GENOMIC VARIATIONS OF HEPATITIS-B VIRUS-STRAINS IN PATIENTS CHRONICALLY COINFECTED WITH HEPATITIS-B AND HUMAN IMMUNODEFICIENCY VIRUSES

Serum samples from 56 human immunodeficiency virus type 1 (HIV-1)-infe cted adult men were analysed for the presence of hepatitis B virus (HB V) serological markers. Two or more samples from each patient, collect ed over an interval of 1-6 years, were tested. The antibody against HB V core antigen (anti-HBc) prevalence was 79%. Three (5%) patients No. 5, 7, and 9 were chronic carriers of HBV surface antigen (HBsAg). HBV DNAs from serial samples of these three patients and from two HIV-sero negative control patients were characterised after amplification of di fferent genome regions by polymerase chain reaction (PCR). Size and re striction analyses of the PCR products showed that samples from patien ts No. 7 (with chronic active hepatitis) and 9 (asymptomatic) containe d heterogeneous HBV DNA populations. In patient No. 7, HBV DNA contain ed a precore gene stop codon mutation at nucleotide (nt) 1896. In addi tion, a deletion in the core gene was found in a sample collected two years after the onset of acquired immunodeficiency syndrome (AIDS). PC R products from serial samples of patient No. 9 indicated a mixture of HBV DNA molecules that were cloned. Sequencing of the pre-S region of the clones and phylogenetic analysis showed that patient No. 9 was su perinfected with three HBV populations of distinct origin, all belongi ng to genotype A. HBV DNA of patient No. 5 (with AIDS) did not present any variability during a 6-year follow-up. Although two of three HIV/ HBV coinfected patients harboured heterogeneous HBV DNA populations du ring the follow-up, no common event with respect to HBV DNA evolution was observed among the coinfected patients.