Coinfection

ICAAC 2013: Treatment of HCV Genotypes 2/3 in HIV/HCV Coinfected People

HIV/HCV coinfected patients, mostly with hepatitis C virus (HCV) genotype 3, responded about as well as HIV negative people to pegylated interferon plus ribavirin after taking into account other factors associated with poor treatment response, according to an Italian study presented at the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2013) this month in Denver. Advanced liver fibrosis was common in the coinfected group, supporting the need for early treatment.

An estimated one-third of HIV positive people are coinfected with HCV, with higher rates in countries where the HIV epidemic is largely driven by injection drug use. Over years or decades chronic hepatitis C can lead to serious liver disease, including advanced fibrosis, cirrhosis, and hepatocellular carcinoma. HIV/HCV coinfected people tend to experience faster liver disease progression and do not respond as well to interferon-based therapy as people with HCV alone.

Paola Nasta from Spedali Civili di Brescia and colleagues compared treatment outcomes amongst HIV/HCV coinfected and HCV monoinfected people with HCV genotype 2 or 3 treated at their hospital between 2005 and 2010. Genotypes 2 and 3 have traditionally been classified as "easier-to-treat" in comparison with "harder-to-treat" genotypes 1 and 4.

This retrospective analysis included 113 HIV/HCV coinfected and 627 HCV monoinfected adults not previously treated for hepatitis C. About 85% of the coinfected patients and two-thirds of the monoinfected patients were men and the mean age was 45 years. All of the HIV positive participants were on antiretroviral therapy with undetectable HIV viral load and the mean CD4 T-cell count was 455 cells/mm³.

Most of the coinfected participants (95%) had HCV genotype 3, whereas the monoinfected patients were more evenly divided between genotypes 2 and 3 (45% and 55%, respectively). Nearly one-quarter of coinfected patients, but only 5% in the monoinfected group, had advanced fibrosis/cirrhosis (stage F4) at baseline. The coinfected group was less likely to have high baseline HCV RNA (33% vs 51%), but more likely to have a low platelet count (mean 163,200 vs 208,400/mcl).

Two-thirds of participants were treated with pegylated interferon alfa-2a (Pegasys) and one-third with pegylated interferon alfa-2b (PegIntron) along with weight-based ribavirin (15 mg/kg/day). All coinfected people were treated for 48 weeks. HCV monoinfected patients could stop at 24 weeks if they had absent-to-moderate fibrosis, low baseline HCV viral load, or rapid virological response at week 4. Both groups stopped due to futility if HCV RNA was still detectable after 12 weeks of therapy.

Anemia and neutropenia can be treatment-limiting side effects of ribavirin and interferon. Patients with cirrhosis were eligible to use erythropoietin (EPO) to stimulate red blood cell production. If hemoglobin remained low despite EPO, they could reduce their ribavirin dose. All HIV positive patients could use granulocyte colony-stimulating factor (GCSF) to promote white blood cell growth, but HIV negative people could do so only if they had cirrhosis. Those with persistent white blood cell deficiency could lower their interferon dose.

Results

• The overall sustained virological response (SVR) rate after completion of treatment was 69%.
• However, SVR was significantly lower in the HIV/HCV coinfected group (58%) compared with the HCV monoinfected group (67%); HIV negative individuals were 50% more likely to respond to treatment (odds ratio 1.5).
• Coinfected and monoinfected patients were equally likely to be virological non-responders (15% vs 16%, respectively).
• Coinfected people were slightly more likely to experience post-treatment relapse even though they were treated longer (50% vs 45%, respectively, not a significant difference).
• A similar proportion in both groups discontinued treatment early for any reason (35% vs 40%, respectively).
• There were not enough HIV positive people with HCV genotype 2 to analyze the genotypes separately, but looking at all participants together, the SVR rate for genotype 2 was significantly higher than for genotype 3 (72% vs 61%, respectively).
• Coinfected people were more likely to lower their ribavirin dose (26% vs 18%), though much less likely to prematurely stop interferon (9% vs 68%).
• A similar proportion of patients in both groups developed anemia (12% vs 10%), but fewer coinfected people used EPO (2% vs 16%).
• The coinfected group was significantly more likely to have neutropenia (42% vs 12%) and to use GCSF (41% vs 4%).
• Factors significantly associated with sustained response were advanced fibrosis -- reducing the likelihood of SVR by 60% -- high baseline HCV viral load, ribavirin dose reduction, and early interruption of pegylated interferon.
• After adjusting for these and other factors influencing treatment response, having HIV itself was not an independent predictor of worse treatment response.

"HCV mono- and HIV/HCV co-infected patients seem to have a similar rate of SVR in our clinical setting," the researchers concluded. They suggested this might be due HIV positive people receiving a longer duration of treatment or being more likely to use GCSF to maintain higher drug doses.

Conversely, the higher proportion of people with HCV genotype 3 might have contributed to lower response in the coinfected group compared with the monoinfected group, which had a more even genotype distribution.

Because HIV/HCV coinfected people have a higher rate of advanced fibrosis -- and because this is one of the most important variables related to poor treatment outcomes -- the researchers recommended that coinfected people with HCV genotypes 2 or 3 should receive early treatment.

9/24/13

Reference

P Nasta, M Giralda, E Chiari, et al. Higher rate of sustained virological response in patients with HCV genotype 2 or 3 infection regardless [of] HIV Infection. 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2013). Denver, September 10-13, 2013. Abstract H-1528.