Hepatitis C subtype-1b and carriage of IL28B gene associated with improved treatment responses in HIV-co-infected patients

Michael Carter
Published:
01 March 2012
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Hepatitis C treatment responses in patients co-infected with HIV are better in patients infected with hepatitis C subtype-1b than 1a, according to Spanish research published in the online edition of the Journal of Acquired Immune Deficiency Syndromes. The research also showed that the presence of the IL28B gene influenced treatment responses.

“We noticed that on treatment responses and SVR [sustained virological response] rates were uniformly worse in HCV-1a as compared to HCV-1b patients,” comment the authors. “Another important finding of our study was that early viral kinetics in HCV-1 patients was significantly influenced by…IL28B.”

HIV and hepatitis C share modes of transmission, and liver disease caused by hepatitis C is now an important cause of death in co-infected patients.

Glossary

IL28B

An inherited gene which all individuals have. There are three genotypes of IL28B; these influence response to hepatitis C and its treatment. People with CC genotype are more likely to spontaneously clear acute infection or (during chronic infection) respond well to interferon-based treatment. The other two genotypes are known as CT and TT.

Standard therapy for hepatitis C consists of pegylated interferon and ribavirin. Only a minority of co-infected patients with chronic hepatitis C infection have a successful response to this therapy. However, several factors are known to be associated with treatment with treatment outcomes.

One of these is hepatitis C genotype. Poorer responses are seen in patients infected with genotypes 1 and 4 compared to genotypes 2 and 3. In addition, it is possible that viral subtype may also have an impact on outcomes.

Studies conducted in both hepatitis C-mono-infected patients and co-infected individuals have also shown that the IL28B gene also influences treatment responses.

Two protease inhibitors were recently approved for the treatment of hepatitis C mono-infection. These drugs works directly against hepatitis C and other such directly acting agents are in development. However, these new protease inhibitors are combined with the existing standard therapy, so an understanding of the importance of viral subtype and genetics to treatment outcomes remains important.

Therefore Spanish investigators designed a retrospective study involving 331 co-infected patients treated with pegylated interferon and weight-based ribavirin. All had a CD4 cell count above 300 cells/mm3, were receiving their first course of hepatitis C therapy, and none had decompensated liver disease or abused alcohol.

The patients’ were tested at baseline to determine their hepatitis C genotype and subtype and to see if they carried the IL28B gene.

Treatment responses were assessed at weeks four and twelve, the end of therapy and then 24 weeks later.

There was a wide distribution of geno/subtypes, with 29% of patients infected with genotype-1 subtype a, 19% with genotype-1 subtype b, 37% with genotype-3 and 15% with genotype-4.

Patients infected with genotype 1 had higher hepatitis C viral loads compared to patients infected with the other genotypes (p = 0.02). Viral load also differed according to subtype, and was slightly higher for patients with subtype 1a infection compared to those with subtype 1b. However, similar proportions of patients with subtype 1a and 1b infection carried the IL28B gene (33% vs. 24%).

Treatment responses at all time points differed according to genotype and subtype.

As expected, response rates were better for patients with genotype-3 infection compared to those with genotypes-1 and -4.

However, responses also differed between subtypes-1a and -1b. Patients with subtype-1b were significantly more likely than those with subtype-1a to have a response at week twelve (p = 0.009), the end of treatment (p = 0.005) and to achieve a sustained virological response (p = 0.03).

Therapeutic response also differed according to IL28B status.

Restricting analysis to patients with genotype-1 infections showed that the lowest response was seen in individuals with subtype-1a infection who did not carry the IL28B gene and the best response in those with subtype-1b infection who carried this gene (p < 0.05).

After controlling for potentially confounding factors, the investigators confirmed that subtype-1b and carriage of IL28B were associated with improved treatment responses.

“This is the first study demonstrating an important role for both IL28B variant and HCV-1 subtype in predicting on-treatment virological responses to pegylated interferon/ribavirin in HIV/HCV-co-infected individuals,” comment the investigators. They explain: “this effect is largely mediated by an enhancement in viral kinetics during the first twelve weeks of therapy.”

The authors conclude: “Baseline IL28B testing may helpfully assist treatment  decisions in the new era of triple combination therapy, including directly acting agents.”

Reference

Rallon NI et al. Differences in virological response to peginterferon-alpha plus ribavirin in HIV-positive patients coinfected with HCVsubtyles 1a or 1b. J Acquir Immune Defic Syndr, online edition. DOI: 10.1097/QAI.0b013e31824f5506, 2012 (click here for the free abstract).