How Close Are We to a Cure for HIV?

While there is currently no cure for the human immunodeficiency virus (HIV), researchers believe they are heading toward one. HIV, which can lead to AIDS, can be controlled with antiretroviral therapy (ART, a combination of medicines). At the current time, ART is the only form of treatment available for HIV.

In 2018, 37,832 people were diagnosed with HIV infection in the United States, and approximately 1.7 million people became newly infected with HIV worldwide. HIV-prevention tools like a vaccine are important to limiting the spread of HIV. However, there is as yet no vaccine that can prevent or treat infection with the virus, though scientists are working on creating one.

An experimental vaccine for HIV was shown to have a 31% success rate in a 2009 study. The National Institutes of Health is conducting two late-stage, multinational clinical trials to develop a preventive vaccine for HIV that will hopefully work for diverse populations.

Researchers at the University of Pittsburgh in Pennsylvania have similarly begun clinical trials to test a vaccine for treating HIV infection after they found, in 2019, a treatment that targets HIV hiding in cells and then kills the virus.

These advances are promising, but challenges presented by the virus have long held back research efforts to find a cure or vaccine.

Challenges

Researchers have been investing time and money into developing a cure for HIV and AIDS for more than 30 years. They are still working to understand HIV and AIDS.

Discovery of an HIV cure and vaccine requires long-term research and commitment from scientists. A 2013 study, however, found that young scientists believe the HIV field is overpopulated and that they should focus their research elsewhere. Research in the field has yet to find a cure or vaccine, so more work is still needed in these research efforts. 

The virus also presents several challenges that explain why a cure or vaccine for HIV has not been developed.

Genetic Variability

HIV is a moving target because it replicates quickly, producing hundreds of new copies of the virus every day, and mutates in the process. These mutations can result in errors that make the virus resistant to ART.

Because of this, some strains of the virus attack a person's immune system more aggressively than other strains. This results in constant viral evolution and genetic variability of the virus within populations and within individuals.

For HIV-1—one strain of HIV alone—there are 13 distinct subtypes and sub-subtypes that are linked geographically, with 15%–20% variation within subtype and variation of up to 35% between subtypes. The genetic diversity of HIV viruses makes it difficult to create a vaccine that will produce immune responses capable of providing protection against their tremendous diversity of variants.

Latent Reservoirs

HIV also has the ability to hide in tissues throughout the body and evade the immune system. HIV is typically found in the blood, where it can be detected by an HIV test. However, when the virus goes into a proviral state, in which the virus is latent (inactive) and hides itself, the body’s immune system is not alerted to it.

In this state, the virus will insert its genetic materials into that of its host cells (living cells invaded by the virus) and replicate as the host cells (living cells invaded by the virus) replicate.

The virus can remain latent for a long time, resulting in a latent infection. The term "latent reservoirs" is used to describe host cells that are infected by but not actively producing HIV. Even though ART can reduce the level of HIV in the blood to an undetectable level, latent reservoirs of HIV can continue to survive. When a latently infected cell is reactivated, the cell begins to produce HIV again. For this reason, ART cannot cure HIV infection.

Scientists therefore try to target latent reservoirs when developing a cure by following the "kick and kill" (also called "shock and kill") concept. They want to kick the virus out of hiding and kill it. The challenge is finding out which cells are harboring HIV.

Two types of HIV cures that could eradicate HIV reservoirs are currently being developed. They are:

• Functional cure: Controls the replication of HIV long term without treatment
• Sterilizing cure: Eliminates the virus

Immune Exhaustion

Antigens, the part of a virus that triggers an immune response, go after CD4 helper cells, which are also known as T helper cells or T cells (white blood cells that fight infection). T cells are responsible for killing infected host cells and regulating the immune system. However, persistent exposure of T cells to high levels of antigens during HIV infection can result in a severe T cell dysfunctional state called immune exhaustion.

It becomes incredibly hard for the immune system to fend off HIV infection once T cell exhaustion is triggered. In the final stages of exhaustion, the T cells will die. Losing these protective cells renders the immune system defenseless against HIV infection, resulting in progression to AIDS.

Scientists are looking into developing a T cell HIV vaccine to treat HIV infection, since evidence shows that cellular immunity mediated by T cells can sustain long-term disease-free and transmission-free HIV control. A T cell–stimulating vaccine can potentially help destroy cells infected by HIV and lower the level of HIV in those who are infected.

Unfortunately, a vaccine that induces the production of T cells may actually increase susceptibility to infection, because some T cells are important reservoirs for HIV-infected cells. None of the T cell vaccine concepts tested to date have shown sufficient efficacy.

Goals

HIV has been cured in one person, Timothy Ray Brown, also known as the Berlin Patient. He was diagnosed with acute myeloid leukemia in 2006. He had been living with HIV for years and had been treating it properly with medication. After a long bout with chemotherapy, he decided to get two bone marrow transplants from an HIV-resistant donor. Brown was cured of leukemia and HIV. 

However, other HIV patients who have undergone similar treatments have not been cured. Brown is a scientific anomaly, and researchers cannot figure out what made his situation different. To this date, he is the only person to be functionally cured of HIV. 

Another case involves a baby from Mississippi (nicknamed the Mississippi Baby), who was born with HIV. Doctors gave her treatment, and she became HIV free until her mother stopped giving her antiretroviral therapy, after which the HIV eventually returned. Before testing HIV-positive, the child went 27 months with no positive test results.

She’s currently back on antiretroviral therapy, and probably will be for life. Researchers are fascinated by her remission period. The Mississippi Baby case gives doctors hope that early and aggressive therapy can control HIV. 

These cases have given researchers insights into what they may need to explore in order to create an effective vaccine and cure. The theoretical strategy called kick-and-kill is a two-step strategy that may very well be the cure for HIV. By reactivating the latent infection through latency-reversing drugs, HIV comes out of its hiding place. The reservoir cells are then killed by other cells in the immune system.

Models for a Cure

While the kick-and-kill method may bring the virus out of hiding, researchers also need to find ways to eradicate the virus before it can mutate or establish new reservoirs. A combination of treatments may be the cure to completely wipe out the virus and salvage the immune system. 

Latency-Reversing Agents 

Histone deacetylase (HDAC) inhibitors are used for hematological cancers as chemotherapy agents. The Food and Drug Administration (FDA) has approved the anticancer drugs Zolinza (vorinostat), Farydak (panobinostat), and Istodax (romidepsin) to be used for HIV patients. These HDAC inhibitors purge the latent HIV reservoirs. 

Although this sounds promising, the drugs also blunt the body's immune response. Since reservoirs are self-renewable and extensive, the treatment may be most successful in conjunction with another treatment. This method is being tested in clinical studies with hopes that it will lead to the complete eradication of an HIV infection.

Reversing immune exhaustion by using HDAC inhibitors was also once thought to be possible, but research has shown that antigens mutate and escape the drug, making it an unlikely solution.

Broadly Neutralizing Antibodies

A group of people (one in 300) who are HIV-positive have undetectable HIV viral loads (the amount of virus found in your body) without using ART or any other HIV drugs. Called elite controllers, these people have a low risk of infection and have well-maintained immune systems.

An antibody type called broadly neutralizing antibodies (BNabs), which kill various HIV genetic types, is produced faster in elite controllers than regular people, meaning these antibodies are able to kill off a wider net of HIV. By contrast, a regular person would take years to produce BNabs, and by then the HIV would already be hiding in latent reservoirs.

Although elite controllers fight HIV more rapidly, they are hospitalized for non-HIV-related diseases twice as often as non-elite controllers. While the studies surrounding BNabs may lead to a vaccine, more clinical trials are needed to evaluate the potential of these antibodies in curing HIV.

Immunologic Agents

Immunologic agents can help target and kill HIV after the virus is out of reservoirs and hiding places. Moderna, a biotech firm, is developing an HIV vaccine that has been tested in monkeys. The vaccine in designed to teach the body to recognize HIV variants and induce the production of virus-like-particles (VLPs) in the body. A similar vaccine that has been successful is the human papillomavirus vaccine, which also uses VLPs.

The antibiotic concanamycin A is another immunologic strategy researchers are looking into. One team of researchers has homed in on a protein called Nef, which HIV uses to evade the body’s immune system. A pleicomacrolide, or a class of antibiotics, called concanamycin A was found to hinder Nef. Researchers believe that, when combined with ART, this type of therapy could clear HIV from the body.

A Word From Verywell

Most studies on an HIV cure or vaccines are now being performed in vitro (outside a body) or on animals, or are in the early stages of clinical trials. The search for a definitive cure for HIV is ongoing, and new discoveries continue to emerge in scientific research.

For now, antiretroviral therapy is the only treatment available for HIV-positive individuals. Until a cure or vaccine for HIV is developed, prevention of HIV infection through safe practices, postexposure therapy and pre-exposure therapy—along with testing to identify active cases—remain the only ways to steer clear of the virus.