Early German data from patients taking injectable cabotegravir and rilpivirine (CAB/RPV – Vocabria/Rekambys in Europe, Cabenuva in North America and Australia) in a demonstration project, shows that patient dissatisfaction with taking antiretroviral therapy (ART) halved after six months’ experience (involving their first four injections). During this time, 89.5% of participants remained on the therapy and with a viral load below 50 copies.
Out of 22 cohort members who did not stay on the therapy or maintain viral undetectability, only two had virological failure, defined as two consecutive viral loads over 200, at the six-month mark and only four others had a viral load above 50 copies. Six others stopped due to intolerance of injection site reactions.
One of the two with virological failure should have never been in the study, because it was found afterwards that a previous regimen containing NNRTI drugs had failed, leading them to develop resistance to rilpivirine. But the other is puzzling, as they had no apparent risk factors.
The data were presented at the International Congress on Drug Therapy in HIV Infection (HIV Glasgow) by Dr Celia Jonsson-Oldenbüttel of the Goetheplatz Community Health Centre in Munich, on behalf of the CARLOS cohort, a post-licensing cohort of HIV patients taking CAB/RPV injections at six clinics in Berlin, Cologne and Munich. CARLOS is supported by ViiV, the manufacturers of cabotegravir.
All participants were virally suppressed on other antiretrovirals before taking CAB/RPV. This analysis is of the first group of patients who started CAB/RPV more than six months ago.
Most of the 230 patients took an oral ‘lead in’ of one month of cabotegravir and rilpivirine pills; the first two injections were then spaced a month apart, and then injections continued every two months. The CARLOS cohort will continue for three years and will enrol more patients who switch to the injectables.
Personal preference was the reason for 92% of people to take the injections. Doctors recommended them to 5% due to prior poor adherence and the other 3% for medical reasons such as swallowing difficulties or nausea.
Ninety-five per cent were men – reflecting the predominance of men in the German HIV epidemic – and their average age was 43; no ethnicity or nationality data were given. They had been on ART for an average of eight years and 45% had had at least three previous ART regimens.
In terms of pre-existing risk factors for virological failure, only 2% had the A6 or A1 subtypes of HIV and 12% had a BMI of over 30, indicating obesity. The biggest problem was the lack of resistance testing. With 39% not having had a resistance test in the last few years prior to switching to injectables, a large minority could have had HIV with pre-existing resistance mutations to integrase inhibitors or, more likely, NNRTIs. As mentioned above, one person who failed virologically did turn out to have NNRTI resistance.
The lack of a resistance test was not a reason for exclusion for CAB/RPV treatment, but previous failure of an NNRTI regimen was. People who have switched from a previous regimen and are already virally suppressed cannot have their viral RNA sequenced for a resistance test. It is possible to sequence proviral DNA, but this is expensive, and most clinics don’t do it. The only alternative is to rely on clinical history and this will not always be fully available.
At the six-month mark, only two patients had confirmed virological failure. One, as mentioned above, had NNRTI resistance, but the other is puzzling; they had no pre-existing risk factors and had had all their injections at the right time, but nonetheless treatment failed, and when it did, they turned out to have a large number of integrase resistance mutations. Whether this was a genuine breakthrough due to some drug-absorption problem or whether they had had pre-existing resistance that had gone undetected is a matter for further investigation.
Fifty-five people (27.5%) had 218 injection site reactions such as pain, redness or tenderness in a total of 866 injections. All were mild (grade 1 or 2) but as mentioned, six people dropped out due to them. Fifty other drug-related adverse events were reported in 21 people, the most common being fever, pain unrelated to injection site, headache, fatigue or sleep disorders, and nausea. Some of these happened during the oral lead-in. All were grade 1 or 2. There was one grade 3 adverse event, but this was an exacerbation of a pre-existing anxiety disorder.
Ninety-one per cent of injections took place within a week before or after the scheduled appointment: 19% on the exact day, 43% in the week before, and 29% in the week after. There were 6.5% which were more than a week early and 2.8% that were more than a week late (half of those were more than two weeks late). In all cases where more than a week had passed after the scheduled date, people were given a week’s worth of oral therapy to take to cover the trough in drug levels. One person had a one-month gap between their next two injections.
Patient satisfaction with their therapy was measured with a validated questionnaire which asked 11 questions scored from zero (totally unsatisfied) to six (totally satisfied), leading to a maximum possible score of 66 points. The average score at baseline was already high at 55.3 but after six months had risen to 60.6 – or, to put it another way, the dissatisfaction score had halved from 10.7 to 5.4.
In general, then, the injectable therapies were popular in those coming forward for this study, at least as virologically effective as oral therapies, and pretty well tolerated – only 3% dropped out due to injection site reactions, when another 2% dropped out due to intolerance of the lead-in oral pills.
The biggest issue would appear to be the difficulty of establishing if people have prior resistance: as another study at HIV Glasgow established, a combination of two or more risk factors (resistance, A6/A1 subtype and obesity) is associated with a higher risk of viral failure, though a single risk factor would not necessarily disqualify people from the injectables.
Borch J et al (presented by Jonsson-Oldenbüttel C). Six-month outcomes of every 2-months long-acting cabotegravir and rilpivirine in a real-world setting: effectiveness, adherence to injections and patient-reported outcomes from PLWHIV in the German CARLOS cohort. International Congress on Drug Therapy in HIV Infection (HIV Glasgow), abstract O43, October 2022.