An ultralong-acting tenofovir ProTide nanoformulation achieves monthslong HBV suppression

Das, Srijanee; Wang, Weimin; Ganesan, Murali; Fonseca-Lanza, Franchesca; Cobb, Denise; Bybee, Grace; Sun, Yimin; Guo, Lili; Hanson, Brandon; Cohen, Samuel M.; Gendelman, Howard E.; Osna, Natalia A.; Edagwa, Benson; Poluektova, Larisa Y.

doi:10.1126/sciadv.ade9582

Cited by 11 publications

(8 citation statements)

References 45 publications

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“…The advent of long-acting formulations of tenofovir could facilitate its prescription either as treatment or prevention 92,93 . An additional indirect benefit of using tenofovir chemoprophylaxis would derive from reducing the chances of hepatitis delta acquisition, since this virus requires HBV for transmission 94 .…”

Section: Long-acting Antiviralsmentioning

confidence: 99%

Viral hepatitis in persons living with HIV in the post-COVID era

Soriano¹,

Moreno-Torres²,

Mendoza³

et al. 2024

AIDSRev

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Coinfection with hepatitis viruses A to E is frequent in persons living with HIV (PLWH) and causes significant morbidity and mortality. Oro-fecal transmissible hepatitis A and E mostly produce acute self-limited episodes in poor income regions and in non-vaccinated travelers. In high-income countries, outbreaks of hepatitis A occur in men having sex with men (MSM) and chronic hepatitis E is occasionally reported among PLWH with severe immunodeficiency. Chronic hepatitis B, C, and D are frequent in PLWH in highly endemic regions and globally in persons who inject drugs (PWID) and MSM. Progression to liver cirrhosis and development of hepatocellular carcinoma (HCC) is major clinical complications in coinfected patients. Current estimates for PLWH are of 38 million worldwide. Roughly 12% have chronic viral hepatitis (5 million). Coinfection figures are of 5-10% for HBV (2-4 million), 4% for HCV (1.5 million), and 15% of HBsAg+ for HDV (0.5 million). Oral direct-acting antivirals (DAA) cure almost all treated patients with hepatitis C. However, given that there is no protective HCV immunity, PLWH with high-risk behaviors may experience HCV reinfection episodes. Tenofovir is the drug of choice in PLWH with chronic hepatitis B, given its dual effect on HIV and HBV. Lifelong oral tenofovir suppresses HBV replication and ameliorate liver damage. However, the risk of HCC persists even in the absence of cirrhosis. Finally, HDV causes the worst of viral hepatitis with faster progression to cirrhosis and HCC. An entry inhibitor, bulevirtide, has recently been approved and another drug, lonafarnib, is completing Phase 3 trials. Combination antiviral therapy for hepatitis D could improve dramatically the poor prognosis of HIV-HDV coinfected patients. The resumption of good medical practices in PLWH after the big disruption caused by COVID-19 will reduce the burden of viral hepatitis coinfections. Renewed efforts on HAV and HBV vaccination of susceptible individuals and earlier and wider prescription of antiviral therapy for HBV, HCV, and/or HDV coinfection should be prioritized in PLWH. The benefits of innovative strategies for viral hepatitis, including pre-exposure prophylaxis or use of long-acting antivirals, warrant further consideration in PLWH.

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Section: Long-acting Antiviralsmentioning

confidence: 99%

Viral hepatitis in persons living with HIV in the post-COVID era

Soriano¹,

Moreno-Torres²,

Mendoza³

et al. 2024

AIDSRev

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“…The advent of long-acting formulations of tenofovir [ 38 , 39 , 40 ] would represent an attractive alternative option for both treatment and prophylaxis of hepatitis B. Long-term adherence to medications is generally challenging, as many patients tend to forgive daily dosing.…”

Section: Long-acting Antiviral Formulations For Hepatitis Bmentioning

confidence: 99%

Prospects for Controlling Hepatitis B Globally

Soriano,

Moreno-Torres,

Treviño

et al. 2024

Pathogens

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Infection with the hepatitis B virus (HBV) is highly prevalent globally. Over 250 million people suffer from chronic hepatitis B, and more than 800,000 patients die each year due to hepatitis B complications, including liver cancer. Although protective HBV vaccines are recommended for all newborns, global coverage is suboptimal. In adults, sexual transmission is by far the most frequent route of contagion. The WHO estimates that 1.5 million new HBV infections occur annually. Oral nucleos(t)ide analogues entecavir and tenofovir are the most frequent antivirals prescribed as HBV therapy. Almost all patients adherent to the medication achieve undetectable plasma viremia beyond 6 months of monotherapy. However, less than 5% achieve anti-HBs seroconversion, and viral rebound occurs following drug discontinuation. Therefore, nucleos(t)ide analogues need to be lifelong. New long-acting formulations of tenofovir and entecavir are being developed that will maximize treatment benefit and overcome adherence barriers. Furthermore, new antiviral agents are in development, including entry inhibitors, capside assembly modulators, and RNA interference molecules. The use of combination therapy pursues a functional HBV cure, meaning it is negative for both circulating HBV-DNA and HBsAg. Even when this goal is achieved, the cccDNA reservoir within infected hepatocytes remains a signal of past infection, and HBV can reactivate under immune suppression. Therefore, new gene therapies, including gene editing, are eagerly being pursued to silence or definitively disrupt HBV genomes within infected hepatocytes and, in this way, ultimately cure hepatitis B. At this time, three actions can be taken to push HBV eradication globally: (1) expand universal newborn HBV vaccination; (2) perform once-in-life testing of all adults to identify susceptible HBV persons that could be vaccinated (or re-vaccinated) and unveil asymptomatic carriers that could benefit from treatment; and (3) provide earlier antiviral therapy to chronic HBV carriers, as being aviremic reduces the risk of both clinical progression and transmission.

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“…These drugs are also associated with little drug resistance, are easy to take orally, have few side effects, and generally do not require frequent patient monitoring [ 45 ]. Long-acting forms of tenofovir have also been under clinical development and may have the added benefit of sustained therapeutic drug concentrations and improved patient compliance [ 46 ].…”

Section: Section Ii: Enrollmentmentioning

confidence: 99%

Consensus Guidelines: Best Practices for the Prevention, Detection and Management of Hepatitis B Virus Reactivation in Clinical Trials with Immunosuppressive/Immunomodulatory Therapy

Cohen,

Regev,

Garg

et al. 2024

Drug Saf

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Hepatitis B virus reactivation (HBVr) during and after immunosuppressive/immunomodulatory (IS/IM) therapy is associated with significant morbidity and mortality, including hepatic decompensation and acute liver failure. The risk of HBVr with IS/IM has been heterogeneous and often unpredictable. As a result, patients with active or previous HBV infection are often excluded from clinical drug trials of such agents. Thorough screening for HBV infection, antiviral prophylaxis, and careful monitoring for HBVr have proven to be effective in reducing the rate of HBVr and improving its outcome in the context of IS/IM. Therefore, safe enrollment and management of certain HBV-marker–positive patients in clinical trials is possible. There is a great, unmet need for consistent, evidence-based recommendations for best practices pertaining to enrollment, monitoring, and management of HBVr in clinical trial participants receiving IS/IM. The aim of these consensus guidelines is to provide a step-by-step blueprint to safely enroll, monitor and manage the patient with inactive chronic or resolved HBV in IS/IM clinical trials from the time of screening through to the end of post-treatment follow up.

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An ultralong-acting tenofovir ProTide nanoformulation achieves monthslong HBV suppression

Cited by 11 publications

References 45 publications

Viral hepatitis in persons living with HIV in the post-COVID era

Viral hepatitis in persons living with HIV in the post-COVID era

Prospects for Controlling Hepatitis B Globally

Consensus Guidelines: Best Practices for the Prevention, Detection and Management of Hepatitis B Virus Reactivation in Clinical Trials with Immunosuppressive/Immunomodulatory Therapy

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