Breakthrough Trials Offer Hope for Long-Term HIV Remission

Around the globe, approximately 40 million individuals are living with HIV. While advancements in treatment have transformed the virus from a fatal diagnosis to a manageable condition, the quest for a cure has persisted. In 2025, researchers announced significant progress suggesting the potential for a “functional” cure, which could allow HIV to be controlled long-term without the need for continuous treatment.

Two independent clinical trials—the FRESH trial and the RIO trial—have demonstrated promising results using engineered antibodies. In the FRESH trial, conducted by Thumbi Ndung’u from the University of KwaZulu-Natal and the Africa Health Research Institute in South Africa, four out of twenty participants maintained undetectable levels of HIV for a median of 1.5 years following the cessation of antiretroviral therapy. Similarly, the RIO trial, led by Sarah Fidler at Imperial College London, reported that six out of thirty-four participants sustained viral control for at least two years.

These trials mark a significant milestone, indicating that the immune system can be trained to combat HIV effectively. Researchers are now planning larger trials to determine if these antibody treatments can be optimized for broader application. Fidler remarked, “I do think that this kind of treatment has the opportunity to really shift the dial,” emphasizing the long-lasting potential of these therapies.

Living with HIV can still pose challenges, as individuals often face shorter lifespans compared to those without the virus. Daily antiretroviral pills or even bi-monthly injections can create social and financial burdens, compounded by stigma. As Fidler pointed out, “For the last about 15 or 20 years, there’s been this real push to go, ‘How can we do better?’” The ultimate goal remains clear: achieving what many describe as a cure or at least a significant remission of HIV.

The complexity of HIV makes this endeavor particularly challenging. The virus evolves rapidly, often evading the immune system, and some HIV persists in dormant states, making it undetectable. Although only a few exceptional cases have resulted in complete cures through stem-cell transplants, the search for a functional cure is gaining momentum.

A noteworthy aspect of the research is the identification of broadly neutralizing antibodies that some long-term HIV patients eventually produce. These antibodies can target critical regions of the HIV virus, which do not change significantly. Scientists are now exploring the most effective ways to harness these antibodies into viable treatments.

In the FRESH trial, researchers selected two antibodies specifically targeting HIV-1 clade C, prevalent in sub-Saharan Africa, enrolling young women from a high-prevalence area. The RIO trial focused on two well-documented antibodies effective against HIV strains, with participants largely consisting of middle-aged white men who had started antiretroviral therapy shortly after infection.

Both trials involved administering modified antibodies that remain active for approximately six months. After the injections, participants paused their antiretroviral treatments, with the expectation that the antibodies would work alongside the immune system to control the virus. Remarkably, both trials showed that some participants developed an independent immune response, akin to a vaccine effect.

In the RIO trial, 22 out of 34 participants who received the antibodies did not experience a viral rebound after 20 weeks. By the end of the trial, six individuals maintained low viral levels and remained off antiviral medications long after the antibodies had been metabolized. In contrast, control participants who received saline infusions resumed treatment within weeks.

The FRESH trial observed a similar trend, with six of twenty participants retaining viral suppression for 48 weeks post-infusion. Among them, four managed to remain off treatment for over a year. One participant has now been off antiretroviral medication for two and a half years. Although researchers exercise caution about labeling these individuals as functionally cured, the evidence indicates that the antibodies may encourage a robust immune response.

The antibodies signal to immune cells to attack infected cells, potentially activating CD8+ T cells, which are crucial in identifying and eliminating HIV-infected cells. This could establish an “immune memory” that helps manage the virus even after the antibodies are no longer present. The outcomes resemble the immune control seen in elite controllers—fewer than 1% of individuals with HIV who can suppress the virus without treatment.

Dr. Joel Blankson, an infectious diseases expert at Johns Hopkins Medicine, expressed optimism about the implications of these trials. He noted, “It might teach us how to be able to do this much more effectively, and we might be able to get a higher percentage of people in remission.”

Early initiation of antiretroviral therapy after infection appears to improve the chances of achieving sustained viral control. Nevertheless, successful post-treatment control has been observed in chronically infected patients as well, albeit less frequently.

Another exciting finding from the RIO trial is the impact of antibodies on dormant HIV within cells, a major reason for viral rebound upon treatment cessation. Researchers speculate that boosted T cells can recognize and eliminate these latent cells, which are typically immune to antibodies. The FRESH trial also included a drug called vesatolimod, aimed at stimulating immune responses to dormant HIV, potentially “shocking” the virus into activity so the immune system can attack it.

As Ndung’u noted, the initial results from FRESH indicate that the treatment regimen may be effective to a degree. He plans to conduct a larger trial in South Africa targeting chronically infected individuals. Meanwhile, Fidler’s team is working on expanding the RIO trial to explore whether delaying antiretroviral treatment before antibody administration enhances immune response.

For now, researchers continue to monitor participants who have achieved viral suppression, providing them a chance to live free from daily medication demands. This promising research paves the way for potential breakthroughs in HIV treatment, highlighting the ongoing commitment to improving the lives of those affected by the virus.