London School of Hygine and Tropical Medicine
Selected Studies of HIV/HCV Co-infection from the 52nd Annual Meeting of the American
Association for the Study of Liver Disease (AASLD,)Dallas, Texas, USA
The
52nd annual meeting of the AASLD centered along two main lines with
regard to issues concerning co-infection of HIV with HCV: Studies of the
natural history of co-infection and studies concerning the treatment of HCV in
individuals who also have HIV.
Treatment and Survival
One
of the central questions addressed at this meeting was “When should anti-HCV
therapies begin for individuals also infected with HIV?”. In a study by Tarek
Hassanein from the University of California at San Diego, individuals with
HIV+HCV co-infection who were deemed “compliant” in their medical care were
compared to those with similar co-infection who were not “compliant”, and also
to those with HIV mono-infection. The study found significant differences in
survival rates between the groups, and found that those who were adherent to
therapy and who actively sought specialized care for their co-infection had
better survival rates than coinfected individuals who did not. In a study from
France, it was observed that those with HIV+/HCV co-infection got liver
cirrhosis earlier and tended to suffer more problems related to liver failure
when compared to those with HCV alone. The authors concluded that treatment for
HCV should be initiated as soon as possible and that liver transplantation for
those who do not respond should be discussed as well. Taken together, these
studies suggest individuals with co-infection should be encouraged to seek
specialist medical care as early as possible.
With
respect to therapy, a central topic of this year’s meeting was whether drugs
used to treat hepatitis C were well-tolerated and as efficacious in individuals
co-infected with HIV. Preliminary data were presented on treatment of
150 individuals with HIV+HCV co-infection with Roche’s Pegasys (a type of
pegylated interferon, which is a longer lasting form of interferon that is
currently going through trials).
In the treatment of HCV, anti-HCV drugs are typically
given for 12 weeks, and if they achieve a virologic response (undetectable
viral levels, which is typically <100 copies of virus/mL of blood), treatment is continued. The length of this treatment varies, depending upon the
genotype of virus an individual is infected with. Genotype 1 viruses are
treated for a longer period of time than others. The virus levels at the end of
the treatment period are assessed at this point. Then, 6 months after
discontinuation of therapy, viral levels are assessed again. If viral levels
are still undetectable at this point, an individual is considered a “sustained
responder.”
The
Pegasys study found that the drug appeared to be well-tolerated and that
no unexpected adverse events were seen. It is worth noting that these are
preliminary data based on week 12 of treatment and that the trial has not been
completed yet. In this study, participants received monotherapy with Pegasys for 12 weeks and then intensified treatment with ribavirin. 19% had undetectable HCV RNA at week 12, and a further 33% had experienced an HCV RNA reduction of more than 2 log (from a mean baseline HCV RNA of 6 log IU/ml).
Another
study, by Edmund Bini, found no significant differences with respect to end of
treatment response in those with HIV+HCV and HCV alone with the use of
interferon + ribavirin on 32 individuals with HCV+/HIV and 64 with HCV
alone. In the entire group studied,
26.6% with HCV alone and 21.9% with co-infection achieved sustained response.
These differences are not statistically significant. Subgroup analysis
suggested that infection with HCV genotype 1 or genotypes 2 and 3 made no
difference to response either. There was no significant reduction in CD4 cell count in the HIV/HCV group as a result of ribavirin treatment. No serious adverse events or deaths in either
group were observed. The authors concluded that “combination therapy with
interferon and ribavirin is safe and efficacious for the treatment of HCV in
patients co-infected with HIV. Co-infected patients have a sustained virologic
response rate that is no different from patients who are not infected with
HIV.”
In
contrast, a study comparing daily induction dosing of interferon and ribavirin
to standard three times weekly interferon and ribavirin for 6 months showed
differences in response rates between HCV genotype 1 and non-1 infection.
Individuals infected with genotype 1 were less likely to achieve a sustained
response. This may be due to the fact that these patients received only 6
months of therapy (individuals infected with genotype 1 viruses normally
receive 1 year of therapy). Overall, however, they found interferon/ribavirin
to be well-tolerated in individuals co-infected with HCV and HIV.
References:
Hassanein
TI, et al. Survival in HCV/HIV co-infected patients. AASLD, Dallas,
Abstract 234, 2001.
Di
Martino V, et al. Impact of HIV co-infection on the age and the cause of
death in patients with HCV cirrhosis. AASLD, Dallas, Abstract 1095, 2001.
Bini
EJ, et al. Safety and efficacy of interferon alpha-2b and ribavirin combinations
therapy for the treatment of hepatitis C in patients co-infected with HIV.
AASLD, Dallas, Abstract 653, 2001.
Juarez
A. et al. Randomized trial of interferon A plus ribavirin versus
peg-interferon and ribavirin in HIV HCV co-infected patients: interim report on
safety data. AALSD, Dallas, Abstract 985, 2001.