The development of highly effective antiretroviral therapy (ART) has transformed Human Immunodeficiency Virus (HIV) infection from a manageable, chronic medical condition. Despite this success, lifelong adherence to medication is necessary because the virus embeds itself into the DNA of immune cells, creating a latent reservoir that ART cannot fully eliminate. This persistent challenge drives the ongoing search for a permanent solution, a goal proven achievable by a handful of extraordinary medical events. These rare cases show that eradicating the virus is possible, providing a blueprint for future, scalable treatments.
Understanding What a Cure Means
The scientific community distinguishes between two types of HIV cure: a functional cure and a sterilizing cure. The distinction centers on whether any trace of the replication-competent virus remains in the body after treatment.
A functional cure, often referred to as long-term remission, is achieved when the viral load remains suppressed below detectable levels without the use of ART. In this scenario, the virus’s genetic material is still present in cellular reservoirs, but the immune system or a therapeutic intervention controls its replication.
A sterilizing cure represents the complete elimination of all replication-competent HIV from the body, including the latent viral reservoirs. This means the virus is no longer present, and the individual requires no further treatment to prevent viral rebound. This total eradication is the ultimate goal of HIV cure research.
The Patients Who Have Been Cured
The first person to achieve a sterilizing cure was Timothy Ray Brown, widely known as the “Berlin Patient.” Diagnosed with both HIV and acute myeloid leukemia (AML), Brown underwent a radical treatment that unexpectedly resolved both conditions. Following the procedure, he stopped taking ART and remained virus-free for over a decade until his death from a cancer relapse in 2020.
Subsequent successes confirmed that Brown’s case was not unique. Adam Castillejo, the “London Patient,” and Marc Franke, the “Düsseldorf Patient,” both achieved long-term HIV remission after similar procedures to treat their hematologic malignancies. More recently, the “New York Patient” and the “City of Hope Patient” (Paul Edmonds) have also been reported as cured following stem cell transplants. These individuals provide evidence that, under specific and extreme conditions, the persistent HIV infection can be eradicated.
The Specific Mechanism That Worked
The common factor linking these rare cases is a specific, highly aggressive medical procedure: allogeneic hematopoietic stem cell transplantation (HSCT). This procedure was performed not to treat HIV, but to cure life-threatening blood cancers such as leukemia or lymphoma. Before the transplant, patients undergo chemotherapy and sometimes radiation to destroy their existing immune and blood-forming cells.
The success hinges on the selection of a donor who possesses a natural genetic mutation known as CCR5 Delta 32 (CCR5-Δ32). HIV typically gains entry into immune cells, particularly CD4+ T-cells, by attaching to the CCR5 co-receptor on the cell surface. The CCR5-Δ32 mutation causes a deletion in the gene, resulting in a non-functional protein that is not expressed on the cell surface.
This genetic defect acts like a “locked door” for the HIV strain that uses the CCR5 receptor. The transplant replaces the patient’s HIV-susceptible immune system with the donor’s new, HIV-resistant stem cells. As these transplanted stem cells engraft and produce new immune cells, the patient’s entire immune system becomes naturally resistant to the virus, eliminating the viral reservoir.
Why This Treatment Is Not Standard
Despite the success of the CCR5-Δ32 stem cell transplant, the procedure is not a viable option for the millions of people living with HIV. The treatment is extremely invasive and carries significant risks, including a high mortality rate, which can be as high as 25% to 40% in the first year following the procedure. This level of risk is unacceptable for individuals whose HIV infection is already well-controlled with daily medication.
The process involves intense chemotherapy and sometimes total body irradiation, which is highly toxic and severely compromises the patient’s health. A major complication is Graft-versus-Host Disease (GvHD), where the transplanted donor immune cells recognize the recipient’s body as foreign and attack the organs. Finding a suitable stem cell donor with the CCR5-Δ32 mutation who is also a close human leukocyte antigen (HLA) match is exceptionally difficult, limiting the procedure’s applicability.
Current daily ART regimens are safe, well-tolerated, and allow people with HIV to live near-normal lifespans with virtually no risk of transmission. Consequently, the severe risks and logistical challenges of the stem cell transplant only justify its use in HIV-positive patients who also require the transplant to treat a life-threatening blood cancer.
Alternative Pathways to a Cure
The knowledge gained from the cured patients has catalyzed research into safer, more scalable treatments that mimic the CCR5-Δ32 mechanism without the dangers of a full transplant. One promising area is gene therapy and gene editing, which seeks to modify a patient’s own cells outside the body and then reinfuse them. Techniques like CRISPR/Cas9 are being explored to directly disrupt the CCR5 gene in a patient’s T-cells or hematopoietic stem cells, creating the CCR5-Δ32 resistance in situ.
Another strategy focuses on targeting the latent viral reservoir using an approach known as “shock and kill.” This involves using latency-reversing agents (LRAs) to “shock” the dormant HIV out of its hiding places in the immune cells, forcing it to become active and express viral proteins. Once activated, the infected cells can then be eliminated by the patient’s own immune system or by newly developed drugs.
A related concept is the “block and lock” strategy, which aims to permanently silence the integrated viral DNA within the host cell. This approach uses compounds to lock the virus into a deep, permanent state of latency, preventing it from producing new viral particles. Both “shock and kill” and “block and lock” are systemic approaches that hold the potential for a cure administered to a large population.