Cytomegalovirus Viremia Increases Mortality Risk in HIV-Associated Meningitis - Infectious Disease Advisor

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Cytomegalovirus (CMV) viremia is associated with an increased risk of mortality at 18 weeks among patients with HIV-associated cryptococcal or tuberculous (TB) meningitis, according to study findings published in the International Journal of Infectious Diseases.

In this study, researchers prospectively enrolled patients (N=340) with HIV-associated cryptococcal (n=308) or TB meningitis (n=32) to assess whether CMV viremia increases the risk of all-cause mortality. Researchers retrospectively quantified CMV DNA concentrations using blood samples previously obtained from the patients. The researchers defined CMV viremia as plasma or serum concentrations above the threshold of polymerase chain reaction detection (88.5 IU/mL). The primary outcome was all-cause mortality at 18 weeks. Risk factors for 18-week all-cause mortality were determined via univariate Cox proportional hazards regression.

Among 121 patients with and 219 without CMV viremia at baseline, 43% and 37% were women, the median age was 35 (IQR, 29-40) and 35 (IQR, 30-40) years, 47% and 45% were receiving antiretroviral therapy (ART), the median CD4+ T-cell count was 14 (IQR, 6-53) and 24 (IQR, 8-61) cells/µL, respectively. Of patients with CMV viremia, the median CMV viral load was 452 (IQR, 142-2450) IU/mL.

At 18 weeks, 61 (50%) patients with and 74 (34%) without CMV viremia died, indicating a significant association between CMV viremia and an increased risk of all-cause mortality through week 18 (hazard ratio [HR], 1.66; 95% CI, 1.18-2.33; P =.003). Patients with CMV viremia were then stratified into 3 groups by CMV viral load, including those with low- (n=76; <1000 IU/mL), moderate- (n=21; 1000-5000 IU/mL), and high-grade viremia (n=24; >5000 IU/mL). Results showed that all-cause mortality rates were highest among those with high-grade CMV viremia (71%), followed by those with moderate- (57%) and low-grade viremia (42%).

In a subgroup analysis, the presence of CMV viremia was significantly associated with 18-week all-cause mortality in patients with either cryptoccocal (HR, 1.48; 95% CI, 1.04-2.09; P =.03) or TB meningitis (HR, 17.1; 95% CI, 2.04-142.6; P =.009).

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Among patients who were (n=155) and were not (n=185) receiving ART at baseline, 57 (37%) and 64 (35%) had detectable CMV viremia, respectively. Stratified by baseline ART status, the rate of 18-week all-cause mortality was increased among patients with vs without CMV viremia who were ART-naïve (52% vs 38%; P =.08) and ART-experienced (49% vs 29%; P =.01).

This study was limited by its prospective design, and the generalizability of these findings applies to only patients with HIV-associated cryptococcal or TB meningitis.

"A randomized clinical trial is needed to determine if preventing or treating CMV viremia in persons with HIV-associated meningitis can reduce mortality and improve survival in this vulnerable population," the researchers concluded.

Reference

Skipper CP, Hullsiek KH, Cresswell FV, et al. Cytomegalovirus viremia as a risk factor for mortality in HIV-associated cryptococcal and tuberculous meningitis. Int J Infect Dis. 2022;S1201-9712(22)00430-1. doi:10.1016/j.ijid.2022.07.035

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