Abstract
With increasing access to antiretroviral therapy (ART) in Africa, most children born to HIV-infected mothers are not themselves HIV-infected. These HIV-exposed, uninfected (HEU) children are at increased risk of mortality and have immune, growth, development, and health deficits compared to HIV-unexposed children. HEU children are known to be at higher risk than HIV-unexposed children of acquiring cytomegalovirus (CMV) infection in early life. This risk is largely unaffected by ART and is increased by breastfeeding, which itself is critically important for child health and survival. Early CMV infection, namely in utero or during early infancy, may contribute to reduced growth, altered or impaired immune functions, and sensory and cognitive deficits. We review the evidence that CMV may be responsible for the health impairments of HEU children. There are currently no ideal safe and effective interventions to reduce postnatal CMV infection. If a clinical trial showed proof of the principle that decreasing early CMV infection improved health and development of HEU children, this could provide the impetus needed for the development of better interventions to improve the health of this vulnerable population.
Highlights
Specialty section: This article was submitted to HIV and AIDS, a section of the journal Frontiers in Immunology
We review the evidence in support of the hypothesis that one potential cause, early cytomegalovirus (CMV) infection, which appears widespread across sub-Saharan Africa, is an important contributor to impaired health and development of both HIV-infected and HEU children in many African populations, and increases the risk of postnatal HIV infection
It is worth noting that several reports have indicated that children of HIV-positive mothers, both infected [33] and HEU [34], are more likely than their unexposed counterparts to have impaired hearing; other mechanisms, including exposure to HIV itself, may have contributed to deafness in these children, it could well be an indication of congenital CMV infection that was not diagnosed at birth
Summary
Most African infants acquire CMV infection during infancy [13, 14]. The risk of congenital CMV infection was higher among infants of HIV-infected than uninfected Zambian mothers [15]. A secondary analysis of a randomized controlled trial of breastfeeding versus formula-feeding by HIV-infected Kenyan women in the pre-ART era found that breastfeeding was associated with a significantly increased proportion of infants CMV-infected by age 1 year (89 versus 69% in the formula group), as well as earlier median acquisition of CMV infection (4.26 versus 9.87 months) [18]. The World Health Organization recommends provision of ART during pregnancy and lactation as the best way of promoting HIV-free survival of infants [20]. This protocol is becoming standard across Africa and is effective at decreasing HIV transmission, it does not appreciably alter the rate of African infant CMV acquisition. A recent study of American women whose ART did or did not include the protease inhibitor, nelfinavir, which has some ability to inhibit CMV replication, found no protection of nelfinavir against congenital CMV infection [23]
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