The Dynamics of Human Cytomegalovirus Markers in Tuberculosis Disease Among People With Human Immunodeficiency Virus on Long-term Antiretroviral Therapy: A Nested Case-Control Study

Abstract

Background. Emerging evidence suggests that human cytomegalovirus (HCMV) infection is associated with tuberculosis (TB) disease. This study aimed to assess the relationship between the dynamics of HCMV markers and TB disease in people with human immunodeficiency virus (PWH). Methods. In a case-control study nested within a Thai HIV cohort, stored samples from people with HIV who were diagnosed with TB disease after antiretroviral therapy (ART) (cases) and TB-negative controls matched 1:2 on ART duration. HCMV DNA, immunoglobulin M (IgM), and immunoglobulin G (IgG) were measured at 3 timepoints: (i) 6–24 months before TB diagnosis (pre-TB visit), (ii) at TB diagnosis (TB visit), and (iii) 6–24 months after TB diagnosis (post-TB visit). Results. We enrolled 34 TB cases and 68 controls, the majority of whom were male (56% vs 60%). At the pre-TB visit, all participants were IgG seropositive, and there were no significant differences in the proportion with HCMV viremia or in HCMV IgM or IgG levels. At the TB diagnosis visit, the proportion of HCMV viremia was higher among TB cases compared with controls (34.5% vs 13.8%; P = .028). HCMV IgM geometric mean concentration (GMC) was higher in cases (0.17 vs 0.12 AU/mL; geometric mean ratio, 1.38 [95% confidence interval, 1.01–1.87]; P = .039). At the post-TB visit, HCMV viremia remained more frequent in cases (31.8% vs 4.5%; P = .006). Conclusions. HCMV viremia and serology measured 6–24 months before TB diagnosis in cases did not differ from those in matched controls. At TB diagnosis, people with HIV with TB had higher proportion of HCMV viremia and higher GMC of HCMV IgM, possibly reflecting HCMV reactivation due to TB disease.