Improved kidney function in patients who switch their protease inhibitor from atazanavir or lopinavir to darunavir

José, Sophie; Nelson, Mark; Phillips, Andrew; Chadwick, David; Trevelion, Roy; Jones, Rachael; Williams, D I; Hamzah, Lisa; Sabin, Caroline; Post, Frank A.

doi:10.1097/qad.0000000000001353

Cited by 31 publications

(27 citation statements)

References 30 publications

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“…Interestingly, in our study, we found lower baseline eGFR, nadir CD4 counts, uncontrolled viremia, and current PI/r use associated with incident CKD. Although we did not have adequate power to determine which PI/r was associated with CKD, previous analyses have indicated that ATV causes nephrolithiasis and is associated with development of interstitial nephritis, switching from ATV/r or LPV/r to DRV/r is associated with improvement in kidney function, and use of a concomitant PI/r with TDF amplifies the renal toxicity of the later due to inhibition of Multi‐resistant Protein 4 (MRP‐4) efflux channels in the proximal tubular cells by ritonavir leading to TDF accumulation in the cells …”

Section: Discussionmentioning

confidence: 99%

Changes in renal function with long‐term exposure to antiretroviral therapy in HIV‐infected adults in Asia

Joshi¹,

Boettiger

Kerr

et al. 2018

Pharmacoepidemiology and Drug

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Introduction: Renal disease is common amongst people living with HIV. However, there is limited information on the incidence and risk factors associated with renal dysfunction among this population in Asia. Methods: We used data from the TREAT Asia HIV Observational Database. Patients were included if they started antiretroviral therapy (ART) during or after 2003, had a serum creatinine measurement at ART initiation (baseline) and had at least two follow-up creatinine measurements taken ≥3 months apart. Patients with a baseline estimated glomerular filtration rate (eGFR) ≤60ml/min/1.73m2 were excluded. Chronic kidney disease was defined as two consecutive eGFR values ≤60ml/min/1.73m2 taken ≥3 months apart. Generalized estimating equations were used to identify factors associated with eGFR change. Competing risk regression adjusted for study site, age and sex, and cumulative_incidence plots were used to evaluate factors associated with CKD. Results: Of 2,547 patients eligible for this analysis, tenofovir was being used by 703 (27.6%) at baseline. Tenofovir use, high baseline eGFR, advanced HIV disease stage and low nadir CD4 were associated with a decrease in eGFR during follow up. CKD occurred at a rate of 3.4 per 1000 patient/years. Factors associated with CKD were tenofovir use, old age, low baseline eGFR, low nadir CD4, and protease inhibitor use. Conclusions: There is an urgent need to enhance renal monitoring and management capacity among at-risk groups in Asia and improve access to less nephrotoxic antiretrovirals.

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Section: Discussionmentioning

confidence: 99%

Changes in renal function with long‐term exposure to antiretroviral therapy in HIV‐infected adults in Asia

Joshi¹,

Boettiger

Kerr

et al. 2018

Pharmacoepidemiology and Drug

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“…The chronic kidney disease-epidemiology formulation was used to convert creatinine measurements to eGFR [14], and serial eGFR measurements were used to generate eGFR slopes which capture the direction and rate of change of eGFR and as such provide an indicator of changing renal function over time [15]. Follow-up was stratified by time exposed to TDF (from first to last exposure irrespective of interruptions), time exposed to TAF (censored at TAF discontinuation or last visit on TAF), and time on no ART or non-tenofovir-containing ART (excluded from the analyses).…”

Section: Methodsmentioning

confidence: 99%

“…The models were fully adjusted for the following factors: age at switch, gender, ethnicity, eGFR at TDF/ TAF initiation, and time-updated CD4 cell count, HIV RNA [undetectable (< 50 HIV-1 RNA copies/mL) or detectable] and cumulative TDF use (where relevant). Subgroup analyses were performed that restricted analyses to those with rapid eGFR decline (we considered two definitions: decline in eGFR of > 3 or 5 mL/min/1.73 m 2 / year [15] as estimated from unadjusted eGFR slopes in the mixed effects model) or CKD (defined as eGFR < 60 mL/min/1.73 m 2 ) while receiving TDF. All analyses were performed using STATA 15 (StataCorp LLC, College Station, TX).…”

Section: Methodsmentioning

confidence: 99%

Estimated glomerular filtration rate slopes on tenofovir alafenamide

Ibrahim

Campbell

Bailey³

et al. 2020

HIV Medicine

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Objectives The aim of the study was to analyse and compare estimated glomerular filtration rate (eGFR) slopes during exposure to tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) in individuals who initiated TAF, regardless of prior regimen, before October 2016. Methods An observational cohort study was conducted at 11 clinics in the UK and Ireland. Mixed effects models with random intercept and time terms fitted were used to generate and compare eGFR slopes while participants were exposed to TDF and TAF, with adjustment for age, eGFR at TDF/TAF initiation, gender, ethnicity, and time‐updated CD4 cell count and HIV RNA measurements. Results Data were available for 357 subjects (median age 50 years; 80% male; 82% white/other ethnicity; 51% men who have sex with men; median nadir CD4 count 216 cells/µL). The median duration of exposure to TAF was 2.0 (interquartile range 1.6, 2.3) years. At TAF initiation, the median CD4 count was 557 cells/µL, the median eGFR was 80 mL/min/1.73 m2, and 86% had suppressed HIV infection. The mean adjusted eGFR slope during TDF and TAF exposure was −2.08 [95% confidence interval (CI) −2.24, −1.92] and 1.18 (95% CI 0.20, 1.52) mL/min/1.73 m2/year, respectively (P < 0.001). Individuals who experienced rapid eGFR decline (> 3 or 5 mL/min/1.73 m2/year) while receiving TDF experienced significant eGFR recovery while on TAF (P < 0.001). Conclusions Significant improvement in eGFR slope was observed in patients who switched from TDF‐ to TAF‐containing antiretroviral regimens. These data provide further support for the renal safety of TAF, and for switching those who experience progressive worsening of renal function from TDF to TAF.

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“…[85][86][87][88][89] Observational cohort studies have also linked atazanavir and lopinavir/ritonavir to rapid eGFR decline and incident CKD, 78,79 and switching from ritonavir-boosted atazanavir or lopinavir to boosted darunavir has been associated with improved kidney function. 90 In settings where TAF, abacavir, and darunavir are available, the use of TDF, atazanavir, and lopinavir/ritonavir should ideally be avoided in those with CKD, rapid eGFR decline (>3-5 ml/min per 1.73 m 2 per year), or at high CKD risk. The threshold for avoiding or discontinuing these agents may be influenced by local circumstances.…”

Section: K D I G O E X E C U T I V E C O N C L U S I O N Smentioning

confidence: 99%

Kidney Disease in the Setting of Hiv Infection: Conclusions From a Kidney Disease: Improving Global Outcomes (Kdigo) Controversies Conference

Сванепоэль

Atta

D’Agati

et al. 2018

Nefrologiâ (St.-Peterbg.)

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HIV-positive individuals are at increased risk for kidney disease, including HIV-associated nephropathy, noncollapsing focal segmental glomerulosclerosis, immune-complex kidney disease, and comorbid kidney disease, as well as kidney injury resulting from prolonged exposure to antiretroviral therapy or from opportunistic infections. Clinical guidelines for kidney disease prevention and treatment in HIV-positive individuals are largely extrapolated from studies in the general population, and do not fully incorporate existing knowledge o f the unique HIV-related pathways and genetic factors that contribute to the risk of kidney disease in this population. We convened an international panel of experts in nephrology, renal pathology, and infectious diseases to define the pathology of kidney disease in the setting of HIV infection; describe the role of genetics in the natural history, diagnosis, and treatment of kidney disease in HIV-positive individuals; characterize the renal risk-benefit of antiretroviral therapy for HIV treatment and prevention; and define best practices for the prevention and management of kidney disease in HIV-positive individuals.

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Improved kidney function in patients who switch their protease inhibitor from atazanavir or lopinavir to darunavir

Abstract: Supplemental Digital Content is available in the text

Cited by 31 publications

References 30 publications

Changes in renal function with long‐term exposure to antiretroviral therapy in HIV‐infected adults in Asia

Changes in renal function with long‐term exposure to antiretroviral therapy in HIV‐infected adults in Asia

Estimated glomerular filtration rate slopes on tenofovir alafenamide

Kidney Disease in the Setting of Hiv Infection: Conclusions From a Kidney Disease: Improving Global Outcomes (Kdigo) Controversies Conference

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