Early data on injecting CAB/RPV-LA into thigh muscle
AIDS 2022 included results from a phase 1 study looking at whether lateral thigh muscle could be an alternative injection site for long-acting cabotegravir/rilpivirine-LA (CAB/RPV-LA). 
Current formulations involve injections into gluteal muscle every two months by a health worker.
The study enrolled 15 HIV negative participants (9 men, 6 women). Median age was 33 years (range: 21 to 49) and 7/15 were Black and 5/15 Hispanic/Latinx. Median weight was 93 kg (range 67 to 107) and BMI was 31 kg/m2 (range: 24 to 34).
The study protocol involved daily oral lead-in (CAB 30 mg plus RPV 25 mg) for 28 days, followed by a 14-day washout and single 3 mL IM injections of CAB (600 mg) and RPV (900 mg) in the lateral thigh muscle. Pharmacokinetic (PK) parameters were observed for one year.
Median and geometric mean were > 4 x protein adjusted IC90 for both drugs at week 8. Although some individuals dropped below this target, all remained above the IC90 at this timepoint.
Median levels of both drugs dropped below the IC90 after approximately 18 weeks and became undetectable at 24 weeks for cabotegravir but remained detectable at 52 weeks for rilpivirine.
At week 8, CAB and RPV levels were 5.3-fold and 2.4-fold higher than their PA-IC90 threshold.
Low grade adverse events were reported by all 15/15 participants and included injection site reactions (ISRs), chills and headache. Grade 3 ISRs were due to pain at the injection site. Pain was reported up to 4 days post-injection and this was participants generally reported as acceptable.
These data indicate that giving LA formulations in thigh muscle achieves target plasma levels out to 8 weeks and that the injections were tolerable.
These early data are encouraging but need to be confirmed in larger numbers and in people living with HIV (as HIV can affect PK).
If alternative injection sites are validated, this might allow self-administration of therapies.
Further studies are required to evaluate the potential of the thigh and other relevant muscles as potential injection sites.
- Hang K et al. Pharmacokinetics and tolerability of cabotegravir and rilpivirine long-acting intramuscular injections to the vastus lateralis (lateral thigh) muscles of healthy adult participants. AIDS 2022 (Montreal). 29th July to 2nd August. E-poster EPB176.