A modeling study suggests that, in people with a high body mass index (BMI), long-acting cabotegravir/rilpivirine injections may need to be administered more frequently to maintain sufficient drug levels—particularly if a patient is currently on an every-two-months injection schedule.
About This Study
“Effect of obesity on the exposure of long-acting cabotegravir and rilpivirine: a modelling study” was published online on Feb. 3, 2024, in Clinical Infectious Diseases. The lead author is Sara Bettonte of the Division of Infectious Diseases and Hospital Epidemiology in the Departments of Medicine and Clinical Research at University Hospital Basel and of the Faculty of Medicine at the University of Basel, Switzerland.
Key Research Findings
Researchers modelled long-acting cabotegravir/rilpivirine exposure in a simulation of people living with HIV who had different body mass indices to determine whether the standard dose is sufficient for everyone. BMI was modeled in 5 kg/m2 increments up to 60 kg/m2. (A person with a BMI >30 kg/m2 is considered obese and someone with a BMI >40 kg/m2 is considered morbidly obese.) The use of longer needles for obese people, to ensure injection into muscle rather than fat, was assumed.
Steady-state concentrations were modeled 96 weeks after starting treatment. Researchers found several notable examples of downward trends in drug concentrations as baseline BMI increased. For example, in the lower obesity range (BMI 30-35 kg/m2), the cabotegravir trough concentration and area under the curve dropped by >35%. In the morbidly obese range, the rilpivirine pharmacokinetic markers decreased by >18%.
At the highest BMI range (50-60 kg/m2), more than half of the simulated people had insufficient drug concentrations (cabotegravir: 50%; rilpivirine: 60%) when they received the standard every-other-month injections. By contrast, with monthly dosing, <10% of simulated people had ineffective drug levels (cabotegravir: 9%; rilpivirine: 4%).
Discussion Highlights and Implications for Practice
Reported study limitations included the demographic characteristics of the simulated people modeled: white and 20-50 years old. Injections were also assumed to go into the muscle, which is not always the case in real-world clinical practice.
The researchers suggested that lower drug concentrations in obese people may be related to higher liver and renal blood flows. In addition, medications for common comorbidities among obese people were not expected to affect drug levels.
The study authors concluded that reducing the dosing interval for cabotegravir/rilpivirine from eight weeks to four for people with BMI >30 could increase the number of those people whose drug concentrations reach minimal thresholds. They recommended therapeutic drug monitoring in obese people on long-acting cabotegravir treatment to determine whether monthly dosing is needed to maintain sufficient drug concentrations.