Hepatitis B Virus Genotypes and Lamivudine-resistant Mutations in HIV-HBV Coinfected Patients

As with HIV and hepatitis C, various factors appear to influence clinical and therapeutic outcomes in patients with chronic hepatitis B virus (HBV) infection. For HBV, these include differences in viral subtypes, hepatitis B "e" antigen (HBeAg) negative viral variants, and drug-resistance mutations.

To shed more light on factors affecting outcomes, researchers identified all HIV-infected patients with persistent serum hepatitis B surface antigen (HBsAg) and detectable HBV viremia at a reference HIV clinic in Madrid, Spain. HBV viral load, HBV subtypes, presence of precore and basal core promoter variants, and mutations conferring resistance to lamivudine (3TC; Epivir-HBV) were analyzed; the median time on lamivudine was 40 months.

Results

• A total of 81 HIV-HBV coinfected individuals (4.1%) were identified out of a population of 1968 HIV positive patients.

• Plasma specimens with detectable HBV viremia were obtained from 62 subjects; this was the study population that underwent further characterization.

• HBV genotype distribution was as follows:

- A: n = 27;
- D: n = 27;
- E: n = 1;
- F: n = 2;
- G: n = 3;
- mixed HBV genotypes (A/E and A/F): n = 2.

• HBV subtype A was predominant (74%) among patients infected through sexual contact, whereas subtype D was most frequent (74%) among injection drug users (P < 0.001).

• Precore and basal core promoter mutants were more common in patients with HBV subtype D than in those with subtype A (63% vs 18%; P < 0.01).

• Patients with HBV subtype A tended to be more likely to have lamivudine resistance mutations (53% vs 44%) and to develop them earlier (35 vs 45 months), compared to patients with subtype D.

• The dual L180M + M204V/I mutant was the predominant resistance pattern, although a triple rt173V + 180M + 204V pattern (which acts as a vaccine escape mutant) was observed in 1 individual.

• In a multivariate analysis, patients with lamivudine-resistance mutations were significantly more likely to be HBeAg positive and were older than individuals with wild-type HBV.

• Hepatitis-delta virus (HDV) was identified in 13 (21%) of the 62 HBV viremic patients, with no association with specific HBV variants.

Conclusion

In conclusion, the researchers wrote, "Risk transmission group, age, and positive serum HBeAg are the main determinants of distinct HBV virologic variants, including HBV genotypes and lamivudine-resistant mutants, in HBV/HIV coinfected patients."

02/06/07

Reference
B Ramos, M Nunez, L Martin-Carbonero, and others. Hepatitis B Virus Genotypes and Lamivudine Resistance Mutations in HIV/Hepatitis B Virus-Coinfected Patients. Journal of Acquired Immune Deficiency Syndromes. January 11, 2007 [Epub ahead of print].