Injectable HIV medications are superior to oral medications for patients who often skip doses

When a person is diagnosed with HIV, they are put on lifelong HIV treatment called antiretroviral therapy to control the virus. However, for many people, taking their medications every day can be difficult for a variety of reasons, leading to missed doses and poor health.

To address this issue, Jose Castillo-Mancilla, MD, PhD, a volunteer associate clinical professor in the Division of Infectious Diseases at the University of Colorado, co-led a national clinical trial in 2014 with Aadia Rana, MD, PhD, a professor at the University of Alabama. Called Long-Acting Therapy to Improve Treatment Success in Daily Life (LATITUDE), the study examined whether a monthly injectable form of HIV medication was a better treatment option than taking a daily pill.

Nearly a decade later, interim data from the clinical trial showed what Castillo-Mancilla had long suspected: Long-acting antiretroviral therapy was superior to daily pills in suppressing HIV replication. In fact, its superiority was so great that the National Institutes of Health recommended that all study participants take long-acting drugs.

"To learn that our study results confirmed our hopes and that we were able to prove that this treatment strategy could help these patients was incredible," says Castillo-Mancilla. "I admit I shed a lot of tears of joy."

The Need for This Research Castillo-Mancilla has been interested in helping people with HIV since the late 1990s, when he was doing research at the National Cancer Institute in Mexico and saw very sick patients with advanced HIV.

For HIV patients, achieving viral suppression, also known as "undetectable," is important, he says. That means the patient has HIV under control and cannot transmit it to others.

"Controlling HIV is important to prevent progression from HIV to AIDS," he says. "Being undetectable is also important to prevent the development of drug resistance and other complications such as cardiovascular disease."

But to achieve this, it’s important to take your medication consistently, which can be a challenge for some. Up to 25% of people prescribed traditional antiretroviral therapy stop taking their medications at some point, the NIH said in 2019.

“Sticking to lifelong treatment is a very challenging task, even for the most committed patients,” says Castillo-Mancilla. “Many of our patients face competing priorities that make it difficult to take their pills every day. This includes barriers such as employment, child care, transportation, stigma, active mental illness or substance use, and others.”

Designing a study that focused on a patient population that has difficulty taking daily medications was important because traditionally such patients have not been included in clinical trials, despite the fact that they represent a vulnerable group for whom available treatment options do not work.

"Given that one-third of people living with HIV in the United States have trouble maintaining viral suppression," he says, "identifying new, successful strategies to help these patients could be critical in our efforts to end the HIV epidemic."

The Making of LATITUDE Castillo-Mancilla worked with Rana to conceptualize the LATITUDE study in 2014, when long-acting HIV therapy was still being developed. They wanted to see if two injectable forms of long-acting antiretroviral therapy—specifically the drugs rilpivirine and cabotegravir, which are injected every four weeks—would help people with HIV who have difficulty taking their daily medications become undetectable and stay that way.

Together with their research team, Castillo-Mancilla and Rana wrote proposals that were submitted to Advancing Clinical Therapeutics Globally (ACTG), formerly known as the AIDS Clinical Trials Group. They were able to create a study protocol and a partnership with ViiV Healthcare, which provided the study drug.

Through extensive work and collaboration, an open-label clinical trial has begun, involving 31 sites across the country, including Puerto Rico, and recruiting nearly 350 volunteers. Castillo-Mancilla co-led the study with Rana until he joined ViiV Healthcare in 2023.

How interim data changed the study The LATITUDE study was broken down into several phases. Initially, as part of phase 2, participants were to continue taking their standard oral HIV drugs or switch to longer-acting drugs.

However, interim data from a randomized trial showed that long-acting antiretroviral therapy was superior in suppressing HIV replication compared with daily pills.

Based on these interim data, in February of this year, the National Institutes of Health recommended stopping randomization and offering all eligible study participants long-acting therapy. The NIH accepted this recommendation, meaning that Phase 2 of the study was stopped and participants were no longer randomized; instead, all eligible participants were offered long-acting therapy.

"The fact that phase 2 was stopped doesn't mean the study was stopped. It just means that every participant in the study is now being offered long-term therapy," says Castillo-Mancilla. "In fact, the study has a phase 3, which lasts 48 weeks, to assess the durability of the treatment strategy."

After completing Phase 3 and ending their participation in the study, participants can decide with their doctor whether they want to continue receiving long-acting injectable therapy or not.

"If they decide to continue this therapy, they can receive it through their regular clinical care rather than as study participants," he says.

Looking Ahead Given the positive results of the clinical trial, the research team now aims to complete the study and disseminate the results to the medical community so that patients can benefit, says Castillo-Mancilla.

"The key message for the medical community is that we have new treatment strategies for our patients who face barriers to adherence and are unable to take their daily medications," he says.

He wants HIV patients to know that this is a new option that can help them achieve viral suppression, a state of "undetectable" so they can live longer, healthier lives. It's what he hoped for nearly a decade ago when the study began.

"This clinical trial has been my life for the last 10 years. It has allowed me to meet and work with incredible colleagues and friends like Dr. Rana and colleagues at ACTG and ViiV Healthcare," says Castillo-Mancilla. "Most importantly, it has allowed us to contribute to the fight to end the HIV epidemic."

The results of the work are described in detail in an article published in Clinicaltrials.