Rescue TDF monotherapy effective in multidrug resistant chronic HBV

Jan 26 2016

By Shreeya Nanda, Senior medwireNews Reporter

Researchers from the Republic of Korea say that rescue therapy with tenofovir disoproxil fumarate (TDF) alone is an appropriate option for patients with multidrug resistant chronic hepatitis B virus (HBV) infection.

Although current guidelines recommend combination nucleos(t)ide analogue treatment for multidrug resistant patients, the team believes it is important to evaluate TDF monotherapy in this setting as long-term use of multiple drugs has cost and safety implications.

Of 446 patients included in this medical review, 156 were resistant to two prior antiviral therapies and thus considered multidrug resistant, while 290 displayed resistance to lamivudine alone.

After a median 15 months of rescue treatment with TDF alone, the cumulative virological response rates at 24 months from treatment initiation were a comparable 81.4% for the 43 patients with resistance to adefovir plus lamivudine, 84.1% for the 113 resistant to entecavir plus lamivudine and 82.8% for those resistant to lamivudine alone.

The researchers note that patients in the lamivudine-resistant group attained a virological response, defined as undetectable serum HBV DNA as assessed by real-time polymerase chain reaction, “more rapidly” than multidrug resistant patients, but they emphasize that cumulative response rates did not differ significantly between groups.

And multivariate analysis showed that multiplicity of antiviral resistance was not a significant predictor of virological response.

However, baseline HBV DNA levels were significantly associated with achievement of a virological response to TDF monotherapy (p=<0.001), such that the “higher the HBV DNA level, the lower the virological response rate”, write the authors.

Stratification of the study population by baseline HBV DNA levels showed that the cumulative response rate was 94.7% for patients with levels below 2 log₁₀ IU/mL, 84.3% for those with levels between 2 and 4 log₁₀ IU/mL, and 57.5% for participants with HBV DNA levels of 4 log₁₀ IU/mL and above. And the differences between the groups were significant (p=<0.001).

Therefore, Sang Hoon Ahn (Yonsei University College of Medicine, Seoul) and colleagues suggest that “the HBV DNA level should be considered when clinicians decide to initiate rescue therapy” for multidrug resistant chronic HBV patients.

Highlighting the lack of a TDF-based combination therapy control arm, they conclude in the Journal of Medical Virology that “[a]dditional comparative studies are needed to determine whether TDF mono-rescue therapy is inferior to combination therapy for patients with [multidrug resistance].”

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