By Theo Smart

First, a cautionary tale.

“Putting someone with hepatitis C on antiretroviral therapy (ART) is like passing a death sentence on him,” an Indian patient advocate was quoted saying in an article in the Indian press last year. (In the hope that he was misquoted, we won’t reprint his name or organisation.) The news story went on to declare that “hepatitis rules out the use of [antiretroviral drugs] - which are toxic to the liver - to arrest the effects of the AIDS-causing virus.”

Such misinformation and confusion about hepatitis and ART is quite common in a number of resource limited settings. According to Chris Green, a treatment advocate working in Indonesia, “Even doctors are confused - and scared - by liver problems, tending to stop ART when liver enzymes rise [to twice the upper limit of normal].”

In general, clinical data show that people with both HIV disease and hepatitis fare much better on ART. Nevertheless, liver toxicity can occur on ART, and HIV management can be more complicated in the context of liver disease. In addition, chronic hepatitis itself needs ongoing care.

In this issue of HATIP, we review what is and isn’t known about HIV and hepatitis co-management. We’ll focus primarily on hepatitis B and C viruses (HBV and HCV) as the most important causes of chronic hepatitis, while keeping in mind that other common factors, such as alcohol and other pharmaceutical and traditional medications, can contribute to liver problems.

Though both HBV and HCV affect the liver, there are important differences in how the viruses are transmitted, the populations most at risk, and how the infection evolves. Understanding the pattern and distribution of each liver infection is important in gauging the potential for coinfection in settings — particularly as screening for either virus is not common before initiating ART.

In much of the developing world, HBV is endemic among the general population. Exposure to HBV is common; about a third of the planet’s population have at one time had the infection.

HBV is transmitted in more or less the same way as HIV: through exposure to infected blood and other bodily fluids — but it is far more infectious.

As a result, most infections occur early in life — perinatally (from mother-to-child) and between children in household situations. Unsafe injections and transfusions account for some exposure. Sexual transmission is less common in the developing world though it remains a possibility.

The timing of HBV transmission influences both the likelihood of a chronic infection and the severity of its outcome — the earlier in life someone is infected with HBV, the more likely the infection is to become chronic and to later progress to cirrhosis or liver cancer. 90% of infants infected in their first year, and 30 to 50% of children infected between one to four years of age, develop chronic infection. The risk of death from HBV-related liver cancer or cirrhosis is approximately 25% for persons who become chronically infected in childhood. People who contract HBV as adults, however, have less than a 5% chance of developing chronic disease.

In 1999 and 2000, the World Health Organisation published estimates on the global prevalence of chronic HBV (see graphic 1). According to their calculations, around 10% of the general population of sub-Saharan Africa and much of Asia have chronic HBV. Globally, about 387 million people are chronically HBV infected.

However, there are differences in frequency of chronic HBV from country to country. For example, a recent analysis of HBV and HIV coinfection in Africa reported that as many as 20% of the general population in the Democratic Republic of Congo carry HBV surface antigen (Burnett). There is also considerable variation between rural and urban settings within countries: in South Africa, for example, the predominantly rural Eastern Cape reports a prevalence of 15.5%, compared with 1.3% in the township of Soweto (see http://www.aidsmap.com/en/news/9E241956-2B80-420D-BFA3-8361511B46FC.asp).

350 million HBV carriers worldwide

3-5 million HIV co-infected*

HCV, on the other hand, is transmitted via blood-blood exposure (most commonly from reuse of inadequately sterilised medical equipment, or needle-sharing among drug-users or from blood transfusions), and is only rarely transmitted perinatally or through sexual contact. In contrast to HBV, HCV is much more likely to be found clustered in risk groups than among the general population, especially injecting drug users.

HCV may be more difficult to contract than HBV, but the consequences are more likely to be serious regardless of how the infection occurs. Approximately 40% of those infected with HCV are likely to go on to develop some form of liver damage, with liver cancer and liver failure the most serious consequences of HCV infection. The risk of developing liver damage increases with the duration of infection, and is seriously exacerbated by alcohol consumption. The average time from infection to development of cirrhosis of the liver is between 30 and 40 years in HIV-negative people, which is why the public health consequences of HCV infection are still poorly recognised in most countries.

In 1999, WHO estimated that 170 million people were living with HCV worldwide. The highest prevalence is in Asia and Africa, where WHO estimated between four and five per cent of the population are infected.

HIV and HCV are co-epidemics in countries where injecting drug use is the main driver of the HIV epidemic, just as HIV and TB are co-epidemics in Africa and much of Asia.

In one recent study of IDUs in Russia, the anti-HCV prevalence was 87%, and 56% were HIV-positive, of whom 93% were coinfected with HIV. (Rhodes).

A cross-sectional study of HIV-positive patients at Ramathibodi hospital in Bangkok, Thailand found that 8.7% had hepatitis B infection and 7.8% had HCV infection (Sunkanuparph 2004). However a recent vaccine preparedness study found that 50% of men who were HIV-positive also had HCV (Paris 2003).

HIV and HCV will be inextricably linked as long as an absence of harm reduction measures assists the spread of both viruses. The absence of opiate substitution programmes throughout Asia and Eastern Europe, the extreme criminalisation of drug use and the lack of needle exchange programmes all create conditions that can only complicate the treatment of HIV infection where it occurs.

170-200 million carriers worldwide

10 million HIV co-infected*