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CROI 2024 Inclusivity in LA ART and LA PrEP
Inclusivity in Studies of LA ART and LA PrEP: Implications From CROI 2024 for Western Europe

Released: March 20, 2024

Expiration: March 19, 2025

Cristina Mussini
Cristina Mussini, MD
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Key Takeaways
  • A gender-targeted approach to clinical trial inclusion is urgently needed to rectify the lack of transgender and nonbinary representation in clinical trials of long-acting (LA) injectable antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP).
  • Although many people living with HIV find LA ART preferable to oral ART, one study demonstrated lower acceptability of LA ART among Black people vs White people, which could indicate treatment access inequity.
  • A study of LA cabotegravir plus rilpivirine in adolescents, many of whom acquired HIV via vertical transmission, demonstrated that this therapy is safe, tolerable, and effective in this population.

A major limitation of clinical trials of long-acting (LA) injectable agents for HIV treatment and prevention has always been the lack of diversity among enrolled patients. The demographics of enrolled patients are often not an accurate reflection of the global diversity of people at risk for and living with HIV. I would like to highlight 3 studies presented at CROI 2024 on the use of LA pre-exposure prophylaxis (PrEP) and LA antiretroviral therapy (ART) in populations historically underrepresented in clinical trials.

Gender Inclusion in Clinical Studies of LA PrEP and LA ART
Lack of diversity in clinical trial enrollees was confirmed by a study conducted by the SHARE group (Abstract 620). Researchers evaluated published studies of either LA PrEP or LA ART to determine the extent to which cisgender or transgender women and nonbinary people were included in phase I-III clinical trials. The authors analyzed 41 studies—14 on LA PrEP and 27 on LA ART—and found that even though the proportion of female participants in HIV PrEP and treatment studies has significantly increased over time (98-fold in PrEP studies conducted since 2014, and 361-fold in treatment studies conducted since 2010), inclusion of females remained unacceptably low (20%) in HIV treatment studies conducted in 2022 and 2023. By contrast, gender-targeted PrEP studies have been effective at increasing the number of female participants included. Transgender individuals and nonbinary people are still greatly underrepresented in clinical trials of both LA PrEP and LA ART. The study authors concluded that a gender-targeted approach to inclusion in HIV prevention and treatment studies is urgently needed and long overdue.

Implementation of LA ART in the Community Setting
Another study (Abstract 621), conducted by the SHARE group, investigated implementation of LA ART in a real-world clinic setting comprising a study population representative of the global population of people living with HIV. This study enrolled 114 people living with HIV, of whom 55% were female, 51% were Black, 30% were White, 40% were older than 50 years of age, 68% identified as heterosexual, and 75% were employed. Participants received LA cabotegravir (CAB) + rilpivirine (RPV) in the clinic for 6 months and then were presented with the option to continue receiving the drug in the clinic or switch to receiving it in a community setting for Months 6-12.

At baseline and after 4 months, participants received 4 validated questionnaires to measure feasibility, acceptability, and appropriateness of the intervention, as well as HIV treatment satisfaction. Overall, participants reported that they found the LA injections increasingly feasible, appropriate, and satisfactory and preferred them to oral ART. However, prespecified subgroup analyses based on gender, race, and ethnicity revealed that the perception of treatment appropriateness and acceptability of receiving treatment in a community setting was significantly lower in Black participants compared with White participants. This difference in perception could signal a treatment inequity among Black vs White participants.

LA ART for Adolescents
The IMPAACT 2017/MOCHA study (Abstract 188) assessed LA CAB + RPV use in a population that has historically been excluded in clinical trials: adolescents. This study was needed as healthcare professionals and investigators alike know that reaching and treating this population can be challenging. The primary outcome was safety and tolerability of switching to LA CAB + RPV after 24 weeks of treatment. The study included 144 adolescents who were virologically suppressed on oral ART. The median age was 15 years, more than 50% of patients were female, 74% were Black, the median BMI was 19.5 kg/m2, and 92% of patients had acquired HIV via vertical transmission.

Treatment with LA CAB + RPV was well tolerated, with 35% of patients reporting injection-site reactions, most of which were mild and did not result in treatment discontinuation, and 86% spontaneously resolved within 7 days. Regarding pharmacokinetic data and virologic efficacy, CAB + RPV trough concentrations were comparable to those previously reported in adults: 97% of patients maintained virologic suppression (HIV-1 RNA <50 copies/mL), and at Week 24, there were no confirmed virologic failures (2 consecutive HIV-1 RNA ≥200 copies/mL). These results underscore how LA ART could be important and useful in this population, freeing individuals who were born with HIV from having to take oral ART every day during one of the most developmentally critical periods of their lives. This could vastly improve their quality of life and optimism for the future.

Conclusions
These 3 studies, taken together, reflect challenges and opportunities that we have encountered with LA PrEP and LA ART implementation in Western Europe, a region where LA injectables should be readily available to appropriate candidates. I hope to see more inclusive representation of transgender and nonbinary people in future LA PrEP and LA ART studies. We need to make an effort to understand differences in access to and acceptability of LA ART in different patient groups within the community. Finally, I have increased confidence in using LA CAB + RPV in adolescents living with HIV.

Your Thoughts?
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