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Roughly half of young children with HIV in Botswana treated with two broadly neutralizing antibodies (bNAbs) were able to remain virally suppressed for 24 weeks, even in the absence of antiretroviral therapy (ART), a researcher said.

In a small proof-of-concept study of 25 children ages 2-5 years, 11 children (44%, 95% CI 24%-65%) who stopped ART for 24 weeks in place of monthly combination bNAb therapy remained virally suppressed, which exceeded the 30% predefined threshold for success, reported Roger Shapiro, MD, of Harvard T.H. Chan School of Public Health in Boston.

Moreover, certain clinical characteristics helped predict success on bNAbs, such as low viral reservoir at birth and never experiencing viral rebound while on ART.

At a press conference at the virtual Conference on Retroviruses and Opportunistic Infections (CROI), Shapiro noted that bNAbs hold several advantages over ART, including the "potential to improve immune recognition of HIV and possible depletion of viral reservoirs to a greater degree than ART."

In addition, he said, the treated children's parents found the infusion therapy highly acceptable, even preferred over ART, which surprised the investigators.

ART is "usually syrups for younger kids and they can be not the best tasting syrups and difficult for kids to take," Shapiro noted. "Parents found this a welcome break from ART."

The Tatelo study recruited young children living with HIV from the Early Infant Treatment cohort, who had been on ART since the first week of life. The children were age 96 weeks or older, and had HIV RNA less than 40 copies/mL for 24 weeks prior to entry.

The study had three phases:

• ART plus dual bNAb therapy with VRC01LS and 10-1074 from 8-32 weeks

• Dual bNAbs alone for up to 24 weeks, with HIV RNA checked every 1-2 weeks

• bNAbs stopped and ART restarted after 24 weeks or viral RNA >400 copies/mL, whichever came first

Intravenous bNAb infusions were administered every 4 weeks. Viral suppression was defined as viral RNA <40 copies/mL.

The 28 children who entered the study had a median age of about 4, and all were receiving lopinavir/ritonavir-based ART. Of these, three experienced viral rebound while on bNAbs and ART, and only 25 continued to the next phase of the study.

Importantly, Shapiro noted the first six children in the first phase of the study received bNAbs and ART together for 32 weeks, while the remaining children only did so for 8 weeks. Five of six children in this extended interval maintained viral suppression while on bNAb therapy, he added.

Fourteen children had viral rebound prior to achieving 24 weeks of bNAb-only treatment, and the median time to failure was 4 weeks.

Shapiro pointed to two significant clinical predictors of bNAb success in this cohort: sustained viral suppression on ART prior to bNAb intervention (82% of successes versus 29% of failures), and significantly lower median DNA in peripheral mononuclear blood cells at birth (155 copies/10⁶ vs 784 copies/10⁶, respectively).

He noted that even the children who rebounded were able to achieve re-suppression to <40 copies/mL at a median of 4 weeks later.

CD4 counts remained at safe levels in all children, and there were no safety concerns associated with the therapy, Shapiro said.

CROI Chair Elaine Abrams, MD, of Columbia University Medical Center in New York City, who moderated the session, but was not involved with the research, asked about the future implications of this treatment in children.

"This is the first evidence that you can treat with a different strategy and keep viral loads suppressed in some kids," Shapiro said. "It offers the possibility of longer intervals between treatment [with] fewer toxicities and side effects."

He also looked down the road at longer-term implications, pointing to the effect of bNAbs to "deepen reductions" in the viral reservoir and become "a strategy for some kids to control HIV on their own."

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