Plasma mcfDNA Sequencing May Improve Usual Care Diagnostics to Detect HHV-8 Among Outpatient People with Advanced HIV
Background: Human herpesvirus-8 (HHV-8), or Kaposi sarcoma (KS)-associated herpesvirus (KSHV), causes severe disease in people with profound immunosuppression. Yet, diagnosing KS can be challenging given the diverse manifestations and current limited usual care diagnostic methods (UC; polymerase cha...
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Case Western Reserve University
2025-02-01
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| Series: | Pathogens and Immunity |
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| Online Access: | https://www.paijournal.com/index.php/paijournal/article/view/788 |
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| author | Sarah Park Brian Epling Morgan Richey Daniel Lupu Mona Mughar Irini Sereti |
| author_facet | Sarah Park Brian Epling Morgan Richey Daniel Lupu Mona Mughar Irini Sereti |
| author_sort | Sarah Park |
| collection | DOAJ |
| description | Background: Human herpesvirus-8 (HHV-8), or Kaposi sarcoma (KS)-associated herpesvirus (KSHV), causes severe disease in people with profound immunosuppression. Yet, diagnosing KS can be challenging given the diverse manifestations and current limited usual care diagnostic methods (UC; polymerase chain reaction, histopathology).
Methods: Pathogen-agnostic plasma microbial cell-free DNA sequencing was applied to banked samples from 116 outpatients included in 2 previous prospective studies of patients with antiretroviral treatment-naïve, advanced HIV (CD4 count ≤100 cells/µL). We then reviewed clinical and laboratory data for any people who tested positive for HHV-8 by mcfDNA sequencing or UC at baseline.
Results: HHV-8 was detected in 21 (18%) outpatients with advanced HIV by any method, with males comprising the majority (86%) and one-third originally from non-US countries (including Africa, Central America, and the Caribbean). Adding mcfDNA sequencing to UC proportionally increased HHV-8 detection by 38%, while also identifying in 18 (86%) people other microbes of potential interest, including common herpesviruses, Mycobacterium tuberculosis, and Pneumocystis jirovecii.
Conclusions: Plasma mcfDNA sequencing may improve UC in detection of HHV-8 infection, especially in immunocompromised outpatients, in whom early detection may facilitate appropriate management to prevent severe KS disease. The potential added benefit of the detection of other pathogens by mcfDNA sequencing may be particularly relevant for this population.
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| format | Article |
| id | doaj-art-4620f66d64c64d9d90513dd1b560598c |
| institution | Kabale University |
| issn | 2469-2964 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Case Western Reserve University |
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| series | Pathogens and Immunity |
| spelling | doaj-art-4620f66d64c64d9d90513dd1b560598c2025-02-11T20:48:09ZengCase Western Reserve UniversityPathogens and Immunity2469-29642025-02-0110110.20411/pai.v10i1.788Plasma mcfDNA Sequencing May Improve Usual Care Diagnostics to Detect HHV-8 Among Outpatient People with Advanced HIVSarah Park0https://orcid.org/0000-0002-5997-2723Brian Epling1Morgan Richey2Daniel Lupu3Mona Mughar4Irini Sereti5Medical Affairs, Karius, Inc., Redwood City, CaliforniaHIV Pathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious DiseasesClinical Affairs, Karius, Inc., Redwood City, CAClinical Affairs, Karius, Inc., Redwood City, CAClinical Affairs, Karius, Inc., Redwood City, CAHIV Pathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious DiseasesBackground: Human herpesvirus-8 (HHV-8), or Kaposi sarcoma (KS)-associated herpesvirus (KSHV), causes severe disease in people with profound immunosuppression. Yet, diagnosing KS can be challenging given the diverse manifestations and current limited usual care diagnostic methods (UC; polymerase chain reaction, histopathology). Methods: Pathogen-agnostic plasma microbial cell-free DNA sequencing was applied to banked samples from 116 outpatients included in 2 previous prospective studies of patients with antiretroviral treatment-naïve, advanced HIV (CD4 count ≤100 cells/µL). We then reviewed clinical and laboratory data for any people who tested positive for HHV-8 by mcfDNA sequencing or UC at baseline. Results: HHV-8 was detected in 21 (18%) outpatients with advanced HIV by any method, with males comprising the majority (86%) and one-third originally from non-US countries (including Africa, Central America, and the Caribbean). Adding mcfDNA sequencing to UC proportionally increased HHV-8 detection by 38%, while also identifying in 18 (86%) people other microbes of potential interest, including common herpesviruses, Mycobacterium tuberculosis, and Pneumocystis jirovecii. Conclusions: Plasma mcfDNA sequencing may improve UC in detection of HHV-8 infection, especially in immunocompromised outpatients, in whom early detection may facilitate appropriate management to prevent severe KS disease. The potential added benefit of the detection of other pathogens by mcfDNA sequencing may be particularly relevant for this population. https://www.paijournal.com/index.php/paijournal/article/view/788SarcomaKaposiHerpesvirus 8HumanOutpatientsHIV Infections |
| spellingShingle | Sarah Park Brian Epling Morgan Richey Daniel Lupu Mona Mughar Irini Sereti Plasma mcfDNA Sequencing May Improve Usual Care Diagnostics to Detect HHV-8 Among Outpatient People with Advanced HIV Pathogens and Immunity Sarcoma Kaposi Herpesvirus 8 Human Outpatients HIV Infections |
| title | Plasma mcfDNA Sequencing May Improve Usual Care Diagnostics to Detect HHV-8 Among Outpatient People with Advanced HIV |
| title_full | Plasma mcfDNA Sequencing May Improve Usual Care Diagnostics to Detect HHV-8 Among Outpatient People with Advanced HIV |
| title_fullStr | Plasma mcfDNA Sequencing May Improve Usual Care Diagnostics to Detect HHV-8 Among Outpatient People with Advanced HIV |
| title_full_unstemmed | Plasma mcfDNA Sequencing May Improve Usual Care Diagnostics to Detect HHV-8 Among Outpatient People with Advanced HIV |
| title_short | Plasma mcfDNA Sequencing May Improve Usual Care Diagnostics to Detect HHV-8 Among Outpatient People with Advanced HIV |
| title_sort | plasma mcfdna sequencing may improve usual care diagnostics to detect hhv 8 among outpatient people with advanced hiv |
| topic | Sarcoma Kaposi Herpesvirus 8 Human Outpatients HIV Infections |
| url | https://www.paijournal.com/index.php/paijournal/article/view/788 |
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