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.
Hepatitis B: Both Truvada and Descovy are also active against hepatitis B. Your clinic tests for hep B before you start. If you have chronic hep B, oral PrEP is daily only, and you should never stop it without your clinic — stopping can trigger a serious liver flare. If you're not immune, get vaccinated.
🟢 Mode 1: Daily Oral (The Gold Standard)
If you want maximum coverage and a single habit to keep — this is your mode. One pill, every 24 hours, and you're always ready.
- Startup: You need 7 days of pills before you're protected for anal sex.
- Missed a dose? If you hit 4+ pills a week you still have high protection for anal sex. But aim for 7/7.
- The habit: Pin the pill to something you already do every day — brushing your teeth, your morning coffee. Keep a few spares in your bag. Daily PrEP is the easiest routine you'll run, but it's still a routine.
🔀 Mode 2: On-Demand (2-1-1)
If you have sex less frequently and can plan at least 2 hours ahead, this uses fewer pills with near-identical protection — but only if you follow the timing exactly. Truvada (TDF/FTC) or generic equivalents only — not Descovy.
The Protocol:
- Double Dose (2 pills): Take 2 pills 2 to 24 hours BEFORE sex.
- Single Dose (1 pill): Take 1 pill 24 hours after the first dose.
- 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.
Not for you if you have chronic hepatitis B. Starting and stopping tenofovir around sex can cause hep B flare-ups that damage the liver. Use daily PrEP (or injectable, with separate hep B care) instead.
💉 Mode 3: Injectable PrEP (Cabotegravir / Apretude)
No pills, no daily routine. If adherence to a daily pill is genuinely hard, this is the option. You swap a daily habit for a clinic appointment you can't miss. Brand name Apretude (US, EU, UK) — the same drug is called Vocabria when used as part of HIV treatment, so tell your doctor which you're on.
- 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:
- Month 0: First injection at the clinic.
- Month 1: Second injection (4 weeks later).
- 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.
- Hepatitis B: Cabotegravir has no effect on hep B. If you have chronic hep B, you'll need separate hep B monitoring or treatment alongside it — and if you're switching from oral PrEP, don't stop the pills until your clinic has that covered.
Twice-Yearly Injectable (Lenacapavir / Yeztugo, Yeytuo)
One injection under the skin of the abdomen every 6 months, after a short start-up (injections plus tablets on days 1 and 2). In the PURPOSE 2 trial, which included cisgender gay and bisexual men as well as trans and non-binary people, 2 of 2,179 people on lenacapavir got HIV: 96% fewer infections than expected, and 89% fewer than on daily Truvada.
It's approved in the US, the EU and the UK, and recommended by WHO. But approval isn't the same as access: whether it's funded or offered depends on your country and health system. Ask your clinic whether it's available where you live. Like cabotegravir, it doesn't treat hepatitis B.
🔁 Keeping It Running
PrEP works while you take it. Whichever mode you pick, the protection lives in the habit, not the prescription.
- The clinic visit: Most PrEP prescriptions come with a check-in every 3 months — HIV test, STI swabs, and kidney bloods. That appointment is how you keep your supply coming. Book the next one before you leave.
- The supply: Reorder when you're down to two weeks of pills, not two days.
- The disruptions: Travel, a new job, a breakup, a long weekend on chems. These are when doses slip. Plan for them before they happen.
- Coming off: If you stop, stop properly. The rules for stopping depend on your mode — ask your clinic, don't just let the pack run out. If you have chronic hep B, this matters even more: stopping oral PrEP without a plan can cause a liver flare.
⚠️ Side Effects & What to Expect Long-Term
Starting oral PrEP: the first couple of weeks can bring nausea, headaches, or what some people charitably call "gurgle-gut." It passes within 1–2 weeks for most people. Don't stop — try taking it with food or right before bed to sleep through it. Mild nausea for a week versus HIV risk: the maths is simple.
Injectable PrEP: mainly injection-site reactions — some soreness, occasionally a small nodule. Usually gone within days.
The long-term picture (oral PrEP):
- Kidneys: your doctor checks creatinine (kidney function) every 6–12 months, typically alongside your quarterly swabs.
- Bones: TDF has rare, reversible density effects. Descovy has a better bone and kidney profile if that becomes a concern.
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