Background
For people with HIV (PWH) on antiretroviral therapy (ART), transitioning to bimonthly long-acting (LA) injectable cabotegravir (CAB) plus rilpivirine (RPV) can be done either directly (non-OLI) or after an optional one-month oral lead-in (OLI). Recent data suggest lower CAB trough concentrations (Ctrough) with non-OLI initiation. This study aimed to assess pharmacokinetics (PK) and virological outcomes based on OLI use in a real-world setting.
Methods
We conducted a prospective cohort study of PWH on stable oral ART transitioning to bimonthly CAB+RPV LA. Participants were sequentially assigned to non-OLI (01-04/2023) or OLI (05-12/2023) groups. Plasma HIV-1 viral load (VL) and CAB and RPV plasma levels were measured before each injection over a 9-month follow-up. Virological failure (VF) was defined as 2 consecutive VL≥200 cp/mL or one VL≥1000 cp/mL. Non-sustained viral suppression (non-suppression) was defined as any VL≥20 cp/mL. Statistical analyses were conducted using R v4.2.3 with linear mixed-effects models adjusted for OLI use, age, sex, BMI and smoking status. Models included a random intercept and slope for each patient.
Results
A total of 707 plasma samples from 176 PWH were analyzed. The median age was 48 years (IQR: 38-56) with 14.8% female and 77.3% Spanish. The median time since HIV diagnosis was 12 years (IQR: 5-23). Of the participants 46.6% initiated LA therapy directly, while 53.4% used OLI. Baseline characteristics, including age, sex, BMI, CD4 count and smoking status were similar between groups (p>.1). Over the 9-month follow-up, no significant differences were observed in non-suppression rates between non-OLI and OLI groups (43.2% vs 38.5%, p=.633) or VF (1.2% vs 3.2%, p=.624). CAB and RPV Ctrough levels, regardless of OLI use, remained well above the 4xPAIC90 threshold from clinical trials (see Figure). In multivariable models, lower CAB Ctrough was significantly associated with higher BMI (p=.017), and showed trends towards lower levels in males (p=.067) and smokers (p=.055), with no influence of OLI use. Lower RPV levels were significantly associated with smoking (p=.011) and younger age (p=.047). Secondary analyses of participants with baseline VL<20 cp/mL (N=147) showed similar trends.
Conclusions
In conclusion, the use of an oral lead-in did not result in significant differences in pharmacokinetics or virological outcomes for PWH transitioning to CAB+RPV LA over 9 months.