What are the recommended guidelines for initiating Apretude (cabotegravir) injectable PrEP in a patient, including baseline HIV and hepatitis B testing, renal/hepatic labs, pregnancy testing, oral lead‑in, injection schedule, and contraception requirements?

Guidelines for Initiating Apretude (Cabotegravir Injectable PrEP)

Apretude should be initiated with mandatory HIV testing immediately before the first injection and before each subsequent injection, using FDA-approved tests for acute/primary HIV-1 infection, followed by 600 mg gluteal injections at months 0 and 1, then every 2 months thereafter, with a 7-day oral PrEP overlap after the first injection. 1, 2

Pre-Initiation Requirements

HIV Testing (Critical - Boxed Warning)

• Perform HIV testing immediately prior to initiating Apretude using an FDA-approved test capable of detecting acute or primary HIV-1 infection (ideally antigen/antibody and RNA assay if available within 7 days). 1, 2
• Do not initiate if HIV status is unknown or positive - this is an absolute contraindication due to risk of drug resistance. 2
• If substantial HIV exposure occurred within the past 72 hours, provide 28-day post-exposure prophylaxis (PEP) first, then transition to PrEP only after negative HIV testing at PEP completion. 1
• Screen for signs/symptoms of acute HIV infection before each injection throughout treatment. 1, 2

Baseline Laboratory Testing

While the 2025 International Antiviral Society-USA guidelines emphasize rapid PrEP initiation with minimal delays 1, baseline safety assessments should include:

• HIV testing (mandatory) 2
• Hepatitis B testing (contraindication for some oral PrEP alternatives, relevant for transition planning) 1
• Pregnancy testing in individuals of childbearing potential 2
• Renal and hepatic function (for safety monitoring and oral PrEP selection if needed) 1

Note: PrEP can be initiated while awaiting additional diagnostics if HIV testing from the past 7 days is negative. 1

Oral Lead-In Decision Algorithm

When to Use Oral Lead-In (4-5 weeks)

• Individuals with severe atopic histories - recommended to assess tolerability 1
• Patient requests it - recommended if desired 1

When to Skip Oral Lead-In

• Individuals with adherence challenges to daily oral medications - oral lead-in is NOT recommended as it defeats the purpose of long-acting therapy 1
• Most other patients - oral lead-in is optional, not required 1, 2

Injection Schedule and Dosing

Initial Dosing

• 600 mg (3 mL) gluteal intramuscular injection 1, 2
• First two injections: 1 month apart (4 weeks) 1, 2
• Subsequent injections: every 2 months (8 weeks) 1, 2
• Gluteal administration only - do NOT use anterior thigh (failed to reach pharmacokinetic targets and had poor tolerability) 1

Critical Timing Considerations

• 7-day oral PrEP overlap after the first injection is mandatory - protection onset takes approximately 7 days after first injection 1
• If using oral cabotegravir lead-in: continue oral cabotegravir for 7 days after first injection 1
• If no oral lead-in or transitioning from tenofovir-based PrEP: use tenofovir-based oral PrEP for 7 days after first injection 1
• Provide 1-month supply of tenofovir-based oral PrEP for bridging if injection delays ≥7 days occur 1

Managing Missed Injections

• Injection 2 delayed ≥8 weeks from injection 1 (≥12 weeks total): Restart with "reloading" - give two injections 4 weeks apart before resuming every-8-week schedule 1
• Injections 3+ delayed ≥8 weeks from previous (≥16 weeks total): Restart with "reloading" - give two injections 4 weeks apart before resuming every-8-week schedule 1
• This 2025 guideline differs from FDA labeling but represents expert consensus 1

Contraception and Pregnancy Considerations

• Pregnancy testing should be performed at baseline in individuals of childbearing potential 2
• If breastfeeding: Assess benefit-risk carefully as cabotegravir has residual systemic concentrations for up to 12 months or longer after discontinuation 2
• The FDA label emphasizes assessing benefit-risk for breastfeeding due to prolonged drug exposure 2

Drug Interactions (Critical)

Absolute Contraindications

• Do NOT use with potent UGT1A1 inducers (rifampin, rifapentine, carbamazepine, phenytoin, phenobarbital) - these significantly decrease cabotegravir concentrations 1, 2

Dose Adjustments Required

• Rifabutin: Requires dose adjustment if coadministered 1

Special Precautions

• Use caution in individuals with gluteal implants or fillers 1

Ongoing Monitoring Requirements

At Each Injection Visit

• HIV testing before every injection - this is mandatory per boxed warning 2
• Assess for signs/symptoms of acute HIV infection 2
• Monitor for injection site reactions (occurred in up to 81% in trials) 3
• Consider hepatotoxicity monitoring with clinical and laboratory assessment 2
• Evaluate for depressive symptoms if reported 2

If HIV Acquisition Occurs

• Immediately transition to complete HIV treatment regimen - continuing Apretude alone risks resistance 2
• Cabotegravir remains detectable for up to 12 months or longer after last injection, creating prolonged risk for resistance if HIV is acquired 2

Discontinuation Planning

• Transition to alternative HIV prevention is mandatory if stopping Apretude but HIV risk continues 1
• Use tenofovir-based oral PrEP or other appropriate prevention strategies 1
• Continue alternative prevention as long as HIV exposures persist 1
• Remember: residual cabotegravir concentrations persist for up to 12 months or longer, creating ongoing resistance risk if HIV is acquired during this tail period 2

Common Pitfalls to Avoid

• Do not skip HIV testing at any injection visit - this is the most critical safety requirement 2
• Do not use oral lead-in in patients with adherence challenges - it contradicts the purpose of long-acting therapy 1
• Do not forget the 7-day oral PrEP overlap after first injection - protection is not immediate 1
• Do not use anterior thigh injections - only gluteal administration is supported by data 1
• Do not continue Apretude monotherapy if HIV is acquired - immediate transition to full treatment is required 2