Hepatitis B vaccine scale-up and treatment of HIV/HBV co-infection present challenges

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Hepatitis B vaccine coverage has increased dramatically in recent years, but some regions still lag behind and collaboration with broader health programmes would aid scale-up, according to a symposium presentation on viral hepatitis at the 5th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention last week in Cape Town, South Africa.

In the absence of timely vaccination, management of patients with HIV and hepatitis B co-infection presents challenges related to drug resistance and liver disease flare-ups.

Hepatitis B vaccination

Hepatitis B virus (HBV) is "extremely prevalent", according to Steven Wiersma, a medical officer with the World Health Organization (WHO) in Geneva, but it is not evenly distributed globally, with the highest rates in parts of Asia and Africa.

Of an estimated two billion people infected with HBV, of whom more than 350 million have chronic infection, about 88% live in areas with high (> 8%) or moderate (2 to 7%) prevalence. Hepatitis B is among the leading causes of mortality worldwide, accounting for more than 600,000 deaths annually.

Glossary

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.

mother-to-child transmission (MTCT)

Transmission of HIV from a mother to her unborn child in the womb or during birth, or to infants via breast milk. Also known as vertical transmission.

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

eradication

The total elimination of a pathogen, such as a virus, from the body. Eradication can also refer to the complete elimination of a disease from the world.

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

While most people infected as adults clear HBV without treatment, those infected as infants or children – often through mother-to-child transmission in endemic areas – usually develop chronic disease. Over years or decades, chronic hepatitis B can lead to advanced liver fibrosis, cirrhosis and liver cancer. In fact, hepatitis is thought to be responsible for about half of all liver cancer cases.

Dr Wiersma said that, according to current WHO policy, all regions – not just those where hepatitis B has traditionally been considered endemic – should develop goals for widespread vaccination. Early life offers the best opportunities for prevention, and WHO recommends that all infants should receive the first dose of the vaccine within 24 hours of birth, with two follow-up doses, usually given one and six months later, to complete the series.

Several countries in Asia and Africa have achieved "dramatic" increases in hepatitis B vaccine coverage, Dr Wiersma said. As of 2007, more than 88% of WHO member countries had introduced HBV vaccination and 65% provided universal three-dose coverage for infants.

But some countries, he added, are "lagging". WHO estimates that more than 44 million babies still do not receive a full course of the vaccine, with the largest gap – 24 million infants – in India.

To improve vaccination rates, Dr Wiersma advocated more collaboration with maternal and child health programmes, including HIV treatment and prevention of mother-to-child transmission programmes and vitamin K distribution efforts. But the most commonly used hepatitis B vaccines present a logistical challenge in resource-limited settings because whilst they should be refrigerated, they can become ineffective if frozen.

Later in life, people who did not receive the hepatitis B vaccine as young children can still benefit from "catch-up" vaccination. Dr Wiersma said WHO is interested in integrating adult hepatitis B vaccination into HIV and sexually transmitted disease prevention and treatment programmes.

"It doesn’t take a lot of cost to make adult vaccination available," he said. With a price as low as US $0.42 per dose, he said advance seromarker screening to determine which individuals would benefit from the vaccine (that is, those who have not already been exposed to HBV) may not be cost-effective, and it may be better to just vaccinate everyone.

Dr Wiersma noted that experts believe age cohorts who receive three doses of the vaccine now will be protected for life, and are not expected to need booster shots later. Since vaccination prevents not only illness and death but also onward transmission, WHO considered hepatitis B "a primary candidate for elimination or eradication".

HIV/hepatitis B co-infection

While vaccination offers hope for a large decrease in hepatitis B in the future, many people today are co-infected with HIV and HBV, particularly in regions where both diseases are common. As Sharon Lewin from Monash University in Australia described in an overview of HIV/HBV co-infection at the same session, hepatitis B has an "enormous impact" on liver-related mortality, even amongst patients on effective combination antiretroviral therapy.

Co-infection presents some unique challenges, since drugs that are dually active against both HIV and HBV – including the widely-used tenofovir (Viread, also in the Truvada and Atripla combination pills – can trigger resistance in either virus if used improperly, and stopping them can lead to temporary worsening of liver disease known as 'flares'.

Discussing the management of HIV/HBV co-infection, Sanjay Bhagani from the Royal Free Hospital in London noted that many ART roll-out programmes in resource-limited countries do not test people for hepatitis B before starting dually active antiretroviral drugs, raising the risk of resistant HBV and potentially limiting future hepatitis B treatment options. This risk can be overcome by using two dually active drugs together, for example tenofovir plus either 3TC (Epivir) or FTC (Emtriva).

Treatment of hepatitis B in co-infected patients not receiving ART is also a challenge, since using these dually active drugs without a more potent antiretroviral agent (such as a protease inhibitor or NNRTI) can lead to HIV resistance mutations.

Few drugs are active against HBV but not HIV, and recent studies have shown that entecavir (Baraclude) and possibly telbivudine (Sevibo) have previously unrecognised anti-HIV activity. For this reason, many experts – and US HIV treatment guidelines – now recommend that HIV/HBV co-infected patients who need hepatitis B treatment should receive a full combination ART regimen that contains dually active drugs.

Along similar lines, Juan Pineda from Hospital Universitario de Valme in Seville, Spain, explained that whilst HIV/HBV co-infected patients should receive regular liver enzyme (ALT and AST) monitoring and liver cancer screening, they usually do not need liver biopsies, because they can be pre-emptively treated with dually active ART regardless of the extent of liver damage.

Further information

Powerpoint presentations and a webcast of the conference session in which they were presented are available on the IAS 2009 website.

References

Wiersma S Scaling up global access to Hepatitis B vaccination. 5th IAS Conference on HIV Treatment, Pathogenesis and Prevention, Cape Town, abstract WeBS102, 2009.

Lewin S Pathogenesis of HIV-HBV co-infection. 5th IAS Conference on HIV Treatment, Pathogenesis and Prevention, Cape Town, abstract WeBS101, 2009.

Pineda JA Diagnosis and Monitoring of Hepatitis B and C co-infection. 5th IAS Conference on HIV Treatment, Pathogenesis and Prevention, Cape Town, abstract WeBS103, 2009.

Bhagani S Management of Hepatitis B and C co-infection. 5th IAS Conference on HIV Treatment, Pathogenesis and Prevention, Cape Town, abstract WeBS104, 2009.