For the past four decades, HIV has been a major global public health issue. Worldwide, more than 40 million people have died from the disease. Since then, scientists have worked toward effective treatments, vaccines, and a cure. So far, there has only been one effective treatment that stops the virus's progression.

Despite the seriousness of the disease, people with HIV can live long, healthy lives. However, they have to make sure they take medication daily. They also need to stay up to date with vaccines since HIV increases the risk of infections.

A handful of people have been cured, but there isn't a broad cure for HIV yet. Scientists believe a cure is possible, and research is getting them one step closer to developing one.

What treatments currently exist for HIV?

HIV treatment involves medicines called antiretroviral therapy (ART) that work to control the virus. It is recommended for everyone with HIV. ART should be started as soon as possible after an HIV diagnosis. Some people even start it the same day they are diagnosed.

The Food and Drug Administration (FDA) approved the use of azidothymidine (AZT) in 1987. AZT belongs to a class of drugs called nucleoside reverse transcriptase inhibitors (NRTIs). It prevents HIV from making new copies of itself. AZT was developed as a potential cancer therapy in 1964. It was shelved at the time because it wasn't effective. AZT was included in a screening program to identify drugs to treat HIV/AIDS in the 1980s. Although it decreased deaths and opportunistic infections, it had severe side effects.

The FDA approved more NRTIs for HIV treatment in the early 1990s. But single-drug treatments had limitations. HIV developed a resistance that made single-drug treatments ineffective. Combining drugs made it more difficult for HIV to develop a resistance. AZT and an NRTI called dideoxycytidine were more effective than AZT by itself, but the effects didn’t last long. Researchers soon discovered that a triple-drug therapy might be more effective.

The early days of triple-drug therapy were complicated. Patients often had trouble sticking to their medication regimen. But now, many patients can take one pill once a day to control their HIV. There are over 30 antiretroviral drugs currently available. 

What are the challenges of finding a cure for HIV?

Although there has been a massive global effort to find a cure for HIV, scientists face several challenges. HIV hides in the genome of some of the body’s immune cells. It escapes detection by remaining inactive in tissue that supports immune responses. Since the cells are not circulating in the blood, ARTs cannot eliminate them. However, the cells can become active at any time. HIV also attacks Helper T cells that support the functioning of a healthy immune system. HIV reduces the number of functional T cells and ruptures the cellular membrane, which kills the cells.

Have there been recent advances in HIV research?

Researchers have learned a lot about HIV over the years and are still making discoveries. In 2022, scientists at Northwestern Medicine used a CRISPR gene-editing approach to identify genes that were important for HIV infection in the blood. They found 86 genes that may play a role in how HIV makes new copies of itself and causes disease. More than half the genes were never examined from an HIV viewpoint. Gene editing allows scientists to change an organism’s DNA. They can add, remove, or alter genetic materials.

The FDA approved using a long-acting injectable ART called lenacapavir for HIV treatment in 2022. It works differently from other HIV treatments and can be used against resistant HIV. 

In 2016, UCLA researchers found that an immunotherapy used to treat cancer could also be used against HIV. Certain antibodies could generate chimeric antigen receptors (CARs) that kill HIV cells infected with HIV. CARs are artificially created immune T cells that target and kill cells containing viruses or tumor proteins. The researchers reprogrammed the CAR cells to kill HIV-infected cells.

What’s next for HIV research?

Scientists are constantly making discoveries that may lead them to an HIV cure. New research offers insights into why at least five people were cured of HIV after receiving a stem cell transplant.

A study conducted by researchers at Oregon Health & Science University described how macaques were cured of the monkey form of HIV after receiving a stem cell transplant. Eight macaques had HIV, and four received a stem cell transplant from HIV-negative donors. The other four did not receive transplants. Two of the macaques that received transplants were cured of HIV.

The researchers found that two circumstances must co-exist for a cure to occur. First, transplanted donor stem cells help kill HIV-infected cells by recognizing them as foreign invaders. Second, in the macaques that received transplants but were not cured, HIV “jumped” into the donor cells. The virus infected donor cells while they were attacking HIV. Researchers realized that HIV must be stopped from using a certain protein to infect donor cells. That knowledge can help scientists evaluate the effectiveness of potential HIV cures down the line.

Although HIV is no longer a death sentence, it is still a serious disease. Treatment options have evolved over the years, but a cure is still the ultimate goal for the 38 million people living with HIV.

Resource Links:

• “HIV” via World Health Organization
• “Antiretroviral Drug Discovery and Development” via National Institute of Allergy and Infectious Diseases
• “Why Is It So Difficult to Find an HIV Cure?” via American Gene Technologies
• “CRISPR and HIV: New technique in human blood unveils potential paths toward cure” via Northwestern Medicine
• “OHSU research offers clues for potential widespread HIV cure in people” via Oregon Health & Science University
• “Cancer-fighting gene immunotherapy shows promise as possible treatment for HIV” via UCLA Health
• “Lenacapavir” via HIV Info