LA ART and HRQoL
Can Long-Acting ART Improve Health-Related Quality of Life in People Living With HIV?

Released: August 31, 2023

Iskandar Azwa
Iskandar Azwa, MBChB, MRCP

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Key Takeaways
  • Long-acting ART has the potential to improve quality of life in people living with HIV by alleviating adherence anxiety, stigma, and the daily reminder of their HIV status.
  • Patient-reported outcomes in long-acting ART studies consistently favor long-acting injectables vs oral ART in people who want to receive injectable therapy.
  • Patients report greater preference and treatment satisfaction after switching that continuously improves over time.

Antiretroviral treatment (ART) has come a long way. However, despite the successes of oral integrase strand transfer inhibitor‒based ART in terms of tolerability, high resistance barriers, and durability of virologic suppression, oral combination ART still requires a lifelong commitment to daily oral therapy, which can lead to psychosocial challenges. Injectable long-acting (LA) ART is a significant advance that offers important options for treatment of people living with HIV—and, with its less frequent dosing, it is a priority for them.

Factors Associated With Interest in LA ART

People living with HIV are acutely aware that an undetectable HIV-1 RNA is crucial to maintaining good health and quality of life. However, for some, the social stigma of daily ART or the inability to adhere to a daily oral medication reduces their ability to maintain viral suppression. People in these groups demonstrate the greatest interest in LA ART. In a survey of 688 people living with HIV accessing care in European healthcare settings, interest in LA ART was highest among people with perceived stigma (83%), people stressed by daily dosing with oral ART (78%), younger people living with HIV (70%), and people more recently diagnosed with HIV (84%).

Benefits of LA ART Regimens

LA ART has the potential to vastly improve an individual’s quality of life. The reduced dosing frequency is much more convenient, helps avoid pill fatigue, and increases options for both patients and healthcare professionals. It helps reduce the anxiety of suboptimal adherence in patients struggling with taking daily pills or patients who have a medical need to avoid oral medications, such as malabsorption and dysphagia. By reducing the visibility of taking daily medication, LA ART protects health privacy, prevents potential unintentional disclosure, averts HIV-related stigma, and reduces the daily reminder of one’s HIV status.

Patient-Reported Outcomes

The benefits of LA ART directly align with the UNAIDS Global AIDS Strategy goal of adopting a more holistic, person-centered approach to HIV care that focuses on long-term well-being, health-related quality of life, multimorbidity (noncommunicable diseases and mental health), and avoiding stigma and discrimination. 

Patient-reported outcomes (PROs) are important for holistic assessment of how new medications and treatment options, such as LA ART, affect quality of life for people living with HIV. This is illustrated in the studies of LA cabotegravir (CAB) + rilpivirine (RPV), where several methods were used to assess PRO endpoints, including the HIV Treatment Satisfaction Questionnaire to assess treatment satisfaction, the “General Acceptance” domain of the Chronic Treatment Acceptance (ACCEPT®) questionnaire to assess treatment acceptance, the Perception of Injection questionnaire to assess tolerability of pain and injection-site reactions, and a treatment preference questionnaire to determine patient preference for LA ART vs oral therapy. Data from these PROs comprehensively show that people who switch from daily oral ART to injectable LA ART report high treatment acceptance and satisfaction.

Recent Studies of PROs With LA ART

PROs from recent clinical studies confirm that people living with HIV consistently favor LA ART vs daily oral ART.

The CARISEL study was a multicenter, open-label, implementation-effectiveness phase IIIb study across 18 diverse European healthcare settings in virologically suppressed patients who switched from daily oral therapy to LA CAB + RPV every 2 months. More than 99% (275/277) of those who completed the PRO questionnaire preferred LA ART vs <1% (2/277) who preferred daily oral therapy at Month 12. Approximately 80% (307/379) of participants felt that LA ART was less stigmatizing than oral therapy. The 2 most common reasons for preferring LA ART vs daily therapy included not having to carry HIV medication and the convenience of receiving every-2-month injections. HIV treatment satisfaction scores improved over time, and 95% of patients agreed or completely agreed that they would recommend LA ART to others.

The SOLAR study was another randomized, open-label, multicenter phase IIIb study assessing virologically suppressed adults who switched from once-daily oral ART to LA CAB + RPV every 2 months. At baseline, 47% (315/670) of patients reported psychosocial challenges associated with daily oral therapy, including fear of unintentional HIV disclosure, adherence anxiety, or dissatisfaction with a daily reminder of their HIV status. By the end of the study, patients reported a strong preference for LA injectables: 90% (382/425) of the participants who switched from bictegravir/emtricitabine/tenofovir alafenamide to LA CAB + RPV preferred LA ART at 12 months post switch vs 5% who preferred daily oral ART. Like patients in the CARISEL study, participants reported that their primary reasons supporting this preference were not having to worry about remembering to take daily HIV medication and the convenience of every-2-month injections. Patients who switched to LA CAB + RPV reported significant improvements in treatment satisfaction from baseline through Month 12 vs those who remained on oral ART. LA CAB + RPV also was well tolerated, with 98% of injection-site reactions being mild to moderate in severity and leading to withdrawal in only 2% of participants.

The CAPELLA study investigated an even longer‒acting injectable ART. In this phase III study, patients with multidrug-resistant HIV switched from their failing ART regimen to SC lenacapavir every 6 months with optimized background therapy. Most participants (64/72) reported favorable PROs consistently throughout the study in terms of health-related quality of life, including physical and mental health and tolerability of injections.

Altogether, these data support continued development of LA ART and demonstrate why we also must prioritize implementation of LA ART in the clinical setting. LA ART has the potential to relieve people living with HIV of the burden of daily oral ART—and the stigma and anxiety that come with it—without compromising health-related quality of life. With more widespread adoption of LA ART, we come closer to achieving the fourth 90 and optimizing quality of life for people living with HIV.

Your Thoughts?

Have you had the opportunity to prescribe LA ART to any of your patients? Do you foresee any challenges to more widespread implementation of LA ART? Join the discussion by posting a comment.