Analysis of hepatitis B virus precore/core promoter variations in monoinfected and HIV coinfected patients in a 3-year follow-up study

CASSINO L., LAUFER N., SALOMON H., QUARLERI J.

Montreal, Canada

Conferencia; 16th. Conference on Retroviruses and Opportunistic Infections; 2009

Analysis of hepatitis B virus precore/core promoter variations in monoinfected and HIV coinfected patients in a 3-year follow-up study. Cassino L., Laufer N., Salomon H., Quarleri J. Background: The curse of chronic HBV infection is modified by HIV coexistence. We and others have reported a high prevalence of HBV-genotype (Gt) A among HIV co-infected patients in contrast with HBV monoinfected ones. The role of HBV genomic heterogeneity in basal core promoter (BCP) and precore (Pc) genomic regions is analyzed as potential contributor to that differential molecular epidemiology in a 3-yr retrospective study. Methods: Thirty-nine HBV infected patients (20 monoinfected and 19 HIV-coinfected) were included. From them, 115 serum samples were collected during the follow-up.  The basal core promoter (BCP) and Precore (Pc) regions were amplified, cloned and sequenced. Clinical records were reviewed to obtain data on antiviral therapy (3TC therapy and resistance mutations), immunological (CD4+ cell counts) and virological parameters (i.e. HBV-VL, HIV-VL),   Results: Among 19 HIV-coinfected patients, 12 expressed HBeAg.  They were ascribed to GtA (9/12), GtD (2/11) and GtF (1/11). Twenty HBV isolates from HBV mono-infected patients were analyzed. We have chosen 12 isolates (8 GtA and 4 GtF) from HBeAg (+) patients and 8 (4 GtA, 4 GtF) from HBeAg (-) patients. Among HBeAg (+) co-infected individuals, only 2 GtA exhibited 8bp deletions at BCP; in one -H19-, in almost all clones, during the 3-year study. The other isolate (H7) exhibited 2/15 deleted clones at baseline and then reverted to wt. A1762T/G1764A BCP mutations were only found in one GtF in the majority of its clones.When sequences from co-infected patients were compared with ones from mono-infected individuals, we found that 4/8 GtA isolates exhibited A1762T/G1764A in a few clones and only one (M6) exhibited 2 clones with an 8bp deletion at baseline. However, all GtF isolates showed a higher proportion of clones with A1762T/G1764A mutations during the follow up study.  So, variations in BCP were more frequently found in HBV isolates from monoinfected patients (p=0.0095, T test). Seven HBV isolates were from HBeAg (-) coinfected patients (GtA). Two isolates exhibited a few clones with A1850T/C1858T Pc variations and were ascribed to GtD and E respectively. Nevertheless, Pc 1858C /1896A mutations among isolates from HBeAg (-) patients were more frequent among GtF isolates from mono-infected patients (p=0.02, T test). Gt A isolates from monoinfected patient, though, displayed 8/10 clones with A1762T/1764A BCP mutations that were not found among HBV genomes from co-infected individuals (p=0.02).