Dually active antiretroviral therapy protects against hepatitis B infection

Kees Brinkman, Onze Lieve Vrouwe Gasthuis, Amsterdam, presenting at CROI 2013. © Liz Highleyman / hivandhepatitis.com
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Use of antiretroviral therapy that includes drugs active against both hepatitis B virus (HBV) and HIV reduces the risk that people living with HIV will become infected with HBV – in effect acting as HBV pre-exposure prophylaxis (PrEP) – according to a study reported yesterday at the 20th Conference on Retroviruses and Opportunistic Infections (CROI 2013) in Atlanta.

Approximately 6 to 10% of people with HIV are also infected with HBV, and co-infection is associated with more rapid liver disease progression than hepatitis B mono-infection. Although guidelines recommend that people with HIV be vaccinated against HBV, many do not finish the vaccine series or do not fully respond to immunisation and therefore remain susceptible to infection.

Yet the rate of new HBV infections at Onze Lieve Vrouwe Gasthuis – the largest HIV clinic in Amsterdam – has recently been very low, leading Kees Brinkman and colleagues to ask whether antiretroviral drugs with dual activity against HIV and HBV might have contributed to a reduction in the likelihood of primary, or initial, hepatitis B.


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.

acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).


Immunisation is the process whereby a person is made immune or resistant to an infectious disease, typically by the administration of a vaccine. Vaccines stimulate the body’s own immune system to protect the person against subsequent infection or disease.


These dually active agents include tenofovir (Viread, also in the Truvada, Atripla, Complera and Stribild coformulations), 3TC (lamivudine, Epivir), and FTC  (emtricitabine, Emtriva).

Out of a cohort of nearly 3000 people seen at the clinic (2280 of them men who have sex with men [MSM]), investigators retrospectively selected 350 individuals with serological markers indicating that they were uninfected but susceptible to HBV, and who had subsequent samples available for testing to see if their status changed.

At baseline, 1498 participants (51%) were HBV-infected, 389 people (13%) were vaccinated and 871 people (30%) – including 590 MSM – were HBV susceptible.

Looking just at the initially susceptible group, second samples showed that 530 (61%) – including 349 MSM – remained susceptible, 171 (20%) were vaccinated and 35 (4%) were newly HBV-infected. Thirty-three of the people with new HBV infections were MSM, one was a heterosexual man and one was a woman.

People taking no dually active antiretroviral drugs became infected with HBV significantly sooner than those who did so. People taking HBV-active therapy without tenofovir became infected sooner than those who included tenofovir. (Most tenofovir users were also taking 3TC or FTC.)

Based on these findings, the researchers concluded that incident or new HBV infections were indeed "rare". The 35 HBV infections in this study, compared with more than 200 cases of acute hepatitis C virus infection in this population since 2002.

"HBV-active combination ART protects against primary HBV infection", acting as HBV pre-exposure prophylaxis, the investigators concluded, and tenofovir-containing ART is more protective than regimens with 3TC as the only HBV-active drug.

"The necessity to (re)vaccinate against HBV is reduced for patients receiving these drugs," they suggested.


Heuft M et al. Protective effect of hepatitis B virus-active cART against primary hepatitis B virus infection. 20th Conference on Retroviruses and Opportunistic Infections, Atlanta, abstract 33, 2013.

View abstract 33 on the conference website.

A webcast of the session in which this research was presented, Advances in hepatitis therapy, is available on the conference website.