Nucleoside/nucleotide analogue therapy slows liver disease in HIV/HBV-co-infected patients

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The progression of liver disease is slowed in patients co-infected with HIV and hepatitis B when their antiretroviral therapy includes drugs that are active against both infections, Spanish investigators report in the online edition of AIDS.

A minority of patients cleared hepatitis B infection and 17% of individuals experienced an improvement in their fibrosis stage.

However, one patient developed liver cancer despite having only mild fibrosis.



Scarring of the liver – the development of hard, fibrous tissue. See also ‘cirrhosis’, which is more severe scarring.

hepatitis B virus (HBV)

The hepatitis B virus can be spread through sexual contact, sharing of contaminated needles and syringes, needlestick injuries and during childbirth. Hepatitis B infection may be either short-lived and rapidly cleared in less than six months by the immune system (acute infection) or lifelong (chronic). The infection can lead to serious illnesses such as cirrhosis and liver cancer. A vaccine is available to prevent the infection.

hepatitis D virus (HDV)

The hepatitis D (or Delta) virus only affects people who are already infected with hepatitis B, as it needs the hepatitis B virus to be able to survive in the body. Coinfection with HBV and HDV results in more severe complications than with HBV alone. The HBV vaccine protects against HDV because of the latter's dependence on the former.


Severe fibrosis, or scarring of organs. The structure of the organs is altered, and their function diminished. The term cirrhosis is often used in relation to the liver. 

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

Nevertheless, the investigators believe that the results of their study “strongly suggest that long-term control of HBV [hepatitis B virus] replication with potent anti-HBV active antiretroviral regimens may slow down liver fibrosis progression in HIV-HBV-co-infected patients.”

Co-infection with HIV accelerates the pace of liver disease caused by hepatitis B. However, some anti-HIV drugs from the nucleoside/nucleotide reverse transcriptase inhibitor class – 3TC (lamivudine, Epivir), FTC (emtricitabine, Emtriva), and tenofovir (Viread) – are also active against hepatitis B. It is therefore recommended that HIV/hepatitis B co-infected patients should be treated with an antiretroviral regimen that includes a combination of these drugs.

Encouraging short-term results have been seen in co-infected individuals, but longer-term data concerning the impact of therapy with these drugs on liver disease are currently lacking.

Investigators in Madrid therefore designed a retrospective study involving 92 co-infected patients. Liver fibrosis was assessed using FibroScan, a non-invasive scan for liver damage, and both virologic and clinical outcomes were monitored.

Most of the patients (88%) were men and the median on entry to the study was 41 years. At baseline, the patients had been living with diagnosed HIV/hepatitis B co-infection for a median of four years.

A total of 42 patients were HBeAg-positive, and 75% were taking anti-HIV drugs with activity against both viruses. A quarter of patients had a FibroScan before starting HIV therapy, 21% were co-infected with hepatitis delta, and a further 31% with hepatitis C.

Fibrosis stage at baseline was null or mild in 48%, moderate to severe in 28%, and 24% had cirrhosis.

The patients were followed for a median of 35 months. Overall, 13 individuals were lost to follow-up, and of the 79 remaining patients, all but two took antiretroviral therapy that included drugs with activity against hepatitis B.

At the end of follow-up, 71 patients had an undetectable hepatitis B viral load. HBsAg was cleared by seven patients, all of whom had achieved an undetectable hepatitis B viral load. Two of the patients were co-infected with hepatitis delta.

In addition, eleven patients cleared HBe-Ag.

Six patients died, and the overall mortality rate was 2.2 per 100 person-years. Four of the deaths were directly attributable to liver disease. Eight patients experienced at least one episode of decompensated liver disease, the incidence rate being 2.9 per 100 person-years. One of the patients, a 62-year old man, had only mild fibrosis at baseline and did not have any other hepatitis co-infections. He nevertheless developed liver cancer.

The investigators emphasise that half of the patients who experienced decompensated liver disease were co-infected with hepatitis delta.

A repeat FibroScan was performed on 71 patients. Compared to baseline, there was a significant increase in the proportion of patients with either no or mild fibrosis (65% vs. 48%, p = 0.03).

Overall, fibrosis stage remained unchanged in 75% of individuals, worsened in 8% and improved in 17%.

Factors associated with the development of cirrhosis were co-infection with hepatitis C (p < 0.01) and a low CD4 cell count (p <0.01).

“The use of potent nucleos(t)ide analogues as part of antiretroviral therapy in HIV-HBV-coinfected patient seems to be associated with increased rates of serum HBeAg and HBsAg clearance and amelioration of liver fibrosis progression, which ultimately leads to an improvement in survival,” comment the researchers.

However, they emphasise, “oral nucleos(t)ide analogue therapy does not entirely annul the risk of hepatic decompensation events or death in this population, including the development of hepatocellular carcinoma.”


Martin-Carbonero L et al. Clinical and virological outcomes in HIV-infected patients with chronic hepatitis B on long-term nucleos(t)ide analogues. AIDS, online edition: DOI: 10. 1097/QAD.0b013e328340fde2, 2010 (click here for access to the free abstract).

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