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LA ART IDWeek and EACS 2023
Real-world Experiences With Long-Acting Injectable ART From IDWeek and EACS 2023

Released: November 09, 2023

Don E Smith
Don E Smith, MD, FRCP (London) FAChSHM
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Key Takeaways
  • Real-world reports from IDWeek and EACS 2023 show that the confirmed virologic failure rate of injectable CAB + RPV is low, similar to the data reported from clinical trials.
  • Incidences of resistance are rare, but caution must be used when interpreting low-level viremia.

Injectable cabotegravir (CAB) plus rilpivirine (RPV) has been a treatment option in Australia for more than 1 year now. People living with HIV who have switched to the injectable option certainly seem to be enthusiastic about it, although some healthcare professionals still have hesitancy regarding its potency and the risk of virologic resistance if virologic failure (VF) occurs. Fortunately, a plethora of abstracts from the IDWeek and EACS 2023 conferences described “real-world” experience from a range of clinical sites to help inform us and the people living with HIV whom we treat.

Real-world Rates of VF
First and foremost, real-world data show that CAB + RPV is highly effective at preventing viral replication across many different outpatient settings in international treatment centers. In France, within the Dat’AIDS cohort, 14 cases of VF occurred among 1134 individuals who switched to CAB + RPV for a VF rate of 1.2%.  Other studies in France reported 1 case of VF among 142 people living with HIV and 6 cases of VF among 127 people living with HIV for VF rates of less than 1% and 4%, respectively. A clinic in Brighton, UK, screened 160 candidates for consideration of injectable therapy: One third of the people screened did not qualify, and one third declined the switch, but the remaining one third who took up injectable ART remained suppressed with no VF reported. Similarly, studies in Rome and Padua, Italy, reported 0 cases of VF in 38 participants through 28 weeks of follow-up and 1 case of VF in 65 people living with HIV, respectively. In Hong Kong, investigators reported 0 cases of VF in 18 people living with HIV through 5 months.

Other studies showed that CAB + RPV is highly effective in a range of people living with HIV. Data from the OPERA cohort, which involved 96 US clinics, revealed that of 1578 participants with viral load <50 copies/mL at initiation who received CAB + RPV for a median of 7.4 months, having a BMI >30 kg/m2 did not influence VF rates. Confirmed VF was found in just 16 individuals after 2 years, resulting in a VF rate of 1%. Hsu and colleagues presented data from a smaller subset of 229 individuals within this cohort who had viral load >50 copies/mL when initiating CAB + RPV and reported 7 confirmed failures for a VF rate of 4%.

Altogether, these data show that, even outside the idealized realm of clinical trials, the failure rate of CAB + RPV remains very low. 

Risk of Virologic Resistance
Confirmed VF rates from these real-world reports seem to hover in the 1% zone, reassuringly similar to the data reported from clinical trials. However, one concern that I still had prior to these conferences was how to interpret low-level viremia in people living with HIV receiving injectable CAB + RPV. When low-level viremia occurs in people receiving either dolutegravir- or bictegravir-based oral regimens, we as healthcare professionals are more comfortable in continuing with therapy, knowing that low-level viremia probably represents viral leakage from the latent reservoir rather than new viral replication. The potency of current daily oral ART regimens ensures that resistance almost never happens if people are adhering to their ART.

However, it is often difficult to distinguish between a viral “blip” and sustained new viral replication. In addition, CAB + RPV has a lower genetic barrier to resistance compared with other ART drugs, and incurring resistance in a 2-drug regimen risks resistance to both components, resulting in loss of both drug classes as treatment options. My anxiety about drug resistance was reinforced by results from 3 different studies: The Dutch ATHENA Cohort reported that 2 participants out of 588 experienced VF with multiclass virologic resistance, a study from the NEAT ID Network in Europe reported that 1 participant out of 120 had confirmed VF with resistance, and a study comprising 3 hospitals in France reported that 2 participants out of 283 experienced VF with confirmed new resistance mutations after initiation of CAB + RPV.   

However, despite these concerns, the data show that VF in people living with HIV who are receiving CAB + RPV is very infrequent and the occurrence of virologic resistance is exceedingly rare. A growing body of real-world evidence shows that switching to injectable CAB + RPV is not associated with increased risk of VF compared with standard daily ART. I hope that the results presented at these conferences will ease concerns about the safety and efficacy of switching to this long-acting injectable therapy, especially because accessible, long-acting ART has been a longstanding priority for people living with HIV.

Your Thoughts?
How does this new real-world data affect your confidence in prescribing long-acting injectable ART? Leave a comment to join the discussion, and visit our program page for additional coverage of IDWeek and EACS 2023.