What is the window period for cabotegravir (Apretude) to reach maximum protection against HIV infection?

Window Period for Cabotegravir (Apretude)

Cabotegravir injections reach maximum protection within approximately 7 days after the first injection when initiated without oral lead-in, though protection begins within 1-4 days depending on sex assigned at birth. 1

Time to Maximum Protection

Without Oral Lead-In (Direct Injection Start)

• 80% of participants achieve protective drug levels (4× PA-IC90) within:

  • 1.2 days for assigned-male-at-birth individuals 1
  • 1.8 days for 50% assigned-female-at-birth populations 1
  • 2.8 days for assigned-female-at-birth individuals 1

• 50% of participants achieve higher protective levels (8× PA-IC90) within:

  • 1.4 days for assigned-male-at-birth individuals 1
  • 2.1 days for 50% assigned-female-at-birth populations 1
  • 3.8 days for assigned-female-at-birth individuals 1

• Maximum protection is established within approximately 7 days after the first injection 1

With Oral Lead-In (Optional 30-Day Oral Cabotegravir Course)

• Protection is immediate if the first injection is given within 3 days of the last oral dose, as drug levels remain above protective thresholds during this transition period 1
• Pharmacokinetic profiles become identical to direct injection initiation within 1-2 weeks after the first injection 1

Dosing Schedule

• Initial two injections are given 4 weeks apart (loading phase) 2, 3
• Subsequent injections are administered every 8 weeks (maintenance phase) 4, 2
• Each injection consists of 600 mg (3 mL) administered intramuscularly in the gluteal region 2

Critical Implementation Considerations

HIV Testing Requirements

• Perform comprehensive HIV testing (combination antigen/antibody test AND HIV RNA test) before each injection 2, 5
• This is crucial because cabotegravir can delay HIV seroconversion and mask early infection 5

Bridging for Missed Injections

• Keep a 1-month supply of tenofovir-based oral PrEP available for bridging if injections are delayed by 7 days or more 2
• If injections are delayed by 8 or more weeks, restart with two loading injections 4 weeks apart before resuming every-8-week dosing 2

Common Pitfalls to Avoid

• Do not assume immediate protection without considering sex assigned at birth differences - females may require up to 3-4 days to reach protective levels 1
• Do not skip HIV RNA testing - standard antibody tests alone may miss acute HIV infection, particularly important given cabotegravir's long half-life and resistance risk 2, 5
• Do not allow injection gaps >3 days when using oral lead-in - longer gaps may result in subprotective drug levels during the transition 1
• Do not forget to counsel patients about the prolonged drug tail - cabotegravir remains detectable for months after discontinuation, requiring continued HIV monitoring 6

Comparison to Oral PrEP

• Oral tenofovir/emtricitabine reaches maximum protection in 7 days for non-MSM populations 4
• For MSM using oral PrEP, a double-dose loading strategy achieves protection within 24 hours 4
• Cabotegravir demonstrated superior efficacy to daily oral TDF-FTC in preventing HIV acquisition 7