Study: Neutralizing Antibodies May Harm Babies of HIV-Positive Mothers

Manish Sagar, MD, associate professor of medicine, Boston University School of Medicine

Manish Sagar, MD

Mothers who are infected with HIV and have high levels of neutralizing antibodies are more likely to pass the virus to their babies through breast milk, and those babies face higher overall mortality rates, regardless of whether they contract HIV, according to a new study from scientists at Boston University, the University of North Carolina, and the US Centers for Disease Control and Prevention (CDC).

The research bucks conventional wisdom and raises a cautionary flag for scientists experimenting with neutralizing antibodies (nAbs) as a means of preventing transmission of HIV.

Study author Manish Sagar, MD, associate professor of medicine, Boston University School of Medicine (BUSM), said the results of earlier studies on the topic had been contradictory due to differences in methodology and the timing of sample collection.

In launching his study, Sagar said he hoped to show that a strong antibody response in infants would help prevent transmission.

“We were aware however, that although neutralizing antibodies have been shown to be protective in animal models, there remains no definitive evidence for this protection in humans,” said Sagar, an attending physician in infectious diseases at Boston Medical Center. “Our results were surprising; we did not expect to find an increased risk of transmission and infant morbidity with a stronger maternal nAb response.”

In conducting the study, Sagar and colleagues looked at plasma antibodies data from Malawian mothers who had HIV-1 subtype C, and their infants. The study population included babies who contracted HIV and others who did not.

The researchers were careful to compare pairs based on similar times of blood sample collection and similar maternal viral loads of CD4 T-cell counts. Samples from mothers were taken prior to estimated transmission in order to gain an accurate reading of pre-existing plasma antibodies.

After comparing matching groups, researchers found that babies without nAbs had lower rates of HIV infection. They also found that mothers with high nAb levels were more likely to pass on HIV to their infants.

Perhaps most striking, however, was the finding that babies born to mothers with high levels of nAbs were more than 3 times as likely to have a serious illness or die post-partum.

Sagar said the study didn’t identify a mechanism for the higher serious illness and mortality rates, though other research has shown babies born to HIV-positive mothers tend to fare worse, regardless of whether they themselves contract the virus.

“It is not completely understood why this is, but our findings suggest that the maternal immune response to her own virus may play a role,” Sagar told MD Magazine. “Previous studies have found that high levels of broad and potent HIV-specific nAbs in mothers may reduce transfer of antibodies against other potentially harmful pathogens, such as tetanus or measles, or may alter the infant immune response, putting the baby at increased risk of illness or death.”

Another theory is that mothers with high nAbs may have a greater variety of virus circulating in their bodies, thus theoretically increasing the odds of transmission of HIV.

Some research also indicated that exposure to antigens can be immunosuppressive in babies, meaning that babies who don’t contract HIV could still be at a greater risk of other illnesses.

The study, “Maternal but Not Infant Anti-HIV-1 Neutralizing Antibody Response Associates with Enhanced Transmission and Infant Morbidity” was published in mBio.

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