Early triple therapy may offer path toward curing newborn HIV

Clinical takeaway: This preclinical study suggests that treating HIV through multiple mechanisms within the first days of infection could potentially prevent lifelong infection. Human studies are needed, but the findings point toward a strategy aimed at eliminating persistent virus rather than requiring lifelong suppression with antiretroviral therapy.

HIV treatment can suppress the virus to undetectable levels, but it does not normally eliminate infection. HIV can persist silently in cells and begin replicating again if antiretroviral therapy (ART) is stopped, which is why people with HIV generally require lifelong treatment.

A new preclinical study suggests there may be a brief opportunity soon after infection to change that trajectory. Researchers found that combining ART with two types of antibody therapy within 72 hours of infection eliminated all detectable evidence of an HIV-like virus in eight infant rhesus monkeys — and the virus did not return after treatment was stopped.

The approach attacks HIV in three different ways. ART suppresses viral replication; broadly neutralizing antibodies target circulating virus; and the investigational monoclonal antibody leronlimab blocks CCR5, a receptor HIV commonly uses to enter immune cells. None of these approaches was consistently able to eliminate infection when tested alone or in two-part combinations, suggesting that their combined effects were important.

The result persisted well beyond treatment. After ART was discontinued, all eight animals remained free of detectable virus. Researchers also found no viral DNA in blood or sampled tissues and no evidence of intact virus capable of persisting in cells. At the end of the 84-week study, extensive testing still found no detectable virus in the triple-therapy group.

That distinction is important. Rather than simply keeping HIV suppressed, the strategy appeared to prevent the virus from establishing the long-lived foothold that allows infection to return after treatment ends.

Whether the same approach can eliminate HIV in human newborns remains unknown. The treatment was started very early after infection, and the study cannot rule out virus persisting in tissues that were not sampled. Still, the components of the regimen already have human clinical experience: ART is standard treatment, while broadly neutralizing antibodies and leronlimab have been studied in clinical trials. That could help accelerate testing of the combination in people.

“The really exciting part is that it could go to clinical trials immediately to eliminate HIV infection in newborns,” said co-lead author Jonah Sacha, PhD, professor and chief of pathobiology and immunology at Oregon Health & Science University’s Oregon National Primate Research Center and Vaccine and Gene Therapy Institute.

Source: Sacha JB, et al. (2026 Aug 10) Nat Microbiol. Combination therapy with broadly neutralizing antibodies, antiretroviral therapy and CCR5 blockade limits viral reservoir seeding in infant macaque model of HIV