July 26, 2005
How safe are antiretroviral nucleosides in HIV-infected individuals who are coinfected with hepatitis B or hepatitis C? The question is an important one, because of two reasons: Firstly, up to one third of people with HIV are coinfected with hepatitis B or C. Secondly, there have been concerns that individuals who are coinfected with hepatitis B or hepatitis C may be at greater risk for nucleoside-mediated toxicities. This is particularly an issue due to the continued widespread use of abacavir (ABC, Ziagen) and lamivudine (3TC, Epivir) in the treatment of coinfected patients. Lamivudine is among the anti-HIV nucleosides that are known to possess potent anti-hepatitis B properties.
In this study, conducted by Henry Zhao et al from GlaxoSmithKline and presented by Trevor Scott, researchers looked at the safety in coinfected individuals of the fixed-dose combination drug abacavir/lamivudine (ABC/3TC, Combivir) in the context of 4 large, randomized clinical trials. Each trial had been conducted with HIV treatment-naive patients; abacavir/lamivudine was employed in combination with efavirenz (EFV, Sustiva, Stocrin) or any of a variety of protease inhibitors on a once-daily or twice-daily basis. The trials lasted a protracted period of time, i.e., greater than 48 weeks.
Of a total of 1,985 patients evaluated in the 4 trials, approximately 20% had been coinfected with hepatitis B and/or hepatitis C. The baseline characteristics and demographics of patients in both the non-coinfected and coinfected categories were similar, with the exception of baseline alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values, which were understandably much higher among coinfected patients.
The most important result of this analysis is that no differences were observed between the 2 groups in the overall incidence of adverse events, nor were differences observed in the type or incidence of specific adverse events. This similarity persisted regardless of whether patients received abacavir or lamivudine on a once-daily or twice-daily basis. Particularly reassuring was the finding that coinfected individuals did not demonstrate higher rates of abacavir-related hypersensitivity reactions than individuals infected only with HIV.
In conclusion, this study provides reassurance to clinicians and patients as to the relative safety of abacavir and lamivudine for use in coinfected individuals. Unfortunately, this study did not provide additional information on whether doubly coinfected individuals (patients with both hepatitis B and hepatitis C) may have developed greater rates of resistance to lamivudine in regard to mutations in the YMDD motif of the hepatitis B virus polymerase.