Renal effects of novel antiretroviral drugs

Milburn, James; Jones, Rachael; Levy, Jeremy

doi:10.1093/ndt/gfw064

Cited by 48 publications

(57 citation statements)

References 45 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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“…With respect to CKD screening, in contrast to routine lab-monitoring, a targeted approach based on a CKD risk score could be adapted to African populations and applied during treatment initiation [ 29 ]. Additionally, HIV programmes should consider the use of newer ARTs with less nephrotoxic effects such as integrase inhibitors and Tenofovir alafenamide (TAF), in particular if continuous renal monitoring is not feasible [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Assessment of renal function in routine care of people living with HIV on ART in a resource-limited setting in urban Zambia

et al. 2017

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IntroductionData on renal impairment in sub-Saharan Africa (SSA) remains scarce, determination of renal function is not part of routine assessments. We evaluated renal function and blood pressure in a cohort of people living with HIV (PLWH) on antiretroviral treatment (ART) in the Renal Care Zambia project (ReCaZa).MethodsUsing routine data from an HIV outpatient clinic from 2011–2013, we retrospectively estimated the glomerular filtration rate (eGFR, CKD-Epi formula) of PLWH on ART in Lusaka, Zambia. Data were included if adults had had at least one serum creatinine recorded and had been on ART for a minimum of three months. We investigated the differences in eGFR between ART subgroups with and without tenofovir disproxil fumarate (TDF), and applied multivariable linear models to associate ART and eGFR, adjusted for eGFR before ART initiation.Results and discussionAmong 1118 PLWH (63,3% female, mean age 41.8 years, 83% ever on TDF; median duration 1461 [range 98 to 4342] days) on ART, 28.3% had an eGFR <90 ml/min, and 5.5% <60 ml/min at their last measurement. Information on other conditions associated with renal impairment was not systematically documented. Fourteen per cent of the PLWH who later switched to TDF-free ART had an initial eGFR lower 60ml/min. Nineteen percent had first-time hypertensive readings at their last visit. The multivariable models suggest that physicians acted according to guidelines and replaced TDF-containing ART if patients developed moderate/severe renal impairment.ConclusionsAssessment of renal function in SSA remains a challenge. The vast majority of PLWH benefit from long-term ART, including improved renal function. However, approximately 5% of PLWH on ART may have clinically relevant decreased eGFR, and 27% hypertension. While a routine renal assessment might not be feasible, strategies to identify patients at risk are warranted. Targeted monitoring prior and during ART is recommended, however, should not delay ART access.

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“…However, comorbidities and ART may lead to renal injury [ 2 ]. The incidence of chronic kidney disease (CKD) in patients living with HIV (PLWH) ranges from 2 to 17% although the extent of renal injury depends on individual patient factors [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Renal effects of non-tenofovir antiretroviral therapy in patients living with HIV

McLaughlin¹,

Guerrero²,

Merker³

2018

DIC

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A review of literature published regarding non-tenofovir antiretroviral agents causing renal adverse effects was conducted. The literature involving renal adverse effects and antiretroviral therapy is most robust with protease inhibitors, specifically atazanavir and indinavir, and includes reports of crystalluria, leukocyturia, nephritis, nephrolithiasis, nephropathy and urolithiasis. Several case reports describe potential nephropathy (including Fanconi syndrome) secondary to administration of abacavir, didanosine, lamivudine and stavudine. Case reports documented renal events such as acute renal failure, nephritis, proteinuria and renal stones with efavirenz administration. Regarding rilpivirine, a small increase of serum creatinine levels (SCr) was found in clinical trials; however, the clinical significance and impact on actual renal function is unknown. The integrase strand transfer inhibitors and enfuvirtide have a relatively safe renal profile, although studies have shown dolutegravir and raltegravir cause mild elevations in SCr without an impact on actual renal function. This is similar to the reaction observed with cobicistat, the pharmacokinetic enhancer frequently given with elvitegravir.

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Renal effects of novel antiretroviral drugs

Cited by 48 publications

References 45 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

Assessment of renal function in routine care of people living with HIV on ART in a resource-limited setting in urban Zambia

Renal effects of non-tenofovir antiretroviral therapy in patients living with HIV

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