Hepatitis C (HCV) infection is more common in those people living with HIV than in the general population with the two viruses sharing some key routes of transmission. In the early stages of the HIV epidemic, large cohorts of haemophiliacs receiving regular blood products became infected with both HIV and HCV. Sharing of needles for injecting drug use remains an important driver of transmission. However, in urban, westernized centres, the majority of new hepatitis C infections are seen in people living with HIV, particularly amongst men who have sex with men (MSM) and engaged in high risk sexual practices (including “bloody sex”) and recreational use of injected party drugs (including crystal methamphetamine).
Diagnosing hepatitis C can be more problematic in HIV positive individuals. Generally, the approach is similar to that in HIV negative individuals and uses serological screening. However, in recent (acute) infections these antibody responses can be slow to develop and direct methods of detecting the components of the virus are preferred (PCR for detection of HCV genetic material is the most commonly used, but HCV antigen testing is a possible alternative). Early detection not only allows earlier treatment to prevent complications but can also help to reduce the chance of ongoing transmission to HCV uninfected individuals.
The distribution of Hepatitis C genotypes tends to differ from the non-HIV infected populations. These distributions differ from clinic to clinic and country to country. However, the current transmission of HCV in MSM tends to be dominated by genotypes 1 and 4. Mixed genotypes are frequently seen in those individuals with acute HCV infection, particularly when newer methods of sequencing are employed.
Not all hepatitis C requires treatment. In HIV positive individuals, 15-20% of acute HCV infections resolve without treatment so patients are often monitored for up to three months before a decision to treat is made. A small proportion of individuals appear to progress very rapidly to cirrhosis after acute infection, but currently there are not reliable methods for predicting who these individuals will be. Once infection becomes chronic (i.e. has been detectable for 6 months or more), untreated hepatitis C progresses more rapidly to decompensated liver disease, cancer and death in the presence of HIV. This faster progression was probably greater before the advent of potent HIV treatment, but persists nonetheless.
The traditional treatment for HCV involves the use of interferon and other drugs (such as ribavirin, boceprevir and telaprevir), all of which have potentially severe side effects. Interferon based therapies are more challenging in the setting of HCV/HIV co-infection. Treatment cure rates are lower than in HCV mono-infections, side effects are more common (including falls in CD4 counts) and have challenges with drug-drug interactions, which often require adjustment of HIV treatment before HCV treatment can begin. However, new interferon-free treatment combinations have the potential to transform the outlook for those co-infected with HCV and HIV and appear to improve on all these aspects. The first interferon-free trials (e.g. PHOTON-1 and 2) demonstrated good cure rates across all genotypes tested with cure rates similar to those only infected with Hepatitis C. Further studies with other combinations are expected to follow. Toxicity in co-infection does not seem to be a major challenge and many of the newer direct acting antivirals seem to have minimal drug-drug interactions.
Overall the emerging picture from studies of interferon-free treatment is that patients with HIV/HCV co-infection can be managed in a very similar way to those with Hepatitis C mono-infection.
How to best to manage those individuals who become re-infected (and/or relapse) after curative treatment remains a crucial emerging question at a time when access to new treatments is likely to be restricted in many settings. Re-infection rates are high and estimated in some cohorts to be as high as 20%. There is no reason to think that re-infections cannot be treated as easily as first infections, however, with 12 weeks interferon-free treatment currently estimated between $57 -84,000, justifying re-treatment to payers will be challenging. A greater emphasis on secondary prevention has the potential to substantially reduce the number of re-infections as well as curb the rate of new infections.