For most of us, dealing with HIV is enough of a burden. But if you’re also living with hepatitis C, decisions about treatment are more complex and taking care of yourself is even more important.
It’s a major challenge for public health authorities: a quarter of a million Australians are infected the hepatitis C virus (HCV), a blood-borne virus that can cause serious and sometimes fatal disease, typically takes decades to develop, and is notoriously difficult to treat.
For people living with both HIV and HCV (called HIV/HCV coinfection), dealing with the combined burden of two serious infections can also present significant challenges. Coinfected people face a much higher likelihood of experiencing hep C-related illness, and may be less likely to respond to hep C treatment.
Recent estimates put the number of people living with HCV in Australia at 242,000, but a 2004 study1 opened the possibility that the number could well be much higher—perhaps as high as 433,000. By comparison, there are only about 14,000 people living with HIV.
Similarities in the ways the two viruses are transmitted, and the degree to which the affected communities overlap, also mean that people living with HIV/AIDS are much more likely than the wider Australian population to be infected with HCV. Around 10-13 percent of HIV-positive people have HCV coinfection2.
How HIV and HCV interact
While HIV and HCV are quite similar in some ways (they are both classified as ‘blood-borne infections’ and can be transmitted by some of the same routes), they give rise to quite separate diseases and go about their work quite differently.
Understanding the way the two diseases interact in people who are coinfected has been a focus of research since HCV was discovered in the late 1980s.
The impact of HIV on hep C disease progression has been clear for some time, but the other side of the equation—the effect of HCV on HIV—has been the subject of more debate.
Most studies in coinfected people have shown little impact on HIV progression—a large retrospective analysis of people who participated in the CAESAR trial of 3TC in the 1990s, for example, found that HCV coinfected participants were no more likely to progress to AIDS or die than their monoinfected counterparts3.
But questions have been raised about whether the picture would change with improved treatments efficacy leading to longer survival times for people with HIV/AIDS.
An Italian study published last November did find that coinfected people had more rapid HIV disease progression4. But, in this and other studies, there were differences in the pattern of antiretroviral use between the monoinfected and coinfected groups, attributed to the fact that the majority of the coinfected patients were injecting drug users (IDUs) who were less likely to access health care.
Associate Professor Greg Dore of the National Centre in HIV Epidemiology and Clinical Research told PL that he believes the evidence now strongly supports the view that hep C doesn’t negatively impact on HIV progression. When study data is adjusted to take injecting drug use out of the picture, he says, the impact of coinfection in studies is minimal or non-existent.
While people who are coinfected are unlikely to experience additional challenges in managing their HIV infection, they do face a higher risk of HCV disease progression.
In HIV-negative people, the initial (acute) phase of HCV infection leads to chronic (long-term) hep C in about 70 percent of cases. Progression to severe liver disease (such as cirrhosis or liver cancer) is very slow, usually taking at least 20-40 years to develop. Many people with hep C never progress to this stage at all.
HIV-positive people tend to have higher HCV viral loads, are more likely to develop the chronic infection (around 80 percent) and are more likely to develop liver disease (around twice as likely to develop cirrhosis compared with HIV-negative people).
Progression to liver disease can also be much more rapid in coinfected patients, with the average time to develop cirrhosis estimated to be about ten years shorter than in monoinfected people (23 versus 32 years).
On the brighter side, there is evidence that in people with stable, well-controlled HIV infection (low or undetectable HIV viral load and higher CD4 counts) these differences are less pronounced.
“In someone who is able to maintain their CD4 count or restore their immune function through antiretroviral therapy, the risk of progression to advanced liver disease is much reduced,” Dore explains.
Sexual transmission?
The degree to which sexual transmission of HCV occurs is a major area of controversy.
The vast majority of HCV diagnoses are attributed to direct blood-to-blood contact — unsafe injecting, tattooing or body piercing practices or, before screening began, blood transfusions.
But sexual transmission of the virus can occur, especially where blood is present during sex. Examples of where this might happen include some ‘esoteric’ sex practices, such as fisting or use of sex toys.
More controversially, there is also the possibility that ordinary anal sex could provide a more viable transmission route than vaginal sex, raising the possibility of increased rates of sexual transmission among men who have sex with men (MSM).
Recent research has been somewhat reassuring. In the largest study to date, published in March 2005, a group of 1085 HIV-negative Canadian men were followed for a total of 2653 person-years to determine rates of hep C seroconversion5.
At the start of the study, HCV infection rates were very low in participants with no history of injecting drug use (0.3%) compared with those who had injected drugs (32.9%), and only one participant—an injecting drug user who had shared needles—acquired hep C in the study period. The researchers concluded that sexual hep C transmission among MSM was rare.
Greg Dore points to this and other recent research as evidence that male-to-male sexual transmission of hep C is uncommon, at least in HIV-negative men, just as it is for heterosexual sex: “If you are an HIV-negative gay man, the risk of sexual acquisition of hep C is incredibly low,” he says.
Among HIV-positive gay men, however, Dore concedes that “the question is still unanswered” and that further research is needed to establish the facts.
“There have been some reports out of London that appear to show an ‘epidemic’ of sexually-transmitted hep C among HIV-positive gay men, possibly associated with a syphilis outbreak,” he says. “So there’s some concerns about whether there’s greater susceptibility for gay men who have HIV, particularly if they have other sexually-transmissible infections at the time of hep C exposure,” he says.
One possible explanation for this is the fact that HIV/HCV coinfected people often have higher HCV viral loads than those with HCV alone. Additional risk factors could include sexual practices with greater likelihood of blood-to-blood contact (such as fisting and sharing sex toys) as well as concurrent STIs, especially syphilis.
For sexually active HIV-positive people who wish to protect themselves from hep C, Dore reiterates that he believes the risk is not high, but concedes that it is “somewhat unknown, and it could be significant.” HIV-positive men who have negotiated unprotected sex with positive partners should be aware that there may be “a small risk of hep C transmission” if their partner is hep C positive, he says.
“To be honest, I think the risk is low,” he says, pointing out that the risk of more common STIs such as syphilis or gonorrhoea is much higher.
Treatment and care
An important question is whether to treat HIV or HCV first. Until a few years ago, most clinicians took the view that because HIV is likely to become life threatening sooner, it should be the first priority in treatment.
Doctors now recommend different courses of action depending on the individual patient’s circumstances. HIV often remains the first priority, especially as people with higher CD4 counts may respond better to HCV treatment and may be less prone to side effects.
The only treatments currently available for hep C consist of interferon or pegylated interferon combined with ribavirin.
Interferon is a naturally occurring protein produced in the body in response to viral infection. Synthetic interferon has been used for some years in treatment of hepatitis C, as well as some other infections and cancers.
Pegylated interferon is a modified form which makes the interferon last longer in the body. There are two different pegylated interferons available under the PBS: Roche’s Pegasys and Schering-Plough’s Peg-Intron, both of which are given by injection.
The second drug in the combination, ribavirin, is an antiviral medicine which comes in tablet or capsule form.
Like HIV medications, these expensive and highly specialised medicines can only be prescribed by specially licensed physicians and are subject to strict eligibility criteria.
Access to hep C combination treatment is available to coinfected patients in Australia under the same criteria as for people with HCV alone: they must have documented chronic hep C, elevated liver enzymes, and some evidence of liver fibrosis—scarring of the liver tissue.
Fibrosis, the key measure of liver disease progression, is determined via a liver biopsy, in which a small amount of tissue (about the size of half a matchstick) is removed through a needle inserted into the liver, and studied under a microscope.
Dore is hopeful that the requirement for a liver biopsy will be relaxed in the next 6-12 months: while biopsy remains an important tool in hep C management, he is concerned that the invasive and sometimes painful procedure is a barrier to patients considering treatment. “I think a lot of people are still holding back because of the liver biopsy requirement,” he says.
Results from two major international studies of hepatitis C treatment in coinfected people—APRICOT and ACTG 5071—were published last year.
The largest of these, the APRICOT study6, included 860 coinfected people in 19 countries, who were divided into three arms:
- Standard interferon three times weekly, plus daily ribavirin.
- Pegylated interferon (Pegasys) once weekly, plus daily ribavirin.
- Pegasys once weekly, plus placebo.
After 48 weeks, the numbers of patients in each arm who achieved a ‘sustained virological response’ (SVR)—essentially an undetectable HCV viral load—were 12, 40 and 20 percent respectively.
The effectiveness of the treatment was better for HCV genotypes 2 and 3 (62 percent in the Pegasys/ribavirin arm) than for genotype 1 (29 percent).
While lower than the response rates seen in HCV-monoinfected patients with the same treatment, these are some of the best-ever trial results in people coinfected with both viruses, and “demonstrate that the current regimen used for the treatment of chronic hepatitis C alone can also be applied to patients coinfected with HIV and HCV,” the researchers concluded.
The second study, ACTG 5071, enrolled 133 coinfected patients in the US who received either standard or pegylated interferon, plus ribavirin. Response rates after 48 weeks were similar to the APRICOT study, however after 72 weeks the response rate in the pegylated arm dropped to 27 percent due to large numbers of relapses, especially among patients with genotype 1. Possible explanations for this include the lower dosage of ribavirin used, and the different racial characteristics of the participants.
An interesting finding of the ACTG trial is that anti-HCV therapy is beneficial even when a sustained virological response can’t be attained—liver biopsy results showed that 35 percent of participants had improvements in fibrosis, regardless of whether there was a virological response.
In Australia, Greg Dore says treatment results for coinfected patients have been very good: “At the St Vincent’s Hospital Hepatitis Clinic we’re running at a sustained virological response rate of above 60 percent, which is better than any of the clinical trials, and as high as 75 to 80 percent in people with genotype 2 and 3,” he says. Even for genotype 1 (the most common type in Australia) the response rate has been better than 50 percent, according to Dore.
“In fact, there’s very little difference in terms of our response rates between those who are coinfected and those who are monoinfected,” he says.
While these results have been important in demonstrating that anti-HCV treatment is viable and (at least partly) effective in people coinfected with HIV, there is clearly some way to go before we have hepatitis C treatments with similar efficacy as those we now have for HIV/AIDS.
Several pharmaceutical companies are currently working on experimental protease inhibitors for HCV, however to date human trials have proved disappointing. Greg Dore remains hopeful, however, that new HCV treatments will start to become available within 3-4 years.
“There’s a lot of development out there, but we’re probably stuck with pegylated interferon and ribavirin, possibly with the addition of another agent that might slightly increase response rates, for the next three or four years,” he says.
The decision to start hep C treatment can be a complex one, especially for HIV coinfected patients. Hep C genotype, baseline HCV viral load, and levels of liver fibrosis are all factors that can influence the decision. Dore points out the importance of also taking into account the individual’s personal circumstances—their employment, social and family situation—in making the decision to go through “what can be a pretty difficult six or 12 months of treatment.”
The side effects of hep C treatment—both physical and mental—can be debilitating, so it’s important to choose the right time to treat.
The individual’s HIV disease status—CD4 count and viral load—can also affect the decision. People with very advanced HIV disease may benefit from delaying hep C treatment until their immune system recovers, as there is evidence that people with higher CD4 counts respond better to hep C treatment. But Dore points out the difference in response rates levels off quickly for people with even moderate-range CD4 counts: “I don’t think there’s a lot of difference between a CD4 count of 250 and 550—response rates to hep C treatment are very good across all those strata,” he says.
Once people have started treatment, Dore points out the importance of strong support for patients as a reason why Australians seem to do better on treatment than people in other countries. Early detection and treatment of depression, peer support and involvement of social workers all help people stay on treatment and improve outcomes.
Dore is a strong supporter of peer support for people going on treatment, and says the encouragement, understanding and camaraderie gained by people in support groups is invaluable.
Taking action
While treatments are improving and can be expected to improve further in the future, in the meantime there are worthwhile steps anyone can take—whether coinfected or not—to maintain their health.
If you’re HIV positive and you’re sexually active or have ever used intravenous drugs (whether or not you’ve shared needles), you should be tested for hep C. Early detection increases the options for treatment and makes it possible to make lifestyle changes to protect your liver from damage.
There is no vaccine for hepatitis C. The best way to avoid becoming infected is to avoid high-risk behaviours, including unsafe injecting practices, unsterile tattooing or body piercing, or any activity which could allow direct blood-to-blood contact. Wear latex gloves for fisting, don’t share sex toys and practice safe sex.
If you are coinfected, talk to your doctor about treatments, and ask to be referred to a liver specialist with experience in HIV coinfection. Get vaccinated for hepatitis A and B, and reduce the intake of substances which could harm your liver, such as alcohol, recreational drugs and fatty foods. Maintain safe behaviours to protect others and yourself (reinfection with a second HCV genotype is possible and can significantly reduce treatment effectiveness).
References
1 Amin J et al. Hepatitis C prevalence—a nationwide serosurvey. Commun Dis Intell 2004; 28:517-521.
2 Lincoln D et al. HIV/HBV and HIV/HCV Coinfection, and Outcomes Following Highly Active Antiretroviral Therapy. HIV Med 2003 4(3):241-249.
3 Amin J et al. HIV and hepatitis C coinfection within the CAESAR study. HIV Med 5: 174-179, 2004.
4 Dorrucci, M et al. The effect of hepatitis C on progression to AIDS before and after highly active antiretroviral therapy. AIDS 18: 2313-2318. 2004.
5 Alary M et al. Lack of evidence of sexual transmission of hepatitis C virus in a prospective cohort study of men who have sex with men. Am J Public Health. 2005 Mar;95(3):502-5.
6 Torriani FJ et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. NEJM 351: 438-450, 2004.
Additional resources for people with HIV/HCV coinfection
- ATPA factsheet (40kB PDF)
- ASHM monograph “Coinfection – HIV and viral hepatitis”
- The Australian HepatitisCouncil’s National Hepatitis C Resource Directory
- For support groups and further information, contact your local AIDS council (details here) or the Hepatitis C Council in your state or territory:
