Tenofovir monotherapy is just as effective for the treatment of hepatitis B virus (HBV) after the emergence of 3TC (lamivudine, Epivir/Zeffix) resistance in HIV/HBV coinfected individuals as combination therapy with 3TC and tenofovir (Viread) in individuals with no prior 3TC resistance, according to the results of a pan-European study presented to the Second International Workshop on HIV and Hepatitis Coinfection, held in Amsterdam earlier this month.
Due to the approval and availability of 3TC for HBV infection prior to other oral anti-HBV drugs with higher genetic barriers to resistance, a substantial number of HIV/HBV coinfected individuals have developed HBV that is resistant to 3TC.
Currently, two other oral anti-HBV drugs are approved in the United States - adefovir (Hepsera) and entecavir (Baraclude) - although only adefovir currently has European Union approval. Both have been shown to be effective in individuals whose HBV has acquired 3TC resistance. However, treating coinfected individuals with adefovir may not be the best strategy because the dose of adefovir that is active against 3TC-resistant HBV is not active against HIV. Entecavir also has no anti-HIV activity.
Some experts have suggested that tenofovir may be a more attractive option for HIV coinfected people whose HIV has already developed resistance to 3TC, as tenofovir has activity against both HIV and HBV. However, tenofovir is not approved as an anti-HBV drug in the US or the EU.
In order to determine whether combination therapy with 3TC/tenofovir could be superior to sequential therapy with tenofovir for the treatment of chronic HBV infection after the development of 3TC resistance, Dr Stefan Mauss and colleagues from Germany, Spain, Italy and the United Kingdom identified 75 coinfected individuals via a retrospective chart review who were both HBe-antigen positive and had an HBV DNA >100.000 copies/mL.
Fifty individuals whose HBV had developed 3TC resistance (defined via genotyping as having mutations M204V or M204I with or without L180M and/or V173L) were matched with 25 individuals with no 3TC resistance. The participants whose HBV was 3TC-resistant were given tenofovir as part of their anti-HIV therapy; those without 3TC resistance were given 3TC/tenofovir as part of their anti-HIV therapy.
At baseline, the individuals on 3TC/tenofovir had a median HBV DNA of 59,000,000 (range 125,000-15x109) compared to 137,000,000 (range 110,000-11.4x109) in the tenofovir arm (p=0.32). In addition, at baseline the participants in the 3TC/tenofovir arm were significantly younger (median age 38 vs. 43 years; p=0.01); had a lower median CD4 cell count (255 vs. 379; p=0.04) and had a higher median HIV viral load (7851 vs.
After a median of 27 months' follow-up, no difference was seen between the two arms with regards the following endpoints: HBV-DNA
A total of 84% (42/50) of 3TC-resistant individuals achieved an HBV viral load below 1000 copies/mL on tenofovir compared with 76% (19/25) on 3TC/tenofovir. Normalisation of ALT (defined as
The study also found that there was no statistical difference in median baseline CD4 counts between those participants who did or did not achieve the loss of HBe-antigen. For those on tenofovir monotherapy the median CD4 count was 420 cells/mm3 in those who achieved the loss of HBe-antigen versus 374 cells/mm3 for those who did not (p=0.81). For those on 3TC/tenofovir the median CD4 count was 340 cells/mm3 in those who achieved the loss of HBe-antigen versus 235 cells/mm3 for those who did not (p=0.52).
Dr Mauss closed his presentation by saying that in this cohort of 75 HIV/HBV coinfected individuals, "strong and lasting HBV DNA suppression was achieved in the majority of patients independently of treatment allocation" and that HBe-antigen loss was not statistically different in both treatment arms.
He concluded by saying that sequential therapy with tenofovir was as effective as 3TC/ tenofovir in coinfected individuals with highly replicative HBV infection over a median period of 27 months.
Mauss S et al. First-line combination therapy of chronic hepatitis B with tenofovir plus lamivudine versus sequential therapy with tenofovir monotherapy after lamivudine failure. 2nd Intl Workshop HIV/HCV Coinfection, Amsterdam, abstract 42, 2006.