Safety and efficacy of adefovir dipivoxil in patients infected with lamivudine-resistant hepatitis B and HIV-1

Benhamou, Yves; Thibault, Vincent; Vig, Pamela; Cálvez, Vincent; Marcelin, Anne–Geneviève; Fievet, M.‐H.; Currie, Graeme; Chang, Chuy G.; Lu, Binfeng; Xiong, Shelly; Brosgart, Carol; Poynard, Thierry

doi:10.1016/j.jhep.2005.08.020

Cited by 85 publications

(67 citation statements)

References 23 publications

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“…A limited number of studies suggest that transition to adefovir dipivoxil following development of lamivudine-resistant HBV variants is safe and efficacious. [97][98][99][100] Further clinical trials are still required to validate these findings. A multidrug, tiered strategy of HBV reactivation prophylaxis and/or treatment, would allow indefinite lamivudine prophylaxis to be recommended if routine monitoring for YMDD mutants is performed with transition in anti-viral therapy, including adefovir or entecavir, if detected.…”

mentioning

confidence: 98%

Systematic review: lamivudine prophylaxis for chemotherapy‐induced reactivation of chronic hepatitis B virus infection

Kohrt

Ouyang

Keeffe

2006

Aliment Pharmacol Ther

113

107

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mentioning

confidence: 98%

Systematic review: lamivudine prophylaxis for chemotherapy‐induced reactivation of chronic hepatitis B virus infection

Kohrt

Ouyang

Keeffe

2006

Aliment Pharmacol Ther

113

107

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“…The treatment of HBV infection in patients coinfected with HIV-1has become an important health issue due to the increased morbidity and mortality resulting from HBV-related chronic liver disease (15). Several nucleoside/nucleotide inhibitors with dual activities against both HIV-1 and HBV have been used as part of combination antiviral regimens in coinfected patients, including lamivudine, emtricitabine, adefovir, and tenofovir (2,(4)(5)(6)16). However, few options exist for patients who are infected with HBV but who do not meet the current criteria for treatment with highly active antiretroviral therapy (HAART), as treatment with these anti-HBV agents alone has a proved (lamivudine and tenofovir) or theoretical (adefovir) risk of inducing resistance in HIV-1.…”

mentioning

confidence: 99%

Telbivudine Exhibits No Inhibitory Activity against HIV-1 Clinical Isolates In Vitro

Lin

Karwowska

Lam³

et al. 2010

Antimicrob Agents Chemother

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Most approved drugs with activity against hepatitis B virus (HBV) have activity against human immunodeficiency virus type 1 (HIV-1), which precludes their use in patients who are coinfected with HBV and HIV-1 and who are not receiving antiretroviral therapy due to the risk of inducing resistance. The activity of telbivudine, a highly selective HBV inhibitor, against temporally and geographically distinct wild-type and multidrug-resistant HIV-1 clinical isolates was evaluated in vitro. No inhibition was observed with up to 600 M drug, which supports further exploration of telbivudine as a therapeutic option for the treatment of HBV infections in patients coinfected with HIV-1.

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“…Although 3TC is safe and effective, its therapeutic value is limited by the timedependent development of drug-resistant HBV mutants (32); therefore, various combination therapies have long been proposed to counter drug resistance in HBV infection. More recently, the nucleotide analog adefovir dipivoxil (ADV) was licensed for the treatment of HBV infection and was shown to inhibit the replication of 3TC-resistant virus mutants in patients also treated with 3TC (1,3,4,16,37,47,66). In fact, in chronic HBV carriers, even monotherapy with ADV for up to 5 years had a high degree of safety and efficacy, and resistant mutants developed less frequently than in parallel studies with 3TC alone (2,19,35,48,65).…”

mentioning

confidence: 99%

Antiviral Effects of Lamivudine, Emtricitabine, Adefovir Dipivoxil, and Tenofovir Disoproxil Fumarate Administered Orally Alone and in Combination to Woodchucks with Chronic Woodchuck Hepatitis Virus Infection

Menne

Butler

George

et al. 2008

Antimicrob Agents Chemother

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Adefovir dipivoxil (ADV) and tenofovir disoproxil fumarate (TDF) are nucleotide analogs that inhibit the replication of wild-type hepatitis B virus (HBV) and lamivudine (3TC)-resistant virus in HBV-infected patients, including those who are coinfected with human immunodeficiency virus. The combination of ADV or TDF with other nucleoside analogs is a proposed strategy for managing antiviral drug resistance during the treatment of chronic HBV infection. The antiviral effect of oral ADV or TDF, alone or in combination with 3TC or emtricitabine (FTC), against chronic woodchuck hepatitis virus (WHV) infection was evaluated in a placebo-controlled study in the woodchuck, an established and predictive model for antiviral therapy. Oncedaily treatment for 48 weeks with ADV plus 3TC or TDF plus FTC significantly reduced serum WHV viremia levels from the pretreatment level by 6.2 log 10 and 6.1 log 10 genome equivalents/ml serum, respectively, followed by TDF plus 3TC (5.6 log 10 genome equivalents/ml), ADV alone (4.8 log 10 genome equivalents/ml), ADV plus FTC (one survivor) (4.4 log 10 genome equivalents/ml), TDF alone (2.9 log 10 genome equivalents/ml), 3TC alone (2.7 log 10 genome equivalents/ml), and FTC alone (2.0 log 10 genome equivalents/ml). Individual woodchucks across all treatment groups also demonstrated pronounced declines in serum WHV surface antigen, characteristically accompanied by declines in hepatic WHV replication and the hepatic expression of WHV antigens. Most woodchucks had prompt recrudescence of WHV replication after drug withdrawal, but individual woodchucks across treatment groups had sustained effects. No signs of toxicity were observed for any of the drugs or drug combinations administered. In conclusion, the oral administration of 3TC, FTC, ADV, and TDF alone and in combination was safe and effective in the woodchuck model of HBV infection.Chronic infection with the hepatitis B virus (HBV) is a major public health problem and is responsible for 1.2 million deaths per year worldwide (64). It is estimated that more than 2 billion people have serological evidence of previous or current HBV infection, and over 350 million people are chronic carriers of HBV (64). Carriers of HBV are at high risk of developing chronic hepatitis, hepatic cirrhosis, and hepatocellular carcinoma (HCC). Although safe and effective prophylactic vaccines against HBV are available, improvements in drug and/or immunotherapeutic strategies for the treatment of chronic HBV infection are still needed. Therapy with alpha interferon and nucleoside analogs alone or in combination can be effective against HBV; however, side effects of interferon and the emergence of nucleoside-resistant mutants often limit treatment outcomes (34).Lamivudine (3TC) was the first nucleoside analog licensed for the treatment of chronic HBV infection. Although 3TC is safe and effective, its therapeutic value is limited by the timedependent development of drug-resistant HBV mutants (32

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Safety and efficacy of adefovir dipivoxil in patients infected with lamivudine-resistant hepatitis B and HIV-1

Cited by 85 publications

References 23 publications

Systematic review: lamivudine prophylaxis for chemotherapy‐induced reactivation of chronic hepatitis B virus infection

Systematic review: lamivudine prophylaxis for chemotherapy‐induced reactivation of chronic hepatitis B virus infection

Telbivudine Exhibits No Inhibitory Activity against HIV-1 Clinical Isolates In Vitro

Antiviral Effects of Lamivudine, Emtricitabine, Adefovir Dipivoxil, and Tenofovir Disoproxil Fumarate Administered Orally Alone and in Combination to Woodchucks with Chronic Woodchuck Hepatitis Virus Infection

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