Hepatitis C: high rate of treatment success in recently infected HIV positive gay men

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An Australian study comparing treatment of acute and early hepatitis C (HCV) infection between HIV-positive and HIV-negative patients has found that the HIV-positive patients were very significantly more likely to be gay men who acquired hepatitis sexually.

However, it observed few clinical differences in the features of hepatitis infection, and found high rates of treatment success in the HIV-positive patients. At least 80% of HCV/HIV co-infected patients achieved an HCV cure, or sustained viral response (SVR), defined as an undetectable HCV viral load at least 24 weeks after the end of treatment. In order to achieve this, however, they had to have longer and more intense treatment than HIV-negative patients.

The Australian Trial in Acute Hepatitis C (ATAHC) is a prospective cohort study of both HIV-negative and HIV-positive patients who acquire HCV. It includes patients who test positive for HCV antibodies no more than six weeks before being enrolled in the study group, and then follows them to establish rates of treatment acceptance and success.

Glossary

sustained virological response (SVR)

The continued, long-term suppression of a virus as a result of treatment. In hepatitis C, refers to undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 12 or 24 weeks after ending treatment and is considered to be a cure (SVR12 or SVR24).

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).

detectable viral load

When viral load is detectable, this indicates that HIV is replicating in the body. If the person is taking HIV treatment but their viral load is detectable, the treatment is not working properly. There may still be a risk of HIV transmission to sexual partners.

pegylated interferon

Pegylated interferon, also known as peginterferon, is a chemically modified form of the standard interferon, sometimes used to treat hepatitis B and C. The difference between interferon and peginterferon is the PEG, which stands for a molecule called polyethylene glycol. The PEG does nothing to fight the virus. But by attaching it to the interferon (which does fight the virus), the interferon will stay in the blood much longer. 

protocol

A detailed research plan that describes the aims and objectives of a clinical trial and how it will be conducted.

In order to exclude patients who had previously undiagnosed chronic hepatitis C, to be included patients also had to have had either clinical symptoms of acute hepatitis C infection no more than a year before their positive HCV test, or, if they have been asymptomatic, to have had a negative HCV test no more than two years before their positive one. Approximately half of the patients, in fact, had had acute HCV symptoms, regardless of HIV status. The average time of infection before testing HCV-positive was estimated as seven months.

This study enrolled 103 patients, of whom 27 (26%) also had HIV. There were significant differences between the HIV-positive and negative patients. All the HIV-positive patients were male and half of them appeared to have acquired HCV through sex with another man. In contrast, no more than one in ten of the 76 HIV-negative patients appeared to have acquired HCV sexually, and only one of these through male/male sex.

Eighty per cent of the HIV-negative patients and 44% of the HIV-positive appeared to have acquired HCV through injecting drugs. However, the pattern of injecting drug use was totally different: 100% of the HIV-infected patients who had got HCV through injection had done so injecting methamphetamine or amphetamines; in contrast 55% of the HIV-negative drug injectors had been injecting heroin.

High rates of treatment response were achieved in the HIV-positive patients. Nearly two thirds (64%) of co-infected patients with the predominant and hard-to-treat genotype 1 variety of HCV achieved an SVR, and 100% of the one-third of patients who had another HCV genotype.

Hepatitis C treatment uptake was higher in HIV-positive patients, with 22 out of 27 patients (81%) starting treatment compared with 50 out of 76 HIV-negative patients (66%).

The paper does not compare treatment outcome rates in people with HIV with the rates seen in HIV-negative patients. This is because, although both groups initially took the same treatment, it appeared to be ineffective for patients with HIV and the regimen had to be intensified for them. The HIV-negative patients took twelve weeks of pegylated interferon without ribavirin. The first two HIV-positive patients also took this but neither achieved an SVR, so the protocol for HIV-positive patients was altered to 24 weeks of pegylated interferon plus ribavirin.

All 20 of the HIV-positive patients who took the modified regimen achieved an early viral response, meaning they had no detectable HCV by week twelve of treatment. However four patients did not achieve an SVR. In one case this was because a patient disappeared twelve weeks after stopping treatment. He had had an undetectable HCV viral load four weeks after starting treatment and would almost certainly have achieved an SVR, bringing the likely overall rate of treatment success to 85%.

Of the three who failed, one had poor adherence due to heavy alcohol use, one never achieved an undetectable viral load and one was undetectable at week 24 but detectable at week 48.

This study is the first cohort study to document sexual HCV transmission in HIV-positive gay men outside the USA or Europe and establishes, as the authors comment, that “sexual or ‘permucosal’ transmission of acute hepatitis C within HIV-infected populations is a global phenomenon”.

They comment that this, plus the treatment success rates observed, “support the importance of regular HCV testing among HIV-infected [gay men], with consideration given to commencement of early treatment.”