Commentary: Beyond Prevention of Vertical HIV Transmission—Improving Outcomes of HIV-uninfected Infants Born to Mothers With HIV Infection

    loading  Checking for direct PDF access through Ovid


HIV infection in pregnant women in Africa is associated with poorer health and survival outcomes for their children, including their children who were spared HIV infection.1 Such HIV-exposed but uninfected (HEU) infants fare better than their peers with HIV infection but experience higher rates of morbidity and mortality than infants born to women without HIV infection, or HIV-unexposed and uninfected infants. In particular, HEU infants suffer higher rates and more severe episodes of pneumonia and other infectious illnesses in the first few months of life because of encapsulated bacteria and other common pediatric pathogens.1,2 Factors that have been linked to higher risk of infectious disease and death in HEU infants infectious disease and death include advanced maternal HIV disease, lack of maternal antiretroviral (ARV) treatment, preterm delivery and lack of exclusive infant breastfeeding (often as a strategy to reduce infant HIV transmission risk). However, potential biologic and psychosocial mechanisms underlying such associations are complex and incompletely understood. Furthermore, while routine ARV therapy (ART) for pregnant women with HIV infection dramatically reduces the risk of vertical HIV transmission and improves women’s health status, it is less clear how and to what extent maternal ART may reverse biologic effects linked to poorer health outcomes in HEU infants.
In this issue of Pediatric InfectiousDisease Journal, Bosire et al3 present an elegant analysis that advances our understanding of how maternal ART may mediate more robust immunoprotection against infectious disease in the first months of life in HEU infants. The authors measured total immunoglobulin G (IgG) and IgG specific to several common pathogens (measles, rotavirus and virulent pneumococcal serotypes) in women during pregnancy and at delivery as well as in cord blood, using stored specimens from Kenyan participants in the Kesho Bora trial (2013–2015). In this trial, pregnant women with HIV and CD4 counts of 200–500 were randomized in late pregnancy (28–36 weeks’ gestation) to receive zidovudine alone or ART (composed of zidovudine, lamivudine and lopinavir/ritonavir). The authors found that pathogen-specific IgG levels were similar at entry and declined similarly by delivery in both arms, suggesting no impact of ART on maternal seroprotection. However, the cord blood levels—reflecting placentally transferred IgG—for rotavirus and measles (but not pneumococcal) IgGs were higher in the ART arm. Furthermore, in multivariable analysis, after adjustment for maternal total IgG and pathogen-specific IgG levels, maternal ART use was associated with significantly higher levels of cord blood measles and pneumococcal serotype IgGs and with a trend (P = 0.06) for higher level of cord blood rotavirus IgG. In short, maternal ART in late pregnancy appeared to be more effective than zidovudine alone in enhancing the transplacental transfer of pathogen-specific IgG to HEU infants even though there was no evidence of increased maternal levels of these specific antibodies.
Higher levels of maternally derived pathogen-specific antibodies play a major role in protecting infants against pneumonia and other infectious illnesses in the first months of life, before immunizations can provide full protection. Thus, the current policy and programmatic efforts to ensure that all pregnant women with HIV receive ART to protect women’s health and prevent infant HIV infection will likely also improve the protection against infectious disease morbidity in the first months of life of their HEU infants. With successful prevention of HIV infection in infants, the number of infants with HIV infection is already dwarfed by the number of HEU infants, highlighting the importance of learning how to improve the health outcomes of this growing population of children.

Related Topics

    loading  Loading Related Articles