Medically reviewed by Charles Maddix, MSN, APRN, PMHNP-BC
Last updated: July 2026

Switching from Daily PrEP to Apretude: Step by Step

If you're already on daily Truvada or Descovy and you're tired of the pill, the switch to injectable cabotegravir (Apretude) is one of the more straightforward transitions in HIV prevention — but it has a few steps that matter, and one or two that people are surprised by. Here's what the process actually looks like, from the last pill to the first every-two-months rhythm.

Step 1: Confirm you're a good fit

Apretude is FDA-approved for adults and adolescents weighing at least 35 kg (77 lb) who are at risk of HIV through sex. The switch makes the most sense if you've struggled with daily adherence, don't want a pill bottle around, or simply prefer six clinic visits a year to a daily task. In the approval trials, cabotegravir outperformed daily oral PrEP: the HPTN network reported a 69% lower HIV incidence versus daily Truvada in HPTN 083 (men who have sex with men and transgender women) and 92% lower in HPTN 084 (cisgender women) — a gap driven largely by missed pills, which is exactly the problem the injection removes.

Two groups need extra thought. First, anyone on a strong enzyme inducer — the label lists rifampin, rifapentine, carbamazepine, oxcarbazepine, phenobarbital and phenytoin as contraindicated, because they drive cabotegravir levels down (rifabutin isn't contraindicated but requires a modified monthly schedule). Second, the label carries a warning about depressive disorders reported with cabotegravir; mention any history of depression at your consult, not as a barrier but so it's on the radar.

Step 2: The HIV tests that gate the first injection

This is the step people underestimate. Starting a single integrase inhibitor in someone with a very early, undetected HIV infection risks resistance to an entire drug class, so the testing bar is higher than it was for your pills. CDC's current PrEP clinical guidance says to test with both an HIV antigen/antibody assay and an HIV-1 RNA assay before starting and at every injection visit, and to check for symptoms of acute HIV. The National HIV Curriculum notes why: standard antigen/antibody tests have performed less well at catching very early infections in people already on PrEP, and the RNA test closes that gap.

Practically: expect a blood draw right before your first shot and a repeat HIV test at every injection appointment after that. STI screening continues on its usual cadence. If your last PrEP labs were recent, some baseline work may already be done, but the HIV test has to be fresh.

Step 3: Decide on the oral lead-in (most switchers skip it)

Apretude's prescribing information offers an optional lead-in: 30 mg of oral cabotegravir (Vocabria) once daily for at least 28 days, with the first injection given on the last day of the tablets or within three days after. The purpose is to test-drive the drug in a form you can stop instantly — if you have a reaction to the tablet, nothing is sitting in your muscle for months. CDC's guidance frames the lead-in as optional and mainly for people worried about side effects.

The honest trade-off: the label also notes there are no safety or efficacy data for Apretude started without a lead-in, because the trials all used one — yet skipping it is explicitly permitted and common in practice. If you tolerated years of oral PrEP without drama, going straight to the injection is reasonable; if you're the cautious type, a month of tablets costs you little. That's a conversation for your prescriber, not a rule.

Step 4: The last pill and the first shot

Here's a gap in the official guidance worth being upfront about. Neither Apretude's label nor CDC's guideline spells out an overlap protocol for people coming off Truvada or Descovy — no instruction to stop the pills a set number of days before the injection, none to keep taking them afterward. No interaction between tenofovir-based PrEP and cabotegravir is flagged. In practice, many clinicians have you take your daily pill through the day of the first injection and then stop, so you stay covered while the injection takes hold. Ask your prescriber what they want, and if you've been inconsistent with pills in the weeks before the switch, say so — it changes how carefully they'll look for early HIV before injecting.

The injection itself is 600 mg (3 mL) into the gluteal muscle, given by a clinician — not a self-injection. The second initiation dose comes one month later; after that it's one every two months.

Step 5: Living inside the 7-day window

Apretude's label allows each injection to be given up to 7 days before or after its scheduled date. Overshoot and the fix depends on where you are in the schedule. Per the label: if the second initiation injection is late but it's been two months or less since the first, you get the shot as soon as possible and carry on; past two months, you restart with two initiation doses a month apart. For a continuation injection, the line is three months since the last shot — inside it, catch up and continue; beyond it, restart the initiation sequence. A badly missed appointment costs you an extra injection and an extra month of visits, not permanent trouble. Put the appointments in your calendar the day you get each shot.

What the first few weeks feel like

Injection-site reactions are the headline side effect. Per the label, 82% of the 2,117 cabotegravir recipients in HPTN 083 had at least one, mostly mild or moderate, with a median duration of four days and pain or tenderness accounting for nearly all of them; in HPTN 084 the figure was 38%. The National HIV Curriculum notes reactions typically start about a day after the injection, last around three days, and lead roughly 2% of people to stop. The first two shots are usually the worst. The label also carries warnings for hypersensitivity reactions (including rare severe skin reactions) and hepatotoxicity — new rash, fever or jaundice after a shot warrants a call, not a wait.

What you stop worrying about — and what you don't

One quiet upgrade: CDC's guidance says kidney-function monitoring isn't necessary on cabotegravir, so the creatinine checks that came with Truvada go away. HIV testing and STI screening don't. If you're also using DoxyPEP, nothing changes — doxycycline isn't among the interactions flagged on Apretude's label. Cost is its own topic: the list price is far higher than generic Truvada's, and what you actually pay depends on insurance and the manufacturer's copay program — see the Apretude cost guide, and confirm coverage before the first injection, not after.

Before you switch, know how you'd switch back

This is the part people skip. Cabotegravir doesn't leave the body when you stop showing up for shots — it tapers over many months, and the label says residual drug can remain in circulation for 12 months or longer. During that "tail," levels are high enough to select for resistance if you acquire HIV but too low to reliably prevent it. CDC's guidance is specific: if you stop injections and still have HIV risk, start daily oral PrEP within 8 weeks of the last injection and keep quarterly HIV-testing visits going for 12 months. Switching to Apretude isn't a one-way door, but the exit has a protocol: back to pills is easy, back to nothing is the risky move.

Also worth knowing: Apretude is no longer the only injectable. Lenacapavir (Yeztugo), given every six months, joined CDC's recommendations in September 2025 — if the two-month cadence is what gives you pause, raise that comparison at the same visit. (And Cabenuva is HIV treatment, not PrEP — same molecule, different drug.)

When to talk to a clinician

Bring the switch up if you keep missing pills, if you're anxious about having PrEP visible at home, if you travel in ways that make daily dosing hard, or if you simply prefer the shot. Raise it with more care if you take seizure or TB medication, have a history of depression, have had a serious drug rash, or have been off your pills for stretches recently. Our reviewing clinical team prescribes and coordinates injectable PrEP by telehealth — the injections themselves have to happen in person, so part of the visit is arranging where — and the $25/month membership covers the visits and lab coordination. You can book a visit directly.

The bottom line

Switching from daily PrEP to Apretude comes down to a fresh HIV test with an RNA assay, an optional month of tablets, two shots a month apart, and then one every two months inside a 7-day window. The trade is fewer decisions for more appointments, some sore days, and a real commitment to showing up — plus a plan for oral PrEP if you ever stop. For the right person, it's the most protective PrEP option they'll ever have actually stuck with.