Long-Acting Injectable HIV PrEP — Apretude and Lenacapavir

Daily oral PrEP is one of the great public-health interventions of our time — but daily pills don't work for everyone. The long-acting injectable options have transformed HIV prevention for people who struggle with daily adherence, want more discretion, or simply prefer a fewer-touchpoint regimen.

Here's the practical guide to Apretude (cabotegravir, every 2 months) and Lenacapavir (every 6 months) as PrEP.

The short answer

Why injectable PrEP exists

Daily oral PrEP (Truvada or Descovy) is highly effective but requires:

• Daily pill-taking
• Storage and transport of medication
• Disclosure of HIV-prevention status (pill bottles can be seen)
• Visit-based prescription refills
• Strong adherence to maintain protection

For some people, this is hard:

• Inconsistent housing
• Mental health challenges
• Substance use
• Privacy concerns
• Trauma history
• Forgetfulness
• Travel patterns

Injectable PrEP solves the adherence problem by giving you protection that lasts for months on a single injection.

Apretude (cabotegravir IM)

What it is

• Cabotegravir is an integrase inhibitor
• Injected into the buttock muscle (gluteal IM)
• Long-acting nanosuspension — slowly releases over weeks

Dosing

• Optional oral lead-in: 30 days of oral cabotegravir to assess tolerability
• Initiation: Two doses 1 month apart
• Maintenance: Every 2 months thereafter

Effectiveness

• In HPTN 083 trial (MSM and transgender women): 99% reduction in HIV vs placebo; superior to daily oral Truvada
• In HPTN 084 trial (cisgender women): 89% reduction in HIV vs placebo; superior to daily oral Truvada in this population too

Side effects

• Injection-site reactions: pain, swelling, lump at site — most common
• Fatigue, mild fever for 1-3 days post-injection
• Mild GI symptoms — occasional
• Rare: liver enzyme elevations, hypersensitivity

Drug interactions

• Phenytoin, carbamazepine, rifampin — may reduce cabotegravir levels
• Most other medications don't significantly interact

Eligibility

• HIV-negative confirmed (must test before each dose)
• Adequate kidney function
• Not pregnant (use is being studied in pregnancy)

Access

• Available at HIV clinics, some primary care, sexual health clinics
• ~$3,500 per dose without insurance
• Most insurance covers
• Patient assistance program available

Lenacapavir (every-6-month subcutaneous)

What it is

• Lenacapavir is a capsid inhibitor — a first-in-class drug
• Injected subcutaneously (under skin) into abdomen
• Lasts for 6 months from a single injection

Dosing

• Oral lead-in: 14 days of oral lenacapavir
• Initiation: Single subcutaneous injection
• Maintenance: Every 6 months thereafter

Effectiveness

• PURPOSE-1 (cisgender women, sub-Saharan Africa): 100% reduction in HIV cases vs placebo
• PURPOSE-2 (MSM, transgender women, gender-diverse people): 99-100% reduction vs placebo
• Possibly the most effective PrEP option ever tested

Side effects

• Injection-site reactions: lump (subcutaneous nodule) at injection site — common, may persist for weeks
• Mild headache, nausea initially
• Rare: hypersensitivity reactions

Approval and access

• FDA approved as PrEP in 2025 (originally approved for treatment of multidrug-resistant HIV in 2022)
• Distribution is still expanding
• Pricing in development; expected to be expensive initially but with patient assistance programs

Best candidates

• People who would benefit most from 2x/year dosing
• High HIV-acquisition risk
• Limited access to frequent healthcare
• People who tried other PrEP and had issues

How to access injectable PrEP

Step 1: Find a provider

• Most HIV-prevention clinics offer Apretude
• Lenacapavir access is more limited; ask at specialty clinics
• LGBTQ+ health centers often have streamlined access
• Some primary care providers prescribe both

Step 2: Insurance navigation

• Most insurance covers Apretude
• Lenacapavir coverage is being worked out in real time
• Patient assistance programs (ViiV, Gilead) cover uninsured patients

Step 3: Schedule injections

• Set recurring appointments
• Apretude requires every-2-month visit
• Lenacapavir requires every-6-month visit
• Plus regular HIV/STI screening

Step 4: Monitoring

• HIV test before each injection
• Regular STI screening (every 3-6 months recommended)
• Kidney function checks periodically

Choosing between oral and injectable PrEP

Choose oral PrEP if:

• You have good daily medication routines
• You want flexibility to stop quickly
• You're in a stable situation
• Cost is a major factor (generic oral PrEP very cheap)
• You want to test PrEP before committing

Choose injectable PrEP if:

• Daily pill-taking is hard for you
• You want maximum discretion
• You travel frequently
• You've had issues with oral adherence
• You're at very high HIV risk and want best protection

Choose Apretude (every 2 months) if:

• You want established efficacy data
• You're a candidate per current guidelines (MSM, transgender women, cisgender women)
• You can handle bi-monthly clinic visits

Choose Lenacapavir (every 6 months) if:

• You want minimal-touchpoint protection
• You're at very high risk
• You can access it (limited availability)

The "long tail" — what happens if you miss a dose?

Apretude

• 2-month dose late by < 2 weeks: just take it
• More than 2 weeks late: consider oral PrEP bridge or restart with oral lead-in
• Stopping completely: long "tail" of drug remains in body for months; switch to oral PrEP for tail period if continued exposure expected

Lenacapavir

• Even less data on missed doses
• Long-acting profile means residual protection
• Bridge with oral PrEP if dose is late

This is why HIV testing before each dose matters — to catch any breakthrough infection during a missed-dose period.

What about other long-acting options?

Cabenuva (cabotegravir + rilpivirine)

• For HIV TREATMENT (not PrEP)
• Combination injectable for HIV+ patients
• Approved 2021

Vocabria (oral cabotegravir)

• Oral version used as lead-in for Apretude
• Not typically used as standalone PrEP

Future

• Annual or 12-month dosing in development
• Implants and patches being studied
• New mechanism drugs in trials

Bottom line

Injectable HIV PrEP options give you:

• Apretude — every 2 months IM; well-established
• Lenacapavir — every 6 months SC; newest and possibly most effective

Both are highly effective. Both eliminate daily pill burden. Both require recurring clinic visits but at much lower frequency than daily medication.

If oral PrEP isn't working for you — for any reason — talk to your provider about injectable options. There's a PrEP regimen that fits almost everyone now.

For more on HIV prevention: PrEP vs PEP, PrEP side effects, PEP eligibility, and our HIV pillar guide.