Model-informed intermittent tenofovir disoproxil fumarate and emtricitabine dosing for HIV pre-exposure prophylaxis in subjects with renal impairment: a case report

Zino, Leena; Jacobs, Tom; Nieuwenstein, Thomas; Grintjes, Karin; Colbers, Angela; Burger, David M.

doi:10.1097/qad.0000000000003438

Cited by 2 publications

(2 citation statements)

References 9 publications

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“…16 Propositions to adapt the on-demand dosing regimen for users with eGFR ranging from 15 to 50 mL/minute has also been made. 17 Besides, our study pointed out that some CKS were related to the misclassification by creatinine-based equations of users with high-protein intake for weight training. This suggests that the incidence of renal impairment has probably been overestimated in previous PrEP cohorts of MSM.…”

Section: Discussionmentioning

confidence: 76%

Brief Report: Incidence and Management of Complex Kidney Situations Among On-Demand and Daily HIV Pre-Exposure Prophylaxis Users

Liegeon,

Brun,

Hamet

et al. 2024

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background:We evaluated complex pre-exposure prophylaxis (PrEP) situations linked to kidney issues in a cohort of on-demand and daily PrEP users. Setting:We conducted a single-center retrospective cohort study in France including all PrEP users who received a tenofovir disoproxil (TD)-emtricitabine (FTC) prescription between January 1, 2012 and December 31, 2019 with at least 1 creatinine measurement available before and after PrEP initiation.Methods: A complex kidney situation (CKS) was defined as an estimated glomerular filtration rate (eGFR) ,60 mL/minute/1.73m 2 on 2 consecutive measurements. We estimated the incidence of this event, described case management, and identified associated factors using a Cox model.Results: Three thousand one hundred and fourteen individuals were included in this study. Almost all were men (99%) with a median age of 35 years, 25% had an eGFR ,90 mL/minute/1.73m 2 at baseline, and 65% used on-demand PrEP. Nine users (0.29%) had a CKS at baseline; 8/9 initiated on-demand PrEP without renal function worsening after a median (interquartile range [IQR]) follow-up time of 14 months (7-31). Thirteen cases of CKS occurred during the follow-up for a 0.25 per 100 person-years incidence (95% confidence interval [CI]: [0.14; 0.45]). On-demand PrEP was used in 7/13 participants with no further episode of confirmed eGFR ,60 mL/ minute/1.73m 2 after a 17-month median follow-up . CKS was associated with an age $50 years (hazard ratio [HR] 13, 95% CI: [4-39]) or with a baseline eGFR ,90 mL/minute/1.73m 2 (HR 34, 95% CI: [4-261]). 9/22 CKS were linked to high-protein intake for weight training.Conclusions: CKS were rare in our cohort. On-demand PrEP did not result in subsequent renal function worsening in these few situations.

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Section: Discussionmentioning

confidence: 76%

Brief Report: Incidence and Management of Complex Kidney Situations Among On-Demand and Daily HIV Pre-Exposure Prophylaxis Users

Liegeon,

Brun,

Hamet

et al. 2024

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…As their population model did not allow for mechanistic scaling of kidney parameters, an additional pragmatic clearance component was included to correct for a reduction in tubular secretion in children with CKD. In contrast, we adopted a more mechanistic approach by reducing kidney size and PTCPGK, similar to previous PBPK studies with adult CKD populations [ 27 , 28 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Lamivudine and Emtricitabine Dosing Proposal for Children with HIV and Chronic Kidney Disease, Supported by Physiologically Based Pharmacokinetic Modelling

et al. 2023

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Dose recommendations for lamivudine or emtricitabine in children with HIV and chronic kidney disease (CKD) are absent or not supported by clinical data. Physiologically based pharmacokinetic (PBPK) models have the potential to facilitate dose selection for these drugs in this population. Existing lamivudine and emtricitabine compound models in Simcyp® (v21) were verified in adult populations with and without CKD and in non-CKD paediatric populations. We developed paediatric CKD population models reflecting subjects with a reduced glomerular filtration and tubular secretion, based on extrapolation from adult CKD population models. These models were verified using ganciclovir as a surrogate compound. Then, lamivudine and emtricitabine dosing strategies were simulated in virtual paediatric CKD populations. The compound and paediatric CKD population models were verified successfully (prediction error within 0.5- to 2-fold). The mean AUC ratios in children (GFR-adjusted dose in CKD population/standard dose in population with normal kidney function) were 1.15 and 1.23 for lamivudine, and 1.20 and 1.30 for emtricitabine, with grade-3- and -4-stage CKD, respectively. With the developed paediatric CKD population PBPK models, GFR-adjusted lamivudine and emtricitabine dosages in children with CKD resulted in adequate drug exposure, supporting paediatric GFR-adjusted dosing. Clinical studies are needed to confirm these findings.

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Model-informed intermittent tenofovir disoproxil fumarate and emtricitabine dosing for HIV pre-exposure prophylaxis in subjects with renal impairment: a case report

Cited by 2 publications

References 9 publications

Brief Report: Incidence and Management of Complex Kidney Situations Among On-Demand and Daily HIV Pre-Exposure Prophylaxis Users

Brief Report: Incidence and Management of Complex Kidney Situations Among On-Demand and Daily HIV Pre-Exposure Prophylaxis Users

Lamivudine and Emtricitabine Dosing Proposal for Children with HIV and Chronic Kidney Disease, Supported by Physiologically Based Pharmacokinetic Modelling

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