Mutations
Associated with Lamivudine (3TC; Epivir) Resistance in Previously Untreated Hepatitis
B Patients with and without HIV
By
Liz Highleyman
Treatment of HIV-HBV
coinfected patients is complicated by the fact that certain drugs -- including
lamivudine (3TC; Epivir), emtricitabine
(Emtriva), tenofovir (Viread),
and to a lesser extent entecavir
(Baraclude) -- are active against both viruses and can encourage either virus
to develop resistance mutations if used as monotherapy.
In resource-limited
settings such as South Africa, where combination antiretroviral therapy has only
recently begun to ramp up, little is known about the prevalence of lamivudine-resistance
HBV in individuals with and without HIV.
S.G. Selabe from the University
of Limpopo in Pretoria, South Africa, and colleagues conducted an exploratory
study to investigate lamivudine-resistant HBV strains in 35 selected lamivudine-naive
HBV infected participants, 15 of whom had chronic HBV monoinfection and 20 of
whom had HIV-HBV coinfection. The coinfected group was further subdivided into
13 with occult HBV (HBsAg negative but detectable HBV DNA) and 7 with overt HBV
(HBsAg positive).
Hepatitis B surface antigen (HBsAg), hepatitis B surface
and core antibodies, and HIV-1 and HIV-2 antibodies were determined as part of
routine diagnosis. Serum samples were amplified and sequenced across the YMDD
motif of the major catalytic region in the C domain of HBV reverse transcriptase
to assess lamivudine resistance.
Results •
Lamivudine-resistant
HBV strains were detected in 3 of 15 HBV monoinfected patients (20%) and 10 of
20 HIV-HBV coinfected patients (50%).
•
HBV
viral loads for monoinfected patients ranged from 3.32 x 102 to 3.82 x 107 copies/mL.
•
For
coinfected patients, the range was < 200 to 4.40 x 103 copies/mL.
Conclusion
"To
the best of our knowledge, this constitutes the first report of HBV lamivudine-resistant
strains in therapy-naive HBV-HIV coinfected patients," the authors wrote
in conclusion. "It remains to be seen whether such pre-existing antiviral
mutations could result in widespread emergence of HBV resistant strains when lamivudine-containing
highly active antiretroviral treatment
(HAART) regimens become widely applied in South Africa, as this is likely
to have potential implications in the management of HBV-HIV coinfected patients."
10/12/07 Reference
SG
Selabe, A Lukhwareni, E Song, and others. Mutations associated with lamivudine-resistance
in therapy-naive hepatitis B virus (HBV) infected patients with and without HIV
co-infection: Implications for antiretroviral therapy in HBV and HIV co-infected
South African patients. Journal of Medical Virology 79(11): 1650-1654.
November 2007.
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