Viral dynamics of hepatitis B virus DNA in human immunodeficiency virus-1–hepatitis B virus coinfected individuals: Similar effectiveness of lamivudine, tenofovir, or combination therapy

✍ Scribed by Sharon R. Lewin; Ruy M. Ribeiro; Anchalee Avihingsanon; Scott Bowden; Gail Matthews; Pip Marks; Stephen A. Locarnini; Kiat Ruxrungtham; Alan S. Perelson; Gregory J. Dore

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 377 KB
• Volume: 49
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.22754

✦ Synopsis

Following treatment of hepatitis B virus (HBV) infection with nucleos(t)ide reverse transcriptase inhibitors (NRTIs), there is a biphasic clearance of HBV, similar to that seen following treatment of human immunodeficiency virus-1 (HIV-1) and hepatitis C virus. Little is known about the impact of combination NRTIs and HIV-1 coinfection on HBV viral kinetic parameters following the initiation of HBV-active highly active antiretroviral therapy (HAART). HIV-1-HBV coinfected patients (n ‫؍‬ 21) were enrolled in a viral kinetics substudy of the Tenofovir in HIV-1-HBV Coinfection study (TICO). TICO was a randomized (1:1:1) trial of tenofovir disoproxil fumarate (TDF, 300 mg) versus lamivudine (LMV, 300 mg) versus TDF/LMV within an efavirenz based HAART regimen initiated in HIV-1-HBV coinfected antiretroviral naı ¨ve individuals in Thailand. HBV DNA was measured frequently over the first 56 days. To fit the viral load data, we used a model of HBV kinetics that allows the estimation of treatment effectiveness, viral clearance and infected cell loss. We observed a biphasic decline in HBV DNA in almost all patients. We did not observe any significant differences in HBV viral dynamic parameters between the three treatments groups. Overall, median (interquartile range) HBV treatment effectiveness was 98% (95%-99%), median HBV virion half-life was 1.2 days (0.5-1.4 days), and median infected cell half-life was 7.9 days (6.3-11.0 days). When we compared hepatitis B e antigen (HBeAg)positive and HBeAg-negative individuals, we found a significantly longer infected cell halflife in HBeAg-positive individuals (6.2 versus 9.0 days, P ‫؍‬ 0.02). Conclusion: HBV viral dynamic parameters are similar following anti-HBV NRTI monotherapy and dual combination therapy in the setting of HIV-1-HBV coinfection. HIV-1 coinfection has minimal effect on HBV viral dynamics, even in the setting of advanced HIV-1-related immunosuppression. (HEPATOLOGY 2009;49:1113-1121.) C oinfection with human immunodeficiency virus-1 (HIV-1) alters the natural history of chronic hepatitis B virus (HBV) infection with higher serum HBV DNA, lower alanine aminotransferase (ALT) levels and higher rates of cirrhosis, particularly in those with low CD4ϩ T cell counts. 1,2 Liver-related mortality has now become the leading cause of non-acquired immune deficiency syndrome-related death, and a signif-