PrEP (Pre-Exposure Prophylaxis) isn't just "take a pill every day." You have three distinct options depending on your lifestyle, all with near-identical protection when used correctly.

Important: Oral modes apply to Truvada (TDF/FTC) and generic equivalents. Descovy (TAF/FTC) users must take it daily—On-Demand is NOT approved for Descovy.

Mode 1: Daily Oral (The Gold Standard)

Best for: Peace of mind, spontaneous sex, poor planning.

  • Protocol: 1 pill, every 24 hours.
  • Startup: You need 7 days of pills before you are protected for anal sex.
  • Missed a dose? If you take 4+ pills a week, you still have high protection (for anal sex). But aim for 7/7.
  • The Vibe: "Set and forget." You are always ready.

Mode 2: On-Demand (2-1-1)

Best for: Guys who have sex less frequently, or can plan 2 hours ahead. Only works with: Truvada (TDF/FTC) or generic equivalents—not Descovy. Risk: If you mess up the timing, protection drops.

  • The Protocol:

    1. Double Dose (2 pills): Take 2 pills 2 to 24 hours BEFORE sex.
    2. Single Dose (1 pill): Take 1 pill 24 hours after the first dose.
    3. Single Dose (1 pill): Take 1 pill 24 hours after the second dose.

  • The "Weekend" Scenario:

    • Friday 6 PM: Take 2 pills (Planning for 8 PM sex).
    • Saturday 6 PM: Take 1 pill.
    • Sunday 6 PM: Take 1 pill.
    • If you keep having sex on Saturday/Sunday: Continue taking 1 pill daily until 2 days after your last hookup.

  • Critical Warning: You MUST take the "after" pills. If you skip the tail, the virus can sneak in.

Mode 3: Injectable PrEP (Cabotegravir / Apretude)

Best for: Guys who struggle with daily pill adherence, or who want zero pills. Brand name: Apretude (US), Vocabria (EU and other markets).

  • How it works: A long-acting injectable (given as a gluteal IM injection by your doctor or nurse). No pills. No daily routine.
  • The Schedule:
    1. Month 0: First injection at the clinic.
    2. Month 1: Second injection (4 weeks later).
    3. Every 2 months after that: One injection every 8 weeks.
  • The Startup: Unlike oral PrEP, you are not fully protected between your first and second injection. Use condoms or oral PrEP during that first 4-week gap.
  • Efficacy: Non-inferior to daily oral TDF/FTC—the HPTN 083 trial showed it was actually slightly more effective in practice (because adherence is easier when there's no daily pill to forget).
  • The Catch: If you stop injections (or miss one), the drug lingers in your body for months at slowly declining levels. During this "tail," you could be exposed with levels too low to protect you but still high enough to allow resistance to develop. If you stop, bridge immediately with oral PrEP until your doctor confirms the drug has cleared.
  • Availability: Not yet universally available. Check your country's healthcare access guides.

Emerging Option: Twice-Yearly Injectable (Lenacapavir)

Lenacapavir (PURPOSE 2 trial) showed approximately 96% efficacy in a broad population including gay and bisexual men, with only two injections per year. As of early 2026 this is in the process of regulatory approval in various countries. Ask your sexual health clinic if it has become available in your region.

Side Effects (Oral PrEP Startup Phase)

When you start oral PrEP, you might feel:

  • Nausea
  • Headache
  • "Gurgle-gut"

This usually passes in 1–2 weeks. Do not stop. Try taking it with food or before bed to sleep through the nausea.

Injectable PrEP side effects are mainly injection-site reactions (soreness, nodule at injection site) which typically resolve within a few days.

Long Term (Oral PrEP)

  • Kidneys: Your doctor checks creatinine every 3 months.
  • Bones: Rare density issues with TDF (reversible). Descovy has a more favorable bone/kidney profile.

The Trade-off: Mild nausea for a week vs. HIV risk. The math is simple.

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