Follow-Up HIV-1 RNA and STI Testing After Cabotegravir PrEP Initiation
For routine monitoring during cabotegravir PrEP, HIV RNA testing is NOT recommended; instead, use rapid HIV antibody testing plus laboratory-based antigen/antibody testing at each injection visit (every 8 weeks after the initial 4-week interval), with STI screening every 4 months. 1
HIV Testing Schedule
At Each Injection Visit (Every 8 Weeks)
- Perform rapid point-of-care HIV antibody testing on the day of injection before administering cabotegravir 2
- Send laboratory-based antigen/antibody testing simultaneously, but do not delay the injection while awaiting results 2
- Do NOT routinely perform HIV RNA testing during follow-up because it has low positive predictive value and false-positive results cause significant harm 1
Critical Exception for HIV RNA Testing
- HIV RNA testing IS indicated only at initiation (or resumption after ≥6 months hiatus) along with laboratory-based antigen/antibody testing 1
- If HIV acquisition is suspected during PrEP use, two sequential tests showing HIV RNA detection at any level (even below quantification limits) is highly predictive of true HIV infection 1, 2
STI Testing Schedule
Perform comprehensive STI screening every 4 months (at every second injection visit): 2
- Nucleic acid amplification testing (NAAT) for gonorrhea and chlamydia at all exposure sites (genital and non-genital)
- Blood testing for syphilis
- Quarterly STI screening is recommended for all persons on PrEP 1
Additional Monitoring Requirements
Laboratory Safety Monitoring
- Liver enzyme testing every 6 months 2
- Pregnancy testing (if applicable) every 4 months, aligned with STI testing intervals 2
Late Injection Protocol
- If an injection is ≥8 weeks late from the due date, complete HIV testing before resuming injections 2
- Restart with the initial dosing schedule: first two injections separated by 4 weeks before returning to 8-week intervals 2
Critical Caveats About HIV Detection on Cabotegravir PrEP
The LEVI Phenomenon
Diagnosis of HIV during cabotegravir PrEP is challenging due to "long-acting early viral inhibition" (LEVI), which causes delayed and inconsistent detection of viremia, antigen, and antibodies 1. This is why routine RNA testing is discouraged—it creates more confusion than clarity in most cases.
Why RNA Testing Is Not Routine
- False-positive RNA results have significant negative consequences including unnecessary treatment initiation, psychological distress, and partner notification 1
- The positive predictive value of single RNA tests is low in this population 3
- Antibody-based testing combined with antigen/antibody testing provides adequate surveillance when performed consistently at each visit 1
When to Suspect Breakthrough Infection
If acute HIV symptoms develop (fever, fatigue, rash, lymphadenopathy, sore throat, myalgias), immediately perform both antigen/antibody and RNA testing, as these symptoms may indicate recent HIV acquisition 4. Contact the PrEP Warmline at 1-855-HIVPrEP for discordant or difficult-to-interpret results 1.
Resistance Concerns
Breakthrough infections on cabotegravir PrEP have been associated with integrase strand transfer inhibitor (INSTI) resistance mutations 5, 6, making early detection critical to prevent resistance development and allow appropriate treatment selection.