Liver-related outcomes are poorer in HIV-positive patients
who are co-infected with hepatitis B virus genotype B compared to co-infected
patients with hepatitis B genotype C, Taiwanese investigators report in the
online edition of Clinical Infectious
The prospective, observational study involved individuals
who commenced antiretroviral therapy containing 3TC (lamivudine, Epivir, also in the combination pill Combivir), a drug which has activity
against both viruses. The patients were recruited between 1997 and 2008, and
followed until 2010.
[hepatitis B virus] genotype B co-infection were at higher risk of developing
hepatitis flares, liver disease-related deaths, HBeAg seroconversion, and
lamivudine resistance mutations than those with genotype C coinfection,” write
the authors. Genotype did not affect HIV-related outcomes.
HIV and hepatitis B share transmission modes. Therefore,
large numbers of patients are co-infected with these viruses. There are eight
hepatitis B genotypes (A – H). The distribution of genotypes varies according
to geographical region, and genotypes B and C predominate in Asia.
Little is known about the differential impact of these two
genotypes on liver-related outcomes in patients co-infected with HIV and
Therefore, investigators in Taiwan recruited 145 co-infected
patients starting antiretroviral therapy to a study analysing the clinical,
immunological and virological outcomes of patients according to hepatitis B
The hepatitis B-related outcomes included the risk of
hepatitis flares, liver disease-related death, hepatitis B e antigen (HBeAg)
seroconversion, and the development of strains of hepatitis B with resistance
to 3TC. Changes in CD4 cell count and HIV viral load were also compared
according to genotype.
A total of 96 patients were co-infected with genotype B and
49 with genotype C were recruited. There were no significant baseline
differences between the patients.
However, they had severe immune suppression at the time they
started HIV treatment, and their median CD4 cell count was just 117 cells/mm3.
Median baseline HIV viral load was approximately 125,000 copies/ml. Median
hepatitis B viral load at the start of the study was 63,000 copies/ml.
Patients were treated with 3TC-containing antiretroviral
therapy for a median of 2.8 years. During this time, none of the patients
received any other antiretroviral drugs with activity against hepatitis B.
Compared to patients with genotype C, those with genotype B
co-infection were significantly more likely to experience hepatitis flares (44%
vs. 27%, p = 0.04), die of liver-related causes (9% vs. 0%, p = 0.03), have
HBeAg seroconversion (62% vs. 25%, p = 0.03), and developed strains of
hepatitis B with resistant to 3TC (31% vs. 12%, p < 0.001).
Analysis that controlled for potentially confounding factors
confirmed the relationship between genotype B co-infection and a number of
Compared to individuals with genotype C, those with genotype
B had a higher risk of hepatitis flares (AHR = 4.13; 95% CI, 2.87-5.39; p =
0.01) and were also more likely to develop 3TC-resistant hepatitis B (AHR = 8.67;
95% CI, 6.37-10.98, p = 0.001).
However, there was no significant difference in mortality
risk between the genotypes. Nor did HIV-related outcomes differ between the two
groups of patients, who had similar falls in viral load and increases in CD4
“Hepatitis B genotype B is the most predominant genotype in
hepatitis B virus and HIV-co-infected Taiwanese patients,” conclude the investigators.
“Patients with genotype B co-infection are more likely to experience acute
exacerbations of hepatitis, HBeAg seroconversion, lamivudine resistance, and
liver disease-related death than those with genotype C coinfection when they
receive [HIV therapy] containing lamivudine as the only active agent against
hepatitis B virus.”