Chronic Active Hepatitis B Exacerbations in Human Immunodeficiency Virus‐Infected Patients Following Development of Resistance to or Withdrawal of Lamivudine

Bessesen, Mary; Ives, David V.; Condreay, Lynn D.; Lawrence, Steven P.; Sherman, Kenneth E.

doi:10.1086/514750

Cited by 161 publications

(80 citation statements)

References 22 publications

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“…Many patients coinfected with HIV and HBV have received 3TC as part of their combination therapy for HIV. Antiviral activity against HBV in such patients is characteristically transient because of the development of 3TC resistance (6,18,21,60). In several recent studies, HIV patients with 3TC-resistant HBV infection have been treated with TDF or ADV, and a significant inhibition of HBV replication was demonstrated (1,5,7,18,43,45,47,(49)(50)(51).…”

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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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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“…In patients with chronic HIV-infection who experience HIV suppression while receiving ART, flares have been reported following the discontinuation of lamivudine [19], emtricitabine [20], or tenofovir [21] treatment or with the emergence of lamivudine resistance [21].For HIVinfected patients, flares have been reported when they start receiving combination antiretroviral therapy, and the flares may be attributed to drug related hepatotoxicity [22].Also flares have been recorded after the cessation of lamivudine, emtricitabine, adefovir, or tenofovir [19], [23], [24]. It has been observed from this study that a significant elevation of liver transaminase levels (ALT and AST) is a serious risk factor associated with management of HIV management with drugs.…”

Section: Discussionmentioning

confidence: 99%

Transaminase [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] Activity of HIVFemale Patients on Drugs and Female Patients Not on Drugs

Odiba¹,

Iruoghene²,

IROHA³

et al. 2014

IOSRJPBS

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Elevated serum transaminase [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] levels have been reported in human immunodeficiency virus (HIV)-infected patients on combination antiretroviral therapy (cART). (r = 0.201, p < 0.05).It has been observed from the study that a significant elevation of liver transaminase levels (ALT and AST) is a serious risk factor associated with management of HIV management with drugs.

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“…9 This concern stems from data on HIV-hepatitis B virus (HBV) coinfected individuals with chronic hepatitis B infections and cirrhosis who have high rates of hepatitis flares, sometimes leading to hepatic failure if they discontinue treatment for HIV with agents that are dually active against both HIV and HBV. 10,11 The effect of PrEP use on hepatitis B infection is not well understood and most PrEP trials excluded participants with circulating HBV surface antigen at baseline. 2,12 There are no reported cases of flares in HIV-uninfected persons with chronic hepatitis B infection who have discontinued FTC/TDF PrEP, although clinical experience with PrEP remains limited.…”

Section: Introductionmentioning

confidence: 99%

The Safety of Tenofovir-Emtricitabine for HIV Pre-Exposure Prophylaxis (PrEP) in Individuals With Active Hepatitis B.

2016

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background: Pre-exposure prophylaxis (PrEP) with daily oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) prevents HIV infection. The safety and feasibility of HIV PrEP in the setting of hepatitis B virus (HBV) infection were evaluated. Methods:The Iniciativa Profilaxis Pre-Exposición study randomized 2499 HIV-negative men and transgender women who have sex with men to once-daily oral FTC/TDF versus placebo. Hepatitis serologies and transaminases were obtained at screening and at the time PrEP was discontinued. HBV DNA was assessed by polymerase chain reaction, and drug resistance was assessed by population sequencing. Vaccination was offered to individuals susceptible to HBV infection.Results: Of the 2499 participants, 12 (0.5%; including 6 randomized to FTC/TDF) had chronic HBV infection. After stopping FTC/ TDF, 5 of the 6 participants in the active arm had liver function tests performed at follow-up. Liver function tests remained within normal limits at post-stop visits except for a grade 1 elevation in 1 participant at post-stop week 12 (alanine aminotransferase = 90, aspartate aminotransferase = 61). There was no evidence of hepatic flares. Polymerase chain reaction of stored samples showed that 2 participants in the active arm had evidence of acute HBV infection at enrollment. Both had evidence of grade 4 transaminase elevations with subsequent resolution. Overall, there was no evidence of TDF or FTC resistance among tested genotypes. Of 1633 eligible for vaccination, 1587 (97.2%) received at least 1 vaccine; 1383 (84.7%) completed the series.Conclusions: PrEP can be safely provided to individuals with HBV infection if there is no evidence of cirrhosis or substantial transaminase elevation. HBV vaccination rates at screening were low globally, despite recommendations for its use, yet uptake and efficacy were high when offered.

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Chronic Active Hepatitis B Exacerbations in Human Immunodeficiency Virus‐Infected Patients Following Development of Resistance to or Withdrawal of Lamivudine

Cited by 161 publications

References 22 publications

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

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

Transaminase [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] Activity of HIVFemale Patients on Drugs and Female Patients Not on Drugs

The Safety of Tenofovir-Emtricitabine for HIV Pre-Exposure Prophylaxis (PrEP) in Individuals With Active Hepatitis B.

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