Changes in Kidney Function and in the Rate of Tubular Dysfunction After Tenofovir Withdrawal or Continuation in HIV-Infected Patients

Casado, José L.; Rey, José Manuel del; Bañón, Sara; Santiuste, Carmen; Rodríguez, M.R. Diz; Moreno, Ana; Pérez-Elías, María Jesús; Liaño, Fernando; Moreno, Santiago

doi:10.1097/qai.0000000000000986

Cited by 31 publications

(36 citation statements)

References 29 publications

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“…Previously, there have been a few case reports describing the reversal of ADV and TDF-related Fanconi's syndrome after TDF withdrawal in patients with CHB [12,26]. In contrast, our study showed that nucleotide analogue-related PRTD could be resolved in 16 CHB patients after discontinuation of nucleotide analogue similar to the phenomenon that occurs in HIV-infected patients [21][22][23][24][25]. The complete reversal of nucleotide analogue PRTD occurred in 81% of the patients at one year.…”

Section: Discussioncontrasting

confidence: 45%

“…In contrast to these studies [4][5][6]17], PRTD and impaired phosphate renal tubular reabsorption were seen in 15-48% of CHB patients receiving long-term ADV and TDF therapy as in real world clinical experience [8,10,[18][19][20]. Reversibility of renal dysfunction has been shown in HIV-infected patients after cessation of TDF [21][22][23][24][25]. A few cases of reversible TDF or ADV-induced PRTD and Fanconi's syndrome have been reported in CHB patients after stopping treatment with nucleotide analogues [12,26].…”

Section: Introductionmentioning

confidence: 69%

“…The accumulation of TDF within proximal renal tubules can lead to mitochondrial injury, which has been proposed as a mechanism of TDF-induced nephrotoxicity and PRTD [36]. Discontinuation of TDF helps prevent the progression of TDF-induced nephrotoxicity despite incomplete reversibility [21,22,36].…”

Section: ｇ０／mentioning

confidence: 99%

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809 Reversal of Proximal Renal Tubular Dysfunction After Nucleotide Analogue Withdrawal in Chronic Hepatitis B

Sobhonslidsuk¹,

Wanichanuwat²,

Numthavaj³

et al. 2016

Gastroenterology

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Section: Discussioncontrasting

confidence: 45%

Section: Introductionmentioning

confidence: 69%

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809 Reversal of Proximal Renal Tubular Dysfunction After Nucleotide Analogue Withdrawal in Chronic Hepatitis B

Sobhonslidsuk¹,

Wanichanuwat²,

Numthavaj³

et al. 2016

Gastroenterology

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“…Older age or a lower baseline creatinine clearance (≤90ml/min) at the initiation of PrEP were each independently associated with a faster rate of renal decline or a risk of CrCl falling ≤60ml/min or ≤70ml/min, especially with daily dosing, so more intensive safety monitoring in patients with these baseline characteristics may be indicated. Other treatment settings have shown similar risk factors (age and marginal renal function) for TDF-associated toxicity 8–14 and two other PrEP studies have shown that older age predicts greater declines in renal function on PrEP. 5,6 …”

Section: Discussionmentioning

confidence: 81%

“…With TDF/FTC-based treatment, greater declines in renal function are associated with longer duration of TDF use 8–11 , as well as older age 8,12,13 or lower baseline renal function 11,14 at TDF initiation. In the placebo-controlled efficacy trials of PrEP, baseline renal function was required to be within normal range prior to randomization, and trial participants were generally young.…”

Section: Introductionmentioning

confidence: 99%

Association of age, baseline kidney function, and medication exposure with declines in creatinine clearance on pre-exposure prophylaxis: an observational cohort study

et al. 2016

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SUMMARY Background As pre-exposure prophylaxis (PrEP) with tenofovir-disoproxil-fumarate/emtricitabine (TDF/FTC) for the prevention of HIV infection enters a phase of global roll-out, strategies to maintain effectiveness, but minimize adverse effects, merit close consideration. The aim of this study was to evaluate rates and predictors of renal toxicity in a large open-label study of PrEP to help provide guidance on safety monitoring with this important prevention strategy. Methods The iPrEx open-label-extension (OLE) study (NCT00458393) enrolled HIV-negative MSM/transgender participants from three previous PrEP trials from Brazil, Ecuador, Peru, South Africa, Thailand, and the U.S into an open-label PrEP study. There were no restrictions on current renal function for enrollment into iPrEx OLE.. Creatinine clearance (CrCl) on PrEP was estimated every 12 weeks and in a subset, hair samples were collected for measuring tenofovir (TFV)/FTC concentrations via liquid-chromatography/tandem-mass-spectrometry. Change in CrCl from baseline was calculated and predictors identified. Findings Baseline characteristics of participants in iPrEx-OLE (n=1224; 7475 person-visits) and its hair substudy (n=220; 1114 person-visits) were similar. Over 72 weeks (median), the average decline in CrCl was −2·9% (p<0.0001), but declines were significantly greater for those starting PrEP at older ages (−4·2% (95% CI −2·8%, −5·5%), baseline age 40–50 years; −4·9% (−3·1%, −6·8%), age ≥50). Besides age, baseline CrCl of <90ml/min in multivariate models predicted renal decline. There was a monotonic relationship between percent decrease in CrCl and number of doses of TDF/FTC taken per week as estimated by hair levels (p 0.008). Interpretation With the global roll-out of PrEP, our analysis suggests that the frequency of safety monitoring may differ by age group and that pharmacologic measures of adherence can additionally monitor for toxicities. Funding NIH

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Diagnosis, prevention, and treatment of bone fragility in people living with HIV: a position statement from the Swiss Association against Osteoporosis

et al. 2019

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Life expectancy of people living with HIV (PLWH) is reaching similar length as in the general population. Accordingly, age-related comorbidities, including osteoporosis, are increasing. Fracture risk is higher and increases approximately 10 years earlier in PLWH. Classical risk factors of bone fragility are highly prevalent in PLWH but factors specific for HIV infection itself and the type of antiretroviral therapy (ART) (triple combination antiretroviral therapy) regimen (especially tenofovir and protease inhibitors) also contribute to bone loss. The majority of bone loss occurs during virus activity and at initiation of ART (immune reconstitution) and is associated with an increase of bone resorption (upregulation RANKL). Recent data indicate that calcium and vitamin D supplements as ART initiation lower BMD loss. The reduction of tenofovir plasma concentrations with tenofovir alafenamide attenuates BMD loss but it remains unknown whether it will contribute to reduce fracture risk. Hence, special considerations for the management of bone fragility in PLWH are warranted. Based on the current state of epidemiology and pathophysiology of osteoporosis in PLWH, we provide the consensus of the Swiss Association against Osteoporosis on best practice for diagnosis, prevention, and management of osteoporosis in this population. Periodic assessment of fracture risk is indicated in all HIV patients and general preventive measures should be implemented. All postmenopausal women, men above 50 years of age, and patients with other clinical risk for fragility fractures qualify for BMD measurement. An algorithm clarifies when treatment with bisphosphonates and review of ART regimen in favour of more bone-friendly options are indicated.

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Changes in Kidney Function and in the Rate of Tubular Dysfunction After Tenofovir Withdrawal or Continuation in HIV-Infected Patients

Abstract: Our data support the role of use and time on TDF in eGFR decline and tubular dysfunction. In contrast, TDF withdrawal is followed by a rapid and significant, although partial, recovery of eGFR and tubular abnormalities.

Cited by 31 publications

References 29 publications

809 Reversal of Proximal Renal Tubular Dysfunction After Nucleotide Analogue Withdrawal in Chronic Hepatitis B

809 Reversal of Proximal Renal Tubular Dysfunction After Nucleotide Analogue Withdrawal in Chronic Hepatitis B

Association of age, baseline kidney function, and medication exposure with declines in creatinine clearance on pre-exposure prophylaxis: an observational cohort study

Diagnosis, prevention, and treatment of bone fragility in people living with HIV: a position statement from the Swiss Association against Osteoporosis

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