What is the role of Apretude (cabotegravir) in Pre-Exposure Prophylaxis (PrEP) for HIV-1 infection?

Apretude (Cabotegravir) for HIV Pre-Exposure Prophylaxis

Direct Answer

Apretude (long-acting injectable cabotegravir) is a highly effective, FDA-approved PrEP option administered as intramuscular injections every 8 weeks after initial loading doses, demonstrating superior efficacy compared to daily oral tenofovir/emtricitabine in preventing HIV-1 acquisition. 1, 2

Indication and Patient Selection

• Apretude is indicated for HIV-1 PrEP in adults and adolescents weighing at least 35 kg (77 pounds) who are at risk of sexually acquired HIV-1 infection 1, 3
• The drug demonstrated superior efficacy to daily oral emtricitabine/tenofovir disoproxil fumarate in preventing HIV-1 acquisition in cisgender men who have sex with men, transgender women, and cisgender women 2
• Clinical trial data showed HIV incidence of 0.41 per 100 person-years with cabotegravir versus 1.29 per 100 person-years with oral PrEP (hazard ratio 0.31, p=0.0003) 4

Dosing Schedule

The injection protocol consists of two initial 600 mg (3 mL) gluteal injections separated by 4 weeks, followed by maintenance injections every 8 weeks thereafter. 5, 6

• An oral lead-in with cabotegravir tablets may be used to assess tolerability before initiating injections, though this is optional 1
• If injections are delayed by 8 or more weeks, "reloading" with two injections 4 weeks apart is required before returning to every-8-week dosing 5
• Patients should have a 1-month supply of appropriate tenofovir-based oral PrEP available for bridging if injection delays exceed 7 days 5

Mandatory Pre-Initiation Testing

Before the first injection, comprehensive HIV testing including both a fourth- or fifth-generation antigen/antibody test AND an HIV RNA test with lower limit of quantification ≤50 copies/mL is absolutely required. 5, 1

• If clinical suspicion exists for acute HIV infection (flu-like symptoms, tiredness, joint/muscle aches, sore throat, rash, fever, enlarged lymph nodes), do not initiate cabotegravir until HIV RNA results confirm negative status 5, 1
• Additional baseline testing includes: hepatitis B surface antigen, hepatitis C antibody, serum creatinine, estimated creatinine clearance, pregnancy test, and STI screening 5

Ongoing Monitoring Requirements

Before every subsequent injection, perform both a point-of-care rapid HIV antibody test AND a laboratory-based fourth- or fifth-generation antigen/antibody combination test. 5, 6

• HIV RNA testing is NOT routinely recommended at follow-up visits due to low positive predictive value and potential for false-positives with significant negative consequences 5
• HIV RNA testing should be reserved for initial initiation, resumption after hiatus, or when clinical suspicion of acute HIV infection exists 5
• STI screening at all exposed mucosal sites should be performed at each visit based on sexual history 5

Critical Safety Considerations and Contraindications

Absolute Contraindications

• Known HIV-1 positive status or unknown HIV status 1
• History of allergic reaction to cabotegravir 1
• Concurrent use of carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, or rifapentine 1

Important Cautions

• Use with caution in individuals with gluteal implants or fillers as the intramuscular injection site may be compromised 5
• Rifabutin coadministration requires dose adjustment 5
• All potent UGT1A1 inducers should be avoided as they reduce cabotegravir concentrations 5

Risk of Delayed Seroconversion and Resistance

Cabotegravir can delay HIV seroconversion and mask early infection, making comprehensive pre-injection testing absolutely critical. 5, 6

• If seroconversion occurs while on cabotegravir, immediately obtain genotypic resistance testing including integrase mutations 6
• Never continue an integrase inhibitor-based regimen if seroconversion is detected—immediately switch to a protease inhibitor or NNRTI-based antiretroviral regimen due to high risk of multi-drug resistance. 6
• Infection within 6 months of cabotegravir exposure is associated with diagnostic delays and integrase strand-transfer inhibitor (INSTI) resistance 4

Common Side Effects

• Injection site reactions occurred in up to 81% of trial participants but typically diminish in severity over time 5
• The drug was generally well tolerated in clinical trials, though long-term safety data continue to be collected 2
• Incident hypertension in the long-acting PrEP group requires further investigation 4

Transitioning Off Cabotegravir

If transitioning to oral PrEP (such as Descovy), begin oral medication within 12 weeks after the last cabotegravir injection to maintain continuous HIV protection during the pharmacokinetic tail period. 7

• Perform comprehensive HIV testing (antigen/antibody combination test AND HIV RNA test) before initiating oral PrEP to confirm HIV-negative status 7
• Schedule follow-up HIV testing at 4-6 weeks after starting oral PrEP, then continue quarterly HIV testing 7
• Premature discontinuation of cabotegravir without overlap may leave patients vulnerable to HIV acquisition 7

Patient Counseling Points

• Apretude does not prevent other sexually transmitted infections—latex or polyurethane condoms should be used to reduce STI risk 1
• Missing doses or delayed injections increases risk of HIV acquisition 1
• Patients must return for HIV testing before every injection—skipping this testing could result in undetected HIV infection and drug resistance 6
• Know your HIV status and your partners' HIV status; partners with HIV on effective treatment with undetectable viral load significantly reduce transmission risk 1

Advantages Over Daily Oral PrEP

• Long-acting formulation eliminates need for daily adherence, addressing a major barrier to PrEP effectiveness 2, 8
• Superior efficacy demonstrated in head-to-head trials with oral tenofovir/emtricitabine 2, 4
• Convenient dosing schedule (every 8 weeks) may improve adherence and persistence on PrEP 2
• Represents the first long-acting injectable option approved for HIV-1 PrEP 2