Cytomegalovirus IgG Level and Avidity in Breastfeeding Infants of HIV-Infected Mothers in Malawi

Abstract

dCytomegalovirus (CMV) infection is common among infants of HIV-infected mothers in resource-limited settings. We examined the prevalence and timing of infant CMV infection during the first year of life using IgG antibody and avidity among HIVexposed infants in Malawi and correlated the results with the presence of detectable CMV DNA in the blood. The Breastfeeding, Antiretrovirals and Nutrition (BAN) study randomized 2,369 mothers and their infants to maternal antiretrovirals, infant nevirapine, or neither for 28 weeks of breastfeeding, followed by weaning. Stored plasma specimens were tested for CMV IgG and antibody avidity from a random subset of infants who had been previously tested with blood CMV PCR and had available specimens at birth and at 24 and 48 weeks of age. Ninety-four of 127 infants ( C ytomegalovirus (CMV) infection is the most common congenital infection, with an estimated prevalence of Ͼ1% in resource-limited settings (1, 2). Approximately 10 to 20% of congenital CMV infections result in permanent deficits, including sensorineural hearing loss, vision loss, and mental and developmental disability (3). The postnatal acquisition of CMV can occur through horizontal transmission and through breastfeeding, with a high probability of transmission in infants fed with breast milk containing infectious virus (4, 5). The infants of HIV-infected mothers may have higher rates of congenital CMV infection, particularly if the mothers are immunocompromised (6). While postnatal transmission is thought to be generally benign in healthy full-term infants, premature infants or other groups of immunocompromised infants are at risk for more extensive disease and may also experience long-term cognitive delays (7-9).While the increased morbidity and mortality among infants coinfected with HIV and CMV is well recognized (10-14), HIVexposed but uninfected infants may also be at increased risk for morbidity and mortality from CMV infection (15-17). A study in Zambia found that HIV-exposed infants who were CMV seropositive had decreased length for age, reduced head size, and lower psychomotor development than those who were CMV uninfected (5). HIV is endemic in many African countries and the CMV childhood infection burden is high, which may have a substantial impact on child health in the region. It is therefore important to examine when infants acquire primary CMV infection in such settings.In a previous analysis, we reported, using blood CMV PCR, that Ͼ70% of infants of HIV-infected mothers had acquired CMV infection by 24 weeks of age (18). Given that blood is not the optimal sample source for CMV detection, it is possible that our findings underestimated the true incidence of CMV acquisition in the infants. We thus additionally performed CMV IgG antibody titer and avidity testing in the infant plasma specimens at different points in the infants' first year of life. The objectives of this study were to comprehensively assess the rate of CMV acquisition and to further characterize the time of CMV infection in HIV-exp...

Minimal adverse outcomes of postnatal cytomegalovirus infection in term or moderate and late preterm infants

“…One may assume that the CMV IgG in infants is derived from the mothers because of the transplacental transfer of maternal CMV IgG. However, our previous study and others demonstrated that the maternally acquired CMV IgG in infants disappears before the age of 6-8 months (4,18). In the present study, all infants were negative for CMV IgM at birth and were positive for CMV IgG over the age of 7 months.…”

“…Previous study showed that transplacentally transferred maternal CMV IgG in infants disappears before 6-8 months age because of the natural IgG decay (4,18). In the present study, all infants participated were over 7 months age, therefore, we measured the CMV IgG as a marker of CMV infection in the infants.…”

Defective monocyte enzymatic function and an inhibitory immune phenotype in HIV-exposed uninfected African infants in the era of anti-retroviral therapy

“…We also demonstrate evidence of HIV exposure and increased likelihood of hCMV exposure in HEU infants. HIV and hCMV are immunomodulatory viruses 81 , so co-exposure to these two pathogens in early life may contribute to this immune dysregulation. We postulate that the complexity, variable severity and/or persistence of this immunological phenotype explain the variable clinical manifestations reported in HEU infants 8,9,11,40,[82][83][84][85][86] , which may depend on the duration and intensity of exposure to HIV and other infectious co-factors.…”

Cytomegalovirus Infection in Human Immunodeficiency Virus (HIV)–Exposed and HIV-Infected Infants: A Systematic Review

“…CMV PCR testing in urine and saliva has very high sensitivity and specificity (>90%), compared with serological testing [38, 41]. Additionally, a recent study assessing the validity of PCR testing in blood found that PCR detected most infant CMV infections [40]. …”