In routine clinical care in the US, 90% of monthly CAB + RPV LA continuation injections were administered on time, or within 7 days before or after the target date, as per the label. Virologic suppression was maintained throughout follow-up by 96% of individuals with a viral load < 50 copies/mL at initiation. Of note, confirmed virologic failures were infrequent.

The virologic efficacy of monthly CAB + RPV LA injectable was demonstrated in clinical trials [4,5,6,7,8,9,10,11,12]. In an observational study of 39 individuals with at least two continuation CAB + RPV injections, viral suppression was maintained by all 24 individuals with viral load < 30 copies/mL at initiation, and achieved by 12 (80%) of the 15 individuals with viral load ≥ 30 copies/mL at initiation [14]. Among individuals receiving CAB + RPV LA through a compassionate use program, 6/7 (86%) individuals with a viral load < 50 copies/mL maintained suppression, and 16/28 (57%) with a viral load ≥ 50 copies/mL achieved suppression [16].

The timely administration of long-acting medications such as CAB + RPV LA injectable is crucial to their success. In OPERA, 90% of continuation injections were administered on time, and only a history of AIDS-defining events was associated with an increased risk of experiencing a delay. Oral bridging should be used to maintain the therapeutic dose when missed injections are planned or when delays ranging from > 7 days to ≤ 8 weeks occur. Some of the delays observed in this study may not represent true gaps in treatment if oral bridging was used but not documented. In this study, 60% of delayed injections were administered within 28 days of the target date. However, documentation of oral bridging in the electronic health records was inconsistent and often missing. Moreover, bridging regimens and prescriptions are not uniform: some providers chose to maintain the prior ART prescription, some wrote a new prescription at CAB + RPV LA start, and a few wrote a new prescription before a gap that corresponded with the duration and timing of bridging medication use. Importantly, a population pharmacokinetic modeling and simulation study concluded that CAB LA injections could be resumed when injections had been delayed for less than 4 weeks after the target date, with or without oral bridging [17]. Similar proportions of suppression and confirmed virologic failures were observed in the minority of individuals with delays compared to the majority without any delays. Nonetheless, proper adherence to CAB + RPV LA regimen is critical and health care providers should emphasize this with individuals under their care.

While CAB + RPV LA has been approved for virologically suppressed individuals only, 13% of initiators in OPERA had a viral load ≥ 50 copies/mL at first injection. The OPERA cohort is comprised of EHR data from routine clinical care in the US, and, thus, off-label use may be observed when such use is deemed appropriate by the healthcare provider. However, reasons for regimen selection are not consistently recorded in EHRs, so justifications for off-label CAB + RPV LA use could not be investigated.

The short duration of follow-up in this study prevented the assessment of long-term adherence and virologic outcomes. In addition, while no statistical difference was observed in the likelihood of maintaining suppression or experiencing virologic failure between individuals with and without delayed injection, power to detect a difference was limited by the small number of events. However, the main objective of the study was to understand patterns of adherence. This early assessment of CAB + RPV use is important to support clinical decision making as uptake of this new treatment option increases. Recording of target dates was inconsistent in the electronic health records and implemented differently across providers and clinics. Therefore, the target date was reset every month to the same day as the previous injection and a 7-day window before and after the target was implemented in accordance with the label. Another study limitation was the unavailability of resistance testing results for analysis, which could have an impact on virologic effectiveness. The small number of confirmed virologic failures prevented the assessment of its predictors. Safety outcomes could not be assessed in this study. Finally, this study was limited to monthly injections; no inference can be made for the every 2 months dosing schedule.

This study was conducted with data from the OPERA cohort, a large, diverse cohort representative of HIV care in the US. Over 80 clinics ranging from small rural practices to large metropolitan healthcare centers contribute data to OPERA, which, at the time of this study, included EHR data from over 145,000 people with HIV, representing close to 14% of people with HIV in the US [18]. This large database of routine clinical care data provided access to information on procedures such as CAB + RPV LA injectable administration, as well as laboratory testing in a real-world population of people with HIV starting a CAB + RPV LA injectable regimen in the US. With 321 individuals receiving CAB + RPV LA injectables and 1152 continuation injections administered over 13 months, this is the largest real-world assessment of monthly CAB + RPV LA injectable administration and virologic outcomes to date.