Urine test enables early prediction of HIV end-organ diseases

Hong Kong researchers have shown that urine tests for human cytomegalovirus (HCMV) can identify the risk of end-organ diseases earlier in patients who have been infected with human immunodeficiency virus type 1 (HIV-1). The team’s findings, published in the Journal of Clinical Virology, suggest that HCMV detection in urine should be implemented as a routine test for HIV-1 patients who are progressing towards acquired immunodeficiency syndrome (AIDS).

HIV-1 infection is divided into four clinical stages. In the first stage, patients are infected and some experience mild illnesses such as a cold without any apparent symptoms. HIV-1 infection then slowly progresses towards AIDS in the second and third stages of infection. These two stages, collectively regarded as the ‘developing’ stage, usually last several years if they are comprehensively controlled by a range of medications before developing into AIDS, which represents the fourth stage of HIV-1 infection.

HCMV is a DNA virus found in more than half of the human population. It is controlled by an intact immune system and remains dormant in healthy individuals. However, it can be reactivated in patients with poor immune systems, such as those in the fourth stage of HIV-1 infection, and as a result it can become one of the major opportunistic infections that cause life-threatening end-organ diseases. In Hong Kong, HCMV detection is not part of the routine check-ups for HIV-1 patients unless they suffer from apparent end-organ diseases such as such as pneumonitis, gastrointestinal ulcers, hepatitis and myocarditis. In such cases, blood tests are the preferred method of detection.

A research team co-led by Dr Allen Cheung Ka-loon from Hong Kong Baptist University (HKBU) and Professor Chen Zhiwei from The University of Hong Kong, in collaboration with the Third People’s Hospital of Shenzhen, investigated the detection of HCMV in urine for the continuous monitoring of end-organ disease risk in HIV-1 patients. They also examined the relationship between HCMV detection and end-organ diseases in HIV-1 patients in the developing stage.

The team screened the records of more than 130,000 HIV-1 patients in Shenzhen between January 2011 and June 2022, and selected about 13,700 patients with relevant blood and urine test records. They were grouped according to the four stages of HIV-1 infection, and the results of their HCMV blood and urine tests were then compared.

It was discovered that in all the four patient groups, the proportions of patients found to be HCMV-positive were higher in the urine samples than in the corresponding blood samples. The situation was particularly obvious for HIV-1 patients in the developing stage. Urine tests showed that 5.8% of second-stage HIV-1 patients were HCMV-positive, compared to only 0.9% using blood tests. The proportions of third-stage HIV-1 patients found to be HCMV-positive using urine and blood tests were 12.8% and 1.4%, respectively. This suggests that HCMV is more easily detected in urine than in the blood, especially during the developing stage of HIV-1 infection.

The researchers further filtered 233 developing-stage HIV-1 patients with detailed clinical and disease records to evaluate the association between HCMV and the onset of different types of end-organ diseases. Statistical analysis revealed that there is a significant association between the incidence of lung and cardiovascular end-organ diseases and the detection of HCMV in urine.

To study the effect of early interventions with anti-HCMV treatments, the team tracked the data of 54 developing-stage HIV-1 patients who had been hospitalised at least once. They were divided into three groups: those who received no anti-HCMV treatments, those who received treatments but not during each round of hospitalisation, and those who received treatments during all rounds of hospitalisation.

The data showed that those who received anti-HCMV treatments in all rounds of hospitalisation had the lowest incidence of lung and cardiovascular end-organ diseases. Furthermore, compared to those who had not received anti-HCMV treatments, the incidence of such end-organ diseases in patients who had received the treatments was reduced by half. This suggests that continuous anti-HCMV treatments are effective in reducing the onset of lung and cardiovascular end-organ diseases in patients who are progressing towards AIDS.

“Patients have to face a difficult journey once they have tested positive for HIV; they are often at risk of developing end-organ diseases without any apparent symptoms,” Cheung said. “Our study shows that routine urine tests for HCMV can monitor the development of end-organ diseases more effectively, which signals the need for early medical intervention. We thus recommend that HCMV detection in urine should be implemented as a routine test for HIV-1 patients.”

Image caption: The collaborative research team, led by Dr Allen Cheung Ka-loon at HKBU, investigated the detection of HCMV in urine for the continuous monitoring of end-organ disease risk in HIV-1 patients.