Full Circle Moments: Activism and Advancements in HIV Medications

In 2021, the Joint United Nations Programme on HIV/AIDS set a goal of ending AIDS as a public health threat by 2030. For years, activists advocated for quicker development of HIV medications, and their work influenced Food and Drug Administration (FDA) policies that remain in place today. Now, four years away from 2030, emerging HIV therapies are bringing the world closer to that goal. 

HIV in the Human Body

HIV stands for Human Immunodeficiency Virus, which causes a chronic viral infection that can impact people of all sexes, ages, sexual orientations, and races. HIV is a notoriously tricky virus, with a complex multi-step lifecycle. In the human body, the HIV lifecycle starts with the virus binding to and fusing with a human immune cell. Within the cell, HIV can convert its own genetic material into HIV DNA, which can then enter the cell’s nucleus. Inside the nucleus, HIV will incorporate its DNA into the cell’s DNA, allowing it to replicate and create HIV proteins. These proteins are assembled into immature HIV, which is later activated to create mature HIV. The progressive replication of HIV inside the immune cell damages the cell, leading to a weakened immune system, making it harder for the body to fight infection. Thankfully, medication advancements have significantly changed the outlook on HIV management.

How Antiretroviral Therapy Works

The HIV viral lifecycle has many steps, giving scientists multiple targets when creating treatments. HIV medications focus on blocking different steps of the lifecycle to prevent replication and disease progression. The first antiretroviral medication was called zidovudine, approved for use in 1987. Historically, early HIV medications, like zidovudine, were single-drug therapies with only one active ingredient, an approach that increased risk of drug resistance and toxicity. To overcome this, in the mid-1990’s, doctors and researchers started testing how multiple types of HIV medications could be used together, each targeting different stages of the viral lifecycle. This revolutionary practice is called antiretroviral therapy (ART) and is still used today. Modern ART standard of care includes at least two active ingredients focused on different targets in the HIV lifecycle. When used properly, individuals with HIV on ART can reach undetectable levels of HIV, known as viral suppression. While people with undetectable levels still have an HIV infection, they are not at risk of transmitting HIV to others and can have significantly improved health outcomes compared to those with untreated HIV.

Evolution of Antiretroviral Therapies

ART has expanded considerably in recent history, with over 30 antiretroviral drugs currently available. Tablet formats were initially the most common for these medications. Given the need to take different types of antiretrovirals simultaneously, multi-pill regimens were commonplace in earlier treatments. Having to take multiple medications daily can be difficult due to challenges managing prescriptions or costs, which leads many people to stop taking their medications. To reduce this burden, single-tablet regimens (STRs) that include multiple active ingredients entered the market in 2006. Each STR is a complete ART regimen including multiple active ingredients so users can take one combined tablet for HIV treatment. 

Beyond pill formats, the FDA approved the first long-acting injectable HIV regimen, Cabenuva, in 2021. Cabenuva is a complete ART meant to be administered monthly, replacing the need for a daily pill. 

Another injectable drug, Lenacapavir, has also recently entered the market. Lenacapavir is a long-acting medication that uses a capsid inhibition mechanism, offering six months of protection. However, Lenacapavir is not a complete ART, given that it contains only one active ingredient and must be used in combination with another type of antiretroviral medication (pill or injectable) for HIV treatment. As part of a full ART protocol, using Lenacapavir or similar long-acting injectables may space out required provider visits and improve patient medication adherence. Feedback about injectable medication options has been positive from people living with HIV, but further research is needed to follow uptake and usage rates. 

As of 2012, antiretroviral medications are also being used to prevent new HIV infections. Called pre-exposure prophylaxis (PrEP), HIV-negative individuals who are at a higher risk of contracting HIV can be prescribed an antiretroviral medication to reduce their risk of contracting HIV. Typically PrEP, unlike HIV treatment, only requires one type of active ingredient. Many PrEP options are a single daily pill, however injectable medications coming to the market are being considered as PrEP options. In fact, Lenacapavir has been approved as the first long acting injectable PrEP that can give up to 6 months of protection. These innovative kinds of HIV drug development will continue accelerating advancements in both prevention and treatment.

How HIV Activists Changed the FDA

The progression of HIV medications occurred rapidly over the last few decades. Norma Rolfsen, HIV Care Program Director and a Family Nurse Practitioner at the Michael Reese Research and Education Foundation in Chicago, has focused her career on caring for people living with HIV. Rolfsen says that HIV medications were expedited due to HIV activists protesting FDA delays in approving emergent therapies. Prior to antiretroviral medications, there were no treatments for HIV, so fast-paced research and medication approval were essential to save lives. Through lobbying, sit-ins, disrupted news broadcasts, and other demonstrations, activists in the late 1980s successfully pushed the FDA to accelerate drug approvals, paved the way for expanded access, and advanced regulatory guidance for investigational new drugs. This activism expedited experimental medications for individuals with HIV, leading to the progressive work seen in the field today.

Rolfsen notes that the general public has continued to benefit from these regulatory changes, including during the COVID-19 pandemic. During the pandemic, Expanded Access programs were used for compassionate drug use in treating COVID-19. Related to this, experimental HIV vaccine design approaches heavily influenced the SARS-CoV-2 mRNA-based vaccine. Years later, the efforts of HIV activists have continued to impact FDA functions and the development of medications in the US, showcasing the power of the public voice for advancing healthcare.