ViiV Healthcare’s CLARITY Study Highlights Patient and Healthcare Professional Preference for Long-Acting Cabotegravir Over Lenacapavir
ViiV Healthcare, the global specialist HIV company majority-owned by GSK, with Pfizer and Shionogi as shareholders, has released new findings from the phase I CLARITY study demonstrating meaningful differences in the acceptability and tolerability of two long-acting injectable HIV therapies: cabotegravir long-acting (CAB LA) and lenacapavir (LEN). The data were presented at the 20th European AIDS Conference (EACS) held in Paris, France, highlighting important insights that could influence the future use and choice of long-acting injectables in HIV prevention and treatment.
The CLARITY study was an open-label, crossover trial designed to evaluate how healthy, HIV-negative adults perceive injection site reactions (ISRs) and overall acceptability when administered CAB LA and LEN. The study included 63 participants who were randomized to receive a single dose of one therapy at Day 1, followed by the alternate therapy on Day 15. CAB LA was delivered as a single intramuscular injection, whereas LEN was administered as two subcutaneous injections in line with its product labeling. This design allowed for direct comparison of participant and healthcare provider (HCP) experience with both long-acting injectable formulations.
Patient Preference and Acceptability Findings
One of the most notable outcomes of the CLARITY study was the high level of acceptability for CAB LA injections compared to LEN. Seven days after administration, 69% of participants reported CAB LA injections as “totally or very acceptable,” significantly higher than the 48% of participants reporting the same for LEN. A post hoc statistical analysis confirmed that this difference was significant (p=0.019), demonstrating a clear preference for CAB LA at the individual level.
When it came to overall preference, the results were even more pronounced. Ninety percent of HIV-negative participants expressed a preference for CAB LA over LEN following a single dose. This strong preference was mirrored among healthcare professionals, with 86% of HCPs favoring CAB LA injections compared to only 14% who preferred LEN. These findings underscore the importance of patient and provider perspectives in the selection of long-acting injectable therapies, particularly as the field of HIV prevention and treatment increasingly focuses on options that improve adherence, convenience, and overall patient satisfaction.
Participants cited several factors contributing to their preference for CAB LA. The most commonly reported reasons included: less pain during injection administration (reported by 40 of 54 participants), less soreness following the injection (33 of 54), shorter duration of injection site nodules or swelling (31 of 54), and smaller size of injection nodules or swelling (30 of 54). In contrast, the limited number of participants who preferred LEN (six individuals) reported less pain or soreness after injection administration, the duration and size of injection site reactions, and fewer side effects as primary reasons for their preference.
Healthcare providers also highlighted key reasons for preferring CAB LA. Among the six HCPs who favored CAB LA, five cited fewer reported side effects, four noted less severe side effects, and four highlighted less pain during administration. Only one HCP preferred LEN, citing ease of injection preparation as the primary reason.
Injection Site Reaction Analysis
Beyond subjective preference, the study provided detailed objective data on injection site reactions, a critical factor influencing tolerability and patient adherence. Across the 63 participants, a total of 61 CAB LA injections and 124 LEN injections were administered, given that LEN requires two injections per dose. The findings revealed a markedly higher incidence of ISRs with LEN compared to CAB LA. Specifically, LEN was associated with 538 ISR events versus 123 ISR events for CAB LA, representing more than four times as many reactions. Moreover, visible ISR events were reported in 221 participants receiving LEN compared to 36 participants receiving CAB LA, emphasizing the more prominent local reactions associated with LEN.
Pain was the most frequently reported ISR for both injectables, with 82% of LEN recipients and 80% of CAB LA recipients experiencing this symptom. However, there were significant differences in the type and severity of ISRs between the two therapies. Participants receiving LEN had substantially higher rates of palpable or visible reactions, including induration (87% vs. 18% for CAB LA), nodules (74% vs. 33%), erythema (57% vs. 12%), and swelling (58% vs. 34%). The relative risk (RR) analysis further highlighted these differences: induration (RR 0.21), nodules (RR 0.44), erythema (RR 0.20), and swelling (RR 0.59), all favoring CAB LA for better tolerability.
Importantly, the study reported no serious adverse events or discontinuations due to drug-related adverse effects, reinforcing the overall safety of both CAB LA and LEN when administered as single doses in healthy adults.
Implications for HIV Prevention and Treatment
Jean van Wyk, MBChB, MFPM, Chief Medical Officer at ViiV Healthcare, emphasized the significance of these findings, stating: “We believe long-acting innovations will play a critical role in the global response to ending HIV and AIDS. Understanding potential differences in acceptability and tolerability is an important consideration when choosing between long-acting injectables. The CLARITY study showed that after receiving a single dose of each, more individuals and healthcare professionals preferred cabotegravir over lenacapavir injections. These early findings provide valuable insights into long-acting injectable options to help empower individuals and their healthcare providers to make fully informed choices.”
The results of the CLARITY study highlight that patient experience, including comfort, injection site reactions, and overall convenience, is a key factor in the successful implementation of long-acting HIV therapies. Given the critical role of adherence in preventing HIV infection and maintaining viral suppression in people living with HIV, therapies that are both effective and well-tolerated are essential. The strong preference for CAB LA, driven by less pain, fewer and smaller injection site reactions, and shorter duration of nodules and swelling, suggests that CAB LA may offer advantages in real-world settings, where patient satisfaction and adherence are closely linked.
Moreover, the findings underscore the value of healthcare provider perspectives in treatment decisions. Providers’ preferences are informed not only by patient comfort but also by the overall safety profile and the likelihood of adherence. The CLARITY study indicates that CAB LA aligns more closely with both patient and provider priorities, which could support broader uptake and acceptance of this long-acting injectable therapy.
Study Design and Methodology
The open-label crossover design of the CLARITY study allowed for a direct comparison of CAB LA and LEN within the same participants, thereby minimizing individual variability and providing a clearer understanding of acceptability and ISR tolerability. Participants were randomized to receive either CAB LA or LEN first, followed by the alternate therapy 14 days later. This crossover approach is particularly valuable in early-phase studies, as it enables head-to-head assessment of tolerability, pain, and overall preference without the confounding effects of between-group differences.
Injection site reactions were assessed seven days post-injection, capturing both immediate and lingering reactions that could influence patient perception. In addition to subjective measures of acceptability, the study meticulously recorded objective ISR data, including pain, induration, nodules, erythema, and swelling, providing a comprehensive view of the tolerability profile of each therapy.
Future Directions
While the CLARITY study provides critical early insights, ViiV Healthcare notes that additional analyses and further data will be presented at upcoming medical congresses. These future results will provide more extensive information on long-acting injectable options for HIV prevention and treatment, including potential implications for broader patient populations and long-term therapy.
The findings from CLARITY reinforce the need for individualized approaches in HIV care. With multiple long-acting injectable options now available or in development, patient and provider preferences will play an increasingly important role in treatment selection. The combination of high efficacy, favorable safety profile, and strong acceptability is likely to be key in maximizing adherence and achieving optimal outcomes in HIV prevention and treatment programs globally.
