Is an HIV cure possible? The future of HIV therapy

HIV research has come a long way since the virus was discovered in the 1980s. Antiretroviral therapy (ART) marked a turning point in HIV treatment, changing the lives of millions. Today, the focus has shifted to finding a cure.

Back in 2008, Timothy Ray Brown was the first person to be cured of HIV. Known as the “Berlin patient,” Brown received two bone marrow transplants from a donor who was naturally resistant to HIV to treat his leukemia. He remained off antiretroviral therapy until his death in 2020.

When the case was announced, the medical world was ecstatic. Had we finally achieved an HIV cure?

Unfortunately, the answer remains not yet. Since then, only a handful of other people have been reported to remain off antiretroviral therapy thanks to a similar transplant. However, bone marrow transplants carry very high risks for HIV-positive patients, and HIV-resistant donors are rare. 

These cases have been an inspiration for researchers to find better treatment alternatives against HIV. With the recent U.S. Food and Drug Administration (FDA) approval of lenacapavir this June, but at the same time, the U.S. government pulling back on HIV treatment efforts in Africa, now is a good time to take a look at the landscape.

HIV’s biotech journey

In June 1981, American health authorities reported rising cases of a rare pneumonia among previously healthy young men, an early signal of what would become the AIDS crisis. Within a few years, the virus behind this syndrome, HIV, was identified, and the world faced decades of scientific urgency and social stigma.

This section traces how biotech breakthroughs transformed HIV from a fatal disease into a manageable chronic condition, and why that achievement still falls short of a cure.

Antiretroviral HIV therapy: Transformation with limitations

The late 1980s brought the first breakthrough in HIV treatment. AZT offered a glimmer of hope, initially reducing HIV-related deaths. But used on its own, it was limited by side effects, resistance, and cost. The real game-changer came in 1996 with the introduction of HAART involving three or more drugs targeting different stages of the viral cycle. By combining nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors, HAART triggered a significant drop in mortality, 70% less in the U.S. within two years.

These drugs work by interfering with key steps in HIV’s replication process, for example, blocking the enzyme that converts viral RNA into DNA, or preventing the virus from assembling new copies of itself via protease inhibitors.

Since then, ART has evolved: combination pills, integrase inhibitors, and long-acting injectables like Cabenuva have improved adherence and reduced side effects. Equally important, preventing transmission became a central goal. 

While this treatment has certainly redefined what it means to live with HIV, it remains a lifelong management strategy rather than a definitive cure. The virus persists in latent reservoirs, cells where it stays hidden and inaccessible to treatment. If therapy is interrupted, the virus typically rebounds within weeks. This dependency creates challenges around adherence, side effects, and the risk of developing resistance. 

Access is another unresolved issue. In many parts of the world, consistent treatment is far from guaranteed, leaving millions vulnerable to treatment gaps and worse outcomes.

This is why biotech is exploring other avenues to offer HIV patients a more durable solution.

HIV prevention: Redefining the front line

Antiretroviral therapy remains essential for managing HIV, but the last decade has seen growing focus on pre-exposure prophylaxis (PrEP), the use of antiretroviral drugs to prevent infection in the first place.

The first oral PrEP regimen, Truvada, was approved by the FDA in 2012 and proved highly effective. But like daily ART, it came with challenges. Adherence dropped off over time, especially among younger or more vulnerable populations, and access was quite uneven. 

Biotech efforts have since turned toward long-acting PrEP, formulations designed to protect users for months at a time with a single dose.

Cabotegravir, a long-acting integrase inhibitor marketed as Apretude, became the first injectable PrEP approved in the U.S. in late 2021. It is administered every two months and has shown superior protection compared to daily oral PrEP, particularly among women in high-risk areas where adherence to the treatment is key.

But an even more convenient solution reached the market in June 2025, when the FDA approved lenacapavir (Yeztugo) for use as a twice-yearly PrEP injection. In trials, it provided nearly 100% protection, positioning it as a real improvement for populations where daily or even bi-monthly regimens are hard to sustain.

These long-acting preventive drugs aren’t just about convenience; they offer a public health advantage. Reducing the number of missed doses can mean reducing transmission at scale. They may also help overcome structural barriers to access and adherence, especially in underserved communities.

Gene editing and immunotherapy for HIV: Aiming for control without daily treatment

One of the main reasons HIV remains incurable is the presence of what’s known as the latent reservoir, a collection of immune cells where HIV lies dormant. In these cells, the virus integrates its genetic material into the host’s DNA and enters a silent state, remaining invisible to both the immune system and antiretroviral drugs. These latent cells can persist for decades, and if the treatment is stopped, they can reactivate and reignite the infection. 

While most HIV treatments aim to suppress the virus, some of the most ambitious biotech programs today are aiming for the virus’s source:  the latent reservoir. Two of the most promising avenues in this space are gene editing and immunotherapy, both of which aim to reduce or even eliminate the need for lifelong medication.

One of the most closely watched programs in gene editing is EBT‑101, developed by Excision BioTherapeutics. The therapy uses CRISPR-Cas9 gene editing, delivered via an adeno-associated virus (AAV9), to cut out segments of HIV’s integrated DNA from infected cells. 

The program received FDA Fast Track designation in July 2023 and entered phase 1/2 trials shortly afterward. Initial results released in early 2025 confirmed that the therapy was well tolerated, with no serious adverse events. However, the impact on the virus was more limited.

All participants who paused antiretroviral therapy experienced viral rebound, although one individual maintained viral suppression for 16 weeks, compared to the typical three- to four-week rebound seen with standard treatment interruption. This means the approach may be biologically active but not yet strong enough to achieve a cure in its current form. Further studies are expected to refine delivery methods and dosing.

In parallel, another area gaining momentum is broadly neutralizing antibodies (bNAbs). These are engineered antibodies capable of recognizing and disabling a range of HIV strains. When used alone, bNAbs have shown mixed results, but combining them and pairing them with long-acting antivirals appears more promising.

Gilead is currently advancing a combination of two bNAbs, teropavimab and zinlirvimab, alongside lenacapavir approved for PrEP. The trio was presented at the 2025 Conference on Retroviruses and Opportunistic Infections (CROI), where early phase 2 results showed that twice-yearly injections could maintain viral suppression as effectively as daily ART. 

Not only are we moving past daily preventive treatment with a twice‑yearly injection, but we may soon reach the same dosing standard for people living with HIV.

Other immune-based strategies include therapeutic vaccines. Take the HTI therapeutic vaccine from AELIX, now supported by Gilead. It was designed to mirror the immune response seen in rare individuals who naturally control HIV. In a phase 2a trial on 50 men on ART, participants received the HTI vaccine paired with a mild immune booster, vesatolimod. During a controlled interruption of ART, 33.3% participants who received the vaccine maintained suppressed viral levels for six months, compared to 23.5% in the placebo group. The people who responded best were those whose immune systems showed the strongest reaction to the vaccine, proof that a more alert immune response can make a tangible difference.

Another strategy comes from cancer treatment: the checkpoint inhibitor pembrolizumab, originally developed for melanoma, showed signs of waking up dormant HIV in a small study of HIV-positive individuals. Participants saw temporary spikes in viral RNA, suggesting that hidden virus was being exposed. Although the drug doesn’t clear HIV on its own, it could be a valuable part of a combination therapy.

Awakening HIV: RNA therapies

Another promising approach to target the latent reservoir is RNA therapy. Researchers at the Peter Doherty Institute in Melbourne recently reported a breakthrough using lipid nanoparticles (LNPs) to deliver mRNA directly into resting CD4+ T cells, cells in which HIV often hides. The mRNA encodes a viral protein called Tat, which acts like an alarm clock, triggering HIV transcription and coaxing the virus out of latency in ex vivo cells from people on ART.

This new LNP formulation, called LNP X, successfully entered cells previously resistant to mRNA, without causing general immune activation or toxic side effects. Paula Cevaal, co-first author of the study, said: “In terms of specifically the field of HIV cure, we have never seen anything close to as good as what we are seeing, in terms of how well we are able to reveal this virus. So, from that point of view, we’re very hopeful that we are also able to see this type of response in an animal, and that we could eventually do this in humans,” reported The Guardian.

Published in Nature Communications, this research marks the first efficient mRNA delivery into latently infected T cells.

Still, the team emphasizes this is the first step. “Waking up” HIV is necessary, but not sufficient: the reactivated virus may still require additional therapy. Human and animal trials are still years away, but the delivery breakthrough alone could have implications beyond HIV, including cancer therapies.

Another promising direction involves non-coding RNAs, which regulate gene activity without encoding proteins. Certain miRNAs and lncRNAs contribute to maintaining latency by suppressing HIV gene expression, while others may aid its reactivation.

For instance, the lncRNA NRON represses HIV transcription, helping maintain dormancy, whereas MALAT1 plays a role in aiding viral activation. By targeting these molecules, either inhibiting latency-promoting RNAs or enhancing activators, researchers aim for a more controlled latency reversal.

The incidental cure for HIV: Stem-cell transplants

Stem-cell transplants have led to the only documented cases of what appears to be a cure for HIV. But these cases didn’t begin as HIV treatments. In each instance, the patient underwent a transplant to treat a life-threatening blood cancer, such as leukemia or lymphoma. The HIV cure was a secondary outcome, remarkable, but unintended.

The first and best-known case is that of Timothy Ray Brown, known as the Berlin patient. Diagnosed with acute myeloid leukemia, he received a stem-cell transplant from a donor with a rare mutation in the CCR5 gene, which codes for a receptor that HIV uses to enter immune cells. Following the transplant, his immune system was rebuilt with HIV-resistant cells. He stopped antiretroviral therapy and remained virus-free for the rest of his life.

Several other cases have followed, all involving patients receiving stem-cell transplants for cancer. In 2024, a seventh case was reported in Germany, this time involving a donor who carried only one copy of the protective CCR5 mutation. The patient had stopped antiretroviral therapy in 2018, several years before the case was publicly reported, and has shown no sign of viral rebound since.

While these results provide proof that curing HIV is biologically possible, they come with major limitations. Stem-cell transplants are high-risk procedures, typically reserved for patients with otherwise fatal cancers. They involve toxic conditioning regimens and carry the risk of severe complications, including graft-versus-host disease. Additionally, the CCR5 mutation is rare, making donor matching impossible at scale.

This means stem-cell transplantation is not a viable cure strategy for the general population. However, these rare cases have deeply influenced the field. They validate the importance of CCR5 as a therapeutic target and have inspired gene-editing approaches that seek to replicate the transplant’s effects, but without the risks.

Promising science, uncertain support

Progress in HIV research and the promise HIV-focused biotechs represent are undeniable, but while science is moving forward, the broader landscape is shifting in more uncertain ways.

The United States has long played a central role in the global HIV response, not just through research funding, but also by supporting prevention and treatment programs abroad. That support is now on shakier ground. Over the past year, the U.S. has suspended new funding commitments for PEPFAR, the major global HIV program, amid political disagreements. 

Several major players, including the U.S., have also reduced contributions to UNAIDS. As a result, UNAIDS warned in May that it may be forced to lay off more than half its workforce, putting country-level support at risk.

These events don’t negate the scientific momentum, but without political backing, funding continuity, and strong public health infrastructure, even the most promising innovations risk stalling before they reach those who need them.

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