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).