Around 120,000 children worldwide are diagnosed with HIV each year, most acquiring the virus from their mothers during pregnancy, delivery, or breastfeeding. Current antiretroviral therapy (ART) suppresses replication and prevents progression to AIDS but does not eradicate hidden viral reservoirs; the virus can rebound if therapy stops. Researchers at Oregon Health and Science University tested whether a combined, early treatment could prevent reservoir establishment in an animal model and potentially clear infection when initiated shortly after exposure. The study is published in Nature Microbiology.
The investigators evaluated a three-part therapeutic strategy targeting different aspects of early infection. The components were standard ART, a pair of broadly neutralizing antibodies (bNAbs) given as a single dose, and repeated doses of the experimental monoclonal antibody leronlimab. The rationale was to suppress active replication with ART, neutralize circulating virus with bNAbs, and add an additional antibody-mediated mechanism via leronlimab to reduce reservoir seeding or facilitate clearance.
The study enrolled 55 male and female infant rhesus macaques. At approximately one month of age the animals were exposed to simian-human immunodeficiency virus (SHIV), which produces an illness similar to AIDS and is commonly used to model HIV in primates. The researchers compared seven treatment approaches aimed at preventing formation of permanent viral reservoirs, including single agents and various combinations of ART, bNAbs, and leronlimab.
For the final experiment highlighted in the report, eight macaques received the full combination 72 hours after SHIV exposure. At that time point the virus was already detectable in the animals’ blood. The regimen consisted of a single dose of two bNAbs, nine weekly doses of leronlimab, and daily ART continued for 27 weeks. After stopping therapy the team monitored the animals for viral rebound and later depleted CD8 T cells to test whether the virus was truly absent rather than being suppressed by immune control.
Single and two-part regimens lowered viral levels but did not consistently prevent viral return, mirroring prior research. In contrast, all eight macaques in the triple-therapy group experienced suppression of viremia during treatment and showed no viral rebound after ART cessation at week 27.
During over six months of follow-up after stopping treatment, researchers detected no viral DNA in blood samples from these animals. Even after intentional depletion of CD8 T cells—an immune challenge intended to reveal any latent, controlled infection—the investigators still observed no viral resurgence. Tissue samples obtained up to 84 weeks after exposure contained no detectable SHIV. The authors concluded that, in this primate model, initiating the three-part treatment within 72 hours of exposure prevented establishment of a persistent viral reservoir and may have cleared infection.
The study authors and external commentators stressed that translation from primates to human newborns remains uncertain. While the primate model is biologically relevant and has historically provided valuable data for HIV research, several practical and clinical questions must be addressed before human application:
The authors note they cannot yet claim the treatment will work in human newborns; the current results are a proof of concept in an animal model.
Jagdish Khubchandani, PhD, MPH, a public health professor not involved in the research, described the findings as promising and said the multipronged strategy “makes a lot biological sense,” citing the therapies’ complementary targets during early infection. He noted that primate data increase confidence because primates mirror human biology in many relevant ways and have historically contributed valuable HIV insights.
Jagmohan Batra, MD, a pediatric infectious disease specialist also not involved in the study, called the results very important. He observed that single therapies may control replication or reduce reservoir size without eliminating it, whereas combining three approaches may prevent a permanent reservoir from forming. Batra highlighted a practical challenge: unknown timing of acquisition in human infants complicates the ability to intervene before reservoirs become established.
Key limitations inherent to the report include its basis in an animal model and the narrow window of early intervention used. The study did not report human safety or dosing data, and it remains unknown whether the regimen would be effective if initiated beyond the 72-hour postexposure window. Before clinical use in newborns, researchers must determine safe neonatal dosing, verify efficacy in human subjects or clinically relevant trials, and evaluate logistics for identifying exposed infants and administering the multiagent regimen promptly.
In this primate study, a combination of ART, two bNAbs, and leronlimab initiated 72 hours after SHIV exposure prevented viral rebound and left no detectable viral DNA in blood or tissue samples during extended follow-up. The results offer proof of concept that very early, multi-pronged therapy could block reservoir formation in newborns, but translation to clinical care will require additional research on timing, dosing, safety, and feasibility in human neonates.