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Improvements in HIV treatment and care have had no impact on rates of endstage liver disease among HIV-positive patients with viral hepatitis
Michael Carter, 2016-09-05 07:30:00

Incidence of endstage liver disease (ESLD) among HIV-positive patients with viral hepatitis changed little between 1996 and 2010, despite major improvements in HIV treatment and care, investigators from Canada and the United States report in the online edition of Clinical Infectious Diseases

Over 36,000 patients were included in the analysis. There was little evidence that the major advances in HIV therapy that occurred during the study period had a meaningful impact on incidence of ESLD, which remained high among patients co-infected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV). Even in the modern antiretroviral era (2006-2010), over a third of HBV-infected patients were not taking tenofovir – a drug potent against both HIV and HBV – and just 1% of HCV-infected individuals received therapy against this infection.

“This study is the largest and longest prospective evaluation of validated ESLD outcomes conducted in an HIV-infected population,” write the investigators. “ESLD events were common in all time periods studied and occurred more frequently among those with viral hepatitis co-infection.”

End-stage liver disease in this study refers to liver failure leading to liver transplant or laboratory and clinical evidence of severe fibrosis or a clinical event indicating decompensated cirrhosis, such as ascites, bacterial peritonitis, variceal haemorrhage, hepatic encephalopathy or hepatocellular carcinoma.

Around one in five people living with HIV are co-infected with HCV and between 5%-15% are co-infected with HBV. Liver disease is a leading cause of serious illness and death in these patients.

HIV therapy has improved dramatically since it was first introduced in 1996, resulting in greatly improved life expectancy and a steep reduction in illness and death, but it is unclear if these gains in antiretroviral treatment have been accompanied by a fall in rates of ESLD, especially among patients with viral hepatitis co-infection.

Investigators from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) therefore designed a prospective observational study to see if incidence of ESLD as validated by physicians changed according to antiretroviral era – early (1996-2000), middle (2001-2005) and modern (2006-2010) and by viral hepatitis co-infection status. Results were adjusted to take account of hepatitis status, age, sex, race, cohort, CD4 count and HIV viral load.

Adult patients in twelve cohorts were included in the analysis, the study population comprising 34,119 individuals. Overall, 19% were co-infected with HCV, 5% with HBV and 2% were triply infected (HIV/HBV/HCV). Patients were followed for a median of 2.9 years and contributed 129,818 person-years of follow-up. During this time there were 380 incident ESLD events, an incidence ratio of 2.9 per 1000 person years.

Patients developing ESLD were older, more likely to be male, white, had a history of injecting drug use, were co-infected with HCV and/or HBV, had evidence of liver dysfunction or fibrosis at baseline, a low CD4 count and a detectable viral load.

Overall, the proportion of patients developing ESLD did not vary by calendar period or hepatitis status.

The highest incidence of ESLD was observed among triply infected patients (11.57 per 1000 person years), followed by HBV (9.72 per 1000 person years), HCV (6.10 per 1000 person years) and HIV mono-infection (1.27 per 1000 person years). The authors suggest that ESLD in mono-infected patients was probably due to alcohol abuse and/or the side-effects of older anti-HIV drugs.

Comparison between the early and modern antiretroviral eras showed here was little if any evidence in a change of adjusted incidence rate ratios (aIRR) of ESLD among patients with viral hepatitis: HCV = 0.95, 95% CI, 0.61-1.47; HBV = 0.95, 95% CI, 0.40-2.26; triple infection = 1.52, 95% CI, 0.46-5.02.

Increasing rates of HIV suppression were observed over the study period, reaching 85% in the modern treatment era with no difference in suppression rates according to viral hepatitis status.

Could the continuing high rates be explained by sub-optimal hepatitis care? There was some evidence to suggest this could be the case. Only 1% of HCV-infected patients received treatment against this infection, and in the modern antiretroviral era, 35% of HBV-infected patients were not receiving tenofovir.

“HIV infected patients co-infected with HBV or HCV are at markedly increased risk of ESLD compared with those infected with HIV alone,” conclude the investigators. “The continued high incidence of ESLS despite modern ART underscores the urgent need to specifically address HCV and HBV infections in HIV-infected adults. Improved identification, staging, monitoring and treatment of co-infected persons should be prioritized.”

The author of an accompanying editorial calls for further studies to investigate the impact of new HCV therapies on ESLD events in HIV/HCV-co-infected patients, adding “a close follow-up on the effect of cART including drugs active against both HIV and HBV in HBV/HIV co-infected patients is needed to confirm a reduced risk of hepatic decompensation in these patients.”