HIV and Viral Hepatitis: Prevention, Treatment and Coinfection

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Biopharmaceuticals".

Deadline for manuscript submissions: 25 May 2025 | Viewed by 13628

Special Issue Editors


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Guest Editor
Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Madrid, Spain
Interests: hepatitis C virus; HIV; infectious diseases; virology; nanomedicine; neutralizing antibody

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Guest Editor
Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Madrid, Spain
Interests: HIV; hepatitis C; infectious diseases; immunology; virology; genetics; epidemiology; cirrhosis
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Special Issue Information

Dear Colleagues,

Since viral hepatitis and HIV share transmission routes, many HIV-infected individuals are also co-infected with HBV, HCV, and HDV. Hepatitis viruses are a leading cause of morbi-mortality worldwide, leading to cirrhosis, end-stage liver disease, hepatocellular carcinoma, and death. According to the WHO, 1.4 million people die yearly due to viral hepatitis worldwide. Although extraordinary progress has been made in treating hepatitis C, there are still important issues without solving, particularly in treating hepatitis B and D. On the other hand, HIV attacks and weakens the immune system progressively, destroying CD4 cells and leading to AIDS progression. According to the WHO, 37.7 million people living with HIV, and approximately 600,000 died from HIV-related causes. The prevention of HIV infection through antiretroviral therapy is a critical point in combating this infection. The number of drugs to treat HIV-infected patients is large, but none of them has solved the problem of achieving a permanent functional cure, much less the total HIV elimination of the body.

In this Special Issue, we invite contributors to publish their research on discovering drugs with novel mechanisms of action, biomolecules, or novel biological targets to provide very effective tools in treating, preventing, and eradicating these hepatitis viruses and HIV.

Bullet-point topics:

  • Prevention and/or treatment of HIV and HBV, HCV, and HDV
  • Drug discovery and screening: small molecules, biomolecules, natural products
  • Novel anti-HIV, -HBV, HCV, and -HDV inhibitors
  • HIV and hepatitis viruses vaccine development
  • Broadly neutralizing antibodies
  • Drug delivery
  • Microbicides: novel pharmaceutical preparations
  • Nanotechnology
  • In vitro studies
  • Pre- and clinical trials
  • HIV/hepatitis viruses coinfection
  • Coinfection with other sexually transmitted viruses

Dr. Daniel Sepúlveda-Crespo
Dr. Salvador Resino
Guest Editors

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Keywords

  • coinfection
  • drug discovery
  • HBV
  • HCV
  • HDV
  • HIV
  • neutralizing antibodies
  • prevention
  • treatment
  • vaccine

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Published Papers (6 papers)

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Research

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29 pages, 2438 KiB  
Article
The Impact of Hepatitis B and/or C on Liver Function and on the Response to Antiretroviral Therapy in HIV-Infected Patients: A Romanian Cohort Study
by Ruxandra-Cristina Marin, Delia Mirela Tit, Gabriela Bungău and Radu Dumitru Moleriu
Pharmaceuticals 2025, 18(5), 688; https://doi.org/10.3390/ph18050688 - 7 May 2025
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Abstract
Background: Hepatitis B (HBV) and C (HCV) virus coinfections remain major contributors to liver-related morbidity and mortality among people living with HIV (PLWH). This study aimed to assess the prevalence of HBV and/or HCV coinfections in a Romanian HIV cohort and to [...] Read more.
Background: Hepatitis B (HBV) and C (HCV) virus coinfections remain major contributors to liver-related morbidity and mortality among people living with HIV (PLWH). This study aimed to assess the prevalence of HBV and/or HCV coinfections in a Romanian HIV cohort and to evaluate their impact on immunological, virological, and liver function parameters under antiretroviral therapy (ART). Methods: We retrospectively analyzed 462 HIV-infected patients (2018–2021) from the National Institute of Infectious Diseases, Bucharest, stratified into four groups: HIV mono-infection (n = 176), HIV/HBV (n = 114), HIV/HCV (n = 97), and HIV/HBV/HCV (n = 75) coinfections. Immunological (CD4 count, CD8 count, and CD4/CD8 ratio), virological (HIV-1 RNA), and hepatic parameters (ALT, AST, GGT, bilirubin, amylase, and lipase) were compared. Results: No significant differences were observed between groups regarding the immune recovery (mean CD4 count p = 0.89, HIV-RNA suppression p = 0.78). However, liver and pancreatic parameters showed statistically significant deterioration in the coinfected groups. ALT (p < 0.001), GGT (p = 0.009), total bilirubin (p = 0.011), amylase (p = 0.010), and lipase (p < 0.001) were significantly higher in the triple-infection (HIV/HBV/HCV) group compared to HIV mono-infected patients. Coinfection was also associated with a longer duration of illness (p = 0.002) and therapy (p = 0.021) and with a higher number of ART regimens used (p = 0.013). Conclusions: While HIV suppression and immune recovery were not significantly impaired by HBV/HCV coinfections, liver and pancreatic injuries were significantly more prevalent and severe in coinfected patients. Regular monitoring of hepatic function and integrated management strategies are recommended to minimize liver-related complications in this population. Full article
(This article belongs to the Special Issue HIV and Viral Hepatitis: Prevention, Treatment and Coinfection)
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12 pages, 1036 KiB  
Article
Effectiveness and Tolerability of DOR/3TC/TDF in Experienced People with HIV Switching from RPV/FTC/TDF: A Retrospective, Single Center Cohort Study
by Stefania Cicalini, Simone Lanini, Roberta Gagliardini, Rita Bellagamba, Alessandra Vergori, Ilaria Mastrorosa, Valentina Mazzotta, Rozenn Esvan, Maria Maddalena Plazzi, Sandrine Ottou, Elisabetta Grilli, Federico De Zottis, Marisa Fusto, Jessica Paulicelli and Andrea Antinori
Pharmaceuticals 2024, 17(12), 1706; https://doi.org/10.3390/ph17121706 - 17 Dec 2024
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Abstract
Background: With advances in antiretroviral therapy for HIV treatment, newer drug combinations provide improved efficacy, safety, and compliance. This study evaluates switching to a regimen of doravirine (DOR), tenofovir disoproxil fumarate (TDF), and lamivudine (3TC) in a cohort of people living with HIV [...] Read more.
Background: With advances in antiretroviral therapy for HIV treatment, newer drug combinations provide improved efficacy, safety, and compliance. This study evaluates switching to a regimen of doravirine (DOR), tenofovir disoproxil fumarate (TDF), and lamivudine (3TC) in a cohort of people living with HIV (PLWH). Methods: this Italian retrospective study included 426 PLWH who switched from rilpivirine (RPV)/TDF/emtricitabine (FTC) to DOR/3TC/TDF. The analysis focused on treatment effectiveness, safety, and metabolic and renal markers. Results: this study reports a treatment failure (defined as virological failure or discontinuation of the regimen) rate of 2.34% (95% confidence interval, 1.28–4.50%), with significant improvement in CD4 counts (+49.93 cells/µL, p < 0.001). Notably, the switch to DOR/3TC/TDF did not result in adverse metabolic effects or significant changes in renal function. Analysis of lipid profiles showed stabilization in the majority of PLWH. Conclusions: this study indicates that switching to a DOR/3TC/TDF from RPV/TDF/FTC is an effective and well-tolerated option for PLWH, with benefits in terms of maintaining viral suppression, CD4 count recovery, and metabolic health, without evidence of renal impairment. These results support the continued use of DOR/3TC/TDF as part of HIV treatment strategies and highlight the need for ongoing research to refine ART regimens for different populations. Full article
(This article belongs to the Special Issue HIV and Viral Hepatitis: Prevention, Treatment and Coinfection)
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9 pages, 1137 KiB  
Article
Development of a Lateral Flow Assay for the Detection of the Hepatitis C Virus Core Antigen
by Erick Joan Vidal-Alcántara, Sonia Hernández Antón, Paloma Rueda, María Belén Yélamos, Julián Gómez, Salvador Resino, Alba Fresco-Taboada and Isidoro Martínez
Pharmaceuticals 2024, 17(8), 1022; https://doi.org/10.3390/ph17081022 - 4 Aug 2024
Cited by 1 | Viewed by 2181
Abstract
Background: Hepatitis C virus (HCV) infection remains a global health challenge, with millions of people affected annually. Current diagnostic methods, reliant on antibody screening and viral RNA detection, are complex, costly, and often inaccessible, particularly in resource-limited settings. Aim: Development of a lateral [...] Read more.
Background: Hepatitis C virus (HCV) infection remains a global health challenge, with millions of people affected annually. Current diagnostic methods, reliant on antibody screening and viral RNA detection, are complex, costly, and often inaccessible, particularly in resource-limited settings. Aim: Development of a lateral flow immunochromatography-based assay for detecting the highly conserved hepatitis C core antigen (HCVcAg). Methods: The assay relies on the interaction of four highly specific and cross-reactive monoclonal antibodies with recombinant HCVcAg from five different genotypes in a double antibody sandwich format. Latex and colloidal gold were evaluated as detector nanoparticles. Results: Extensive evaluation of 32 antibody combinations led to identifying the most sensitive antibody pairs. The chosen assay, named LN17, demonstrated a target sensitivity of 10 ng/strip, with potential clinical implications for detecting HCV. Furthermore, the study examined matrix effects in serum samples, providing valuable insights for future clinical application. Conclusions: The developed assay holds promise as a rapid, cost-effective, and user-friendly tool to enhance accessibility to hepatitis C screening, especially in high-risk populations and resource-limited environments. Full article
(This article belongs to the Special Issue HIV and Viral Hepatitis: Prevention, Treatment and Coinfection)
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25 pages, 4607 KiB  
Article
HIV-1 Transcription Inhibition Using Small RNA-Binding Molecules
by Pooja Khatkar, Gifty Mensah, Shangbo Ning, Maria Cowen, Yuriy Kim, Anastasia Williams, Fardokht A. Abulwerdi, Yunjie Zhao, Chen Zeng, Stuart F. J. Le Grice and Fatah Kashanchi
Pharmaceuticals 2024, 17(1), 33; https://doi.org/10.3390/ph17010033 - 25 Dec 2023
Cited by 2 | Viewed by 2499
Abstract
The HIV-1 transactivator protein Tat interacts with the transactivation response element (TAR) at the three-nucleotide UCU bulge to facilitate the recruitment of transcription elongation factor-b (P-TEFb) and induce the transcription of the integrated proviral genome. Therefore, the Tat–TAR interaction, unique to the virus, [...] Read more.
The HIV-1 transactivator protein Tat interacts with the transactivation response element (TAR) at the three-nucleotide UCU bulge to facilitate the recruitment of transcription elongation factor-b (P-TEFb) and induce the transcription of the integrated proviral genome. Therefore, the Tat–TAR interaction, unique to the virus, is a promising target for developing antiviral therapeutics. Currently, there are no FDA-approved drugs against HIV-1 transcription, suggesting the need to develop novel inhibitors that specifically target HIV-1 transcription. We have identified potential candidates that effectively inhibit viral transcription in myeloid and T cells without apparent toxicity. Among these candidates, two molecules showed inhibition of viral protein expression. A molecular docking and simulation approach was used to determine the binding dynamics of these small molecules on TAR RNA in the presence of the P-TEFb complex, which was further validated by a biotinylated RNA pulldown assay. Furthermore, we examined the effect of these molecules on transcription factors, including the SWI/SNF complex (BAF or PBAF), which plays an important role in chromatin remodeling near the transcription start site and hence regulates virus transcription. The top candidates showed significant viral transcription inhibition in primary cells infected with HIV-1 (98.6). Collectively, our study identified potential transcription inhibitors that can potentially complement existing cART drugs to address the current therapeutic gap in current regimens. Additionally, shifting of the TAR RNA loop towards Cyclin T1 upon molecule binding during molecular simulation studies suggested that targeting the TAR loop and Tat-binding UCU bulge together should be an essential feature of TAR-binding molecules/inhibitors to achieve complete viral transcription inhibition. Full article
(This article belongs to the Special Issue HIV and Viral Hepatitis: Prevention, Treatment and Coinfection)
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Review

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33 pages, 1718 KiB  
Review
Insights into Immune Exhaustion in Chronic Hepatitis B: A Review of Checkpoint Receptor Expression
by João Panão Costa, Armando de Carvalho, Artur Paiva and Olga Borges
Pharmaceuticals 2024, 17(7), 964; https://doi.org/10.3390/ph17070964 - 21 Jul 2024
Cited by 5 | Viewed by 2725
Abstract
Hepatitis B, caused by the hepatitis B virus (HBV), often progresses to chronic infection, leading to severe complications, such as cirrhosis, liver failure, and hepatocellular carcinoma. Chronic HBV infection is characterized by a complex interplay between the virus and the host immune system, [...] Read more.
Hepatitis B, caused by the hepatitis B virus (HBV), often progresses to chronic infection, leading to severe complications, such as cirrhosis, liver failure, and hepatocellular carcinoma. Chronic HBV infection is characterized by a complex interplay between the virus and the host immune system, resulting in immune cell exhaustion, a phenomenon commonly observed in chronic viral infections and cancer. This state of exhaustion involves elevated levels of inhibitory molecules, cells, and cell surface receptors, as opposed to stimulatory counterparts. This review aims to elucidate the expression patterns of various co-inhibitory and co-stimulatory receptors on immune cells isolated from chronic hepatitis B (CHB) patients. By analyzing existing data, the review conducts comparisons between CHB patients and healthy adults, explores the differences between HBV-specific and total T cells in CHB patients, and examines variations between intrahepatic and peripheral immune cells in CHB patients. Understanding the mechanisms underlying immune exhaustion in CHB is crucial for developing novel immunotherapeutic approaches. This detailed analysis sheds light on the immune exhaustion observed in CHB and lays the groundwork for future combined immunotherapy strategies aimed at leveraging checkpoint receptors to restore immune function and improve clinical outcomes. Full article
(This article belongs to the Special Issue HIV and Viral Hepatitis: Prevention, Treatment and Coinfection)
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13 pages, 1024 KiB  
Review
Development of Anti-HIV Therapeutics: From Conventional Drug Discovery to Cutting-Edge Technology
by Yaping Sun and Lingyun Wang
Pharmaceuticals 2024, 17(7), 887; https://doi.org/10.3390/ph17070887 - 4 Jul 2024
Cited by 5 | Viewed by 3527
Abstract
The efforts to discover HIV therapeutics have continued since the first human immunodeficiency virus (HIV) infected patient was confirmed in the 1980s. Ten years later, the first HIV drug, zidovudine (AZT), targeting HIV reverse transcriptase, was developed. Meanwhile, scientists were enlightened to discover [...] Read more.
The efforts to discover HIV therapeutics have continued since the first human immunodeficiency virus (HIV) infected patient was confirmed in the 1980s. Ten years later, the first HIV drug, zidovudine (AZT), targeting HIV reverse transcriptase, was developed. Meanwhile, scientists were enlightened to discover new drugs that target different HIV genes, like integrase, protease, and host receptors. Combination antiretroviral therapy (cART) is the most feasible medical intervention to suppress the virus in people with HIV (PWH) and control the epidemic. ART treatment has made HIV a chronic infection rather than a fatal disease, but ART does not eliminate latent reservoirs of HIV-1 from the host cells; strict and life-long adherence to ART is required for the therapy to be effective in patients. In this review, we first discussed the scientific history of conventional HIV drug discovery since scientists need to develop more and more drugs to solve drug-resistant issues and release the side effects. Then, we summarized the novel research technologies, like gene editing, applied to HIV treatment and their contributions to eliminating HIV as a complementary therapy. Full article
(This article belongs to the Special Issue HIV and Viral Hepatitis: Prevention, Treatment and Coinfection)
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