Postnatal CMV acquisition risk is not increased among children who are HIV-exposed, uninfected versus HIV-unexposed in the setting of optimized maternal ART

Historically, children who are HIV-exposed, uninfected (CHEU) had higher incidence and earlier postnatal acquisition of cytomegalovirus (CMV) than children who are HIV-unexposed. We assessed whether this difference persists in the current era of universal antiretroviral therapy (ART). Women without HIV and women living with HIV (WLHIV) on ART for ≥6 months were recruited in pregnancy in Nairobi, Kenya and followed weekly with their infant for 12 months postpartum; 89% of WLHIV initiated ART pre-conception. Log10-CMV DNA levels were measured in infant urine, oral swabs, and plasma, and in maternal breast milk, oral swabs, and vaginal swabs. Infant plasma collected at age ≥12 months was tested for CMV IgG antibodies. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to compare CMV acquisition by HIV exposure and assess correlates of CMV infection. Of 65/72 (90%) infants with ascertainable CMV status and timing of acquisition (42% CHEU), 47 (72%) acquired CMV. WLHIV had higher mean CMV DNA levels than women without HIV in breast milk (4.17-log vs 3.12-log, p<0.001) and oral swabs (1.10-log vs 0.78-log, p<0.001). Though higher breast milk and oral swab CMV DNA levels were associated with increased hazard of CMV among all infants (adjusted hazard ratio [aHR]=2.80, 95% CI: 1.77-4.43 and aHR=1.35, 95% CI: 1.14-1.60), HIV exposure was not significantly associated with CMV acquisition (aHR=1.31, 95% CI: 0.71-2.42). Hazard of CMV was lower among CHEU that received cotrimoxazole prophylaxis (aHR=0.19, 95% CI: 0.074-0.47) and whose mothers received a recommended first line ART regimen postpartum (aHR=0.37, 95% CI: 0.15-0.93). Together, these findings suggest that risk of CMV infection among CHEU is modulated by level of maternal mucosal CMV shedding, maternal ART regimen, and cotrimoxazole in this setting of optimized, pre-conception ART. Breast milk remains an important source of postnatal CMV acquisition for all infants.