Infant Boys Better at Resisting HIV Than Girls?

BRISBANE, Australia -- Infant boys appeared more likely than girls to achieve sustained remission following in utero vertical transmission of HIV, even when they had less than optimal adherence to antiretroviral therapy, a longitudinal study showed.

Of 281 mother-child pairs with HIV, five babies -- all boys -- attained sustained undetectable HIV viral loads despite persistent non-adherence to antiretroviral therapy, though 60% of the babies in the study were girls, reported Gabriela Cromhout, a PhD candidate at the University of KwaZulu-Natal in Durban, South Africa, during the International AIDS Society Conference on HIV Science.

All children received antiretroviral therapy at birth, and 92% had received antiretrovirals prior to birth via placental transfer. The goal of the study was to see if babies born with HIV could achieve post-treatment control of HIV without extra interventions, as well as what factors might correlate with maintenance of aviremia.

Cromhout noted that babies who seem to be able to sustain undetectable HIV without antiretroviral therapy have been spottily reported since the so-called "Mississippi baby," whose case was first reported in 2013. That baby remained HIV-free for 2 years. Other examples included a child who remained off antiretrovirals for 2 years without a rebound and another who was antiretroviral therapy-free with undetectable HIV for 12 years.

"Reports of children who have been able to achieve post-treatment HIV control after having started early combination antiretroviral therapy, such as the Mississippi baby case, generated the hypothesis that early combination antiretroviral therapy initiation would facilitate functional care in a subset of children," Cromhout said.

"To explore this, we undertook in 2015 a longitudinal study of mother-and-child pairs who were living with HIV infection in KwaZulu-Natal," she continued. "Due to the standard of care to prevent vertical transmission, as well as the fact that more than 90% of mothers are taking combination antiretroviral therapy prior to delivery, we are seeing lower viral loads in mothers and children living with HIV at baseline. This being said, the challenges around adherence to combination antiretroviral therapy in children in this setting is well documented."

In general, maintenance of undetectable HIV viral loads among infants in the study was highly dependent on adherence to antiretroviral therapy, irrespective of their plasma viral load at baseline.

Cromhout said she and her colleagues were surprised to identify the five boys who appeared to maintain aviremia despite non-adherence to combination antiretroviral therapy.

"The length of time off combination antiretroviral therapy when these children were identified ranges from 3 to 10 months," she noted. "One child was never restarted on treatment, and has now been suppressed off combination antiretroviral therapy for 19 months under supervision. The other children were put back onto their combination antiretroviral therapy, as per the standard treatment guidelines, and three of these boys are now enrolled in an analytical treatment interruption study."

"It's important to note that all five of these children have had two or more positive tests and have non-adherence that was confirmed through various means," she added. Adherence was monitored by checking plasma antiretroviral concentrations via liquid chromatography-tandem mass spectrometry, maternal history, pill-counting, and pharmacy records.

In trying to determine why these boys -- or boys in general -- seemed to be more likely to resist HIV, Cromhout and colleagues studied how boys' immune systems responded to the virus in general. Cromhout suggested that boys tend to become infected with viruses that are interferon-1-sensitive, and girls are more likely to be infected with interferon-1-resistant viruses.

These differences may explain why boys are more likely to control viremia, and more importantly, may show clues that could lead to an HIV cure, she said. "Early-life innate immune responses contribute significantly to post-treatment control in children living with HIV. Distinct immune intervention, taking into account early-life sex differences, are critical to optimize cure potential."

Commenting on the study at a press conference, Sharon Lewin, PhD, director of the Peter Doherty Institute for Infection and Immunity at the University of Melbourne in Australia, noted that "there's a few things going on here: issues around viral control, issues around susceptibility to infection, and issues around interferon sensitivity or resistance."

"But these data tell us that [the] early-life innate immune system is different amongst ... girls and boys," she added, suggesting that the work could lead to better understanding of the risk of vertical transmission, and how that risk may differ between the sexes.

Correction: This story has been updated to clarify that all infants included had HIV detected at birth.

Comment