A cure for HIV: Where do we stand?

HIV is a retrovirus that targets the immune system and, if untreated, can cause AIDS. It is spread by bodily fluids such as blood, semen, vaginal fluids, rectal fluids and breast milk from an individual with a detectable viral load. The virus attacks the immune system by destroying the CD4+ T cells (which protect the body from infection). In 2023, almost 39m people were living with HIV. Nearly 39m individuals worldwide were HIV positive in 2023. Once infected, there is no complete cure for the virus; hence, eradicating it is impossible. Antiretroviral therapy, or ART, is a more recent treatment option. When taken as directed, it can help people live happy, healthy lives by lowering the blood virus load and preventing transmission. It is an epidemic in the world, and WHO (World Health Organization), the Global Fund and UNAIDS are aligned with the Sustainable Development Goal target of ending the HIV epidemic by 2030.

The first case of AIDS in Nepal was reported in 1988. However, the ART service started in 2004 at Sukraraj Tropical and Infectious Disease Hospital, Kathmandu. ART service is free of charge for people living with HIV in various centers in Nepal. Almost 80 ART sites are present in Nepal to provide free services and control infections. According to UNAIDS 2023 Nepal data, the new HIV infection decreased from 2100 (all age groups) in 2010 to less than 500 in 2022.

Notably, AIDS-related deaths declined from 1,700 in 2010 to less than 500 in 2022. People living with HIV who knew their status were 92 percent, and those who were on treatment were 78 percent. Today, people without HIV can take pre-exposure prophylaxis (PrEP) to prevent HIV. It’s a strategy where you can take a daily dose of HIV medication and reduce your risk of getting HIV by 99 percent. Apretude is a new PrEP option that does not need to be taken daily. It is injected every two months to the uninfected partners, significantly reducing the infection.

While we witnessed Covid-19 vaccines being developed within months, creating a vaccine against HIV is challenging due to the unique nature of the virus. The HIV virus mutates rapidly, making it difficult to develop a vaccine that can effectively target all its variations. Almost 250 HIV vaccine trials have been done, but none proved promising. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institute of Health, had launched three mRNA vaccine phase 1 trials. The trial was completed in July 2023. Recently, researchers at the Duke Human Vaccine Institute have successfully induced broadly neutralizing antibodies (which can recognize and block different versions of the virus) against HIV through vaccination for the first time. 

The neutralizing antibodies were produced within weeks, which usually takes years following a natural HIV infection. The phase 1 trial had to be halted due to a non-life-threatening allergy in one of the participants due to additives. Dr Barton F Haynes, director of the Duke Human Vaccine Institute, said, “We are not there yet, but the way is much clearer.” Dr Julie McElrath, the director of the vaccine and infectious disease division at the Fred Hutchinson Cancer Center in Seattle, said, “An effective vaccine is the only way to provide long-term immunity against HIV, and that’s what we need.” As of now, there is no vaccine for HIV, and even after 20 years of failure in HIV vaccine development, there is still hope for one.

In March 2024, news about successfully eliminating HIV using CRISPR-Cas gene editing technology (Nobel Prize in Chemistry, 2020) was circulated. 

CRISPR-Cas is an adaptive immune system found in most bacteria and prevents them from infection by viruses and other foreign genetic elements. Functioning like molecular scissors with the supervision of guide RNA (gRNA), CRISPR-Cas9 can cut DNA at assigned spots, which leads to either the deletion of unwanted genes or the addition of new genetic material into an organism’s cell, paving the way for advanced therapy. The research was only able to eliminate HIV from the infected cells in the laboratory and was not done on humans. However, if this technology can be successfully applied to humans, it could potentially provide a cure for HIV. In 2018, Dr He Jiankui announced the birth of two genetically engineered babies (Lulu and Nana) using the CRISPR Cas9 technology to make them HIV-resistant. 

He Jiankui, a professor at the Southern University of Science and Technology, claims to have disabled the gene for HIV entry into healthy cells. Despite the groundbreaking achievement, serious ethical concerns about using CRISPR remain.

We often hear that there’s no cure for HIV, but at the same time, we also hear about cases where people have been cured of HIV or are in long-term remission. These cases usually involve stem cell transplantation, which was initially done to treat cancer. Stem cell transplantation involves replacing the patient’s immune system with a new one that is resistant to HIV. The primary goal of the transplant is not to cure HIV because the procedure is risky and not suitable for everyone. However, it has shown promising results in some cases. Stem cell transplants replace cancerous cells with healthy stem cells responsible for creating blood, bone and muscle cells.

In this process, HIV can go into a latent stage and remain undetectable. A recent study published in the journal ‘Emerging Microbes and Infections’ found that HIV-virus-like particles (HLP) are 100 times more effective for people living with chronic HIV under cART. If this method is successful in clinical trials, it could potentially help millions of people to be free from HIV. HLP are inactivated HIV particles that can boost immune responses without infecting the person.

Despite extensive research, a cure for HIV remains elusive. Laboratories are continuing their research, exploring various methods in hopes of finding a cure. Currently, the primary treatment for HIV is combined antiretroviral therapy (cART), which involves taking a combination of drugs orally daily. While this regimen does not offer a cure, it has proven effective in reducing viral load and maintaining a healthy immune system. According to the most recent data from the World Health Organization (WHO), 76 percent of people living with HIV were accessing antiretroviral therapy in 2022, a significant increase from 27 percent in 2010. Additionally, in 2021, the FDA approved injectable drugs called Cabenuva and Vocabria for HIV treatment. Administered once a month via intramuscular injection, these drugs offer a more convenient alternative to daily oral medication. 

Considering that prevention is better than cure, taking preventive measures at a personal level can also play a crucial role in stopping the transmission of HIV. This can include using internal or external condoms, avoiding needle sharing, avoiding breastfeeding if you are HIV positive, and utilizing post-exposure precautions if you have been exposed to HIV.

The author is working in a virology lab focusing on HIV drug resistance