Background:
Low cabotegravir and rilpivirine trough concentrations have been associated with virological failure in patients with HIV switching to long-acting cabotegravir and rilpivirine treatment in clinical trials. We wished to assess drug trough concentrations in patients initiating long-acting therapy.
Methods:
Starting in March 2022, we prospectively monitored all patients initiating long-acting cabotegravir and rilpivirine in two University Hospitals in Paris. To be eligible, patients had to have a plasma HIV RNA < 50 copies/ml for at least 6 months, no major INSTI or NNRTI resistance-associated mutations and immunity against HBV infection. Intramuscular injections of long-acting cabotegravir 600 mg and rilpivirine 900 mg were administered at the first visit, 4 and 12 weeks later. These first three injections were administered in the hospital as recommended, with monitoring of plasma HIV RNA and trough plasma concentrations of cabotegravir and rilpivirine.
Results:
Forty-nine patients were enrolled from March to August 2022, 89.8% male, median age 30.3 years. They were mostly men who have sex with men (73.5%), heterosexuals (22.4%), or IV drug user (4.1%) and 6.1% had BMI ≥ 30 kg/m2. Median time since HIV diagnosis was 11.4 years. HIV-1 subtypes were B (61.2%), C (4.1%), F (2%), CRF02_AG (16.3%), or other recombinants (14.1%). Median CD4 T-cell count was 680/mm3. With a median time of follow-up of 3.9 months, all patients received two injections, and 38 (84.4%) the Week-12 injection. Median cabotegravir concentration was 972.5 ng/mL (IQR: 719.2;1449.2) at Week 4, and 629.5 ng/mL (IQR: 467.8;920.0) at Week 12, with respectively 61.2% and 81.1% of patients below the 1120 ng/mL threshold. Median rilpivirine concentration was 49.6 ng/mL (IQR: 28.6;65.5) at Week 4, and 43.3 ng/mL (IQR: 31.6;53.6) at Week 12, with respectively 28.6% and 27% of patients below the 32 ng/mL threshold. Virological failure without resistance mutation occurred in one patient at Week 4 (plasma HIV RNA: 2820 c/mL) with cabotegravir and rilpivirine concentrations at 701.3 ng/mL and 27.7 ng/mL respectively at Week 4. This patient had no other risk factor for virological failure.
Conclusions:
A significant proportion of patients starting long-acting cabotegravir and rilpivirine treatment have low trough concentrations that may increase the risk of virological failure and require careful monitoring.