RESEARCH HIGHLIGHTS Nature Reviews Gastroenterology & Hepatology 11, 517 (2014); published online 5 August 2014; doi:10.1038/nrgastro.2014.145
INFECTIOUS DISEASE
HIV THERAPY GOOD FOR HCV INFECTION Temporary increases in HCV RNA and alanine aminotransferase (ALT) levels do not negate the overall beneficial effects of HIV therapy for HCV infection, according to new research. The clinical trial was set up to evaluate the effect of initiation of combination antiretroviral therapy (cART) on HCV replication and liver injury in patients with HIV and HCV co-infection. A subset of patients (4 of 17) had an HCV RNA ‘flare’ (defined as >0.5 log10 increase in HCV RNA from baseline) between 8–12 weeks of treatment and 82% of patients had a spike in HCV RNA levels at one or more time points during cART. However, the overall trend was a decline in HCV RNA levels by week 72 (of a 96-week treatment period). Patients with a high pretreatment HCVspecific immune response were associated with markedly abnormal serum ALT levels after cART initiation. Corresponding author Kenneth Sherman suggests that an early ALT flare should not automatically be attributed to drug toxicity and instead might be a result of effective HIV therapy in the setting of HCV infection. Gene expression analysis of peripheral blood mononuclear cells identified decreases in IFN-γ-related genes and increases in genes associated with normal CD4+ and CD8+ T-cell responses after treatment initiation. Sherman hypothesizes that these genetic changes could lead to temporarily enhanced HCV replication and immune-mediated liver injury. Using viral kinetic modelling and Granger causality (indicative of a stronger relationship than simple correlation), the authors demonstrated that cART-induced HIV decline was unlikely to be affected by HCV infection and that the HIV RNA level is more likely to alter HCV RNA expression than the reverse. Results from 1 and 4 weeks of treatment showed that declines in HIV viral load correlated with a sizable decline in HCV RNA load. “Our data suggest that the positive effect [of cART] on HCV viral load reduction and decreased hepatic inflammation mandates early antiretroviral intervention in patients with HIV and HCV co-infection,” says Sherman. The group’s future work will continue to focus on the relationship between HIV drug therapy, HCV and other causes of liver injury. Gillian Patman Original article Sherman, K. E. et al. Modulation of HCV replication after combination antiretroviral therapy in HCV/ HIV co-infected patients. Sci. Transl. Med. 6, 246ra98 (2014)
NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY © 2014 Macmillan Publishers Limited. All rights reserved
VOLUME 11 | SEPTEMBER 2014
INFECTIOUS DISEASE
HIV THERAPY GOOD FOR HCV INFECTION Temporary increases in HCV RNA and alanine aminotransferase (ALT) levels do not negate the overall beneficial effects of HIV therapy for HCV infection, according to new research. The clinical trial was set up to evaluate the effect of initiation of combination antiretroviral therapy (cART) on HCV replication and liver injury in patients with HIV and HCV co-infection. A subset of patients (4 of 17) had an HCV RNA ‘flare’ (defined as >0.5 log10 increase in HCV RNA from baseline) between 8–12 weeks of treatment and 82% of patients had a spike in HCV RNA levels at one or more time points during cART. However, the overall trend was a decline in HCV RNA levels by week 72 (of a 96-week treatment period). Patients with a high pretreatment HCVspecific immune response were associated with markedly abnormal serum ALT levels after cART initiation. Corresponding author Kenneth Sherman suggests that an early ALT flare should not automatically be attributed to drug toxicity and instead might be a result of effective HIV therapy in the setting of HCV infection. Gene expression analysis of peripheral blood mononuclear cells identified decreases in IFN-γ-related genes and increases in genes associated with normal CD4+ and CD8+ T-cell responses after treatment initiation. Sherman hypothesizes that these genetic changes could lead to temporarily enhanced HCV replication and immune-mediated liver injury. Using viral kinetic modelling and Granger causality (indicative of a stronger relationship than simple correlation), the authors demonstrated that cART-induced HIV decline was unlikely to be affected by HCV infection and that the HIV RNA level is more likely to alter HCV RNA expression than the reverse. Results from 1 and 4 weeks of treatment showed that declines in HIV viral load correlated with a sizable decline in HCV RNA load. “Our data suggest that the positive effect [of cART] on HCV viral load reduction and decreased hepatic inflammation mandates early antiretroviral intervention in patients with HIV and HCV co-infection,” says Sherman. The group’s future work will continue to focus on the relationship between HIV drug therapy, HCV and other causes of liver injury. Gillian Patman Original article Sherman, K. E. et al. Modulation of HCV replication after combination antiretroviral therapy in HCV/ HIV co-infected patients. Sci. Transl. Med. 6, 246ra98 (2014)
NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY © 2014 Macmillan Publishers Limited. All rights reserved
VOLUME 11 | SEPTEMBER 2014
