Literature Commentary by Dr. John G. Bartlett: HIV/Hep Coinfection, Jan '08
Literature Commentary by Dr. John G. Bartlett: HIV/Hep Coinfection, Jan '08
Cicconi P, Cozzi-Lepri A, Phillips A, et al, for the ICoNA Study Group. Is the increased risk of liver enzyme elevation in patients co-infected with HIV and hepatitis virus greater in those taking antiretroviral therapy? AIDS. 2007;21:599-606.
The purpose of the study was to determine the effect of HAART on the risk of liver enzyme elevation (LEE) in patients with HIV, with or without hepatitis B virus (HBV), and/or or hepatitis C virus (HCV) coinfection.
Methods: The analysis was done for patients in the ICoNA study, which is a multicenter Italian prospective observational study that has followed HIV-infected patients since 1977. The analysis was designed to determine the frequency of grade 3 LEE defined by the ACTG as an alanine aminotransferase (ALT) of at least 5 x the upper limit of normal. For patients with an elevated baseline ALT, the definition was 3.5 x the baseline ALT. The analysis was to compare the frequency of LEE in coinfected patients with or without HAART (before or after starting HAART).
Results: The cohort included 5272 patients, with coinfections in 48%; of the 48%, 86% had HCV, 8% had HBV, and 7% had HCV + HBV. The median ALT at baseline for coinfected patient was 31 International units (IU)/L. During the follow-up period of 18,250 person-years, there were 275 cases of grade 3 LEE. With regard to ART, 54% were treatment-naive and 36% of person-years were pretreatment. The most frequent regimens for HIV were nucleoside reverse transcriptase inhibitors (NRTIs), primarily zidovudine and lamivudine, with a drug from a different class. NRTIs combined with a nonnucleoside reverse transcriptase inhibitors accounted for 30% of patient-years of treatment and NRTIs plus a protease inhibitor accounted for 51% of patient-years of treatment. The protease inhibitors used most frequently were indinavir, nelfinavir, and saquinavir.
The risk of LEE was substantially increased in patients with HIV and coinfection with HBV and/or HCV independent of HAART, with an odds ratio (OR) of 5.1. The frequency of LEE was not significantly increased with HAART. Overall, the OR for LEE was 1.2 for HAART use. For HCV, the OR for LEE was approximately the same with HAART vs no HAART: 4.2 vs 4.5, respectively. However, there appeared to be a significant benefit to HAART with HBV, with an OR of 6.0 with HAART and 14.3 without HAART, but this difference was not statistically significant. These data are summarized in the Table .
Conclusion: The authors conclude that HIV coinfection with HBV or HCV is associated with a substantial risk of LEE and that this is not modified by HAART.
Comment: The study is of interest in the context of the potential value of HAART for prevention of progression of HCV or HBV. This study had large numbers but failed to show any statistically significant benefit in terms of HBV- or HCV-associated liver disease, although there appeared to be a trend for benefit in HBV coinfection.
Cicconi P, Cozzi-Lepri A, Phillips A, et al, for the ICoNA Study Group. Is the increased risk of liver enzyme elevation in patients co-infected with HIV and hepatitis virus greater in those taking antiretroviral therapy? AIDS. 2007;21:599-606.
The purpose of the study was to determine the effect of HAART on the risk of liver enzyme elevation (LEE) in patients with HIV, with or without hepatitis B virus (HBV), and/or or hepatitis C virus (HCV) coinfection.
Methods: The analysis was done for patients in the ICoNA study, which is a multicenter Italian prospective observational study that has followed HIV-infected patients since 1977. The analysis was designed to determine the frequency of grade 3 LEE defined by the ACTG as an alanine aminotransferase (ALT) of at least 5 x the upper limit of normal. For patients with an elevated baseline ALT, the definition was 3.5 x the baseline ALT. The analysis was to compare the frequency of LEE in coinfected patients with or without HAART (before or after starting HAART).
Results: The cohort included 5272 patients, with coinfections in 48%; of the 48%, 86% had HCV, 8% had HBV, and 7% had HCV + HBV. The median ALT at baseline for coinfected patient was 31 International units (IU)/L. During the follow-up period of 18,250 person-years, there were 275 cases of grade 3 LEE. With regard to ART, 54% were treatment-naive and 36% of person-years were pretreatment. The most frequent regimens for HIV were nucleoside reverse transcriptase inhibitors (NRTIs), primarily zidovudine and lamivudine, with a drug from a different class. NRTIs combined with a nonnucleoside reverse transcriptase inhibitors accounted for 30% of patient-years of treatment and NRTIs plus a protease inhibitor accounted for 51% of patient-years of treatment. The protease inhibitors used most frequently were indinavir, nelfinavir, and saquinavir.
The risk of LEE was substantially increased in patients with HIV and coinfection with HBV and/or HCV independent of HAART, with an odds ratio (OR) of 5.1. The frequency of LEE was not significantly increased with HAART. Overall, the OR for LEE was 1.2 for HAART use. For HCV, the OR for LEE was approximately the same with HAART vs no HAART: 4.2 vs 4.5, respectively. However, there appeared to be a significant benefit to HAART with HBV, with an OR of 6.0 with HAART and 14.3 without HAART, but this difference was not statistically significant. These data are summarized in the Table .
Conclusion: The authors conclude that HIV coinfection with HBV or HCV is associated with a substantial risk of LEE and that this is not modified by HAART.
Comment: The study is of interest in the context of the potential value of HAART for prevention of progression of HCV or HBV. This study had large numbers but failed to show any statistically significant benefit in terms of HBV- or HCV-associated liver disease, although there appeared to be a trend for benefit in HBV coinfection.
Source...