Park Sarah Y, Epling Brian, Richey Morgan, Lupu Daniel, Mughar Mona, Sereti Irini
Medical Affairs and Clinical Affairs, Karius, Inc., Redwood City, California.
HIV Pathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases.
Pathog Immun. 2025 Feb 11;10(1):187-197. doi: 10.20411/pai.v10i1.788. eCollection 2024.
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).
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.
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, , and .
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.
人类疱疹病毒8型（HHV - 8），即卡波西肉瘤（KS）相关疱疹病毒（KSHV），可在免疫功能严重低下的人群中引发严重疾病。然而，鉴于KS表现多样且目前常规护理诊断方法（UC；聚合酶链反应、组织病理学）有限，KS的诊断可能具有挑战性。
对来自116名门诊患者的存档样本应用病原体非特异性血浆微生物游离DNA测序，这些患者纳入了之前两项针对未接受抗逆转录病毒治疗、晚期HIV（CD4细胞计数≤100个/μL）患者的前瞻性研究。然后，我们回顾了在基线时通过mcfDNA测序或UC检测HHV - 8呈阳性的任何人的临床和实验室数据。
通过任何方法在21名（18%）晚期HIV门诊患者中检测到HHV - 8，其中男性占大多数（86%），三分之一最初来自非美国国家（包括非洲、中美洲和加勒比地区）。在UC基础上增加mcfDNA测序可使HHV - 8检测比例相应提高38%，同时还在18名（86%）患者中鉴定出其他潜在感兴趣的微生物，包括常见疱疹病毒等。
血浆mcfDNA测序可能会改善UC对HHV - 8感染的检测，特别是在免疫功能低下的门诊患者中，早期检测可能有助于进行适当管理以预防严重的KS疾病。mcfDNA测序检测其他病原体的潜在附加益处可能与此人群特别相关。
