Treating HCV infection in HIV-patients – An interview with Dr. Jan T.M. van der Meer
|
As an internist in the department of Infectious Diseases at the AMC in Amsterdam, Dr. van der Meer treats a broad range of conditions and diseases. In the AMC outpatient facilities the majority of patients he treats are infected with HIV. Within this patient group he is treating an increasing number of HCV infections. Dr. van der Meer met with us to share his expertise in treating HCV infection in HIV co-infected patients. |
 |
Could you please explain when you started to see cases of HCV infection in HIV-infected individuals?
We started to see HCV co-infections around 10 years ago particularly in homosexual men. Before then, HCV was relatively uncommon in HIV-infected patients. We did see co-infections in the known risk groups such as haemophiliacs and injecting drug users but then we started to see HCV co-infections in patients who had not been exposed to HCV along the usual transmission routes. We actually saw the first of these patients in 2004, and in international literature the first HIV/HCV co-infected patient outside the known transmission routes was recorded in 2003. Since then we have seen a substantial increase in the number of acute HCV infections in homosexual HIV-infected patients, and this isn’t happening only in the Netherlands but also in other countries around the world. We originally thought that sexual transmission of HCV was rare, but due to the increasing incidence of HCV we believe that it is a possible route of transmission.
Considering that transmission may be through sexual contact, is HCV present in semen as well as blood?
Yes, HCV can be present in semen, and more often so in HIV-infected patients. As I said, sexual transmission may occur, but I believe that transmission through contact with blood from an infected individual is probably the most likely cause. It has been shown that men who participate in rough sex acts are at a higher risk of contracting HCV. However, I also see some patients to whom this does not apply and where the route of transmission is unknown. (Editors note: HCV is not always present in semen but depends largely on the load of HCV in the blood - a higher blood level increases the likelihood that it will be found in semen. In co-infected patients HCV appears in semen at lower levels in the blood than in mono-infected patients. Consequently, in co-infected patients HCV is more often demonstrable in semen.)
Is it possible that individuals are infected with HCV but there is a delay in showing clinical signs of acute infection?
In patients that aren’t infected with HIV, acute infection generally shows within a couple of weeks. In HIV-infected patients we find that it can take some months before we see any sign of infection. For example, a HIV-infected patient is diagnosed with an acute HCV infection in July based on an increase an increase in liver enzymes, but testing of earlier blood samples shows that he actually had HCV present in the blood in January of that year.
How does the current HCV treatment affect HIV-infected patients on cART?
It’s relatively safe to combine peginterferon and ribavirin with most HIV medications. The exceptions are zidovudine and didanosine, which don’t combine well. There is some speculation that abacavir may decrease the chances of a successful HCV treatment, but that still needs to be proven.
Is there a difference in treatment response in mono- and co-infected individuals?
It is generally more difficult to treat HCV infection in patients with HIV than without. Treatment success also depends greatly on the HCV genotype. Genotypes 1 and 4 are more prevalent in HIV-infected patients and these are generally less responsive to treatment than genotypes 2 and 3. In HIV-infected patients with chronic HCV genotype 1 and 4 infections the treatment success rate is around 30% (versus 40 to 50% in HCV mono-infected patients), and with genotype 2 and 3 infections it is around 40% (versus 70 to 80%). Treatment duration is also longer than in HIV co-infected patients and can be up to 72 weeks in patients infected with HCV genotype 1 or 4 (versus 48 weeks in HCV mono-infected patients). For acute HCV infection, the treatment response in HIV co-infected patients is better than for chronic infections with success rates of around 75%, but this is again less than HCV mono-infected patients who achieve treatment success rates of close to 100%.
Are the treatment side effects different in mono- or co-infected patients?
The consequences of treatment differ. HIV-infected patients have lower numbers of white blood cells including CD4 cells, and that is what makes them more susceptible to opportunistic infections. Otherwise the side effects of treatment are similar.
New HCV medications will soon be available. Will they improve the treatment response of HIV co-infected patients?
Studies of the anti-HCV drugs boceprevir and telaprevir in HIV-infected patients are ongoing but the preliminary results are promising. As treatment was only completed in the studies around three months ago, the final treatment success rate is not yet known, but from preliminary results it appears to be around 60-70%. (Treatment success rates are known six months after treatment and are based on there being no measurable HCV RNA in the blood). As in mono-infected patients, these medications are used in combination with peginterferon and ribavirine and only target HCV genotype 1. If these treatments could improve success rates up to 70% it would be a tremendous improvement on the current success rate of around 30% for HCV genotype 1 infections. The new medications will be available in April and I plan to start prescribing them then.
How will the new HCV medications interact with cART medications?
The new HCV medications are inhibitors of an enzyme that metabolizes some of the antiretroviral drugs, for example, protease inhibitors. In addition, antiretroviral drugs may affect plasma levels of the new HCV medications. As a result, it will not be possible to combine the new medication with all antiretroviral combinations.
In relation to side effects for boceprevir and telaprevir, we will have to see how HIV-infected patients are affected. The more common side effects, such as a rash and anaemia, may be worse in HIV-infected patients but that is still uncertain. We will have to keep a close eye on the severity of side effects in HIV-infected patients.