Evaluation of precore/core promoter sequences in hepatitis B virus and HIV coinfected patients in 3-year follow-up study

CASSINO L, LAUFER N, , MORETTI F ,BOUZAS MB, FERNÁNDEZ S,PEREZ H, CAHN P, SALOMÓN H,QUARLERI J

Mexico

Conferencia; XVII International AIDS Conference; 2008

IAS

Background: Hepatitis B virus (HBV) co-infection is common in HIV-infected persons. Co-infection could lead to a better HBV replication efficiency and less HBeAg seroconversion rate. Considering the crucial role of precore-core (Pc-C) regulatory elements, we evaluated their genomic variations with known impact on HBV replication in HIV co-infected patients. Methods: A 3-year longitudinal study was carried out.  Serum samples were collected from 18 HIV-HBV coinfected patients with detectable HBV DNA at baseline. The basal core promoter (BCP) and Pc regions were PCR-amplified, cloned and sequenced. Clinical records were reviewed to obtain data on 3TC-antiviral therapy, immunological and virological parameters (i.e. HBV-VL and genotype –Gt-). Results: Eleven out of 18 HBV isolates from HBeAg+ patients were ascribed to GtA (8/11), GtD (2/11), GtF (1/11).  Four of them exhibited BCP/Pc mutations/deletions as follows: 1/4 (GtA) showed Pc mutations; 1/4 (GtF) exhibited A1762G/G1764A and G1764A/C1766T/1768A BCP mutations (and 3TC-resistance mutations). The majority of clones from these isolates exhibited those variations and was long-lasting. Remaining 2/4 isolates (GtA) exhibited two different 8bp patterns BCP deletions, being preserved and predominant in only one.  HBV isolates from HBeAg (-) patients (7/18) showed low replicative efficiency and were ascribed to GtA, exhibiting only 3/7 Pc/BCP transient variations in low proportion. One showed 1762T/1764A at BCP (further reverted to wt); remaining 2 exhibited 1850T/1858T Pc mutations, unable to be further analyzed when HBV-DNA was cleared. Conclusions: Considering the high prevalence of HBV-GtA in HIV-coinfected patients, the BCP/Pc mutations were infrequent. Some of the Pc/BCP variations seem to be more durable, tempting to speculate that could contribute to higher replication efficiency in a HBV genotype-dependent manner.