Tenofovir Remains Effective against Hepatitis B Virus after 5 Years in HIV/HBV Coinfected Patients

	SUMMARY: Tenofovir (Viread, also in the Truvada and Atripla combination pills) continues to potently suppress both hepatitis B virus (HBV) and HIV in coinfected patients for at least 5 years, according to a study published in the December 2010 issue of Gastroenterology. The findings support current guidelines recommending that HIV/HBV coinfected people should receive an antiretroviral therapy (ART) regimen that includes drugs with dual action against both viruses.

By Liz Highleyman

Due to overlapping routes of transmission, many people are infected with both HIV and HBV. Although the viruses are not related, some nucleoside/nucleotide analog drugs are active against both, including tenofovir, lamivudine (3TC; Epivir), and emtricitabine (FTC; Emtriva).

Theodora de Vries-Sluijs from Erasmus University Medical Center in the Netherlands and colleagues investigated the long-term efficacy and kidney safety of tenofovir administered to HIV/HBV coinfected patients as part of a complete ART regimen.

This prospective cohort study included 102 coinfected participants at 6 centers in the Netherlands who were treated with tenofovir, either as their sole anti-HBV drug or in combination with lamivudine or emtricitabine. 33 patients had taken lamivudine previously and developed resistance mutations. At baseline 80% had detectable HBV DNA viral load > 20 IU/mL. Participants were followed for an average of 4.5 years.

Results

	Among 67 patients who had detectable HBV DNA at baseline and were hepatitis B "e" antigen (HBeAg) positive, 92% experienced virological response (HBV DNA < 20 IU/mL) after 5 years of treatment.
	Response rates did not differ significantly between patients with or without lamivudine resistance at baseline.
	46% of these patients experienced HBeAg loss and 12 achieved hepatitis B surface antigen (HBsAg) loss.
	Among 15 baseline detectable HBeAg negative patients, 100% experienced virological response after 4 years of treatment.
	2 of these individuals (13%) experienced HBsAg loss.
	20 participants (20%) -- all HBeAg negative -- had undetectable HBV DNA at baseline.
	During a median follow-up period of 52 months, all but 1 (95%) inthis group maintained undetectable HBV viral load.
	2 of these patients (10%) experienced HBsAg loss.
	HBV viral decay occurred at similar rates in people with and without lamivudine resistance mutations.
	Overall, 1 patient developed a combination of drug resistance mutations for anti-HBV drugs and experienced virological breakthrough.
	3 people (3%) discontinued tenofovir due to elevated serum creatinine levels, an indicators of possible kidney dysfunction.
	The estimated decrease in kidney function after 5 years on tenofovir was 9.8 mL/min/1.73 m2, and was most pronounced shortly after starting the drug.
	3 patients -- all with cirrhosis at baseline -- developed hepatocellular carcinoma during follow-up.

"[Tenofovir], administered as part of antiretroviral therapy, is a potent anti-HBV agent with a good resistance profile throughout 5 years of therapy," the investigators concluded. "Only small non-progressive decreases in renal function were observed."

It is well know that anti-HIV drugs must be used in combination regimens to prevent drug resistance, but the issue of whether to start hepatitis B treatment with combination therapy or sequential monotherapy remains a point of controversy.

In an accompanying editorial, Maurizio Bonacini from the HIV-Liver Clinic at California Pacific Medical Center wrote, "In HIV/HBV coinfected patients, the frequent usage of Truvada makes the peace between proponents of sequential monotherapy and those who suggest that combination therapy may be needed from the beginning."

Investigator affiliations: Departments of Internal Medicine-Infectious Diseases, Gastroenterology & Hepatology, Virology, and Biostatistics, Erasmus MC University Medical Center, Rotterdam, Netherlands; Department of Medical Microbiology, Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, Netherlands; Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, Amsterdam, Netherlands; Department of Internal Medicine-Infectious Diseases, University Medical Center, Utrecht, Netherlands; Department of Internal Medicine, Rijnstate Hospital, Arnhem, Netherlands; Department of Internal Medicine, Slotervaart Hospital, Amsterdam, Netherlands.

2/18/11

References

T de Vries-Sluijs, J Reijnders, B Hansen, and others. Long-term therapy with tenofovir is effective for patients co-infected with human immunodeficiency virus and hepatitis B virus. Gastroenterology 139(6): 1934-1941 (Free full text). December 2010.

M Bonacini. Virologic and clinical outcomes in HIV/HBV coinfected patients on tenofovir-containing HAART. Gastroenterology 139(6): 1827-1829. December 2010.