Background
Emerging evidence suggests that human cytomegalovirus (HCMV) infection is associated with the progression of tuberculosis (TB) disease. This study aimed to evaluate the temporal relationship of HCMV infection on TB progression in people with HIV (PWH).
Methods
In a case-control study nested within a Thai HIV cohort, stored plasma samples from PWH who developed active TB after stable ART (cases) were assessed for HCMV infection. For controls, we selected stored samples from PWH in the same cohort who did not develop TB disease, matched in a 1:2 ratio by ART duration. HCMV DNA, HCMV IgM, and IgG were measured at 3 timepoints: (1) 6-24 months before TB diagnosis (pre-TB visit), (2) at TB diagnosis (TB visit), and (3) 6-24 months after TB diagnosis (post-TB visit). HCMV viremia was defined as detectable CMV DNA in plasma. Conditional logistic regression with backwards selection was used to investigate associations with TB disease.
Results
A total of 34 TB cases and 68 control PWH were enrolled. The majority (58.8%) were male with median (interquartile range: IQR) time of ART duration of 10.6 (6.5-17.4) years. The age was 42 (34-51.) and 44 (38-52) years for cases and controls, respectively. 100% of participants were HCMV seropositive. At the pre-TB visit, we observed no significant differences in the proportion of HCMV viremia (21% vs 18%, p=0.719), HCMV IgM geometric mean concentration (GMC) (0.13 (95%CI 0.10-0.16) vs 0.12 (95%CI 0.10-0.13), p=0.402) and HCMV IgG GMC (225.6 (95%CI 210.2-242.1) vs 206.6 (95%CI 190.2-224.6), p=0.179) among TB cases and controls. We found the proportion of HCMV viremia was higher among TB cases at TB visit (35% vs 14%, p= 0.028) and post-TB visit (32% vs 5%, p=0.006) compared to controls. The HCMV IgM GMC at the TB visit was higher in the TB group than control (0.17 (95%CI 0.12-0.23) vs 0.12 (95%CI 0.10-0.14) AU/ml, geometric mean ratio (GMR)=1.38 (95%CI 1.01-1.87, p=0.039). In an adjusted model, the odds of TB in those with middle and high tertile HCMV IgG at the TB visit was 5.45 times higher (p=0.044) compared to the lowest tertile (Table).
Conclusions
We found no evidence suggesting HCMV viremia and HCMV serology were associated with the progression of TB disease in 6-24 months. At the time of TB diagnosis, HCMV IgG levels show an association with TB disease, possibly reflecting HCMV reactivation due to TB disease or another, common cause.
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