What to counsel on for seroconversion in a patient starting cabotegravir (Integrase Strand Transfer Inhibitor) for Pre-Exposure Prophylaxis (PrEP)?

Counseling on Seroconversion Risk for Patients Starting Cabotegravir PrEP

If seroconversion occurs while on cabotegravir PrEP, immediately obtain genotypic resistance testing including integrase mutations and switch to a protease inhibitor or NNRTI-based antiretroviral regimen—never continue an integrase inhibitor-based regimen due to high risk of multi-drug resistance. 1

Critical Pre-Initiation Testing to Prevent Masked Infection

Comprehensive HIV testing is mandatory before the first injection and must include both a fourth- or fifth-generation antigen/antibody test AND an HIV RNA test with lower limit of quantification ≤50 copies/mL. 2, 3, 4 This dual testing approach is essential because:

• Cabotegravir can delay HIV seroconversion and mask early infection, making standard antibody tests unreliable 5
• Standard antibody tests alone may miss acute HIV infection, particularly given cabotegravir's long half-life and resistance risk 5
• If clinical suspicion exists for acute HIV infection, do not initiate cabotegravir until HIV RNA results confirm negative status 2, 3, 4

Ongoing HIV Testing Requirements at Every Injection

Before each subsequent injection (every 8 weeks), perform both a rapid point-of-care HIV antibody test AND send a laboratory-based combination antigen/antibody test. 1 The injection should not be delayed pending laboratory results, but results must be reviewed promptly. 1

Why Resistance Risk is Uniquely High with Cabotegravir

The concern about seroconversion on cabotegravir PrEP is fundamentally different from oral PrEP due to:

• Cabotegravir's extremely long half-life creates prolonged subtherapeutic drug levels that can persist for months after the last injection, providing an ideal environment for resistance development 5
• Integrase resistance mutations (G118R, E92G/Q, G140R) can emerge rapidly when HIV infection occurs during cabotegravir exposure, conferring >800-fold resistance to cabotegravir and cross-resistance to all licensed integrase inhibitors 6
• These resistance mutations have been documented in plasma, vaginal, and rectal fluids as early as day 57 after infection in animal models 6

Specific Treatment Protocol if Seroconversion Occurs

Immediately transition to a dolutegravir-, bictegravir-, or ritonavir-boosted darunavir-based regimen initially, which can be subsequently tailored according to clinical resistance test results. 1 However, the guideline-recommended approach specifically for cabotegravir PrEP seroconversion is:

• Begin a protease inhibitor or NNRTI-based antiretroviral regimen (NOT an integrase inhibitor-based regimen) 1
• Obtain genotypic testing including specific integrase resistance testing 1
• Tailor the regimen based on resistance results 1

Common Pitfall to Avoid

The most critical error is inadequate HIV testing before initiation or at follow-up visits. 2 Specifically:

• Never rely on antibody testing alone—always include HIV RNA testing before the first injection 5, 2
• Never skip pre-injection HIV testing even if the patient seems low-risk or was recently tested 1
• Never continue cabotegravir or switch to another integrase inhibitor if seroconversion is detected, as this will select for multi-drug resistant virus 1, 6

Patient Education Points

Counsel patients that:

• They must return for HIV testing before every injection—missing this testing could result in undetected HIV infection and drug resistance 1
• If they develop symptoms suggestive of acute HIV infection (fever, rash, lymphadenopathy, flu-like illness), they should seek immediate testing before their next injection 2
• Cabotegravir remains in the body for months after the last injection, so continued HIV testing is needed even after discontinuation 5, 7
• If transitioning off cabotegravir, they should start oral PrEP within 12 weeks after the last injection to maintain protection during the pharmacokinetic tail period 7