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Abacavir/lamivudine could be driving liver damage in ART-treated patients with HIV/HCV co-infection
Michael Carter, 2015-10-14 08:20:00
liver fibrosis among ART-treated patients with HIV/HCV co-infection is
associated with the type of nucleoside reverse transcriptase inhibitor (NRTI) “backbone”,
Canadian research published in the online edition of Clinical Infectious Diseases suggests. The study was designed to
see if fibrosis progression was associated with protease inhibitor (PI) or
non-nucleoside reverse transcriptase inhibitor (NNRTI) treatment. However, the
findings showed that progression of liver disease was actually associated with
the NRTIs abacavir/lamividune (Kivexa; ABC/3TC).
progression was assessed by measuring changes in APRI score over five years.
“ABC/3TC use with
either a PI or NNRTI was associated with changes in APRI score over time
regardless of anchor class [PI or NNRTI],” comment the authors. No significant
association between fibrosis progression and treatment with the NRTI backbone
TDF/FTC) was found. The authors do not regard their findings as definitive and
are calling for further research.
A large number of
HIV-positive patients are co-infected with HCV. Co-infected patients experience
faster progression of liver fibrosis compared with HIV-mono-infected patients.
Some antiretroviral drugs have been associated with liver toxicities. However,
no long-term study has evaluated the association between antiretroviral class
and progression of liver disease in co-infected individuals.
the Canadian Co-infection Cohort study therefore designed a study to assess the
progression of liver disease in co-infected patients treated with modern
antiretroviral regimens based – or anchored – on either a PI or NNRTI. The NRTI backbone was
also taken into account.
assessed by measuring changes in APRI score – AST and platelet count. The
authors’ statistical analysis took into account other factors potentially
associated with liver damage, including age, sex, duration of HCV infection,
drug and alcohol use, HIV viral load and CD4 count.
population comprised 628 patients. They were equally divided between PI and
Efavirenz was by
far the most commonly used NNRTI (92%).
frequently used PI was atazanavir/ritonavir (47%), followed by
lopinavir/ritonavir (29%), darunavir/lopinavir (15%) and atazanavir alone (9%).
two-thirds of patients received the Truvada
backbone (PI = 67%; NNRTI = 69%).
The authors’ first
analysis showed that PI therapy was associated with an 11% increase in APRI
score over five years. This compared to a five-year increase of 7% with NNRTI
therapy. The median APRI score was 32% higher among Truvada users when compared to patients treated with Kivexa.
changes in APRI score appeared to be driven by use of the Kivexa backbone. The median five-year increase was 16% when
combined with a PI and 11% when used with a NNRTI.
believe that the association between Kivexa
and liver damage is biologically plausible. “ABC can reduce hepatocyte
proliferation and increase intracellular lipids and lactate levels,” they
explain. “ABC is extensively metabolised by the liver.”
In contrast, Truvada users did not experience a significant increase in APRI
score during follow-up when used with either a PI (8% increase over five years)
or NNRTI (3% increase over five years).
“This study was
designed to investigate the role of the class of anchor agent on progression of
liver fibrosis, not the backbone,” conclude the authors. “Therefore further
investigation is required to better understand how different backbone/anchor
drug combinations can affect the liver of HIV-HCV co-infected persons in the