Cabotegravir: Every other month dosing may carry viral load risks

Clinical trial researchers have found that people who received injectable cabotegravir (Vocabria) and rilpivirine (Rekambys) every other month maintained viral suppression just as well as those who received the drug monthly, but patients on the every other month dosing schedule were more likely to experience a virological failure. The data of the three-year study was presented at CROI 2022.

Injectable cabotegravir (CAB) and rilpivirine (RPV) is currently approved for use in the USA and Europe - both as a once a month injection, or once every other month. The treatment is indicated for people who have already reached viral suppression with oral treatment and are not resistant to either drug. It is administered as two injections, one in each buttock - performed by a medical professional.

Testing the combination

The ATLAS Phase III study recruited 600 participants who already had an undetectable viral load on their existing oral HIV treatment. After switching to CAB + RPV injections once am month 93% had maintained their undetectable viral load (<50 copies/ml) at 48 weeks - compared to 96% who stayed on their original oral combination.

The ATLAS-2M follow up trial was designed to compare the once a month injection with an alternate, once every other month, dosing schedule of the same treatment combination. 1,045 participants, with undetectable viral loads, were recruited to ATLAS-2M (391 carried over from ATLAS Phase III). After a two week lead-in period on oral CAB + RPV, participants were randomised to receive either:

• 400mg CAB + 600mg RPV every four weeks
• 600mg CAB + 900mg RPV every eight weeks

The results were as follows:

• At 48 weeks of follow up (presented at CROI 2020):
  • 94% of participants of both groups maintained viral suppression (<50 copies/ml). This suggested that the every other month dosing schedule is non-inferior to monthly dosing.
    
    
• At 96 weeks of follow up (presented at CROI 2021):
  • 90% in the ‘once a month’ group and 91 in the ‘every other month’ group had maintained an undetectable viral load.
    
    
• At 152 weeks of follow up (presented at CROI 2022):
  • 86% of participants in the ‘once a month’ group and 87% in the ‘every other month’ group had maintained an undetectable viral load.
  • More patients in the ‘once a month group’ were lost to follow up or left the study. Those who left the study from the ‘once a month’ cited frequency of visits (10 vs 4) and intolerability of injections (8 vs 1) as their reasons.
  • During the three years of follow up two people (<1%) in the ‘once a month group’ and eleven (2%) in the ‘every other month’ group met the criteria for virological failure.
  • Thought the study, prolonged use of CAB + RPV remained safe and generally well tolerated, with the most common complaint being injection site reactions.
  • Participants in the study reported “great satisfaction” with injectable CAB + RPV compared to oral treatment, and preferred the ‘every other month’ dosage frequency.

Conclusions

Despite the high rates of viral suppression in both groups a higher frequency of virological failure was recorded in the ‘every other month’ group.

Dr Laura Waters of the NHS Mortimer Market Centre in London calculated that the risk of virological failure was 1 in 200 in the ‘once a month’ group versus 1 in 40 in the ‘every other month’ group.

Dr Waters said that virological failure in the context of 100% commitment from the patient should be discussed with patients, and that it is important that patients are ready for the regimen and the associated risks.

It is also important to recognise that people who develop resistance to CAB + RPV may have substantially fewer treatment options in the future, leading to Dr Waters recommending viral load testing every two months - on each visit.

“As we are not allowed to use monthly dosing in Europe, I call on ViiV to give us, and most importantly, people with HIV, a CHOICE!” said Dr Waters.