The human immunodeficiency virus (HIV) remains a major global health challenge, affecting millions worldwide. Decades of intensive research have transformed HIV from a death sentence into a manageable chronic condition, yet no universal, accessible treatment exists that can completely eradicate the virus from the body. The goal of an HIV cure is now the focus of a massive global effort.
Current Reality: Highly Effective Treatment Versus Eradication
The current standard of care for HIV is Antiretroviral Therapy (ART), which involves taking a combination of drugs daily. ART works by disrupting the HIV life cycle, effectively stopping the virus from replicating within the body. This treatment suppresses the amount of virus in the blood, known as the viral load, to undetectable levels in most people. Achieving an undetectable viral load allows people with HIV to live long, healthy lives and prevents sexual transmission (Undetectable = Untransmittable, or U=U).
Despite this success, ART is not a cure because it cannot eliminate the latent HIV reservoir. This reservoir consists of a small pool of infected immune cells, primarily resting memory CD4+ T cells, where the HIV genetic material (provirus) is silently integrated into the host cell’s DNA. These dormant cells are invisible to both the immune system and antiretroviral drugs. If a person stops taking ART, the provirus can reactivate, causing the virus to rapidly multiply, leading to viral rebound and disease progression. The persistence of this latent reservoir necessitates lifelong medication.
Defining the Types of HIV Cure
The scientific community distinguishes between two major goals in cure research. The first is a sterilizing cure, which is the most challenging objective. A sterilizing cure involves the complete elimination of all replication-competent HIV from the body, including the entire latent reservoir. If achieved, the individual would be completely free of the virus and would no longer require medication.
The second, and potentially more achievable, goal is a functional cure, often described as sustained remission without therapy. This means that viral replication remains permanently suppressed even after the person stops taking ART. A small amount of non-replicating or controlled virus may still be present in the body. The individual’s immune system or therapeutic intervention would keep the viral load below detectable levels indefinitely, avoiding the need for daily pills. This outcome is analogous to cancer remission, where the disease is controlled long-term without active treatment.
Proven Cases of HIV Eradication
Only a handful of individuals worldwide have achieved a sterilizing cure through a specific, high-risk medical procedure. The first documented case, the “Berlin Patient,” was Timothy Ray Brown, who received a specialized bone marrow transplant in 2007 to treat acute myeloid leukemia. This procedure, called allogeneic hematopoietic stem cell transplantation (HSCT), replaced his immune system with stem cells from a donor who possessed a rare genetic mutation. This donor had two copies of the CCR5-delta 32 mutation, which naturally prevents HIV from entering host immune cells by disabling the CCR5 co-receptor the virus typically uses for entry.
The combination of intensive chemotherapy and radiation, followed by the transplant of HIV-resistant cells, effectively eradicated both his cancer and his HIV. Following Brown’s case, several other individuals, including the “London Patient” and the “City of Hope Patient,” have achieved a similar sterilizing cure using the CCR5-delta 32 HSCT mechanism. While these cases prove an HIV cure is biologically possible, the procedure is not a scalable solution for the millions living with HIV. HSCT is a toxic, life-threatening intervention reserved only for individuals who require a transplant to treat a simultaneous blood cancer, due to its high mortality rate and risk of severe complications like Graft-versus-Host Disease.
Emerging Strategies for a Scalable Cure
Current research focuses on developing therapies that can achieve a cure without the extreme risks associated with stem cell transplantation. One leading strategy is “Shock and Kill,” which directly targets the latent reservoir. This approach uses specialized drugs called latency-reversing agents (LRAs) to “shock” the dormant provirus into an active state. This forces the infected cell to produce viral proteins and become visible to the immune system, allowing the cell to be “killed” by the person’s own boosted immune response or by a therapeutic vaccine.
Another promising avenue is gene editing, which seeks to permanently alter the genetic code of the infected cells. Tools like CRISPR-Cas9 are being investigated to either physically cut the integrated HIV provirus out of the host cell’s DNA or to modify host cell genes, such as the CCR5 receptor, making the cells resistant to infection. This approach aims to create a new, HIV-resistant immune system from within the patient’s own body, similar to the CCR5-delta 32 mechanism, but without a donor transplant. Research is also progressing with Broadly Neutralizing Antibodies (bNAbs), which are potent antibodies capable of neutralizing diverse strains of HIV. These bNAbs are being tested for their potential to clear circulating virus and help the immune system eliminate cells within the latent reservoir, offering a potential path to a functional cure.