Entecavir and Truvada an option for HBV for treatment-experienced HIV/HBV-co-infected patients

Michael Carter
30 March 2011

A combination of entecavir with Truvada is an effective and safe option for HIV/hepatitis B-co-infected patients whose current therapy is not suppressing hepatitis B viral load, investigators from the north of England report in the online edition of AIDS.

“Our study shows that this combination in co-infected patients appears safe and has efficacy, with reductions in HBV [hepatitis B virus] DNA and nearly 40% achieving an undetectable viral load in just over a year,” comment the investigators, who emphasise that their patients had extensive experience of hepatitis B therapy.

HIV and hepatitis B share modes of transmission and a significant proportion of HIV-positive patients are co-infected with hepatitis B virus.

Liver disease caused by hepatitis B is a significant cause of illness and death in patients with HIV.

A number of drugs are available to treat hepatitis B, and many of these also have activity against HIV, and their inappropriate use can lead to the emergence of strains of HIV that are resistant to antiretrovirals. Co-infected patients therefore need specialist care and their treatment needs to be closely monitored.

Current European and British treatment guidelines recommend that HIV/hepatitis B-co-infected patients should start antiretroviral therapy when their CD4 cell count is between 350-500 cells/mm3 and should take a combination of drugs that is based upon tenofovir with either FTC or 3TC. These drugs work against both viruses.

Entecavir has been shown to be a safe and effective option for patients with hepatitis B mono-infection and guidelines support the combination of the drug with tenofovir for co-infected patients. However, there is only limited information on the efficacy of this regimen. Investigators in Liverpool and Manchester therefore designed a study involving 13 co-infected patients with previous experience of hepatitis B therapy, but a detectable hepatitis B viral load despite taking tenofovir-based treatment.

All the patients were male, 85% were white, and their median age was 45. The median time since HIV diagnosis was twelve years.

The 13 individuals had extensive experience of hepatitis B therapy, and had taken 3TC for a median of six years, and a combination of tenofovir with FTC or 3TC for a median of 18 months. Despite this therapy, none of the patients had a fully suppressed hepatitis B viral load.

All 13 patients were taking HIV therapy with a tenofovir/FTC (Truvada) backbone, combined with a protease inhibitor.

Hepatitis B resistance tests were performed on eight patients at baseline, and these showed that one individual had mutations associated with previous 3TC therapy. This resistance developed when the patient was taking antiretroviral therapy consisting of a protease inhibitor and Truvada that fully suppressed his HIV viral load.

Seven patients had had a liver biopsy, and results showed that three had cirrhosis.

Therapy with entecavir/Truvada was provided for a median of 72 weeks. By the end of the study, 38% of patients had an undetectable hepatitis B viral load. The median reduction in hepatitis B viral load was 2.53 log10 iu/ml.

In 62% of patients, ALT levels, an important measure of liver function, were within the normal range, and 92% of individuals experienced an improvement in ALT levels compared to baseline.

No entecavir-related side-effects were recorded, and therapy with the drug did not cause any changes in kidney function. However, one patient stopped taking tenofovir after he developed tubular toxicity related to the drug.

“[The] combination of entecavir and Truvada could be considered as a potentially important treatment option,” comment the investigators, who believe their results provide “encouragement for patients who fail to suppress fully over periods of time, particularly in relation to tolerance and side effects as well as viral suppression itself.”

However, the researchers acknowledge that their study was small and write, “further larger studies with longer follow-up are urgently required to assess this combination as well as other approaches.”

They nevertheless conclude that the addition of entecavir to Truvada “is not unreasonable particularly in those with progressing liver disease who will be at high risk of cirrhosis, hepatocellular cancer, hepatic decompensation and death.”