Guideline Summary for Initiating and Managing Apretude (Cabotegravir Injectable PrEP)

Initiation & Mandatory HIV Testing

Perform FDA‑approved HIV testing for acute/primary HIV‑1 infection immediately before the first Apretude injection and before every subsequent injection; then administer 600 mg gluteal injections at month 0 and month 1, followed by injections every 2 months, with a mandatory 7‑day oral PrEP overlap after the first injection. International Antiviral Society‑USA recommendation. 1
If a significant HIV exposure occurred within the prior 72 hours, provide a 28‑day post‑exposure prophylaxis (PEP) regimen first, then transition to PrEP only after a negative HIV test at the end of PEP. International Antiviral Society‑USA guidance. 1, 2

Prior to the first injection, obtain baseline HIV testing, hepatitis B serology, and renal/hepatic function tests to ensure safety and to inform selection of any oral PrEP bridge. International Antiviral Society‑USA emphasizes rapid initiation with minimal delays. 1, 3
PrEP may be started while awaiting additional labs if a negative HIV test has been documented within the previous 7 days. International Antiviral Society‑USA guidance. 1, 3

Use a 4–5‑week oral lead‑in (cabotegravir or tenofovir‑based) for individuals with severe atopic histories to assess tolerability, or when the patient explicitly requests it. International Antiviral Society‑USA recommendation. 1, 2, 3
Do not use an oral lead‑in for individuals who have demonstrated challenges adhering to daily oral medication, as this defeats the purpose of long‑acting therapy; for most other patients the lead‑in is optional. International Antiviral Society‑USA recommendation. 1, 2, 5

Administer 600 mg (3 mL) cabotegravir intramuscularly into the gluteal muscle; the first two injections are spaced 4 weeks apart, and all subsequent injections are given every 8 weeks. Gluteal administration only—anterior‑thigh injections fail to achieve target pharmacokinetics and have poor tolerability. International Antiviral Society‑USA recommendation. 1, 3, 2
A 7‑day oral PrEP overlap after the first injection is mandatory because protective drug levels are achieved only after approximately 7 days. International Antiviral Society‑USA recommendation. 1, 2, 3, 5
If an oral cabotegravir lead‑in was used, continue oral cabotegravir for 7 days after the first injection; if no oral lead‑in or transitioning from tenofovir‑based PrEP, use tenofovir‑based oral PrEP for the same 7‑day period. International Antiviral Society‑USA guidance. 1, 2, 3
Provide a one‑month supply of tenofovir‑based oral PrEP as a bridge if an injection is delayed by 7 days or more. International Antiviral Society‑USA guidance. 1, 2, 3

If the second injection is delayed ≥8 weeks after the first (≥12 weeks total) or any later injection is delayed ≥8 weeks from the prior dose (≥16 weeks total), restart with a “reloading” protocol: give two injections 4 weeks apart before returning to the standard 8‑week schedule. This expert consensus differs from the FDA label. International Antiviral Society‑USA consensus. 1, 2, 4

Cabotegravir must not be co‑administered with potent UGT1A1 inducers (e.g., rifampin, rifapentine, carbamazepine, phenytoin, phenobarbital) because they markedly lower drug concentrations. International Antiviral Society‑USA safety warning. 1, 2
When co‑administered with rifabutin, a dose adjustment of cabotegravir is required. International Antiviral Society‑USA recommendation. 1, 2
Use caution in individuals with gluteal implants or fillers, as they may affect injection site absorption. International Antiviral Society‑USA precaution. 1

If HIV infection is diagnosed while on Apretude, immediately transition the patient to a full HIV treatment regimen; continuing Apretude alone risks the development of resistance. International Antiviral Society‑USA management guideline. 1, 4

When stopping Apretude while HIV exposure risk persists, transition to an alternative prevention strategy (e.g., tenofovir‑based oral PrEP) and maintain it for as long as risk continues. International Antiviral Society‑USA recommendation. 1, 4

All facts are derived from cited references and reflect the 2025 International Antiviral Society‑USA guidelines for cabotegravir injectable PrEP.