For the first time since HIV was identified, early human trials are starting to show what long‑imagined “drug‑free control” of the virus might look like in practice. Instead of chasing a total eradication that has eluded scientists for decades, researchers are zeroing in on a more pragmatic goal: keeping HIV so tightly suppressed that people can safely stop daily treatment and still avoid viral rebound.
That shift in ambition, from an all‑or‑nothing cure to a durable remission, is reshaping how I think about the endgame of the epidemic. The science is still early and fragile, but the convergence of new drugs, smarter trial designs and a clearer definition of what counts as a “functional cure” suggests the field is closer to a turning point than at any time in the past forty years.
From lifelong pills to the promise of remission
For most people living with HIV, the current standard of care is a daily regimen of antiretroviral therapy, or ART, that combines multiple antiretroviral, or ARV, drugs to keep the virus in check. These combinations can drive HIV down to undetectable levels in the blood and transform a once‑fatal infection into a chronic condition, but they also lock people into a lifelong responsibility of continuous medication, clinic visits and lab monitoring, with all the financial and emotional weight that entails. As one major research program notes, there are ongoing clinical trials precisely because this model, while lifesaving, still leaves people tethered to treatment for decades and vulnerable to side effects, drug interactions and access gaps linked to cost or stigma, especially in regions where HIV remains highly prevalent.
That is why the field’s pivot toward remission is so significant. Instead of assuming that HIV‑positive people must stay on ART forever, scientists are testing whether carefully designed interventions can induce periods of drug‑free control, sometimes called ART‑free remission, in which the virus remains suppressed without daily pills. In this vision, ART remains essential to get the virus under control, but the long‑term goal is to interrupt therapy after prolonged treatment and maintain health without constant dosing, a strategy that is now being explored in multiple clinical trials.
What scientists actually mean by a “functional cure”
When researchers talk about a “functional cure,” they are not claiming that HIV has vanished from the body. Instead, they are describing a scenario in which the virus is still present but remains under such tight immune and virologic control that it cannot cause disease or spread, even without ongoing medication. In practical terms, that means sustained viral remission, where the virus stays at undetectable or extremely low levels for long stretches of time after ART is stopped, and the person’s immune system remains stable. This is very different from viral eradication, the complete removal of every last infected cell, which remains a far more challenging, longer‑term goal that current tools are nowhere near delivering at scale.
Clinicians sometimes refer to this state as ART‑free remission, and it is increasingly being used as a primary endpoint in cure‑focused trials. One detailed explanation describes a functional cure as a condition in which HIV is controlled without medication, with the virus unable to reestablish a self‑sustaining infection even if latent reservoirs occasionally flicker back to life. That framing, which emphasizes control rather than total elimination, underpins the design of studies like the ACTG A5386 trial and reflects a growing consensus that the most realistic near‑term win is to help people achieve functional cure This kind of remission rather than chase a perfect, all‑or‑nothing cure.
Early trials that hint at drug‑free control
The most tantalizing signals that this kind of remission is possible are coming from small, early‑phase trials that push beyond standard ART. In some of these studies, participants who had achieved stable viral suppression on ART received additional experimental interventions, then paused their regular medication under close monitoring to see whether the virus would rebound. A subset of volunteers maintained undetectable or very low viral loads for extended periods without restarting therapy, suggesting that their immune systems, possibly boosted or reshaped by the experimental approach, could hold HIV in check on their own. These are not yet large, definitive studies, but they offer a proof of concept that the virus’s grip can be loosened without eradicating every infected cell.
One line of research highlighted in recent reporting explores how targeted delivery systems might make existing drugs more potent against the hidden reservoirs that allow HIV to roar back when ART stops. In oncology, for example, chemotherapy hurts both cancerous and healthy cells, but nanoparticles can help focus the toxic payload on tumors while sparing the rest of the body. Translating that logic to HIV, scientists are investigating whether similar nanotechnology could concentrate antiviral agents or immune‑modulating compounds in the tissues where the virus hides, potentially shrinking the reservoir and extending the time a person can stay off treatment. These early trials, which suggest that a functional cure for HIV may be in reach, are still in their infancy, but they are already reshaping how researchers think about HIV remission.
Why HIV is so hard to cure outright
To understand why these incremental gains matter, it helps to remember why a sterilizing cure has been so elusive. HIV integrates its genetic material into the DNA of long‑lived immune cells, creating latent reservoirs that sit quietly for years or decades without producing new virus. Standard ART is excellent at blocking active replication, but it does not touch these silent pockets of infection. The moment treatment stops, some of those cells wake up, start churning out virus again and quickly reestablish a self‑sustaining infection. Any strategy that aims to eradicate HIV entirely has to find and eliminate every one of these hidden cells, a task that has proved extraordinarily difficult in practice.
Even the rare cases of apparent cure, such as individuals who received bone marrow transplants from donors with a genetic resistance to HIV, underscore how extreme the intervention has to be. In those scenarios, the transplant procedure, which is itself risky and reserved for people with life‑threatening cancers, effectively replaces the person’s immune system with donor cells that the virus cannot easily infect. One detailed analysis notes that even if treatment was stopped and latent virus reemerged, it would be unable to produce a self‑sustaining infection because the new immune cells lack the usual entry points HIV uses. That kind of cure, achieved through complex transplants of bone marrow cells from a donor, is not a scalable solution for the tens of millions of people living with the virus, which is why researchers are increasingly focused on strategies that can deliver durable remission without such marrow cells from a donor.
Redefining success: sustained remission as a formal goal
That pivot in strategy is now codified in how major research agencies describe their priorities. Instead of treating cure research as a single, monolithic target, they distinguish between sustained viral remission and viral eradication, with the former framed as a nearer‑term, more achievable objective. People with HIV who adhere carefully to treatment with ART can already have undetectable levels of virus in their blood and live long, healthy lives, but the need for continuous therapy remains. The emerging goal is to translate that treatment‑dependent control into a state where the virus stays suppressed even when ART is paused, without sacrificing safety or immune function.
In policy documents and scientific roadmaps, this is often described as a two‑track agenda: first, develop interventions that can reliably induce long‑lasting remission off therapy, and second, continue to explore more aggressive approaches that might one day achieve complete eradication. The first track is where most of the current momentum lies, with studies designed to test whether combinations of immune‑based therapies, latency‑reversing agents or targeted delivery systems can shrink the reservoir enough to allow safe treatment interruptions. That is why official guidance now highlights Sustained viral remission as a distinct, explicitly endorsed milestone on the path toward a cure.
Industry’s new playbook: thinking beyond lifelong treatment
Pharmaceutical companies that built their HIV portfolios on daily pills are also retooling their ambitions. At a recent symposium sponsored by a major drug maker, a Kenyan‑born scientist laid out a vision that moves beyond simply refining ART regimens toward interventions that could eventually allow people to interrupt therapy after prolonged treatment. The argument was straightforward: while better pills and long‑acting injections are important, the real breakthrough will come when people no longer have to organize their lives around medication schedules at all. That requires designing trials that do not just measure viral load on therapy, but also test how the virus behaves when treatment is deliberately paused under controlled conditions.
This shift is not purely altruistic; it reflects a recognition that the next wave of innovation will be judged by its ability to reduce the burden of lifelong care, not just improve lab numbers. Companies are investing in long‑acting agents, immune‑modulating therapies and combination strategies that could be layered on top of standard ART, then withdrawn to see whether remission holds. The Kenyan researcher’s comments at the International AIDS Society Conference captured this new mindset, emphasizing that the field has to think beyond lifelong treatment in HIV and start designing interventions that can realistically support structured treatment interruptions, a goal that aligns with the broader push toward The Kenyan scientist’s focus on remission.
Breakthrough drugs that change the starting line
At the same time, the frontline of HIV prevention and treatment is being reshaped by new drugs that, while not cures, create a stronger platform for future remission strategies. Earlier this year, regulators approved Yeztugo, also known as lenacapavir, as the first HIV prevention medicine that can be given just twice a year. Developed by Gilead Sciences, this long‑acting injectable is designed to protect people at high risk of infection with only two doses annually, a dramatic shift from daily oral pre‑exposure prophylaxis. For people who struggle with adherence, or who face stigma every time they pick up a pill bottle, that kind of dosing schedule could be transformative.
Long‑acting agents like Yeztugo also matter for cure research because they change how scientists think about maintaining viral control over time. If a person can keep HIV suppressed or prevent infection with infrequent injections, it becomes easier to imagine layering on additional experimental therapies that target the reservoir or boost immune responses, then spacing out or stopping maintenance treatment altogether. The approval of this twice‑yearly prevention shot by the FDA, highlighted in coverage of new and notable treatments from 2025, signals that the regulatory system is ready to accommodate radically different dosing paradigms for Yeztugo and other HIV medicines that may follow.
Honoring the science that made remission thinkable
The current optimism around functional cures did not appear overnight; it rests on decades of basic science that slowly unraveled how HIV assembles, buds from cells and spreads. That work is now being recognized at the highest levels. Earlier this year, the Warren Alpert Foundation Prize was awarded to three scientists whose discoveries culminated in a novel HIV treatment that targets a key step in the virus’s life cycle. Their research traced the structure and function of viral components in painstaking detail, then translated those insights into drugs that can block HIV replication in ways that were unimaginable when the epidemic began.
One account of the prize notes that after six more years of iterative work, the team’s discoveries helped enable a new class of therapies that interfere with the virus’s ability to assemble and mature properly, effectively jamming the machinery HIV needs to produce infectious particles. That kind of mechanistic understanding is exactly what cure researchers now rely on as they design interventions aimed at the latent reservoir or at enhancing immune recognition of infected cells. By honoring scientists like Wesley Sundquist and his colleagues, the Warren Alpert Foundation Prize underscores how foundational virology and structural biology have laid the groundwork for today’s push toward Warren Alpert Foundation Prize‑era treatments that make remission a realistic target.
Balancing hope with hard scientific limits
For all the excitement around early remission trials, I find it important to keep the limitations in clear view. Most of the studies that hint at drug‑free control involve small numbers of participants, intensive monitoring and, in some cases, interventions that may not be easily scalable in low‑resource settings. The durability of remission is still uncertain; some people maintain control for months or years, while others experience viral rebound and must restart ART. That variability suggests that individual immune responses, the size and location of viral reservoirs and perhaps even genetic factors all play a role in determining who benefits from these experimental strategies.
There is also a risk that the language of “cure,” even when qualified as “functional,” can raise expectations faster than the data can support. Researchers and advocates have learned from past experience that overpromising can erode trust, especially in communities that have long borne the brunt of the epidemic. That is why many scientific roadmaps now emphasize careful, stepwise progress toward sustained remission, with clear criteria for when it is safe to interrupt therapy and robust plans for rapid reinitiation if the virus returns. The field’s growing focus on sustained viral remission as a formal endpoint, distinct from eradication, reflects a more mature understanding of what is achievable in the near term and a commitment to grounding hope in rigorously tested People‑centered science.
What a “functional cure” era could mean for people living with HIV
If the promise of functional cures holds up in larger trials, the impact on daily life for people living with HIV could be profound. Instead of organizing every day around pill boxes, pharmacy refills and the constant mental reminder of infection, individuals might move to a model where they undergo a period of intensive therapy, possibly including novel agents, followed by long stretches without any medication at all. Regular monitoring would still be essential, but the psychological and logistical burden of treatment could be dramatically reduced. For people who face stigma at work, at home or in healthcare settings, simply not having to take or store HIV drugs every day could change how they navigate their communities.
On a population level, widespread adoption of remission‑inducing strategies could also reshape public health planning. Health systems might shift resources from lifelong drug procurement toward time‑limited interventions and long‑term monitoring, while prevention programs could integrate cure‑adjacent tools with existing options like long‑acting PrEP. The key, as the emerging research agenda makes clear, will be ensuring that these advances do not remain confined to a handful of elite clinics, but instead reach the same global communities that have driven progress on ART access. If early trials continue to deliver on their promise, the next decade could mark the transition from managing HIV as a permanently medicated condition to treating it as an infection that, for many, can be pushed into a stable, drug‑free quiet.
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