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10-03-2013 | Genetics | Article

Resistant HBV mutants raise public health concerns


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medwireNews: Researchers have shown that treatment with anti-hepatitis B virus (HBV) nucleoside analogs in HBV-HIV co-infection results in a substantial increase in mutants linked to treatment and vaccine resistance.

Study findings indicated the mutations could be linked to the type of drug therapy used and response to ineffective treatment.

"This finding can be particularly worrisome in settings such as Sub-Saharan Africa and Asia, where there is a constrained access to powerful anti-HBV drugs, virological monitoring, and a high prevalence of HBV-infection," say authors Fabien Zoulim (Lyon University, France) and colleagues.

The study, reported in Hepatology, included 171 patients with concurrent HIV and HBV infection who were treated with nucleoside analogs, including lamivudine, emtricitabine, and tenofovir. HBV DNA was analyzed at enrolment, and at months 12, 24, and 36 using DNA-chip sequencing.

The largest increase in any mutation class was in L-nucleoside-associated pol-genes and antiviral-associated S-genes which increased from 56.8% prevalence at baseline to 68.9% at 36 months. Pol-gene mutations are known to confer resistance to nucleoside analogs, while there is evidence that S- (or surface) gene mutants can result in vaccine failure, explain Zoulim and colleagues.

Cumulative duration of lamivudine treatment was significantly associated with risk for L-nucleoside-associated pol-gene or antiviral-associated S-gene mutations (hazard ratio [HR]=4.61), while tenofovir treatment was associated with a decreased risk (HR=0.94).

The authors also observed S-gene mutants associated with immune-selective pressures which increased from 4.8% prevalence at baseline to 11.3% at 36 months. Tenofovir treatment also seemed to be protective for immune-associated S-gene mutations (HR=0.88), and most patients who developed immune-related mutations had been exposed to lamivudine.

Mutant strains can arise under selective pressure from the body's own immune system, which effective antiviral therapy can relieve, say the authors. However, less potent antiviral treatments such as lamivudine, and ineffective therapy could lead to insufficient virological suppression allowing a pool of mutated virus to form from which immune-associated S-gene mutations could be selected.

The authors explain that while the issue of pol- and S-gene mutants is known to be a public health threat, further research is needed to explore how levels of mutants vary over the course of treatment and what effect they have on disease outcomes and vaccination.

"For the time being, the use of more potent antivirals with a high barrier to resistance and close virological follow-up are highly recommended in co-infected patients in order to reduce the probability of more problematic HBV mutation emerging," say Zoulim and colleagues.

"In HIV-infection, emerging S-gene mutations might jeopardize immunization and prevention strategies aimed at reducing transmission of HBV mutant strains," they caution.

By Kirsty Oswald, medwireNews Reporter

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