cabotegravir

Overview

Cabotegravir (CAB) is an integrase strand transfer inhibitor (INSTI) developed for the treatment and prevention of HIV-1 infection. It exerts its antiviral effect by blocking the integration of viral DNA into the host cell genome, a critical step in the HIV replication cycle. Cabotegravir is distinguished from earlier antiretrovirals by its long-acting pharmacokinetic profile: formulated as a nanosuspension for intramuscular (IM) injection, it achieves sustained plasma concentrations over weeks to months following a single dose, making monthly or bimonthly dosing schedules clinically viable. This property underpins its utility both as a component of long-acting maintenance therapy in people living with HIV-1 and as a long-acting pre-exposure prophylaxis (PrEP) agent.

In the treatment setting, cabotegravir is co-administered with rilpivirine (a non-nucleoside reverse transcriptase inhibitor) as the first complete long-acting injectable regimen approved by the US Food and Drug Administration for virologically suppressed adults with HIV-1. The combination, known as CAB+RPV LA, eliminates the daily oral pill burden characteristic of conventional antiretroviral therapy (ART) and represents a paradigm shift in HIV disease management toward patient-centered, adherence-friendly regimens.

Focus of Latest Publications

Recent publications have investigated cabotegravir across several dimensions — comparative pharmacokinetics, anatomical compartment penetration, real-world effectiveness, and alternative injection site tolerability.

Long-acting combination therapy and real-world outcomes. The ABOVE Study (PMID: 42043923), a US-based retrospective real-world analysis, examined adherence, persistence, and healthcare resource utilization among people with HIV receiving long-acting cabotegravir plus rilpivirine (CAB+RPV LA) compared with oral antiretroviral therapy. As the first FDA-approved complete long-acting regimen for virologically suppressed individuals, CAB+RPV LA demonstrated advantages consistent with its reduced dosing frequency, with results informing managed care and specialty pharmacy perspectives on treatment outcomes in routine clinical practice.

Deltoid administration feasibility. A case series (PMID: 42125948) evaluated the safety and efficacy of deltoid intramuscular injection as an alternative site for long-acting cabotegravir and rilpivirine (CAR-LA). Conventional protocols specify the gluteal muscle as the injection site; this case series explored whether the deltoid site offered comparable tolerability and maintained adequate drug exposure, contributing practical guidance for clinical settings where alternative injection sites may be preferable.

Population pharmacokinetic modeling. A population pharmacokinetic (pop-PK) modeling study (PMID: 42170807) externally evaluated published PK models for cabotegravir during both oral lead-in and intramuscular phases of administration in HIV-infected patients. By benchmarking established models against independent patient data, this work assessed the predictive accuracy and generalizability of existing frameworks, which is essential for optimizing dosing recommendations across diverse patient populations, including those with HIV type 1.

Genital tract penetration for PrEP. A study focused on cabotegravir as long-acting PrEP (CAB-LA PrEP) quantified drug concentrations in seminal plasma of cisgender males receiving the injectable regimen (PMID: 41984100). Given that male genital tract penetration of CAB-LA had not been well characterized, this investigation addressed a critical knowledge gap relevant to the agent's effectiveness in preventing HIV-1 transmission at mucosal sites. Sampling at multiple timepoints (days 3, 7, 28, 84, and 140) allowed longitudinal characterization of drug exposure in this compartment.

Key Publications

Jun External Evaluation of Population Pharmacokinetic Models of Cabotegravir, During Its Oral and Intramuscular Administration in HIV-Infected Patients. (CPT: pharmacometrics & systems pharmacology, 2026, PMID 42170807): "Cabotegravir (CAB), combined with rilpivirine, is the first long-acting injectable therapy approved for HIV-1 maintenance treatment."
May Safety and efficacy of deltoid intramuscular long-acting cabotegravir and rilpivirine, a case series. (Antiviral therapy, 2026, PMID 42125948): "...switching for intramuscular long acting cabotegravir and rilpivirine (CAR-LA)."
May Seminal plasma concentrations of long-acting cabotegravir in men receiving HIV pre-exposure prophylaxis. (Antimicrobial agents and chemotherapy, 2026, PMID 41984100): "To address the lack of data on male genital tract penetration of CAB-LA PrEP, seminal plasma was collected at days 3, 7, 28, 84, and 140 and analyzed by LC-MS/MS."
May Real-world adherence, persistence, and health care resource utilization among people with HIV receiving long-acting cabotegravir plus rilpivirine compared with oral antiretroviral therapy in the United States: The ABOVE Study. (Journal of managed care & specialty pharmacy, 2026, PMID 42043923): "Long-acting cabotegravir + rilpivirine (CAB+RPV LA) is the first US Food and Drug Administration-approved complete long-acting regimen for people with HIV who are virologically suppressed."