There is one complete long-acting injectable HIV treatment: Cabenuva (cabotegravir + rilpivirine), given as two gluteal injections either monthly or every two months, for people already virally suppressed on a stable regimen. Sunlenca (lenacapavir) is a twice-yearly injection used with other antiretrovirals for multidrug-resistant HIV. Twice-yearly lenacapavir sold as Yeztugo is for prevention, not treatment.
Cabenuva: the first complete injectable regimen
FDA approved Cabenuva on January 21, 2021 as the first extended-release injectable complete regimen for HIV-1 in adults, initially once monthly; oral cabotegravir (Vocabria) was approved the same day for the optional lead-in[2].
The current label covers adults and adolescents 12 and older weighing at least 35 kg, to replace a current regimen in people who are virologically suppressed (HIV-1 RNA under 50 copies/mL) on a stable regimen, with no history of treatment failure and no known or suspected resistance to cabotegravir or rilpivirine[1]. That is the key thing to know before hoping for it: Cabenuva is a switch option for people whose treatment is already working, not a rescue for a regimen that is failing. HHS also notes it has not been studied as an option for people who cannot take oral medications[3].
How it's given, and how flexible the schedule is
Cabenuva is given as gluteal intramuscular injections only — two injections at the same visit, at separate sites on opposite sides or at least 2 cm apart, with the ventrogluteal site recommended. Longer needles may be needed at a BMI over 30, and you will be observed for about 10 minutes afterward because of rare post-injection reactions[1].
Two schedules exist[1]:
- Monthly — 600/900 mg to initiate, then 400/600 mg every month
- Every 2 months — 600/900 mg at Month 1 and Month 2, then every two months from Month 4
You can start with an optional oral lead-in — cabotegravir 30 mg plus rilpivirine 25 mg daily with a meal for at least 28 days, to check tolerability — or go direct-to-injection. And life is allowed to happen: injections may be given up to 7 days before or after the scheduled date[1].
What the trials showed
Three trials support the regimen[1]:
- FLAIR — 94% on injections vs 93% on oral therapy had HIV RNA under 50 copies/mL at Week 48
- ATLAS (n=616) — 93% vs 95% suppressed at Week 48
- ATLAS-2M (n=1,045) — 94% suppressed in both the every-2-month and monthly arms at Week 48 (difference 0.8%, 95% CI −0.6% to 2.2%), which is what made every-2-month dosing possible
Resistance is uncommon but real. Among 8 confirmed virologic failures on cabotegravir plus rilpivirine in pooled FLAIR and ATLAS data, 7 of 8 developed NNRTI-resistance substitutions and 5 of 8 developed integrase-inhibitor substitutions[1].
The trade-offs, missed injections, and stopping safely
Injection-site reactions are common — 83% of participants in pooled FLAIR and ATLAS data reported them (pain or discomfort 79%, nodules 14%), with a median duration of 3 days; 1% stopped treatment because of them. Other common reactions included fever, fatigue, headache, musculoskeletal pain, nausea, sleep problems, dizziness, and rash. Labeled warnings include serious hypersensitivity reactions (including SJS/TEN and DRESS), hepatotoxicity, depressive disorders, and rare post-injection reactions[1].
Missing an injection is managed, not catastrophic. For a planned gap longer than 7 days, daily oral cabotegravir plus rilpivirine can bridge for up to 2 months. For unplanned gaps, dosing is either resumed or re-initiated depending on elapsed time — 2 months is the dividing line on monthly dosing, 3 months on the every-2-month schedule[1]. HHS is blunt that people who miss doses or stop without oral bridging face higher risk of virologic failure and resistance[3]. If you know a visit is going to be a problem, call the clinic before the window closes — that call is the whole intervention.
Stopping requires a plan. Residual drug can stay in circulation for 12 months or longer, so an alternative fully suppressive regimen must begin no later than 1 month after the final injections on monthly dosing, or 2 months on every-2-month dosing[1]. HHS adds that the transition should happen within 4 weeks of the last planned injections, with a viral load checked beforehand and resistance testing considered if there is any viremia[3].
Sunlenca — twice-yearly, for multidrug-resistant HIV
Sunlenca (lenacapavir) is the first HIV-1 capsid inhibitor, FDA-approved in December 2022 in combination with other antiretrovirals for heavily treatment-experienced adults with multidrug-resistant HIV-1 whose current regimen is failing because of resistance, intolerance, or safety concerns. After oral loading, maintenance is 927 mg subcutaneously every 26 weeks (±2 weeks); if more than 28 weeks pass, initiation dosing restarts. Residual drug may persist 12 months or longer, and injection-site reactions occurred in 65% of participants, with nodules or induration that can persist[4].
The CAPELLA trial (NCT04150068) enrolled people previously treated with a median of nine antiretrovirals. During 14-day functional monotherapy, 88% (21 of 24) on lenacapavir versus 17% (2 of 12) on placebo achieved at least a 0.5 log10 viral load reduction; at Week 52, 83% (30 of 36) had HIV-1 RNA under 50 copies/mL, with a mean CD4 increase of 82 cells/µL[4]. For people who had been told they were running out of options, that is a meaningful number.
One clean distinction: twice-yearly lenacapavir marketed as Yeztugo was FDA-approved in June 2025 for PrEP — reducing the risk of sexually acquired HIV in people who do not have HIV — and is not an HIV treatment regimen[5]. Same molecule, different job. Other injectable or infused antiretrovirals HHS lists for specific situations include zidovudine, enfuvirtide, and ibalizumab (2,000 mg IV loading, then 800 mg IV every 14 days)[3].
Florida: covered by ADAP, with real-world barriers documented
Both injectables are covered. The Florida ADAP formulary dated July 2026 lists Cabenuva as an integrase-inhibitor/NNRTI combination and Sunlenca as a capsid inhibitor[7], and Florida DOH posts a lenacapavir prior authorization form alongside its ADAP materials (Help Desk 844-381-2327)[8]. Coverage is not the same as convenience, though, and site-by-site availability varies — ask your clinic or case manager directly whether they administer injections on site.
Florida researchers asked people what actually gets in the way. A qualitative study published in AIDS Patient Care and STDs in June 2024 interviewed 16 people living with HIV and 11 HIV care providers across Florida, described as a high-prevalence setting. People living with HIV saw long-acting cabotegravir/rilpivirine as effective, but named real barriers: getting an injection, needing more clinic visits, and “a feeling that this made HIV the center of one's life.” Providers added concerns about integrase resistance. Outside the clinic, both groups pointed to transportation, stigma, access inequities, and payor problems; inside clinics, providers named staffing needs and added burden on existing staff[6]. None of that is a reason not to ask — it is a list of things worth solving out loud with your care team.
Related questions
Can I switch from pills to injections?
Possibly. Cabenuva is labeled to replace a current regimen in people 12 and older weighing at least 35 kg who are virologically suppressed under 50 copies/mL on a stable regimen, with no history of treatment failure and no known or suspected resistance to cabotegravir or rilpivirine. It is a switch option for treatment that is already working, not a fix for a failing regimen.
How often do I need injections?
Cabenuva is given monthly or every two months, as two gluteal intramuscular injections at the same visit. Injections may be given up to 7 days before or after the scheduled date. Sunlenca, used with other antiretrovirals for multidrug-resistant HIV, is given every 26 weeks with a two-week window.
What happens if I miss an injection appointment?
It is managed, not catastrophic — call the clinic as early as you can. For a planned gap of more than 7 days, daily oral cabotegravir plus rilpivirine can bridge for up to 2 months. For unplanned gaps, dosing is resumed or re-initiated depending on elapsed time, with 2 months the dividing line on monthly dosing and 3 months on every-2-month dosing.
Do injections hurt?
Often, briefly. Injection-site reactions were reported by 83% of participants in pooled FLAIR and ATLAS data — most commonly pain or discomfort (79%) and nodules (14%) — with a median duration of 3 days. Only 1% of participants stopped treatment because of them.
Related from RiseUpToHIV
References & Sources
- FDA — Cabenuva (cabotegravir; rilpivirine) prescribing information, label revised November 2025. Indication, gluteal IM administration, both dosing schedules, ±7-day window, FLAIR/ATLAS/ATLAS-2M results, adverse reactions, missed-dose management, and the 12-month drug tail. ↩ ↩ ↩ ↩ ↩ ↩ ↩ ↩ ↩
- HIV.gov — FDA Approves First Extended-Release, Injectable Drug Regimen for Adults Living with HIV. The January 21, 2021 Cabenuva approval and the simultaneous approval of oral cabotegravir for the lead-in. ↩
- HHS/NIH — Discontinuation or Interruption of Antiretroviral Therapy. Guidance on bridging, transitioning off long-acting therapy within 4 weeks, and other parenteral antiretrovirals. ↩ ↩ ↩ ↩
- Gilead — Sunlenca (lenacapavir) FDA approval as a first-in-class twice-yearly treatment option. Sunlenca indication, every-26-week dosing, injection-site reaction rate, and CAPELLA trial results. ↩ ↩
- Gilead — Yeztugo (lenacapavir) approved for HIV prevention (June 2025). Confirms Yeztugo is a PrEP product, not an HIV treatment regimen. ↩
- Fisk-Hoffman RJ, et al. — Perspectives Among Health Care Providers and People with HIV on Implementation of Long-Acting Injectable Cabotegravir/Rilpivirine in Florida, AIDS Patient Care STDS (June 2024). Florida-specific qualitative study of 16 people living with HIV and 11 providers, documenting barriers and facilitators. ↩
- Florida Department of Health — ADAP Formulary, July 2026. Confirms Cabenuva and Sunlenca coverage under Florida's AIDS Drug Assistance Program. ↩
- Florida Department of Health — AIDS Drug Assistance Program. ADAP contacts, eligibility, and the posted lenacapavir prior authorization form. ↩
Community publications like POZ, Positively Aware, and TheBody inform framing and lived-experience context on RiseUpToHIV. Every clinical, epidemiological, or public-health claim above is anchored to a primary source.