antiretroviral therapy is associated with improvements in liver function in
HIV-positive men with and without viral hepatitis co-infection, investigators
from the United States report in the online edition of the Journal of Acquired Immune Deficiency Syndromes.
in the Multicenter AIDS Cohort Study (MACS) had their liver function monitored
using aspartate aminotransferase to platelet ratio index (APRI) before and
after starting HIV therapy. Liver function declined significantly in both mono-
and co-infected men in the period before therapy was started. Initiating
antiretrovirals was associated with an improvement in APRI, and this was
associated with viral load. The beneficial effects of antiretroviral therapy
waned after two years for the mono-infected men, possibly because of the
toxicities associated with older anti-HIV drugs.
that HAART [highly active antiretroviral therapy] is associated with
improvement in APRI in HIV-infected men with and without viral hepatitis,”
comment the researchers. “Our observation that men with undetectable HIV RNA
had the largest decreases in APRI and that the effect was reduced progressively
with increasing HIV RNA supports the hypothesis that the beneficial hepatic
effects of HAART are mediated via suppression of HIV replication.”
Liver disease is a
major cause of serious illness and death in HIV-positive patients who are
co-infected with HBV and/or HCV. Declines in liver function have also been
observed in men with HIV mono-infection. Immune suppression has been postulated
as a cause of liver dysfunction in the context of untreated HIV infection.
Antiretrovirals may improve liver health, but several anti-HIV drugs are known
to have liver toxicities.
To obtain a clear
understanding of the effects of antiretroviral therapy on liver function,
investigators from MACS designed a prospective study involving HIV-positive men
with and without hepatitis co-infection. APRI – an accepted marker of liver
function – was monitored before and after the initiation of treatment.
population comprised 494 men, of whom 53 had viral hepatitis co-infection (24
HIV/HCV, 27 HIV/HBV, 2 HIV/HBV/HCV).
Liver function was
measured four years and one year prior to HIV therapy being started. Analysis was
repeated two and five years after treatment initiation.
three-quarters of patients (79%) started antiretroviral treatment before 2001
and 87% received therapy with toxic NRTIs such as didanosine and
showed significant increases in APRI in the pre-treatment era for both the
mono- and co-infected patients (0.49 to 0.55, p < 0.01; 1.26 to 1.62, p =
0.02, respectively). In contrast, in the first two years following the
initiation of HIV therapy, mean APRI declined in both the mono-infected (0.55
to 0.53, p = 0.01) and co-infected (1.62 to 1.31, p = 0.07) groups.
for factors such as age, race and CD4 cell count, in mono-infected men APRI
increased by 17% in the period before therapy was started. Changes in liver
function in the first two years after initiating treatment were related to
viral load. APRI decreased by 16% for men with viral suppression, by 2% for
patients with a viral load between 500 and 75,000 copies/ml and increased by
47% for individuals with a viral load above 75,000 copies/ml. Analysis through
to five years after treatment initiation showed overall increases in APRI, but APRI did not return to pre-treatment levels..
men, multivariate analysis showed an average increase of 34% in APRI in the
pre-treatment period. Similar to mono-infected patients, changes in APRI in the
two years after therapy initiation were associated with viral load. Patients
with viral suppression had a 22% decrease, while those with a viral load
between 500 and 75,000 copies/ml had a 13% decrease. There were too few
patients with a very high viral load to rigorously analyse the impact of
treatment on liver function.
mono-infected patients, APRI continued to decline among co-infected men with
viral suppression (p = 0.03) through to the five-year follow-up point (mean 8%
exposure to older, more toxic NRTIs was associated with higher APRI after
treatment initiation. After taking this into account, liver function five-years
after starting antiretrovirals among mono-infected men with viral suppression
was significantly better than that observed in the period before treatment was
with suppression of HIV RNA replication in HIV-mono-infected and HIV-viral
hepatitis co-infected men in the first two years after [treatment initiation],”
conclude the authors. “This improvement is greatest in those who achieve an
undetectable HIV RNA.” They call for further research to elucidate the
mechanisms for this improvement and to see if the benefits persist into the
long-term with newer HIV treatment combinations.