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Impact of Diabetes and Age on Kidneys During DAA Therapy for HCV/HIV
  16th European AIDS Conference, October 25-27, 2017. Milan
Mark Mascolini
Older age and diabetes appeared to have a bigger negative impact on kidney function than kidney-toxic drugs during HCV treatment with direct-acting antivirals (DAAs) for people with HIV infection [1]. This 394-person Italian ICONA/HepaIcona analysis found that kidney function tended to improve during DAA therapy in people with initially impaired kidneys, while function tended to worsen in people with initially healthier kidneys.
ICONA investigators who conducted this study noted that people coinfected with HCV and HIV run up to a 75% higher risk of chronic kidney disease (CKD) than people infected only with HIV. But research links successful HCV therapy to slightly lower CKD incidence in people with HIV [2]. ICONA researchers planned this cohort analysis to track changes in renal function by estimated glomerular filtration rate (eGFR) during and after DAA therapy and to identify factors linked to eGFR changes.
The analysis involved HCV/HIV-coinfected ICONA cohort members treated with DAAs between February 2013 and December 2016. Everyone had at least 12 weeks of follow-up after DAA therapy ended and regular eGFR measures by the CKD-EPI formula during and after DAA therapy. The researchers used mixed linear regression models (1) to estimate average eGFR changes from baseline to different follow-up points and (2) to pinpoint baseline factors associated with eGFR changes.
Among the 394 study participants, 16 (4%) had an initial eGFR below 60 mL/min, 112 (28%) had an eGFR of 60 to 90 mL/min, and 266 (68%) had an eGFR above 90 mL/min. Median age did not differ significantly across the three groups (53 years); nor did proportion of men (78% overall), years on antiretroviral therapy (17.1), or proportions with diabetes (9%) or cirrhosis (44%). But proportions with previous kidney disease or hypertension were significantly higher in the group with the lowest baseline eGFR. The three eGFR groups did not differ significantly in baseline CD4 count (median 562 overall), proportion with an HIV load below 50 copies (94% overall), or proportion taking tenofovir disoproxil fumarate (TDF) (68%), an HIV protease inhibitor (34%), or an integrase inhibitor (55%).
Half of the cohort members had previous treatment with interferon/ribavirin, 43% took a sofosbuvir-containing regimen, and 93% attained sustained virologic response 12 weeks after DAA therapy ended (SVR12).
Average eGFR declined significantly from baseline (1) throughout a median 12.9 months of follow-up (-0.36); (2) during DAA therapy (-0.39); (3) 12 weeks after DAA therapy (-0.26), and 24 weeks after DAA therapy (-0.42) (P < 0.0001 for all changes from baseline). But eGFR change differed across the three baseline eGFR groups. Among people below 60 mL/min at baseline, average eGFR rose 12 weeks after DAA treatment ended (+0.62, P = 0.039), but overall change during follow-up was not significant (+0.07, P = 0.732). Among cohort members starting at 60 to 90 mL/min, the 12-week end-of-treatment change (+0.18, P = 0.082) and overall change (-0.13, P = 0.089) did not reach statistical significance. In people starting at more than 90 mL/min, eGFR fell significantly both 12 weeks after treatment ended (-0.52, P < 0.0001) and overall (-0.49, P < 0.0001).
eGFR tended to fall more if people took DAAs with a TDF-containing antiretroviral regimen than with a non-TDF regimen, whether the DAAs were ledipasvir/sofosbuvir (overall -0.28 without TDF, -0.53 with TDF) or a nonsofosbuvir regimen (overall -0.16 without TDF, -0.34 with TDF). But overall eGFR decline was greater with sofosbuvir alone without TDF than with sofosbuvir alone with TDF (-0.49 without TDF, -0.30 with TDF).
Four factors were associated with greater adjusted difference in eGFR change per month:
-- Each additional year of age: -0.23 (95% confidence interval [CI] -0.41 to -0.05), P = 0.013
-- Diabetes: -3.45 (95% CI -6.09 to -0.80), P = 0.011
-- Initial eGFR below 60 versus above 90: +6.07 (95% CI +0.51 to +11.63), P = 0.032
-- Initial eGFR 60 to 90 versus above 90: +5.13 (95% CI +3.19 to +7.08), P < 0.001
There was a trend toward greater decline in adjusted difference in eGFR change with TDF regimens: -1.72 (95% CI -3.59 to +0.16), P = 0.072.
The ICONA team proposed that pre-DAA eGFR may determine eGFR trajectory during therapy, with improving eGFR in people who have worse kidney function at baseline and worsening eGFR in those with a higher baseline eGFR. The researchers suggested that older age and metabolic comorbidities (specifically diabetes) appear to have a greater detrimental impact on kidney function during DAA therapy than do potentially kidney-toxic drugs.
1. Cingolani A, Galli L, Lapadula G, et al. Evolution of renal function during treatment with direct antiviral agents (DAA-t) in HIV/HCV infected patients in ICONA/HepaIcona cohorts. 16th European AIDS Conference. October 25-27, 2017. Milan. Abstract PS9/2. 2. Kovari H, Rauch A, Kouyos R, et al. Hepatitis C infection and the risk of non-liver-related morbidity and mortality in HIV-infected persons in the Swiss HIV Cohort Study. Clin Infect Dis. 2017;64:490-497. www.natap.org/2017/HIV/ciw809.pdf