Association of human cytomegalovirus in urine with end-organ diseases in stage 2/3 HIV-1-infected individuals

Background: Human cytomegalovirus (HCMV) is prevalent in human immunodeficiency virus type 1 (HIV-1)-infected individuals but is suppressed by the host immune system bolstered by antiretroviral therapy. During stage 4 of HIV-1 infection, HCMV becomes a major risk factor for end-organ diseases (EODs). However, the implications of detecting HCMV in patients with stage 2/3 HIV-1 infection have not been established.

Objectives: Conduct a retrospective study of the relationship between HCMV-DNA detection and EODs in patients with stage 2/3 HIV-1 infection.

Study design: We cross-sectionally analyzed data from 134,881 HIV-1-infected patients who visited the Third People's Hospital of Shenzhen (Guangdong, China) between January 2011 and June 2022. Only patients with available data on CD4 counts, HIV-RNA and HCMV-DNA copy numbers, and hospitalized stage 2/3 patients with detailed clinical assessments of EODs were included in this study. The chi-square test and Cox regression model were used to examine the association between HCMV-DNA detection and EOD incidence. Longitudinal analysis was performed to examine the effect of anti-HCMV treatment on the incidence of lung and cardiovascular EODs.

Results: HCMV-DNA had been tested in the blood and urine of 98.6% and 31.8% of the HIV-1-infected patients, respectively. An increased percentage of HCMV was detected in urine (> 2.4-fold) than in blood at different HIV-1 infection stages. In stage 2/3 patients (n = 454), a higher incidence of EODs was observed in those who tested positive for HCMV-DNA in urine (P < 0.0001) than in those who tested positive for HCMV-DNA in blood (P = 0.0977). Using a model for incidence of EODs, we found that HCMV-DNA detection in urine was associated with an increased incidence of lung EOD; the adjusted hazard ratio (HR) was 1.939 (95% confidence interval [CI]: 1.326-2.761, P = 0.0003) for the HCMV^urine+ subgroup and 0.933 (95% CI: 0.523-1.623, P = 0.8605) for the HCMV^urine- subgroup. A significant HR was also observed for cardiovascular EOD, which was 0.696 (95% CI: 0.492-0.953, P = 0.0302) for the HCMV^urine+ group and 1.56 (95% CI: 0.766-3.074, P = 0.2033) for the HCMV^urine- group. Longitudinal analysis showed that treatment for HCMV reduced the incidence rates of lung and cardiovascular EODs in the stage 2/3 patients.

Conclusions: The presence of HCMV in urine is associated with the early prognosis of EODs in patients with stage 2/3 HIV-1 infection and its detection should be implemented as a routine test.