A detectable hepatitis C viral load is
associated with an increased risk of chronic kidney disease for people with
HIV, European investigators report in the online edition of AIDS.
Patients with ongoing hepatitis C
replication were significantly more likely to develop chronic kidney disease,
compared to HIV-positive people who were hepatitis C-uninfected or who had
cleared hepatitis C.
“The incidence of CKD [chronic kidney
disease] was similar between patients with resolved HCV [hepatitis C virus] infection
and in anti[body]-HCV negative patients, while patients with chronic HCV
infection had a two-fold increased incidence of CKD compared with anti-HCV
negative patients,” write the authors.
Kidney disease remains an important cause
of serious illness and death in people with HIV. Earlier research has shown
that people with antibodies to hepatitis C virus infection are between 50
and 75% more likely to develop chronic kidney disease than HIV-positive
people who were not co-infected with hepatitis C.
The impact of ongoing replication of
hepatitis C virus on the progression of kidney disease in co-infected patients
is uncertain. Therefore, investigators from the EuroSIDA cohort designed a study
involving 8235 patients who received care after 2004.
These patients were divided into three
groups according to their hepatitis C infection status:
- Hepatitis C antibody-negative.
- Hepatitis C antibody-positive/hepatitis
C RNA-negative (cleared hepatitis C infection).
- Hepatitis C antibody-positive/hepatitis
C RNA-positive (chronic hepatitis C infection).
Chronic kidney disease was defined as
having either an estimated glomerular filtration rate (eGFR) of or below 60
ml/min/1.73 m2 for patients with an eGFR above this level at
baseline, or a confirmed 25% decline in eGFR for patients with a baseline
measurement of or below 60 ml/min/1.73 m2.
Rates of progression to chronic kidney
disease were compared according to the participants’ hepatitis C infection status.
The investigators also conducted analyses to see if any other factors were
associated with the development of kidney disease.
A quarter of participants were hepatitis C
antibody-positive at baseline. Approximately half (48%) of these people were
hepatitis C RNA-positive; 9% had cleared their hepatitis C virus infection and 43%
had no RNA data available.
During a total of 36,123 person-years of
follow-up, a total of 495 patients (6%) progressed to chronic kidney disease.
The overall incidence was 13.7 per 1000 person-years of follow-up.
Incidence differed according to hepatitis C
It was lowest (7.8 per 1000 person-years)
in people who had never been infected with hepatitis C. Incidence among
patients who had cleared hepatitis C infection was 14.5 per 1000 person-years,
and this increased to 18.7 per 1000 person-years for co-infected patients with
ongoing hepatitis C replication.
Treatment with the anti-HIV drugs tenofovir
(Viread, also in Truvada, Atripla and Eviplera), atazanavir (Reyataz) and lopinavir/ritonavir (Kaletra) were all associated with the
development of kidney disease.
“Current guidelines from the European AIDS
Clinical Sciety recommend that HIV patients initiating ART that includes one
of these drugs should be monitored more frequently for the development of CKD,”
emphasise the researchers.
There was also a significant association
between diabetes and the development of renal problems (p < 0.0001).
The investigator found that, overall,
people with antibodies to hepatitis C (RNA-negative and RNA-positive) were
almost twice as likely to progress to chronic kidney disease as hepatitis C uninfected
individuals (IRR = 1.85; 95% CI, 1.49-2.30; p < 0.0001).
However, further analysis showed that it
was only people with detectable hepatitis C RNA who had an increased risk of
Incidence of kidney disease was comparable
between hepatitis C-uninfected participants and the participants who had cleared
hepatitis C virus infection.
Compared to these people, a hepatitis C
viral load below 500,000 iu/ml increased the risk of progression to chronic
kidney disease by 88% (IRR = 1.88; 95% CI, 1.31-2.71; 0 = 0.0006). The risk was
even higher for patients with a hepatitis C viral load above 500,000 iu/ml (IRR
= 2.10; 95% CI, 1.54-2.87; p < 0.0001).
“These results indicate that the hepatitis
C virus itself is a significant risk factor for the development of CKD in HIV
co-infected patients,” comment the investigators.
The risk of kidney disease was not affected
by hepatitis C genotype.
“If our results are confirmed by others,
future larger studies are warranted to explore the reversibility of CKD in
patients undergoing anti-HCV therapy,” conclude the investigators. The authors
suggest that studies could also “investigate the interaction between HIV/HCV
co-infection and certain antiretroviral drugs known to be nephrotoxic”.