Congenital CMV infection (cCMV) is the most common congenital infection and a leading non-genetic cause of sensorineural hearing loss worldwide. The birth prevalence of cCMV is directly proportional to maternal CMV seroprevalence levels, with substantially higher rates observed in highly seropositive populations. Increased rates of cCMV are observed in African populations, with evidence for a key role for maternal co-infections, such as HIV, as a driver of cCMV in these countries. Despite a high burden of HIV infection in sub-Saharan Africa, the impact of maternal HIV on the frequency of in utero CMV transmission, symptomatic infection at birth and long-term sequelae has not been systematically evaluated. We recently conducted the first study of cCMV birth prevalence among HIV-exposed newborns in the Western Cape, South Africa, and demonstrated a high rate of cCMV (2.93%; 95% CI 1.73-4.13) in the era of prenatal antiretroviral prophylaxis. Infant CMV infection has been widely associated with an increased risk of HIV disease progression and mortality, as well as an adverse impact on growth, development and overall morbidity in HIV-exposed but uninfected Zambian infants. These findings suggest that CMV infection (intrauterine or postnatal acquisition) has an adverse impact on overall childhood morbidity and mortality in children not infected with HIV. We hypothesize that maternal HIV infection increases the risk of intrauterine CMV transmission, and predisposes CMV-infected infants to adverse outcomes even in the era of option B. The proposed study will provide reliable estimates of the birth prevalence of congenital CMV infection in HIV-exposed and HIV-unexposed newborns in sub-Saharan Africa in the context of triple antiretroviral therapy, as well as preliminary data on the frequency and timing of postnatal CMV acquisition during infancy and the impact of CMV infection acquired in infancy on childhood morbidity. In this study, we will screen ~4,200 newborns at the Prince Mshiyeni Memorial Hospital, a regional hospital that provides subsidized health care where 40% of pregnant women are HIV-infected. Newborn CMV screening will be carried out by testing dried saliva specimens using a real-time PCR method developed in our laboratory. Hearing screening of infants and diagnostic audiology testing protocols will be implemented to determine the prevalence of CMV-associated hearing loss. The objectives of the study are: 1) To determine the birth prevalence of congenital CMV infection among HIV-exposed and HIV-unexposed newborns, 2) To determine the prevalence of newborn disease and CMV-associated sequelae in HIV-exposed and unexposed newborns with congenital CMV infection, and 3) To explore the impact of CMV infection (both congenital and postnatal) on overall childhood morbidity and mortality. The proposed studies take advantage of the experience, expertise and commitment of the investigative team with similar interests and motivation to determine the impact of maternal HIV infection on in utero transmission of CMV, CMV-associated hearing loss and whether CMV infection acquired in early infancy affects overall childhood morbidity.
The goals of this study are to investigate the natural history and disease burden associated with congenital CMV infection in a high HIV burden setting. Through this, this project will investigate our hypothesis that maternal HIV infection increases the risk of intrauterine CMV transmission, and predisposes CMV-infected infants to adverse outcomes even in the era of option B. This study will provide reliable estimates of the birth prevalence of congenital CMV infection in HIV-exposed and HIV-unexposed newborns by screening large numbers of newborns. In addition, the project will yield preliminary estimates on the frequency and timing of acquisition of postnatal CMV infection during infancy and begin to examine the impact of CMV infection acquired in infancy on childhood morbidity. Exploring the impact of HIV infection on CMV infection of infants and CMV-associated hearing loss as well as overall childhood morbidity will inform the relevance of CMV infections in populations with high maternal HIV prevalence, as well as the importance of developing strategies to prevent or reduce the disease burden associated with CMV infection.
