Interrupting HIV therapy is associated with the progression
of liver damage in patients co-infected with HIV and hepatitis C, Canadian
investigators report in the online edition of AIDS.
Taking a break from antiretroviral therapy more than doubled
the risk of fibrosis.
“We found a significant, harmful effect of interruption on
the development of fibrosis after accounting for clinical factors,” comment the
investigators, who call for further research into the reasons co-infected
patients take breaks from their HIV treatment.
Liver disease is now a major cause of illness and death in
patients co-infected with HIV and hepatitis C. However, some research suggests that treatment with
antiretroviral drugs protects co-infected patients from the development of
liver disease.
Results of the SMART study showed that interrupting
antiretroviral therapy increased the risk of illness and death from HIV and
non-HIV-related causes, including liver disease.
Although treatment interruptions are not recommended, they still
occur. Canadian investigators hypothesised that breaks from HIV therapy
contributed to the development of liver fibrosis in co-infected patients.
To test this theory they designed a prospective study
involving 514 patients who were enrolled in the Canadian HIV-HCV Co-infection
Cohort (CCC). All the patients were recruited between 2003 and 2009, and none
had fibrosis at baseline.
Liver fibrosis was assessed using a blood test that measured
aspartate aminotransferase (AST)-to-platelet-ratio (APRI). This is a validated
surrogate marker of fibrosis. An APRI score of 1.5 used to diagnose significant
fibrosis and cirrhosis was diagnosed if an individual had an APRI score of 2.0
or above
Patients were assessed at baseline and then at six-monthly
intervals. Blood samples were taken and patients reported if they had
interrupted HIV therapy.
The median duration of follow-up was 1.02 years. During 760
person-years of follow-up, 10% of patients achieved an APRI score of at least
1.5 and 10% interrupted their antiretroviral therapy.
The total number of treatment interruptions was 55, with two
patients interrupting their therapy twice. The median duration of each
interruption was 180 days. Interruptions peaked in 2004 when 15% of individuals
took a break from their HIV treatment.
Overall, only 38% of patients resumed therapy during
follow-up.
Platelet count fell by a median of 2x109/l when
treatment was interrupted and AST increased by 21 u/l.
Statistical analysis that controlled for potentially
confounding factors (including changes in CD4 cell count and viral load) showed
that interrupting HIV therapy more than doubled the risk of liver fibrosis
(hazard ration [HR] = 2.52; 95% CI, 1.20-5.28). A baseline APRI score of
between 0.5-1.49 was also strongly correlated with the progression of liver
disease.
Their analysis also showed a treatment interruptions were
associated with a non-significant increase in the risk of serious clinical
liver disease or cirrhosis (HR = 2.12; 95% CI, 0.87-5.16). The investigators
believe that it was only lack of statistical power that prevented this
relationship from achieving significance.
“Interruption of antiretroviral therapy has been shown to
lead to a greater risk of nonopportunistic disease-related death in randomized
trials, particularly among HIV-HCV co-infected participants,” comment the
investigators.
They believe that the results of their study have for the
first time shown that interrupting HIV treatment “was associated with the
development of significant liver fibrosis among participants co-infected with
HIV and HCV.”
A possible reason for the association is the increased
inflammation that occurs when treatment is interrupted.
However, the investigators acknowledge that their study has
some limitations. Although the APRI score is a validated measure of fibrosis in
co-infected patients, it is known that stopping HIV therapy can lead to changes
in platelet counts. Nevertheless the investigators had confidence in their
findings. Closer analysis of platelet counts and AST scores before and during
treatment breaks lead them to conclude that fibrosis did progress when therapy
was interrupted.
“Studies to determine factors associated with antiretroviral
treatment interruption in co-infected patients would be beneficial to assist
clinicians in reducing treatment discontinuations as would studies aimed at
understanding the underlying mechanisms driving fibrosis in this setting,”
conclude the authors.