HCV/HIV Flashcards
What is the rate of HCV positivity in HIV positive IVDU?
83% (7% in HIV-MSM)
Why is there an overlap between HIV and HCV?
due to transmission routes
How many HCV genotypes are there?
6
What is the most prevalent genotype across the world?
genotype 1
Where is HCV genotype 6 found?
south east asia
What is the difference between the genotypes seen in general UK and HIV positive populations?
general- G1 and G3; HIV-positive- G1 and G4
How many people with acute HCV infection undergo spontaneous clearance?
5-20%
What are the outcomes 30 years after acute HCV in patients who have chronic HCV?
30% no liver disease; 40% liver fibrosis; 30% cirrhosis; HCC
What are the major risk factors for disease progression?
male; older age at acuisition; alcohol
does HIV affect the progression in HCV?
there is a suggestion that HIV patients can have very rapid fibrosis in acute infection but resutls are conflicting and imperfect (surrogate measures); is faster even with HAART?; increased reinfection and recurrence
what is the rate of lvier-related deaths due to HCV in HIV patients in developed coutnries?
10%
What is fibroscan?
ultrasound that estimates liver stiffness as a surrogate marker of fibrosis
What are the differences in acute HCV presentation in HIV patietns?
often asymptomatic; antibody development can be very late so molecular testing is needed (v. expensive)
What is a problem with fibroscan?
can be confounded by inflammation
What are the risk factors for HCV acquisition in HIV positive MSM?
recreational drug use; higher numbers of sexual partners/ group sex; high risk sexual practices- fisting; bloody sex
Why does HCV prevention remain crucial?
no sign of effective vaccine in the near future
What are the non-viral aspects of managing HCV in HIV positive patietns?
co-medication; weight; HAV and HBV vaccinations; alcohol intake; optimise HAART
Why can HBV infection not be fully eradicated?
persistence of viral cccDNA in host cells
Why is cccDNA a problem if not integrated into the cellular genome?
has a long half-life and is able to transmit to progeny cells; reservoir for viral reactivation
Why can a sustained virologic response be achieved in HCV?
has an entirely cytoplasmic life cycle and does not have a known form of persistence or latency in host cells
What does cccDNA stand for?
covalently closed circular DNA
When is HCV deemed to have achieved cure?
if 12 weeks after end of treatment there is no virus in the blood
What is the effect of SVR on mortality?
greatly reduces mortality compared to contorl, especially when coinfected with HIV or when have cirrhosis
What are the problems with curing HCV?
chance of failure; serious AE of Rx and quality of life during Rx; costs
What is the mode of action of pegylated interferon?
directly hinders the replication process of the virus; enhances the immune repsonse
What is pegylation?
a large molecular chain is attached to the integeron to slow the rate at which it is broken down
What is the function of ribavirin?
synthetic antiviral nucleoside analogue that works with interferon but not on its own and inhibits viral growth
What was the problem with all first generation protease inhibitors?
activity against genotype 1, some against 2 and 4 but no activity against 3
What is sofosbuvir?
specific nucleotide analog inhibitor of HCV NS5B
what is the benefit of sofosbuvir?
potent with broad genotype coverage with or without inteferon; high barriers to resistance
What is the current rate of SVR?
94-99%
What was the drug regimen for SVR in 2015?
peg interferon; ribavirin; protease inhibitor
What are the 3 classes of directly acting antivirals for HCV?
NS5a inhibitors; protease inhibitors and polymerase inhibitors
What are the benefits of the newer drugs for HCV?
shorter duration; fewer SEs; better efficacy; avoid inteferons
How many deaths does viral hepatitis cause globally?
7th leading cause of death
What type of virus is hep C?
RNA flavivirus
