This was an interesting session summarizing the epidemiology, natural history, diagnoses and management strategies for HBV and HCV among HIV-infected paitents.

Lewin started by pointing out that the mortality of HIV/HBV co-infected patients is significantly high: >14/100 patient-years, or one order of magnitude over that of either HBV or HIV alone.  This high mortality persists despite the high success rates of HBV-active HAART (high rates of HBV virologic response and HBeAg seroconversions).  He then presented an overview of the pathogenesis of HBV in the context of HIV co-infection, focusing on the factors promoting disease progression and might explain the high mortality.  These include: 1) virological factors (among HIV-infected patients, despite virologic response – assessed by DNA clearance – HbsAg titers do not significantly decline; while cumulative risk of hepatocellular carcinoma is significantly higher if the clearance of HBsAg occurs after age 50); 2) immunological factors (there is reduced HBV-specific CD4+ T-cells in HIV-HBV co-infected patients on HAART); 3) hepatic factors (highlighting the fact that immune activation is an important pathophysiologic mechanism for HBV liver disease, hepatic stellate cells – that drive fibrosis – express high levels of CXCR4; and HIV infection increases their activation); and 4) treatment factors (with HAART hepatotoxicity compounding HBV-induced liver damage, and hepatic flare following discontinuation of HAART being a major issue).

Wiersma from WHO presented an overview of the scaling up of global access to hepatitis B vaccination.  He placed the importance on HBV immunization at birth, pointing out that the immunity is expected to be life-long and that this will make the other intervention (adult immunization) time-dependent and eventually obsolete.

Juan Pineda from Seville, Spain presented a nice overview of the diagnosis and monitoring of hepatitis B and C co-infected patients.

• About HIV/HCV patients, all should get HCV antibody testing at first visit and periodically if negative.  Antibody-positive patients and those with unexplained abnormal liver functions should get HCV PCR is reserved for patients, and genotype should be performed if treatment is planned.  He then advocated the measurement of liver fibrosis because it’s a prognostic indicator and has an impact in management decisions, presenting the relative advantages and drawbacks of liver biopsy, serologic testing of fibrosis and elastography (the latter two being less precise in patients with intermediate fibrosis).  He then had a very clear graphic description of the potential treatment responses from rapid response (undetectable HCV viremia by week 4), complete virologic response (2-log drop in viremia or undetectable viremia at week 12), to sustained virologic response (undetectable viremia 24 weeks after end of treatment). 
• Moving on to HIV/HBV patients, the serologic diagnosis is evidently more complex: all patients should get HBsAg, Anti-HBs, Anti-HBc (EIA) testing at initial visit.  All HBsAg positive patients should get HBeAg, Anti-HBe (EIA) testing and HBV DNA should be performed in all chronic HBV infections and patients with isolated Anti-HBc.  In assessment of liver injury, transaminases should suffice and most HIV/HBV patients should not require liver biopsy.  Non-invasive markers (biomarkers and transient elastography perform as well as in HCV with roughly similar cut-offs for elastography.  A similar pictorial description of the response monitoring was presented.  However, for hepatitis B, besides monitoring virologic response, one should also monitor HBsAg-to-HBsAb and HBeAg-to-HBeAb seroconversions.

Pointing out that the availability of the HCV replicon has made it easier to identify HCV treatment target and assess responses, Bhagani first gave an overview of the substantial HCV drug pipeline which includes protease inhibitors (the closest to the market being telaprevir and boceprevir), polymerase inhibitors, entry inhibitors and others such as immune modulators.  He however pointed out that many questions remain including how the findings apply to HIV-infected patients (as no study involved HBV/HIV co-infected patients), potential emergence of resistance and drug-drug interactions.  He then drew attention to the new epidemic of acute HCV infection among MSMs which has spread beyond Europe.  In concordance with what Lewin discussed earlier, he pointed that progression to end-stage liver disease has improved in the HAART era, but remains significantly higher in HIV/HCV than HCV-only patients.   Also, better control glucose metabolism is associated with improvement in liver fibrosis in HIV-infected patients.

The speaker then went on to outline factors predictive of clinical response to HCV, including acute infection, low viremia, younger age, lack of stage ¾ fibrosis or steatosis, ethnicity, low BMI, high CD4 and lack of insulin resistance.  Finally he discussed potential strategies to maximize treatment response.  We’ll highlight that longer duration of undetectability on treatment increases chance for SVR, which is why the current guidelines total duration of HCV treatment depends on the speed of achieving undetectability.  Increasing the interferon dose did not alter the response rate.

Finally, regarding HBV, he highlighted the importance of lamivudine resistance on disease progression, and the caution about the efficacy of entecavir on HIV replication.

Sarah Lewin presented an overview of the pathogenesis of HIV-HBV coinfection. Liver-related mortality remains high in the HAART era, despite patients being on HBV active drugs. HBV DNA remains the major determinant of liver disease progression and the role of immune activation and microbial translocation in HIV-HBV co-infection needs to be explored. Management of HBV immune reconstitution syndrome needs to be improved. Stephen Wiersma presented data from the global scale-up of Hepatitis B vaccine, with particular attention to the updated recommendation that all infants should be vaccinated within 24 hours of birth even in low-prevalence areas. Efforts to make the vaccine widely available are improved by target-setting and the development of regional strategies. Offering the vaccine to HBc positive individuals with or without prior screening will depend on regional cost-benefit analyses. Juan Pineda reviewed data on diagnosis and monitoring of Hepatitis B and C infections with particular attention to the performance of newer tests using elastography or biomarkers for each viral infection. Lastly, S. Bhagani gave an overview of the clinical management of co-infected patients. There is evidence that the presence of the metabolic syndrome (hepatic steatois,  increased BMI and insulin resistance) adversely influences the course of liver disease in co-infected patients and reduces the likelihood of sustained virological response in patients treated with ribavirin. Longer treatment duration seems to translate to more sustained response. Newer drugs are in the pipeline but their usefulness in co-infected patients remains to be established. Early HAART containing two HBV active agents should be advocated for most co-infected patients, even in those with preserved CD4 counts.