Caplan Margaret R, Wilson Eleanor M P, Schechter Melissa, Cai Catherine W, Venner Allison, Bishop Rachel, Adelsberger Joseph, Higgins Jeanette, Roby Gregg, Wang Jing, Sheikh Virginia, Sereti Irini
Clinical Research Directorate, Frederick National Laboratory for Cancer Research, Bethesda, MD, 20817, USA.
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
J Virus Erad. 2021 Sep 9;7(3):100052. doi: 10.1016/j.jve.2021.100052. eCollection 2021 Sep.
Cytomegalovirus (CMV) end-organ disease (EOD) continues to pose a significant risk to patients with advanced HIV disease despite decreased incidence with combination anti-retroviral therapy (ART) and lower mortality with effective -CMV therapy. Subclinical CMV shedding may also contribute to ongoing inflammation and non-infectious comorbidities.
We examined the occurrence of CMV EOD and CMV shedding in a cohort of patients participating in a prospective observational study of severely immunosuppressed (CD4 ≤100 cells/μl), ART-naïve, HIV-1 infected adult participants.
We studied 206 participants, of whom 193 (93.7%) were CMV IgG positive. Twenty-five participants (12.1%) developed confirmed CMV EOD. At baseline, 47 (22.8%) had CMV viremia detectable by PCR in the absence of clinical disease (CMV viremia). The remaining 134 (65%) had neither CMV EOD nor CMV viremia detected at baseline. Five participants with CMV EOD (2.4% of total cohort, 20% of CMV EOD) met AIDS Clinical Trials Group criteria for CMV immune reconstitution inflammatory syndrome (IRIS). Only one-third of CMV EOD patients had retinitis, while two-thirds presented with histologically confirmed gastrointestinal illness. CMV viremia was associated with higher percentages of activated CD8 T cells even after HIV suppression.
The manifestations of CMV EOD in advanced HIV disease before and after initiation of ART may be more diverse than previously described, with high incidence of gastrointestinal illness. Recognition and treatment of unusual clinical presentations of CMV infection remains important in reducing morbidity and mortality from HIV co-infections.
尽管联合抗逆转录病毒疗法(ART)使巨细胞病毒(CMV)终末器官疾病(EOD)的发病率有所下降,且有效的CMV治疗降低了死亡率,但CMV终末器官疾病仍对晚期HIV疾病患者构成重大风险。亚临床CMV脱落也可能导致持续炎症和非感染性合并症。
我们在一组参与严重免疫抑制(CD4≤100个细胞/μl)、未接受过ART、HIV-1感染的成年参与者前瞻性观察研究的患者中,检查了CMV EOD和CMV脱落的发生情况。
我们研究了206名参与者,其中193名(93.7%)CMV IgG呈阳性。25名参与者(12.1%)发生了确诊的CMV EOD。基线时,47名(22.8%)在无临床疾病的情况下通过PCR检测到CMV病毒血症(CMV病毒血症)。其余134名(65%)在基线时未检测到CMV EOD和CMV病毒血症。5名CMV EOD参与者(占总队列的2.4%,CMV EOD的20%)符合艾滋病临床试验组CMV免疫重建炎症综合征(IRIS)的标准。只有三分之一的CMV EOD患者患有视网膜炎,而三分之二表现为组织学确诊的胃肠道疾病。即使在HIV被抑制后,CMV病毒血症也与活化的CD8 T细胞百分比更高有关。
在启动ART之前和之后,晚期HIV疾病中CMV EOD的表现可能比先前描述的更多样化,胃肠道疾病的发生率很高。认识和治疗CMV感染的不寻常临床表现对于降低HIV合并感染的发病率和死亡率仍然很重要。