Since the first reported case of acquired immunodeficiency syndrome (AIDS) in 1981, the disease has killed approximately 40 million people and infected millions more. The first two decades of the AIDS epidemic were rife with myths and misconceptions about the human immunodeficiency virus (HIV), the precursor to AIDS—causing a global health crisis that still has a major impact upon many countries today.
While the African continent has borne the brunt of the epidemic, around 1.2 million people in the United States currently have HIV, and the U.S. Centers for Disease Control and Prevention (CDC) reported around 30,000 new cases in 2020. Considering the resources invested into stopping the disease, a common question is: Why is HIV so hard to treat, and is there hope for a cure in the future?
While scientists have a comprehensive understanding of how HIV works, its transmission, and its effects on the human body, this knowledge hasn’t always been enough to develop an effective treatment. HIV has several characteristics that make it extremely resistant to common treatments—even anti-retroviral therapy (ART), which is effective at decreasing the viral load, has limitations. When a person stops their ART, their HIV load rapidly rebounds to pre-treatment levels.
HIV is a retrovirus that carries its genetic information in a single strand of RNA. RNA is similar to DNA but is significantly less stable, making HIV prone to frequent mutations. Viruses with high mutation rates, such as HIV and influenza, must balance producing defective particles and adapting to changing conditions.
The largest drawback for any virus with a high mutation rate is that many new viral particles simply don’t work. These inactive particles may not be able to infect new cells or reproduce, significantly reducing viral fitness. However, high mutation rates also have advantages — they allow the virus to respond quickly to evade the immune system (which only looks for virus particles that it recognizes) and lessen the efficacy of drugs by modifying the pathways that the drugs attack.
HIV has one of the highest recorded mutation rates, meaning that it’s constantly one step ahead of the body’s immune system while also having the capability to adapt to current therapies.
When HIV infects a host cell, it incorporates its genetic material into the host’s genome through recombination. This process is when the virus uses the host cell’s enzymes to reverse-transcribe its RNA into DNA, which then integrates with the host cell’s DNA. The cell’s machinery can’t distinguish between its original DNA and the newly incorporated viral DNA, so the cell will start producing viral particles as part of its normal functioning. Every time the host cell reproduces, it copies the viral genetic material, spreading the infection throughout the body.
Recombination makes it almost impossible to completely remove all traces of the virus from the infected person. As long as one cell contains a recombined genome, the virus is always ready to spread again.
The body’s immune system is vital in identifying and removing foreign pathogens. But what happens when the virus attacks the immune system?
HIV attacks CD4+ cells, also known as helper T cells. These white blood cells are essential in all adaptive immune responses, such as telling B cells to secrete antibodies and macrophages to target and destroy foreign bodies and telling cytotoxic T cells to kill infected cells.
By infecting these essential cells, HIV manages to evade immune systems in two ways. First, it kills the cells it infects, which leads to a decreased level of B cell activation. Secondly, it also activates cytotoxic T cells, which will attack the helper cells and further weaken the body’s immune response.
It’s this decreased immune response that causes the transition from HIV to AIDS. Due to a severely weakened immune system and lowered CD4+ count, people with AIDS are more susceptible to opportunistic infections that healthy people can fight. Eventually, even minor colds can become life-threatening, and most individuals with AIDS will die from otherwise preventable diseases.
While most HIV-infected cells will produce large amounts of the virus and then die, some do not activate immediately. Since these cells aren’t actively producing viral particles, they don’t become a target of killer T cells and don’t rupture from producing too many new viral particles. Essentially, these cells form a latent reservoir of HIV particles in lymph nodes, the spleen, the brain, and many other tissues.
Typically, antiretroviral drugs control the levels of active HIV-infected cells, which means that whenever a latent cell activates, the ART deals with it. However, if an HIV-infected person stops their therapy, these latent cells can activate and infect healthy T cells, restoring the HIV viral load to pre-treatment levels.
Current HIV treatment strategies rely on ARTs to stop the reproduction of HIV, preventing an HIV infection from developing into AIDS. However, the moment the infected person stops taking their medication, the virus will start replicating, and the person will eventually develop AIDS.
The sooner the infected person starts ART, the better. ART is more effective in early infections, so knowing your HIV status via same-day STD testing from Rapid STD Testing can be essential to keeping you and your partner safe.
Two methods could possibly get rid of HIV. The first relies on removing the virus from a person’s body (a cure), while the second relies on removing the virus from existence (eradication).
A cure for HIV would mean that a person could undergo a treatment, after which they would not experience the symptoms of HIV and could not transmit the virus to anyone else. The reason why ART isn’t a cure is that if a person stops taking the treatment, they are almost certain to see a rise in their HIV viral load and are likely to develop AIDS.
The term “cure” can mean different things, depending on whom you ask. A functional cure is when the infected person’s viral load is undetectable, though some viral particles remain in the body. A sterilized cure is when the person no longer carries any trace of HIV, either as a latent infection or at undetectable levels.
Any HIV cure needs to target active viral particles and latent cells to prevent the possibility of remission after the treatment.
Eradication is removing a virus from circulation completely, rendering further infections impossible. To date, smallpox is the only successfully eradicated virus—the WHO recorded the last known case in Somalia in 1977 and declared the virus eradicated in 1980.
The United Nations Programme on HIV/AIDS (UNAIDS) aims to reach zero new HIV infections by 2030. While not explicitly an eradication campaign, preventing new infections can eradicate a disease within a generation. While UNAIDS believes that antiretroviral treatments are an important part of the eradication strategy, it focuses on prevention and protection by addressing gender-based violence, providing access to HIV combination protection for vulnerable groups, and helping individuals know their HIV status.
Knowing your HIV status ensures that you can take the necessary precaution to prevent further transmission. Rapid STD Testing offers a 10-panel STD test that detects HIV and several other sexually transmitted diseases.
While anti-retroviral drugs are an effective management tool for HIV infections, they do not represent a cure. Current research aims to cure HIV using one of two broad strategies: removing the latent HIV reservoir and finding an effective vaccine.
Any effective HIV cure must remove any active HIV particles while also cleaning out HIV reservoirs. While ARTs are excellent at removing active HIV, researchers are still trying to find novel ways of removing HIV from its reservoirs.
Currently, most latency-reversing agents work on the “prime, shock, kill” mechanism. This approach works by waking up latent virus particles and killing the cells harboring the virus. By doing so, the treatment reduces the number of latent cells while also killing the virus without doing additional harm to cells around it.
A promising class of latency-reversing agents is histone deacetylase inhibitors. HDAC inhibitors target the mechanism by which HIV switches off active particle production. By turning this mechanism on, the cell starts producing HIV particles, making it vulnerable to targeted therapies that kill HIV-infected cells.
While the current generation of LRAs is toxic and requires careful dosing, scientists are starting to produce safer and more effective compounds, bringing us one step closer to an HIV cure.
Vaccines work by speeding up the immune system’s natural function. Vaccines help the body develop antibodies against a specific virus or family of viruses, which the immune system can use to target and kill cells with receptors that bind to those antibodies. Once the immune system clears an infection, it will still have B cells that “remember” the virus and can produce antibodies on demand, which is why many vaccines offer long-term immunity.
However, the fact that HIV attacks the immune system, its rapid mutation rate, and HIV latency all present large obstacles to developing a vaccine. Some viruses are susceptible to the production of a single antibody, but an effective immune response against HIV requires targeting T cells to produce specific effects while also targeting the innate immune system. To date, only one clinical trial in Thailand has shown any effectiveness against HIV, though several new trials based on the Thai trial are currently ongoing.
Some researchers are still working toward developing an effective vaccine, using complex strategies such as broadly-neutralizing antibodies that target multiple HIV strains, adjuvants to increase the efficacy of vaccine agents, and new viral vectors that may enhance antibody production.
The fact that HIV/AIDS has substantially decreased in the public consciousness proves that the decades of research into HIV treatment have delivered some results. While antiretroviral drugs aren’t a cure, they offer the chance of a normal, healthy life for millions of people across the globe. Combined with the development of a rapid STD test and early treatment interventions, an HIV-positive diagnosis is no longer a death sentence.
While an effective HIV cure is probably years away, there are some reported cases of HIV remission or complete cure. Unfortunately, despite multiple efforts, scientists have been unable to replicate many of these instances, largely due to the dangers and ethical concerns in reproducing these conditions.
The first extensively studied case of complete cure occurred in 2006. An HIV-positive individual, Timothy Ray Brown, underwent a stem-cell transplant to treat his leukemia. He needed to stop his ART during the treatment, but despite this, he had undetectable HIV loads following the stem-cell transplant.
Scientists speculate that his pre-treatment ART removed all active HIV particles in his body, while the stem-cell transplant removed all his latent HIV-infected T cells. The new stem cells he received were HIV-resistant due to a lack of CCR5 receptors (which HIV uses to recognize and enter cells), leading to a total elimination of HIV from the body.
A similar case occurred in 2019, when an HIV-positive man received an HIV-resistant stem cell transplant as a Hodgkin lymphoma treatment. The patient stopped antiretroviral treatment 16 months after the transplant but did not experience a viral rebound for 30 months after stopping treatment.
While these cases may represent a potential mechanism for curing HIV, ethical concerns prevent the widespread adoption of stem-cell transplants as a treatment. Stem cell transplants are risky procedures with prolonged recovery times that doctors only use in extreme cases of certain cancers. This risk makes stem cell transplantation an inadequate treatment for HIV-positive individuals without cancer.
Several treatment combinations for the HIV reservoir have produced long-term remissions, leaving patients with undetectable HIV levels for multiple months after ceasing ART. While not official cures, these remissions represent notable breakthroughs to a successful HIV cure.
For instance, a small-scale Brazilian trial produced undetectable HIV levels in one of the participants for a year and a half after stopping treatment. Unfortunately, the other four trial participants experienced HIV rebound despite following the same treatment.
The best-known case of long-term remission comes from Mississippi. A baby born with HIV received antiretroviral treatment for 18 months after birth. The mother then failed to attend the clinic for several months, effectively stopping the ART for herself and the child. The mother subsequently returned to the clinic, where the baby tested negative for HIV DNA. The baby had an undetectable viral load for 27 months before HIV levels rebounded.
While researchers are making great leaps in finding a cure for HIV, many believe the focus should be reducing transmission rates and eradicating the virus. Knowing your HIV status is your responsibility and can help save your life.
If you’ve recently had unsafe sex or are experiencing symptoms of acute HIV infection or any other STD, don’t hesitate to order an STD kit from Rapid STD testing or visit your local testing center today.