The detection of cytomegalovirus DNA in maternal plasma is associated with mortality in HIV-1-infected women and their infants

Abstract

Objective Cytomegalovirus (CMV) is an important pathogen in healthy neonates and individuals with human immunodeficiency virus (HIV-1). The objective of this study was to determine whether the detection of CMV DNA (CMV DNAemia) in maternal plasma was associated with mortality in HIV-1 infected women or their infants. Methods A longitudinal study was designed to examine the relationship between maternal CMV DNAemia and maternal-infant mortality during two years postpartum. Sixty-four HIV-1 infected women and their infants were studied. CMV DNA loads were quantified in plasma from the mothers near the time of delivery. Baseline maternal CD4 counts, CD4%, HIV-1 RNA, and CMV DNAemia were evaluated as covariates of subsequent maternal or infant mortality in univariate and multivariate Cox regression. Results CMV DNA was detected in 11/64 (17%) of the HIV-1 infected women. HIV-1 and CMV viral load were strongly correlated in CMV DNAemic women (ρ=0.84, p=0.001). Detection of CMV DNAemia was associated with decreased maternal survival at 24 months postpartum (log-rank p=0.006). Additionally, HIV-1 infected infants born to CMV DNAemic women had a 4-fold increased risk of mortality during 24 months of follow-up. Maternal CMV DNAemia remained a significant risk factor for mortality in HIV-1 infected infants after adjusting for maternal CD4 cells/mm3 (adjusted HR=4.3, CI=1.4–13), CD4% (HR=3.2, CI=1.0–10), HIV-1 viral load (HR=4.1, CI=1.4–12) or maternal death (HR=3.7, CI=1.0–13). Conclusions Maternal plasma CMV DNAemia identified a subgroup of Kenyan women and infants at high risk for death in the two years following delivery.

Cytomegalovirus Viremia as a Risk Factor for Mortality Prior to Antiretroviral Therapy among HIV-Infected Gold Miners in South Africa

“…Our data contribute to the very limited information concerning the prevalence of CMV viremia among people with HIV infection in resource-limited settings. In a small study of pregnant women in Kenya, 17% had CMV viremia; the median CD4 count was 335 cells/µl among those with CMV viremia and 420 cells/µl among those without[21]; post-partum survival was shorter among women with CMV viremia. Among 377 adults newly-diagnosed with HIV infection in Cambodia, 55.2% had CMV viremia; this very high prevalence may be explained by the group being severely immunosuppressed with a median CD4 count of 30 cells/µl[22].…”

Acute Cytomegalovirus Infection Is Associated with Increased Frequencies of Activated and Apoptosis-Vulnerable T Cells in HIV-1-Infected Infants

“…CMV viral loads were measured in a subset of 64 infants (32,33); the current report involves a sample of 19 HIV-infected and 6 HIV-exposed uninfected (HIV-EU) infants selected by availability of cryopreserved peripheral blood mononuclear cells (PBMC) (see Table S1 in the supplemental material). CMV DNA was detected in the plasma of all but one infant.…”

Immune Approaches for the Prevention of Breast Milk Transmission of HIV-1

“…Longitudinal cohort studies conducted in West and East Africa suggest more than 80% of children may acquire CMV during their first year of life, regardless of HIV-1 status [20, 21]. Maternal CMV reactivation was associated with a fourfold increased risk of mortality in HIV-infected infants independent of maternal immunosuppression [53]. Among HIV-1 infected infants, co-infection with CMV is associated with higher peak CMV VLs, prolonged detection of CMV in the plasma [21], and a greater than twofold increased risk of mortality [47].…”

“…Among HIV-1 infected infants, co-infection with CMV is associated with higher peak CMV VLs, prolonged detection of CMV in the plasma [21], and a greater than twofold increased risk of mortality [47]. In co-infected women, there is a strong correlation between HIV-1 and CMV loads in both the blood and breast milk [21, 53, 54]. It is yet unclear whether a cause-and-effect relationship links these two pathogens; CMV could potentially act as a co-factor to increase HIV-1 replication directly (reviewed in ref.…”