Long-Acting Antiretroviral Therapy
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Direct answer
Two intramuscular gluteal injections, given as seldom as every two months, can now maintain HIV viral suppression: long-acting cabotegravir (an integrase inhibitor) plus long-acting rilpivirine (an NNRTI) form the first complete injectable antiretroviral regimen for adults already virologically suppressed on oral therapy. The sequence is an oral lead-in of about a month (cabotegravir 30 mg plus rilpivirine 25 mg daily), then two initiation injections one month apart, then maintenance — 600 mg cabotegravir plus 900 mg rilpivirine every eight weeks, validated as non-inferior to monthly dosing in the ATLAS-2M trial after ATLAS and FLAIR established efficacy versus oral therapy. Lenacapavir, a twice-yearly subcutaneous capsid inhibitor, serves multidrug-resistant HIV, and long-acting cabotegravir alone is an evidence-supported PrEP option. The regimen excludes patients with hepatitis B coinfection (no HBV coverage once orals stop), resistance to either class, and — critically — anyone at risk of missing injection windows, because subtherapeutic drug tails breed resistance.
What you must remember
- The regimen: CAB 600 mg plus RPV 900 mg intramuscularly every 8 weeks for maintenance; monthly dosing (400 mg/600 mg) is the alternative; strictly gluteal, not deltoid, injections.
- Lead-in and initiation: about four weeks of oral cabotegravir 30 mg and rilpivirine 25 mg daily to prove tolerability, followed by two initiation injections four weeks apart before the q8-week schedule.
- Anchor trials: FLAIR and ATLAS (monthly dosing non-inferior to continued oral ART in suppressed adults) and ATLAS-2M (every-8-week dosing non-inferior to monthly, with high satisfaction).
- Exclusions: hepatitis B coinfection (stopping the oral backbone with tenofovir/lamivudine coverage risks fulminant HBV), known resistance to cabotegravir or rilpivirine (NNRTI mutations, integrase Q148 pathways), and unwillingness to keep appointments.
- Pharmacokinetic tail: after stopping injections, drug persists sub-therapeutically for months — the period when monotherapy-level pressure selects resistant virus, so discontinuation must transition to a full oral suppressive regimen promptly.
- Failure pattern: virologic failure on CAB/RPV clusters with archived NNRTI resistance (notably K101E, E138A/K), integrase resistance, high baseline VL and low BMI (subcutaneous fat affecting injection kinetics).
- Lenacapavir: first-in-class capsid inhibitor, subcutaneous twice-yearly after oral loading, indicated for heavily treatment-experienced multidrug-resistant HIV (CAPELLE trial); long-acting cabotegravir every 2 months is PrEP-supported (HPTN 083/084), with twice-yearly lenacapavir PrEP now approved in several countries.
- Indian context: national first-line ART under NACO is oral dolutegravir-based TLD (tenofovir-lamivudine-dolutegravir); long-acting formulations remain private-sector, metro-centre options, but their pharmacology is already exam-worthy.
A switch consultation, conducted properly
A 38-year-old woman, suppressed below 50 copies/mL for two years on TLD, asks to stop daily pills because shift work makes adherence erratic — a legitimate driver of long-acting therapy. Checklist before switching: confirm sustained suppression (no blips above 200), no hepatitis B (her HBsAg is negative — had she been positive, the oral tenofovir-lamivudine backbone could not be withdrawn), no prior NNRTI exposure with failure (she is treatment-naive beyond TLD, so no rilpivirine resistance), BMI above about 18-20 for gluteal depot kinetics, and — decisive here — a realistic guarantee of attending every eight weeks, because a missed month plus a late visit is the recipe for a resistance tail. She takes the one-month oral lead-in, reports no rash or mood change, receives two initiation injections four weeks apart, and thereafter attends bimonthly with viral load checks at least every six months; a planned surgical date is managed by bringing the injection forward within the permitted window rather than deferring it. Contrast a patient with archived efavirenz resistance and K101E: switch is refused, because rilpivirine failure is nearly foretold, and an oral regimen with a fully active third agent is chosen instead.
Where students slip
The numbers get muddled under exam stress: remember maintenance as 600/900 every two months, monthly as 400/600, lead-in as 30/25 daily for about four weeks. The second miss is offering the regimen to a hepatitis-B-coinfected patient — the option list will include exactly that trap. Third, students forget the tail: questions about "what to do when injections stop" are answered by prompt transition to a complete oral regimen, never observation.
Frequently asked questions
What is the standard maintenance dose of long-acting cabotegravir-rilpivirine?
Cabotegravir 600 mg plus rilpivirine 900 mg by gluteal intramuscular injection every eight weeks, after an oral lead-in and two initiation injections four weeks apart.
Which trials established two-monthly injectable ART?
FLAIR and ATLAS showed monthly injectable therapy non-inferior to oral ART; ATLAS-2M then showed every-8-week dosing non-inferior to monthly, with better patient satisfaction.
Why is the regimen contraindicated in hepatitis B coinfection?
Because replacing oral ART removes tenofovir-based hepatitis B suppression, risking severe HBV reactivation; the injectables have no anti-HBV activity.
What is lenacapavir and when is it used?
A first-in-class capsid inhibitor given subcutaneously twice yearly after oral loading, indicated for heavily treatment-experienced HIV with multidrug resistance, and now also used as long-acting PrEP in several countries.
What is the pharmacokinetic tail after stopping injectable ART?
Slow release from the gluteal depot maintains sub-therapeutic levels for months — a monotherapy-like pressure that selects resistant virus unless a fully suppressive oral regimen is started promptly.