The world of HIV (Human Immunodeficiency Virus) management has seen remarkable strides over the years, with the advent of antiretroviral therapy (ART) significantly improving the quality of life for people living with the virus. One of the groundbreaking developments in this field is the emergence of long-acting injectable antiretroviral regimens, offering a unique approach to maintaining viral suppression and alleviating the burden of daily oral medication.
Cabotegravir and Rilpivirine, often abbreviated as CAB+RPV LA, form one such long-acting injectable antiretroviral regimen. It was approved by the FDA in January 2021 and was initially indicated for ART-experienced people with HIV with a viral load (VL) of fewer than 50 copies/mL. The approval of CAB+RPV LA marked a significant milestone in the evolution of HIV treatment options, offering a new paradigm for managing the condition.
A demonstration project conducted at Ward 86 in San Francisco offered some intriguing insights into CAB+RPV LA. The project focused on a population with a VL of ≥30 copies/mL at initiation and who faced numerous barriers to adherence to oral medications. The findings from the project were encouraging, showing high rates of virologic suppression with CAB+RPV LA. Specifically, 97.5% of the participants achieved a VL of less than 30 copies/mL at 26 weeks, highlighting the effectiveness of this injectable regimen.
An HIV simulation model further underscored the potential benefits of CAB+RPV LA. The model predicted significant improvements in survival rates with CAB+RPV LA compared to standard of care oral regimens, indicating the potential long-term benefits of this injectable antiretroviral therapy. These findings from the demonstration project and the simulation model suggest the transformative potential of CAB+RPV LA in managing HIV, especially in patients who face barriers to adherence to oral medications.
To delve deeper into the real-world utilization and effectiveness of CAB+RPV LA, a comprehensive study involving more than 155,000 people with HIV was conducted. This study population is representative of approximately 14% of individuals with HIV in the United States, providing a broad and diverse sample for the analysis.
The study had clear objectives: to describe the real-world utilization of CAB+RPV LA over the first two years of its availability in the US, and to describe its effectiveness. The participants were ART-experienced individuals over 18 years old, with a VL of ≥ 50 copies/mL at first injections, and who received their first CAB+RPV LA injections within a specified timeframe. The study design was careful to exclude participants who had been part of CAB+RPV LA clinical trials, ensuring that the findings were reflective of real-world utilization and not influenced by controlled clinical trial conditions.
The study uncovered intriguing findings. Notably, 12% of the participants who received their first injection of CAB+RPV LA had a VL of ≥50 copies/mL, despite the fact that CAB+RPV LA is not FDA indicated for such use. This suggests that in the real world, healthcare providers may be using CAB+RPV LA off-label for patients with higher viral loads.
The results of the study also showed that most of these individuals (82%) were able to suppress their viremia (VL <50 copies/mL) on CAB+RPV LA, indicating the effectiveness of this injectable regimen in achieving virologic suppression in individuals with a detectable viral load at initiation. This highlights the potential role that long-acting injectables like CAB+RPV LA could play for individuals struggling with adherence or tolerability of oral therapy.
The study also provided insights into the demographic and clinical characteristics of the individuals at the first injections. These findings show that CAB+RPV LA is being utilized by a diverse population of people with HIV, including those of different ages, sexes, and races. Further, the clinical characteristics at the first injections provided valuable insights into the health status of these individuals, including their BMI, time from HIV diagnosis, and CD4 count, among others.
The initial dosing schedule was also analyzed, with most individuals receiving injections every two months, while a smaller proportion received monthly injections. This underscores the flexibility in dosing schedules that CAB+RPV LA offers, potentially making the regimen more accommodating to the varying needs and preferences of individuals with HIV.
The study also tracked the progression of the individuals over time, with the median follow-up being 6 months for those with a VL of ≥50 at first injections and 8 months for those with a VL ≥200 at first injections. The follow-up data was crucial in evaluating the virologic outcomes in these individuals.
One of the key outcomes observed was the achievement of virologic suppression – the reduction of HIV viral load to undetectable levels. The study found that a significant majority of individuals were able to achieve virologic suppression during the follow-up period. This was true for both those with a VL of ≥50 copies/mL at initiation and those with a VL of ≥200 copies/mL at initiation.
However, the study also observed instances of confirmed virologic failure, where the VL increased to ≥200 copies/mL during follow-up or following discontinuation. The rate of confirmed virologic failure was relatively low, further underscoring the effectiveness of CAB+RPV LA in managing HIV.
One of the key findings of the study was that 12% of individuals receiving their first injection of CAB+RPV LA had a VL of ≥50 copies/mL, even though CAB+RPV LA is not FDA indicated for such use. This highlights the potential off-label use of CAB+RPV LA in the real-world setting. Importantly, the majority of these individuals (82%) were able to suppress their viremia on CAB+RPV LA, suggesting that long-acting injectables may have a role for individuals with a VL of ≥50 copies/mL who may be struggling with adherence or tolerability of oral therapy.
The study had several strengths. It involved a large population of new users of CAB+RPV LA, providing robust data on its real-world utilization and effectiveness. The data was captured through electronic health records, ensuring accuracy and reliability. Moreover, the study included a diverse representation of people with HIV in the US, enhancing the generalizability of the findings.
However, the study also had certain limitations. The documentation of oral lead-in and oral bridging, which are critical steps in initiating CAB+RPV LA, were not well documented in electronic health records. Additionally, the reasons for administering long-acting injectable ART to those with a VL ≥50 copies/mL were not documented. More follow-up is needed as only a quarter of individuals had ≥10 months of CAB+RPV LA exposure. Future research should focus on assessing the reasons for discontinuation and the individual outcomes after switch.
Despite these limitations, the study provided valuable insights into the real-world utilization and effectiveness of CAB+RPV LA. It highlighted the potential of this long-acting injectable antiretroviral regimen in managing HIV, especially in patients who struggle with adherence or tolerability of oral therapy. The findings also underscore the need for further research in this area to fully leverage the benefits of long-acting injectable regimens like CAB+RPV LA.
In conclusion, the advent of long-acting injectable ART regimens like CAB+RPV LA has opened up new possibilities in the management of HIV. The real-world data from the OPERA cohort underscores the potential of CAB+RPV LA in achieving viral suppression, even in patients with detectable viral loads at initiation. With further research and comprehensive follow-up data, CAB+RPV LA could significantly contribute to improving the quality of life for people living with HIV.
