Presence of Mixed Hepatitis B Genotypes Occurs More Frequently in HIV-HBV Coinfected Patients

By Liz Highleyman

Studies have shown that HIV-HBV coinfected patients are more likely to develop progressive liver disease than those with hepatitis B virus (HBV) infection alone, but the reasons for this difference are not well understood.

Possible contributing factors may include immune suppression, increased HBV virulence, or the effects of antiretroviral therapy. Another possibility is diversity of HBV strains within an individual patient. In past studies, different HBV genotypes have been linked to more severe disease progression (genotype C), better response to antiviral therapy (genotype A), and susceptibility to lamivudine resistance (genotype A).

Recent research has shown that some 16% of HBV monoinfected people have more than one HBV genotype circulating in their blood. In a study presented at the recent 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (July 22-25, 2007), researchers aimed to determine the prevalence of mixed HBV genotypes in HIV-HBV coinfected individuals.

The investigators planned to analyze HBV isolated from serum samples obtained from 150 HIV-HBV coinfected individuals, about half from a cohort in Melbourne and Sydney, Australia, the rest from the U.S. Multicenter AIDS Cohort Study (MACS). Out of the 72 Australian individuals, 44 had detectable HBV DNA and had their HBV sequenced; these results were presented at the conference.

The researchers used PCR amplification and sequencing, as well as the more sensitive Innogenetics INNO-LiPA HBV genotyping assay, to perform genome sequence analysis.

Results

• The predominant HBV genotype was A, detected in 57% of subjects, consistent with prior studies of HIV-HBV coinfected patients.
  
  
• Using the INNO-LiPA genotyping assay, 15 subjects (35%) had evidence of infection with more than 1 HBV genotype:
• 11 with genotypes A and G;
• 2 with genotypes A and D;
• 1 with genotypes C and D;
• 1 with genotypes D and G.
  
  
• In contrast, analysis of samples from 35 HBV monoinfected individuals with genotype A found that only 1 (3%) had evidence of multiple genotypes (A and G).

Conclusion

“We have found the proportion of mixed HBV genotype infections in the setting of HIV-HBV coinfection to be considerably higher (34%) than has been reported in HBV monoinfected patients (16%),” the researchers concluded.

The fact that only 1 HBV monoinfected individual showed evidence of mixed genotype infection “infers that the increase in mixed HBV infections is not due to the predominance of genotype A HBV in this cohort,” they added.

The researchers are currently analyzing HBV samples from the MACS patients, as well as collecting clinical data to determine whether mixed-genotype HBV infection is associated with worse disease progression.

Victorian Infectious Diseases Reference Laboratory, North Melbourne, Australia; National Centre in HIV Epidemiology and Clinical Research, Sydney, Australia; Monash University, Department of Medicine, Melbourne, Australia; Royal Melbourne Hospital, Victorian Infectious Diseases Service, Melbourne, Australia; Johns Hopkins University, Department of Medicine, Baltimore, MD.

08/17/07

Reference
M Littlejohn, A Ayres, P Revill, and others. High proportion of mixed HBV genotypes detected in a cohort of HIV/HBV co-infected patients4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. Sydney, Australia, July 22-25, 2007. Abstract MOPEA079.