Is cabotegravir-rilpivirine (Intramuscular suspension, extended release) medically indicated for the treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection in patients with diagnosis code B20?

Cabotegravir-Rilpivirine is Medically Indicated for HIV-1 Treatment in Patients with Diagnosis Code B20

Yes, cabotegravir-rilpivirine 200 mg-300 mg/mL intramuscular suspension, extended release (J0741) is medically indicated for the treatment of HIV-1 infection in patients with diagnosis code B20, provided the patient meets specific eligibility criteria. 1, 2, 3

Eligibility Requirements That Must Be Met

The patient must satisfy ALL of the following criteria before initiating cabotegravir-rilpivirine:

• Virologic suppression: HIV-1 RNA <50 copies/mL for at least 6 months on current antiretroviral regimen 2, 4, 5
• No history of virologic failure on any prior antiretroviral regimen 2, 4
• No known or suspected resistance to either cabotegravir or rilpivirine based on historical genotypic testing 1, 6, 2
• Age ≥12 years and weight ≥35 kg (77 pounds) 3, 7
• Ability to attend scheduled injections every 4-8 weeks, as poor adherence to injection schedule is a risk factor for virologic failure 2, 5

Critical Contraindications

Do not use cabotegravir-rilpivirine if the patient has:

• Documented or suspected rilpivirine resistance, which would compromise treatment efficacy and lead to 2-class resistance development 6, 2
• Known hypersensitivity to cabotegravir or rilpivirine 3
• Concurrent use of contraindicated medications including carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, or rifapentine 3
• Active hepatitis B co-infection requiring treatment, as cabotegravir-rilpivirine does not provide HBV coverage 2

Guideline-Supported Indications

The 2025 International Antiviral Society-USA guidelines do not list cabotegravir-rilpivirine as a recommended initial therapy regimen for treatment-naive patients. 1 However, it is an appropriate maintenance therapy option for virologically suppressed patients who meet eligibility criteria. 1, 2

For pregnant patients, if pregnancy is diagnosed while receiving long-acting cabotegravir-rilpivirine, switching to an oral triple-drug regimen is recommended (evidence rating: AIII). 1 The regimen should not be initiated during pregnancy due to inadequate data. 1

Dosing Regimens Supported by Evidence

Two FDA-approved dosing schedules exist:

• Every 4 weeks (Q4W): Cabotegravir 400 mg + rilpivirine 600 mg 4, 5
• Every 8 weeks (Q8W): Cabotegravir 600 mg + rilpivirine 900 mg 2, 5

The ATLAS-2M trial demonstrated non-inferiority of Q8W versus Q4W dosing at 152 weeks, with 87% of participants maintaining HIV-1 RNA <50 copies/mL in both arms. 5 The Q8W regimen offers reduced injection frequency (6 injections per year) while maintaining durable virologic suppression. 2, 5

Oral Lead-In Phase Requirement

A 4-5 week oral lead-in phase with oral cabotegravir 30 mg plus rilpivirine 25 mg daily is critical before initiating long-acting injections. 2, 8, 4 This safety assessment period:

• Identifies potential tolerability issues before committing to long-acting formulations 2
• Allows monitoring for gastrointestinal symptoms that could affect rilpivirine absorption 2
• Confirms virologic suppression at 4-6 weeks to ensure adequate drug levels 2

Important Safety Considerations and Monitoring

Virologic failure risk: Even with perfect adherence to injection schedules, cabotegravir-rilpivirine carries a 1-2% risk of virologic failure with emergence of 2-class resistance (integrase inhibitor + NNRTI). 2, 5 This risk is not observed with oral antiretroviral therapy. 2

In the ATLAS-2M study at week 152, confirmed virologic failure occurred in 2.3% of Q8W participants and 0.4% of Q4W participants. 5 Among those with confirmed virologic failure, 75% developed rilpivirine resistance and 60% developed integrase inhibitor resistance. 2

Risk factors for virologic failure include:

• Rilpivirine-associated resistance at baseline 2
• Viral subtype A6 2
• BMI >30 kg/m² 2
• Poor adherence to injection schedule 2, 5

Monitoring schedule:

• HIV RNA at 4-6 weeks after starting oral lead-in 2
• HIV RNA every 3 months for the first year after switching to long-acting injections 2
• HIV RNA every 3-6 months thereafter if stable 2

Injection Site Reactions

Injection site reactions are the most common adverse event, reported by 88% of participants in clinical trials. 4 However:

• 99% were grade 1 or 2 in severity 4
• Median duration was 3 days (IQR 2-4 days) 4
• Frequency decreased over time 4
• Only 1-6% discontinued due to adverse events 2, 4

Quality of Life and Morbidity Benefits

Cabotegravir-rilpivirine prioritizes quality of life through:

• Elimination of daily pill burden, reducing from 365 doses per year to 6-12 injections 2
• Reduction in NRTI-related bone, kidney, and cardiovascular complications 2
• Decreased stigma and anxiety related to daily oral dosing 8
• Maintained durable virologic suppression with 95% suppression rates in clinical trials 2, 5

Common Pitfall to Avoid

Never use cabotegravir-rilpivirine as initial therapy for treatment-naive patients or for post-exposure prophylaxis. 1 A recent animal study demonstrated that long-acting cabotegravir-rilpivirine was only partially effective as PEP with late breakthrough infections. 1 The 2025 CDC guidelines explicitly state that due to lack of data on safety, tolerability, and efficacy in a PEP setting, cabotegravir-rilpivirine was not included in preferred or alternative PEP regimens. 1