Drug Resistance Linked to Faster Hepatitis B Liver Disease Progression in HIV/HBV Coinfected Patients

SUMMARY: HIV/HBV coinfected individuals may be less likely to have hepatitis B virus (HBV) with mutations conferring resistance to lamivudine (3TC; Epivir), but those who do have drug resistance experience faster liver disease progression and are more likely to develop cirrhosis, according to a study from Romania presented last month at the XVIII International AIDS Conference (AIDS 2010) in Vienna.

By Liz Highleyman

Over years or decades, chronic hepatitis B can lead to advanced liver disease including cirrhosis and hepatocellular carcinoma (HCC). Research suggests that this progression happens more rapidly in HIV/HBV coinfected people compared with HIV negative individuals, but effective antiretroviral therapy (ART) may slow the process. A number of drugs used in ART -- including lamivudine, emtricitabine (Emtriva), and tenofovir (Viread) -- are active against both HIV and HBV.

Irina Magdalena from Dumitru Ovidius University in Constanta, Romania, and colleagues looked at the long-term evolution of liver disease among coinfected patients receiving combination ART.

The prospective observation cohort study included 72 HIV/HBV coinfected participants who did not show signs of liver disease at baseline. This group was unlike most US and European HIV cohorts in that just over half (54%) were men and the median age was only 29 years. The median CD4 cell count was low, at 230 cells/mm3. About two-thirds were hepatitis B "e" antigen (HBeAg) negative; none had hepatitis C or D.

Participants were followed for a period of 5 years on ART, and all were taking combination regimens containing a ritonavir-boosted protease inhibitor. Clinical and virological data were collected every 3-6 months and ultrasound imaging was done annually to monitor for liver cancer; FibroScan (transient elastometry) was performed during the last year. All patients with detectable serum HBV DNA viral load were tested for HBV drug resistance.

Results 

• While no patients had signs of liver disease at the beginning of the study, 8 of 72 (11%) had advanced disease after 5 years of follow-up:

          --5 cases of liver cirrhosis;
          --2 cases of hepatocellular carcinoma;
          --1 case of fulminant hepatitis.

• All patients with advanced liver disease had high serum HBV DNA but undetectable HIV.
• All had lamivudine resistance (mutations M204V, M204I, L180M, L80I).
• 5 of these 8 patients died.
• The remaining 64 patients had no signs of active liver disease, with ALT levels normal or < 2 x upper limit of normal and fibrosis stage F0-F1 (absent to mild) according to Fibroscan. 
• Among patients without advanced liver disease, 10 had lamivudine resistance. 

Based on these findings, the researchers concluded, "In HIV/HBV coinfected patients treated with HAART, lamivudine resistance is less frequent (25%) than in immunocompetent patients (higher than 60%), but when [it] occurred, [it] was associated with an accelerated course of liver disease, with faster progression to cirrhosis, liver insufficiency and HCC."

"Appropriate monitoring of chronic viral hepatitis B in HIV positive patients include[s] the recognition of lamivudine resistance in every case of detectable HBV DNA level," they recommended.

Ovidius University Constanta, Faculty of Medicine, Constanta, Romania; Clinical Infectious Diseases Hospital, Constanta, Romania.

8/10/10

Reference
IM Dumitru, E Dumitru, S Rugina, and others. HBV related complications in HIV positive patients during HAART therapy. XVIII International AIDS Conference (AIDS 2010). Vienna, July 18-23, 2010. (Abstract).

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