Acquired immunodeficiency syndrome (AIDS) has always been known as an incurable and deadly disease. The virus that causes AIDS is the human immunodeficiency virus (HIV).
HIV affects the immune system, making the infected person susceptible to other infections and illnesses. Flu-like symptoms in the early stages are common, which include fatigue, fever, sore throat, and chills.
In the later stages, people may also develop more serious infections such as pneumonia or tuberculosis. If left untreated, this will ultimately lead to death.¹ ² ³
HIV can be found in the blood, semen, and other body fluids of infected people. It spreads through contact with these body fluids, such as during unprotected sex or sharing needles.
It remains a serious global health problem as about 18,000+ people in the US died from AIDs-related illnesses in 2020, and it claimed the lives of 690,000 people worldwide in 2021.⁴ ⁵
Despite medical advances over the decades, HIV still continues to claim many lives partly because it's a difficult virus to battle. For one, it mutates quickly, which makes it hard for medications to keep up. In addition, HIV hides in cellular reservoirs throughout the body — meaning that it can infect an immune cell but stay dormant for years. This makes it difficult for the immune system to find and fully destroy every virus strain.⁶ ⁷
For many people living with HIV, the search for a cure can feel like a never-ending struggle. It can nowadays be managed as a chronic illness by taking medication every day to prevent an HIV infection from progressing to AIDS. The advances in taking daily antiretroviral medication mean that there is no difference in overall life expectancy in a person living with HIV in comparison to an HIV-negative person. But finding a cure to eradicate the virus from an infected person completely has eluded scientists for decades.⁸
However, all this may be changing soon with a novel HIV treatment that's been successful in a single patient.
In 2022, a group of researchers reported at the Conference on Retroviruses and Opportunistic Infections that a form of stem cell transplant using umbilical cord blood was effective in treating HIV in an American, mixed-race woman who also has leukemia. She was deemed cured after being free from the HIV virus for 14 months, and she's also been free from leukemia for four years.⁹
This marks a significant milestone in the journey of finding an HIV cure, as previous stem cell-based therapies (bone marrow transplants) had limited success. It's a painful and expensive procedure, and finding a matching donor is difficult. Only three other people have been cured of HIV using bone marrow transplants so far.
The first man was called "the Berlin patient," who was diagnosed with both acute myeloid leukemia and HIV. He received a bone marrow transplant in 2007 and was in HIV remission for 12 years. All other patients also had HIV along with different types of blood cancer.¹⁰ ¹¹
To understand how the latest cord blood transplant was effective in curing HIV, we need to understand a little bit more about how HIV affects the immune system first.
The body's immune system is a complex network of cells and organs that work together to protect the body from infections.
One important part of the immune system is white blood cells. They're produced in the bone marrow and circulate through the body in the blood. When an infection occurs, white blood cells are one of the first lines of defense. They travel to the site of infection and work to destroy the invading microorganisms.¹²
HIV attacks the body's immune system by targeting a specific type of white blood cell called a CD4 cell.¹³
When HIV infects a CD4 cell, it takes over the cell and uses it to produce more copies of the virus. When the infected cell is killed by the virus, it spreads to other CD4 cells to repeat the copying process. The body will try its best to keep making more CD4 cells. But there will come a point where it can't keep up with replacing the dead cells.
Eventually, HIV will destroy so many CD4 cells that the body is unable to effectively fight off infections, leading to AIDS.
Umbilical cord blood transplants (which have been used to treat a wide variety of blood disorders) fight off HIV by introducing healthy stem cells into the affected person's bloodstream.
The medical treatment uses stem cells from a baby’s umbilical cord, which are "immature" when compared to bone marrow stem cells. So when they're introduced into a recipient's bloodstream, they can adapt to the person to make more healthy cells. This reduces the chances of "graft versus host disease," where the recipient's body rejects the new cells.¹⁴ ¹⁵
Umbilical cord blood transplants for HIV also overcame many other challenges associated with bone marrow transplants. It's easier to find a compatible donor between unrelated people, more readily obtained, and has a lower rejection risk from recipients.
For this latest case of HIV remission, the researchers used a specific type of stem cell treatment called a haplo-cord transplant, where two sets of stem cells (an unrelated and related donor) were combined and transplanted into the recipient.¹⁶
The unrelated donor had HIV-resistant cord blood cells (with the CCR5-delta 32 mutation), which serves as the key component in curing HIV.
The CCR5-delta 32 genetic mutation results in structural changes to the CCR5 receptors on the outside of the cell. These receptors are essentially a gateway through which HIV viruses pass through to infiltrate the cell. The mutation changes the shape of this gateway so that the virus can no longer enter.
People who inherit two copies of this mutation (one from each parent) are resistant to HIV infection. About 1% of people of Northern European descent have immunity to HIV because of this mutation. This specific mutation has not yet been found in those of African or East Asian descent.
It's still a mystery as to why the mutation is only found in specific races, but scientists have discovered that it's been around a lot longer than HIV infections began.¹⁷
By introducing these HIV-resistant cells into a recipient's body, the virus no longer has a chance to enter any cells to enter and replicate.
This advance in medical science is giving hope to those living with HIV — which remains in the millions.
The World Health Organization (WHO) estimates that around 38.4 million people globally were living with HIV in 2021, with two-thirds (25.6 million) of them being in the WHO African Region. Approximately 1.2 million people in the US have HIV.¹⁸ ¹⁹
Over the years, the world has reached significant milestones in the fight against HIV. The WHO's "3 by 5" initiative managed to increase the number of people with access to HIV treatment by 15 times. In 2017, 75% of people living with HIV were able to access testing.²⁰
However, socioeconomic inequalities continue to fuel the spread of the virus. Adolescent girls and young women in the sub-Saharan African region are twice as likely to get infected with HIV compared to males of the same age. Other at-risk populations include gay men, sex workers, transgender people, those who inject drugs, and people in prison. The chances of transgender women getting affected by HIV is 49 times more compared to other adults.²¹
A lack of awareness about the importance of early diagnosis and treatment, stigma, and discrimination are also significant barriers preventing these vulnerable from receiving appropriate healthcare.
Unfortunately, the COVID-19 pandemic has also caused some setbacks.
As health efforts were concentrated on fighting COVID-19, prevention programs that involved the distribution of condoms and clean needles were delayed. HIV testing also dropped by 41% in 30 countries.²²
There have been calls to get the fight against HIV back on track if we were to reach our goal of AIDS eradication by 2030.
Could the latest cord blood transplant help us to achieve this sooner? It seems that it's not that simple.
While this latest discovery presents major advancement in HIV treatment, experts state that there are several hurdles to cross before it's hailed as the "holy grail" of HIV cures.
Firstly, we still need to observe the latest case to ensure that a longer-term rebound does not occur. If it happens, it could signal that the immunity is only temporary.
As all four cases of HIV stem-cell treatment were conducted in patients with cancer, more research is also needed to clarify whether cancer or associated chemotherapy had anything to do with HIV remission.
It's been recommended that the next stage of clinical trials should explore using cord blood transplants to treat those with HIV but without any cancer. But there's a significant issue stopping researchers from progressing in this direction. The procedure may also be considered too risky for HIV-positive patients without any other conditions.
Cord blood transplant is actually a highly toxic procedure with many side effects. HIV alone is not enough of a reason for clinicians to suggest stem cell treatment as the risks would still outweigh the benefits.²³ ²⁴
The future of cord blood transplant as an HIV treatment is still uncertain. So advancing other current HIV drug treatments is most likely where we'll see the most relevant strides in the near future.
At present, antiretroviral drugs continue to be the mainstay of HIV treatment, and it's had a long history of ups and downs in the fight against AIDS.
While there are many versions of antiretrovirals, they all generally work by preventing the HIV virus from replicating inside the body.²⁵
At present, there are five classes of antiretrovirals and 2–3 will usually be prescribed in combination for optimal effectiveness.²⁶ ²⁷
nucleoside reverse transcriptase inhibitors (NRTIs or 'nukes')
non-nucleoside reverse transcriptase inhibitors (NNRTIs or 'non-nukes')
Multiple antiretrovirals need to be taken together as they help to stop different pathways through which HIV multiplies.
For example, NRTIs block an enzyme that HIV requires to copy itself, while entry inhibitors stop the HIV virus from entering CD4 cells.
While antiretrovirals are not a cure for HIV, they can dramatically extend life expectancy and improve quality of life while also reducing the risk of transmitting HIV to others.
It's estimated that antiretrovirals have saved millions of lives over the past decade. But it still comes with several drawbacks.
First and foremost, antiretrovirals can cause a range of side effects, including nausea, fatigue, kidney damage, and diarrhea.
Additionally, these medications must be taken on a strict schedule in order to be effective, which can be difficult for some patients to manage. As antiretrovirals only suppress HIV replication (rather than curing the infection), patients must continue taking these medications for the rest of their lives. Failing to comply with the schedule could lead to a rebound of the HIV viral load.²⁸
Drug resistance is also on the rise as the virus continues to change genetically, which means that medications could prove to be less effective in the years to come. A 2021 report from the WHO states that almost 10% of people are already showing resistance to the NNRTI drugs.²⁹
Current research is focused on improving the current shortcomings of antiretrovirals. This includes creating new long-acting therapies that could be taken less frequently, and the possibility of a therapeutic HIV vaccine.³⁰
Long-acting therapies could be taken much less often (potentially just once a week or month), making it easier for people to stay on treatment and increasing the chances of viral suppression. This could be in the form of pills or alternative administration methods like injections or patches.
Researchers are also exploring the use of antibodies as a long-acting treatment for HIV, as they have fewer side effects and can last in the body for longer periods.
Clinical trials for a therapeutic HIV vaccine have also begun. But in contrast to traditional vaccines that are designed to prevent infection, therapeutic vaccines help to treat people who are already infected with HIV. Early results indicate that therapeutic HIV vaccines are effective in controlling viral load when patients temporarily stop taking antiretroviral medications.⁷ ³¹
The latest case of HIV being cured through a cord blood transplant in a woman who also had leukemia is a significant victory in the fight against HIV/AIDS.
However, using it as a widespread treatment option in the near future seems unlikely, as cord blood transplants can be highly toxic.
Humanity's best bet in containing the virus in the years to come will likely be from advancements in the current treatments being used (antiretroviral drugs) while simultaneously addressing socio-economic inequity that prevents specific populations from accessing testing and treatment.
There are still significant hurdles to cross. But thanks to the breakthroughs we've had over the past few decades, HIV is no longer the death sentence it once was.
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Dawn Teh is a health writer and former psychologist who enjoys exploring topics about the mind, body, and understanding what helps humans thrive.
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