AT ESPID 2017
MADRID (FRONTLINE MEDICAL NEWS) – Children who were HIV-exposed antenatally but not infected are at double the risk of hospitalization for infectious diseases during their first year of life, compared with HIV-unexposed controls, according to what’s believed to be the first prospective study examining the issue in a Western industrialized country.
That’s one key take-away message from the study conducted in Brussels. Another key finding was that the sharply increased risk of hospitalization for infection during infancy was erased if HIV-infected mothers started antiretroviral therapy prior to, rather than during, pregnancy, Catherine Adler, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
Prior studies have shown that children who were HIV-exposed but uninfected (HEU) have increased morbidity and mortality, compared with their HIV-unexposed peers, as highlighted in a recent meta-analysis ( AIDS. 2016 Sep 24;30[15]:2351-60 ). However, the great majority of those studies were conducted in sub-Saharan Africa, where infant mortality is extraordinarily high by Western standards and diarrheal disease and pneumonia in particular take a much greater toll than in Western Europe or North America, noted Dr. Adler of the Free University of Brussels.
She presented a prospective study of 125 HIV-positive and 119 HIV-negative pregnant Belgian women of comparable ethnic and sociodemographic backgrounds. All of the HIV-positive mothers were on antiretroviral therapy, which they started either prior to or during pregnancy.
The two groups of women gave birth to 132 HEU and 123 HIV-unexposed babies, all born after 35 weeks’ gestation. The babies didn’t differ in terms of gender, prematurity rate, mode of delivery, or the use of antibiotics at delivery. However, 17% of the HEU babies had a birth weight below 2,500 g, compared with just 3% of the HIV-unexposed controls. Also, as a matter of policy, none of the HEU babies were breastfed, while 95% of the controls were, Dr. Adler explained.
The primary outcome in the study was the rate of hospitalization for infection during the first 12 months of life. The rate was 21% in the HEU babies, significantly greater than the 11% rate in HIV-unexposed babies. In a multivariate analysis adjusted for preterm birth, low birth weight, literacy, and maternal age, HEU status was associated with twofold increased risk of hospitalization for infection in infancy.
“The increased susceptibility of HEU infants to infectious disease is not restricted to children born in developing countries,” she declared.
The disparity in hospitalization rates was driven by hospitalization for viral infections, which occurred at a rate of 20% in the HEU group, versus 9% in controls. Particularly notable were the 10 hospitalizations for respiratory syncytial virus infection in the HEU patients, compared with just 1 in the controls.
Dr. Adler and her coinvestigators will continue following the children out to about 3 years of age. After age 12 months, the two groups no longer differed significantly in their risk of hospitalization for infection.
“The first year is a vulnerable period. Our data highlight the importance of a close follow-up of these infants,” she said.
The biggest risk factor for hospitalization for infectious illness in the HEU group was initiation of antiretroviral therapy during pregnancy. The hospitalization rate in HEU infants whose mothers began therapy prior to pregnancy was the same as in HIV-unexposed infants. The inference is that it’s not in utero exposure to antiretroviral drugs that is responsible for the increased risk of hospitalization during infancy.
“This observation supports the notion that it’s the activity of the maternal HIV infection – the exposure to a strongly proinflammatory state in the mother – that contributes to the risk of severe infection in HEU infants, probably by causing changes in innate immunity cells,” according to Dr. Adler.
Even though the increased risk of hospitalization for infectious illnesses in HEU children falls off after age 12 months, she continued, her group is following them out to about age 3 years because “we have the impression that they are at risk for neurodevelopmental problems, including language delay.”
Other researchers in the audience confirmed this risk, reporting that, as they follow HEU children through adolescence, they see an increased rate of attention deficits and associated comorbidities.
Dr. Adler reported having no financial conflicts of interest regarding her study.
