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HBV Mutations With Monotherapy Versus Combination Therapy
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5th European HIV Drug Resistance Workshop
Cascais, Portugal
March 30, 2007
Mark Mascolini
Note from Jules Levin: in the hepatitis world there have been many studies and it is well accepted that the main identified benefot of combination HBV therapy is the prevention or limiting of resistance mutations from developing. Other than that so far in the limited studies conducted no benefit has yet to be clearly identified with the use of combination therapy including in terms of antiviral activity. However, not all strategies have yet to be explored. The use of tenofovir + entecavir has yet to be studied.
Mutations conferring resistance to anti-HBV drugs emerged in 10 of 14 HIV-coinfected people (71%) taking a single drug active against HBV and in 2 of 14 (14%) taking at least two anti-HBV drugs, according to clinicians from three Lisbon hospitals [1]. They recorded seven different mutations patterns in people taking lamivudine (3TC) and no other anti-HBV drugs as part of an antiretroviral regimen; two or more mutations arose in 4 of these people.
HBV mutations that emerged in the dual-therapy group have not been correlated with resistance to anti-HBV drugs, whereas some mutations that arose with 3TC monotherapy confer cross-resistance to other HBV polymerase inhibitors. Emergence of these 3TC mutations correlated with longer use of that drug (P < 0.05).
The Lisbon team used the TruGene assay to search for resistance mutations in 28 HBV/HIV-coinfected people taking antiretrovirals. Fourteen were taking regimens in which 3TC was the only anti-HBV drug and 14 were taking 3TC or emtricitabine (FTC) plus tenofovir. Median ages of the anti-HBV monotherapy and dual-therapy groups were 45 and 41, and median treatment durations measured 24 and 11 months, a difference that just fell short of statistical significance (P = 0.06). The monotherapy group had twice as many HBeAg-positive members (12) as the dual-therapy group.
HIV loads were equivalent in the two groups at medians of 3.5 log in the monotherapy group and 4.1 in double-therapy group. But 11 (78%) taking only 3TC as an active anti-HBV drug had HBV viremia, compared with 5 (36%) in the dual-therapy group. Respective median log IU/mL measured 8.9 and 3.6, a significant difference (P = 0.04).
Single mutations arose in 2 of 14 people in the dual therapy group, rtQ215Q/S and rtA194V. Three of 10 people with treatment-emergent mutations in the monotherapy group had single mutations, rtM204I, rtM204V, rtQ215P/S. The position 204 mutations also appeared in 4 other people taking only 3TC. M204I confers cross-resistance to FTC, entecavir, and LdT, and M204V makes HBV cross-resistant to entecavir and FTC. The rtQ215S mutation confers cross-resistance to adefovir.
All told, the Lisbon team identified seven distinct resistance patterns in the monotherapy group. The dual and triple mutant virus seen in some of these people may be able to escape vaccine control.
The authors argued that their findings "support the use of combination therapy for HBV infection in HIV/HBV coinfected patients." They also called for HBV genome analysis before starting anti-HBV therapy, noting that an adefovir-related mutation, rtN238D, emerged in 1 person who never took adefovir.
Reference
1. Corte-Real R, Germano I, Teofilo E, et al. HBV genotypic resistance in HIV/HBV co-infected patients HAART treated. 5th European HIV Drug Resistance Workshop. March 28-30, 2007. Cascais, Portugal. Abstract 87.
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