Influence of Hepatitis C Virus Co-Infection and Hepatitis C Virus Treatment on Risk of Chronic Kidney Disease in HIV-Positive Persons

Amanda Mocroft; Lene Ryom; Cristiana Oprea; Qiuju Li; Andri Rauch; Christoph Boesecke; Vilma Uzdaviniene; Dalibor Sedlacek; Josep M. Llibre; Karine Lacombe; Lars N. Nielsen; Eric Florence; Inka Aho; Nikoloz Chkhartishvili; János Szlavik; Gordana Dragovic; Clifford Leen; Helen Sambatakou; Therese Staub; Montse Laguno; Hila Elinav; Janez Tomažič; Lars Peters

Disclosures

AIDS. 2020;34(10):1485-1495. 

In This Article

Abstract and Introduction

Abstract

Background: Hepatitis C virus (HCV) infection has been associated with increased risk of chronic kidney disease (CKD). We investigated the impact of HCV cure on CKD in HIV-positive persons in the EuroSIDA study.

Methods: HIV-positive persons with known HCV status and at least three serum creatinine measurements after 1/1/2004 were compared based on time-updated HCV-RNA and HCV treatment: anti-HCV-negative, spontaneously cleared HCV, chronic untreated HCV, successfully treated HCV, and HCV-RNA positive after HCV treatment. Poisson regression compared incidence rates of CKD [confirmed (>3 months apart) eGFR <60 ml/min per 1.73 m2] between HCV strata.

Results: Fourteen thousand, seven hundred and fifty-four persons were included; at baseline 9273 (62.9%) were HCV-Ab negative, 696 (4.7%) spontaneous clearers, 3021 (20.5%) chronically infected, 922 (6.2%) successfully treated and 842 (5.7%) HCV-RNA positive after treatment. During 115 335 person-years of follow-up (PYFU), 1128 (7.6%) developed CKD; crude incidence 9.8/1000 PYFU (95% CI 9.2–10.4). After adjustment, persons anti-HCV negative [adjusted incidence rate ratio (aIRR) 0.59; 95% CI 0.46–0.75] and spontaneous clearers (aIRR 0.67; 95% CI 0.47–0.97) had significantly lower rates of CKD compared with those cured whereas persons chronically infected (aIRR 0.85; 95% CI 0.65–1.12) and HCV-RNA positive after treatment (aIRR 0.71; 95% CI 0.49–1.04) had similar rates. Analysis in those without F3/F4 liver fibrosis using a more rigorous definition of CKD showed similar results.

Conclusion: This large study found no evidence that successful HCV treatment reduced CKD incidence. Confounding by indication, where those with highest risk of CKD were prioritized for HCV treatment in the DAA era, may contribute to these findings.

Introduction

Hepatitis C virus (HCV) coinfection has been implicated in a range of extrahepatic diseases in HIV-positive persons including kidney disease.[1–6] Some studies found those with chronic HCV infection had more chronic kidney disease (CKD) compared with those with spontaneously cleared infection,[1,3] whereas Butt et al.[7] found no difference comparing those with chronic and cleared infection. Many of the earlier studies were limited by lack of data on HCV-RNA, and were therefore unable to distinguish between chronic untreated or spontaneously cleared HCV infection. The impact of HCV-related systemic inflammation and risk of CKD remains unclear, as highlighted in a recent review.[8]

The introduction of direct-acting antivirals (DAAs) for the treatment of HCV has had a major impact on HCV treatment[9] with cure rates in excess of 90% in persons coinfected with both HIV and HCV.[10] Case reports have shown that achievement of a sustained virological response (SVR) resulted in improvement in kidney function in persons with HCV-related glomerular nephritis.[11] Cohort studies, including 100–350 persons with SVR and with no known underlying renal disorder, have been unable to document an improvement in kidney function in those with SVR compared with those treated for HCV without SVR.[12–14] One further study reported a protective effect of SVR on CKD,[15] which did not reach statistical significance and did not adjust for baseline renal function. Changes in renal function in these studies was measured in a variety of ways, and while slopes or rate of change in estimated glomerular filtration rate (eGFR) might be useful to study short-term changes in renal function, a more rigorous definition of renal decline requiring confirmed low values over a period of 3 months, such as CKD,[2] has greater clinical relevance, given its association with other clinical events, including cardiovascular disease.[16]

Given the lack of consensus from previous studies, methodological issues, and the limited power and/or follow-up, we sought to investigate the incidence of CKD in a large pan-European multicohort study according to HCV status in HIV-coinfected persons across five groups: anti-HCV-negative, spontaneous HCV-RNA clearers, chronic untreated HCV infection, cured HCV, and HCV-RNA-positive following HCV treatment.

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