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Video:HIV/HBV/HDV tri-infection

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Description

Human Immunodeficiency Virus, Hepatitis B virus, and Hepatitis D virus tri-infection is a severe condition due to shared transmission routes. HDV a defective virus, can only cause infection in the presence of HBV. This triple infection accelerates the progression of liver disease, increasing the risk of cirrhosis, liver failure, and liver-related mortality more rapidly than with any single infection. Diagnosis requires blood tests for all three viruses, and management necessitates a combination of antiretroviral therapy for HIV and HBV, and often peginterferon for HDV, with a goal of suppressing all three viruses to minimize liver damage.[1][2]

Presentation

The presentation of this multiple infection is as follows(though this list is not exhaustive):[3][4] jaundice, tiredness, abdominal pain, fever, dark urine and loss of appetite.

Cause

HIV are two species of Lentivirus ,a subgroup of retrovirus, that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS),[5][6] a condition in which progressive failure of the immune system allows life-threatening opportunistic infections .[7]Hepatitis B virus[8]is a partially double-stranded DNA virus,[9] a species of the genus Orthohepadnavirus and a member of the Hepadnaviridae family of viruses.[10]HDV, also known as hepatitis delta, is a unique and severe form of viral hepatitis that only affects individuals who are already infected with hepatitis B virus.[11]

Transmission

In terms of shared routes we find that HIV, HBV, and HDV share common transmission routes, including sexual contact and injection drug use, making tri-infection frequent, especially among intravenous drug users.[12][13]

Mechanism

In terms of the pathophysiology of this multiple infection , we find that since HDV is a defective satellite virus that requires the Hepatitis B surface antigen(HBsAg) produced by HBV to form its viral envelope and infect new cells, means it can only establish infection in a person who is already HBV-positive. When HIV is also present, the resulting immunosuppression, characterized by the destruction of CD4+ T-lymphocytes,hinders the bodys ability to control HBV and HDV replication. This immune problem allows for higher viral loads of HBV and contributes to an accelerated progression of liver disease, leading to a higher risk of severe outcomes, including rapid development of fibrosis, cirrhosis, and hepatocellular carcinoma.[14][2][1][15]

Diagnosis

In terms of the diagnosis of this multiple infection we find the following:[16][17]initial HIV diagnosis is with fourth-generation HIV antigen/antibody combo assay, HBV(screening) serologic panel is HBsAg (surface antigen) which indicates current infection and HDV RNA-PCR confirms active replication and infection of the Hepatitis D virus.

Treatment

As to the management of HIV/HBV/HDV tri-infection we find treatment for HIV and HBV is combined by ensuring the ART regimen includes two drugs with dual activity against both viruses, a combination of Tenofovir plus Emtricitabine. For the HDV component, treatment options include Pegylated Interferon alpha more targeted therapies like Bulevirtide are available. Close monitoring of liver function and surveillance for liver cancer are important due to the high risk of accelerated cirrhosis and end-stage liver disease.[18][19][20][21]

Adverse interaction

In terms of adverse drug-drug interactions we find that the overlap of drug metabolism pathways involving the livers cytochrome P450 (CYP) enzymes, is where many HIV antiretrovirals(ritonavir and cobicistat) can alter the concentration of co-administered drugs. This effect can increase the toxicity of other medications or, conversely lead to failure of HIV, HBV, or HDV therapy; management must balance HIV/HBV-active drugs(tenofovir) with HDV treatments (Bulevirtide).[22][23][24]

Prognosis

The prognosis for individuals with HIV/HBV/HDV co-infection is generally worse than for those with just dual HIV/HBV or HBV/HDV infection due to the cumulative damage and immune complications. It is associated with higher rates of liver cirrhosis, hepatic decompensation, and death.[2]

Epidemiology

A 2022 meta-analysis found a pooled global prevalence of about 7 (point) 4 percent among studied populations, with much higher rates in certain subgroups[1]The epidemiology of HIV/HBV/HDV tri-infection reveals a underestimated public health burden, particularly in high-risk populations and regions with endemic hepatitis B and D. Asian populations show significantly higher rates,21 (point) 4 percent in a meta-analysis, due to endemic HBV and HDV circulation.Men who have sex with men and people with HBV are disproportionately affected with 7 (point) 9 percent prevalence.[1]

History

As to history we find that the clinical characterization of HIV/HBV/HDV tri-infection was significantly advanced by Dr Yu-Shan Huang at National Taiwan University Hospital, whose 2025 study analyzed 534 HIV/HBV coinfected individuals and identified a 10 percent HDV seroconversion rate, predominantly among MSM. Their findings revealed that HDV superinfection increased liver-related mortality, cirrhosis, and hepatitis flares despite tenofovir-based ART, establishing this tri-infection as a distinct clinical entity with serious hepatic outcomes.[25]

References

  1. ↑ 1.0 1.1 1.2 1.3 Chen, Sisi; Ren, Feng; Huang, Xiaojie; Xu, Ling; Gao, Yao; Zhang, Xiangying; Cao, Yaling; Fan, Zihao; Tian, Yuan; Liu, Mei (29 November 2022). "Underestimated Prevalence of HIV, Hepatitis B Virus (HBV), and Hepatitis D Virus (HDV) Triple Infection Globally: Systematic Review and Meta-analysis". JMIR Public Health and Surveillance. 8 (11): e37016. doi:10.2196/37016. PMC 9748799. PMID 36445732.
  2. ↑ 2.0 2.1 2.2 Yen, Debra W.; Soriano, Vicente; Barreiro, Pablo; Sherman, Kenneth E. (1 November 2023). "Triple Threat: HDV, HBV, HIV Coinfection". Clinics in Liver Disease. 27 (4): 955–972. doi:10.1016/j.cld.2023.05.010. ISSN 1089-3261. PMID 37778779.
  3. ↑ "Hepatitis D Basics". Hepatitis D. 27 June 2024. Archived from the original on 6 October 2025. Retrieved 3 October 2025.
  4. ↑ "Clinical Signs and Symptoms of Hepatitis B". Hepatitis B. 13 August 2025. Archived from the original on 1 October 2025. Retrieved 10 October 2025.
  5. ↑ Weiss RA (May 1993). "How does HIV cause AIDS?". Science. 260 (5112): 1273–9. Bibcode:1993Sci...260.1273W. doi:10.1126/science.8493571. PMID 8493571.
  6. ↑ Douek DC, Roederer M, Koup RA (2009). "Emerging Concepts in the Immunopathogenesis of AIDS". Annual Review of Medicine. 60: 471–84. doi:10.1146/annurev.med.60.041807.123549. PMC 2716400. PMID 18947296.
  7. ↑ Powell MK, Benková K, Selinger P, Dogoši M, Kinkorová Luňáčková I, Koutníková H, Laštíková J, Roubíčková A, Špůrková Z, Laclová L, Eis V, Šach J, Heneberg P (2016). "Opportunistic Infections in HIV-Infected Patients Differ Strongly in Frequencies and Spectra between Patients with Low CD4+ Cell Counts Examined Postmortem and Compensated Patients Examined Antemortem Irrespective of the HAART Era". PLOS ONE. 11 (9): e0162704. Bibcode:2016PLoSO..1162704P. doi:10.1371/journal.pone.0162704. PMC 5017746. PMID 27611681.
  8. ↑ Humans, IARC Working Group on the Evaluation of Carcinogenic Risks to (1994). "HEPATITIS B VIRUS". Hepatitis Viruses. International Agency for Research on Cancer. Retrieved 12 October 2025.
  9. ↑ Ryu WS (2017). Molecular Virology of Human Pathogenic Viruses. Academic Press. pp. 247–260. ISBN 978-0-12-800838-6.
  10. ↑ "ICTV Report Hepadnaviridae". Archived from the original on 8 February 2021. Retrieved 15 March 2023.
  11. ↑ "Hepatitis D Basics". Hepatitis D. 27 June 2024. Archived from the original on 6 October 2025. Retrieved 30 September 2025.
  12. ↑ Calle Serrano, Beatriz; Manns, Michael P.; Wedemeyer, Heiner (May 2012). "Hepatitis delta and HIV infection". Seminars in Liver Disease. 32 (2): 120–129. doi:10.1055/s-0032-1316467. ISSN 1098-8971. PMID 22760651. Archived from the original on 2 February 2025. Retrieved 27 September 2025.
  13. ↑ Assoumou, Sabrina A.; Alexander, Raegan N.; Miller, Sarah E. (10 September 2025). "Viral Infections Associated With Injection Drug Use". JAMA. doi:10.1001/jama.2025.13287. PMID 40928771. Retrieved 10 October 2025.
  14. ↑ Zaongo, Silvere D.; Ouyang, Jing; Chen, Yaling; Jiao, Yan-Mei; Wu, Hao; Chen, Yaokai (2022). "HIV Infection Predisposes to Increased Chances of HBV Infection: Current Understanding of the Mechanisms Favoring HBV Infection at Each Clinical Stage of HIV Infection". Frontiers in Immunology. 13 853346. doi:10.3389/fimmu.2022.853346. ISSN 1664-3224. PMC 9010668. PMID 35432307.
  15. ↑ Dastgerdi, Elham Shirvani; Herbers, Ulf; Tacke, Frank (12 June 2012). "Molecular and clinical aspects of hepatitis D virus infections". World Journal of Virology. 1 (3): 71–78. doi:10.5501/wjv.v1.i3.71. ISSN 2220-3249. PMC 3782269. PMID 24175212.
  16. ↑ "Prevention and Management of Hepatitis B Virus Infection in Adults With HIV - Clinical Guidelines Program". hivguide. Archived from the original on 21 June 2025. Retrieved 2 October 2025.
  17. ↑ "Hepatitis D - Liver and Gallbladder Disorders". MSD Manual Consumer Version. Archived from the original on 5 October 2025. Retrieved 11 October 2025.
  18. ↑ "Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV". NIH. Retrieved 29 September 2025.{{cite web}}: CS1 maint: url-status (link)
  19. ↑ "HBV/HIV". HIV Management Guidelines. Archived from the original on 15 August 2025. Retrieved 29 September 2025.
  20. ↑ "Hepcludex | European Medicines Agency (EMA)". www.ema.europa.eu. 12 August 2020. Archived from the original on 12 December 2021. Retrieved 12 October 2025.
  21. ↑ Olsen, Kathryn; Mahgoub, Sara; Al-Shakhshir, Sarah; Algieder, Akram; Atabani, Sowsan; Bannaga, Ayman; Elsharkawy, Ahmed M. (July 2023). "Recent treatment advances and practical management of hepatitis D virus". Clinical Medicine (London, England). 23 (4): 403–408. doi:10.7861/clinmed.2022-0556. ISSN 1473-4893. PMC 10541033. PMID 37353306.
  22. ↑ "Core Concepts - Drug Interactions with Antiretroviral Medications - Antiretroviral Therapy - National HIV Curriculum". www.hiv.uw.edu. Archived from the original on 6 October 2025. Retrieved 7 October 2025.
  23. ↑ Aydın, Nurten Nur; Aydın, Murat (30 December 2024). "Potential Drug-Drug Interactions Between Oral Antiviral Agents Used for Hepatitis B Treatment and Concomitant Systemic Medications". Viral Hepatitis Journal. doi:10.4274/vhd.galenos.2024.2024-7-4. ISSN 2147-2939. Archived from the original on 2025-09-06. Retrieved 2025-10-07.
  24. ↑ "Overview: Drug-Drug Interactions between Antiretrovirals and Other Drugs | NIH". clinicalinfo.hiv.gov. Archived from the original on 8 July 2025. Retrieved 7 October 2025.
  25. ↑ Huang, Yu-Shan; Sun, Hsin-Yun; Ho, Shu-Yuan; Lin, Kuan-Yin; Liu, Wang-Da; Sheng, Wang-Huei; Hsieh, Szu-Min; Chuang, Yu-Chung; Su, Li-Hsin; Su, Yi-Ching; Liu, Wen-Chun; Chang, Sui-Yuan; Hung, Chien-Ching (2 January 2025). "Incidence and Outcome of Hepatitis D Virus Infection in People With Human Immunodeficiency Virus (HIV) and Hepatitis B Virus Coinfection in the Era of Tenofovir-Containing Antiretroviral Therapy". Clinical Infectious Diseases ciae655. doi:10.1093/cid/ciae655. Retrieved 29 September 2025.
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