Study randomized 64 individuals on efavirenz/emtricitabine/TDF to continued therapy versus a switch to darunavir/ritonavir monotherapy (39). At 48 weeks, individuals randomized to darunavir/ritonavir had a statistically significant improvement in BMD at both the lumbar spine and femoral neck compared to those individuals maintained on their baseline TDF-containing therapy (Lumbar spine change: 0.0% vs. +2.6%; p<0.001; Femoral neck change: 0.0% vs. +2.9%, p<0.001), suggesting that the BMD decrease with TDF initiation may be largely reversible.…”

Section: Tenofovir Disoproxil Fumarate: Clinical Datamentioning

confidence: 99%

Tenofovir and bone health

Grant

Cotter

2016

Current Opinion in HIV and AIDS

122

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Purpose of review With continued improvements to the antiviral efficacy and tolerability of antiretroviral therapy (ART), long term safety of ART has become paramount. Low bone mineral density and fragility fractures are more common in HIV-infected individuals than in the general population. The aims of this review are to describe potential mechanisms underlying the adverse effects of tenofovir on bone, clinical studies of tenofovir disoproxil fumarate (TDF) and bone, and more recent bone data on tenofovir alafenamide (TAF). Recent finding Several studies have demonstrated an approximately 1–3% greater bone mineral density loss with TDF compared with other agents. Recent studies with TAF have shown improved bone (and renal) safety with similar virologic efficacy when compared to TDF. Summary Given these findings, TDF-containing regimens may be gradually replaced with non-TDF containing regimens for the treatment of HIV infection, especially in those at higher risk for fragility fracture.

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“…Virologically suppressed patients in the Monarch RCT substudy who were randomized to DRV/r monotherapy experienced an increase in spine and hip BMD compared with those who were maintained on a 2NRTI + DRV/r regimen [45*]. Similarly, results from the MIDAS study demonstrate an improvement in BMD in patients switched from TDF/FTC/EFV to DRV/r monotherapy [46*]. Similar results were seen in a nonrandomized study in which cART experienced, virologically suppressed patients on a PI/r based regimen containing TDF were switched from TDF to RAL [50].…”

Section: The Bone Effects Of the Hiv Protease Inhibitorsmentioning

confidence: 99%

The protease inhibitors and HIV-associated bone loss

Moran

Weitzmann

Ofotokun

2016

Current Opinion in HIV and AIDS

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Purpose of review HIV infection is an established risk factor for osteoporosis and bone fracture. Combination antiretroviral therapy (cART) increases bone resorption leading to an additional 2–6% bone mineral density (BMD) loss within the first 1–2 years of therapy. While tenofovir disoproxil fumarate is often blamed for antiretroviral drug-associated bone loss, evidence abounds to suggest that other agents, including the protease inhibitors (PI) have adverse bone effects. In the current review, we examine bone loss associated with PI use, describing the relative magnitude of bone loss reported for individual PIs. We also review the potential mechanisms associated with PI-induced bone loss. Recent findings As a class, PIs contribute to a greater degree of bone loss than other anchor drugs. HIV disease reversal and the associated immune reconstitution following cART initiation play an important role in PI-mediated bone loss in addition to plausible direct effects of PIs on bone cells. Summary PIs remain an important component of cART despite their adverse effects on bone. A better understanding of factors that drive HIV/cART-induced bone loss is needed to stem the rising rate of fracture in the HIV-infected population.

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Effects on Vitamin D, Bone and the Kidney of Switching from Fixed-Dose Tenofovir Disoproxil Fumarate/Emtricitabine/Efavirenz to Darunavir/ Ritonavir Monotherapy: A Randomized, Controlled Trial (MIDAS)

Abstract: Switching from TDF/FTC/EFV to DRV/r in patients with suppressed HIV RNA resulted in significant improvements in 25(OH)D and bone biomarkers, and a 2-3% increase in BMD.

Cited by 23 publications

References 54 publications

Improvement of bone mineral density and markers of proximal renal tubular function in chronic hepatitis B patients switched from tenofovir disoproxil fumarate to tenofovir alafenamide

Improvement of bone mineral density and markers of proximal renal tubular function in chronic hepatitis B patients switched from tenofovir disoproxil fumarate to tenofovir alafenamide

Tenofovir and bone health

The protease inhibitors and HIV-associated bone loss

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