Low rate of spontaneous hepatitis C clearance in patients with HIV; early HIV treatment recommended for those with chronic hepatitis C infection

Approximately a quarter of patients coinfected with HIV and hepatitis C virus spontaneously clear infection with hepatitis C, according to a study conducted by European investigators and published in the November 1^st edition of the Journal of Infectious Diseases.

Researchers also found that female patients were more likely to spontaneously clear their hepatitis C infection, as were gay men, individuals also infected with hepatitis B virus, and patients living in northern Europe.

Of the patients with chronic hepatitis C infection, most were infected with hepatitis C genotype 1 and had a high hepatitis C viral load – characteristics associated with a poor response to anti-hepatitis C treatment. The authors of an accompanying editorial suggest that patients with these characteristics should received “early antiretroviral treatment” as the “best way to avoid a poor outcome of liver disease.”

Investigators from the large EuroSIDA cohort study wished to establish the number of HIV-positive patients who had been infected with, but spontaneously cleared, hepatitis C infection. They also wanted to determine the virological features of the hepatitis C in the patients with chronic infection.

A total of 14,310 patients enrolled in the EuroSIDA cohort at 93 treatment centres across Europe, as well as in Argentina and Israel were eligible for inclusion in the study. All the patients with hepatitis C antibodies had stored samples tested for hepatitis C RNA. Patients who had detectable hepatitis C virus were then tested to determine hepatitis C viral load and genotype.

Just under a quarter (24%) of the EuroSIDA cohort had antibodies to hepatitis C. However, the investigators excluded 1435 of these patients as they did not have stored serum samples available for analysis. This left a study population of 1940.

Spontaneous clearance of hepatitis C infection occurred in 444 (23%) patients. Factors associated with spontaneous clearance were female sex (adjusted odds ratio, 1.39; 95% CI: 1.06 – 1.81, p = 0.017), coinfection with hepatitis B virus as indicated by hepatitis B surface antigen (adjusted odds ratio, 2.91; 95% CI: 1.94 – 4.38, p

Furthermore, the investigators found that injecting drug users (20%) were significantly less likely than gay men (39%) to spontaneously clear hepatitis C (adjusted odds ratio, 0.36; 95% CI: 0.24 – 0.53, p

Next, the investigators turned their attention to the 1496 patients with chronic hepatitis C infection. They found that the majority of these patients were infected with the hepatitis C genotypes that have the poorest response to the current standard hepatitis C treatment – pegylated interferon and ribavirin. Some 786 patients (53%) were infected with hepatitis C genotype 1 and a further 217 individuals (15%) were infected with genotype 4.

Median hepatitis C viral load was a little over 570,000 iu/ml. However, patients with the genotype 1 infection had a median hepatitis C viral load of 776,000 iu/ml.

The investigators note that approximately a third of patients who are only infected with hepatitis C clear the virus, compared to fewer than a quarter of patients in their cohort. They suggest that this could be due to the immune suppression that HIV can cause. They also suggest, however, that given the large numbers of injecting drug users in the study, reinfection with hepatitis C virus could be an explanation.

An accompanying editorial suggests that a single negative hepatitis C viral load, the threshold for hepatitis C clearance used by the investigators, is not a reliable indicator of spontaneous cure of hepatitis C. They write, “a more-thorough evaluation of viral clearance by patients needs to be done using a more sensitive test, such as a transcription-mediated amplification.”

Noting the increased chances of spontaneous cure for patients in northern Europe, the authors suggest that “spontaneous clearance of hepatitis C virus infection does not solely depend on viral and immunological factors or risk category but also depends on geographical location and other host factors.” They note earlier French research that suggests that genetic variations in hepatitis C virus in men and women were associated with the chance of a spontaneous cure or response to treatment.

Patients infected with the harder-to-treat genotypes and who have a high hepatitis C viral load should receive early antiretroviral therapy to improve their immune function and as “the best way to avoid a poor outcome of liver disease.”