Long-acting injectable antiretroviral therapy improves treatment outcomes in individuals with HIV type 1 (HIV 1) who face adherence challenges, thereby addressing a persistent barrier in routine clinical care. 

In 2021, the US Food and Drug Administration approved an injectable combination of cabotegravir and rilpivirine for the treatment of HIV 1 in individuals with a suppressed viral load, administered monthly or every 2 months. Phase 3 clinical trials that supported this approval largely excluded individuals with active viremia or difficulty adhering to oral therapy, leaving a clinically relevant population without evidence. The LATITUDE study evaluated the safety and efficacy of this regimen compared with daily oral therapy in individuals with adherence challenges in the US.

Adherence to antiretroviral therapy remains central to treatment success. Current regimens, typically single-pill daily combinations, have transformed HIV into a manageable chronic condition with reduced mortality and transmission. Their effectiveness depends on adherence rates exceeding 95%, which remains difficult to sustain in many populations.

Nonadherence reflects more than individual behavior. Social and structural determinants play a critical role. The World Health Organization described five dimensions that influence adherence: socioeconomic, patient-related, clinical, therapeutic, and healthcare system factors. These include education level, which affects the understanding of treatment; income level, which influences access to transportation, food, and healthcare; and working conditions, which may limit consistent access to care. Stigma remains an additional barrier.

Global Gaps

Globally, adherence to antiretroviral therapy remains variable. In 2024, treatment access reached approximately 77%; however, adherence rates ranged from 20% to 93.8% across studies. These differences reflect disparities in access to healthcare and social conditions, limiting the full impact of therapeutic advances.

Trial Findings

The LATITUDE trial evaluated a monthly injectable strategy in 453 people with HIV in the US who had adherence difficulties. This population had a high prevalence of vulnerability factors, including low income, substance use, and housing instability.

The study included two phases. During the first phase, all participants received standard oral treatment with intensive support to improve adherence. Individuals who achieved viral suppression were then randomly assigned to either continue oral treatment or switch to injectable treatment.

After a mean follow-up of 48 weeks, injectable treatment demonstrated superiority. The treatment failure rate was lower in the injectable group than in the oral group (22.8% vs 41.2%), with a difference of -18.4 percentage points (98.4% CI, -32.4 to -4.3; P = .002). Virologic failure occurred less often with injectable therapy (6 vs 34 cases).

These findings showed that, in settings in which adherence is compromised, injectable treatment improved outcomes compared with oral regimens.

Luis Buzón, MD, specialist in infectious diseases, internal medicine, and microbiology at the Hospital Universitario de Burgos and spokesperson for the Spanish Society of Infectious Diseases and Clinical Microbiology, stated that "in scenarios in which adherence is compromised by social, psychiatric, or substance use factors, injectable treatment appeared clearly superior to oral treatment. This evidence challenged the previous assumption that daily oral regimens represented the highest standard."

Practice Shift

The LATITUDE study addressed a population often excluded from clinical trials: individuals with real-world adherence challenges. The results support the adaptation of treatment strategies to living conditions rather than relying solely on ideal clinical criteria.

These implications extend beyond the individual outcomes. Buzón noted that "Studies based on mathematical models suggested that broader use of injectable treatments may reduce HIV transmission more effectively compared with oral treatment, introducing a relevant public health dimension."

Injectable treatment eliminates the need for daily medication, supports structured clinical follow-up, and improves adherence. It is also associated with improved quality of life, including reduced stigma, greater privacy, and improved convenience.

Real-world data supported these findings. In Spain, the RELATIVITY cohort, which included thousands of individuals receiving cabotegravir and rilpivirine, reported adherence rates close to 98%, reinforcing its effectiveness outside controlled trial settings.

Buzón added that "in Spain, thousands of individuals are already receiving cabotegravir and rilpivirine, representing approximately 10% of those on antiretroviral therapy. Development of regimens administered every 4 or even 6 months may further expand impact in the coming years."

Overall, the LATITUDE study not only confirmed an effective therapeutic alternative but also drives a structural change in the approach to HIV, especially in vulnerable populations. Its implementation could become a key tool for improving adherence and advancing global control of the epidemic.

Conflicts of interest of the authors are available in the original article.

This story was translated from Univadis Spain, part of the Medscape Professional Network.