How Effective Are Long-Acting Injectable HIV Treatments?
A shot every month or two can replace daily HIV pills for many people. Does it control the virus as well? We go through the trial numbers behind Cabenuva, what happens in the small share of people whose virus breaks through, the new evidence for people who struggle with daily pills, and the October 2026 report on lenacapavir plus cabotegravir, so you can have a sharper conversation with your HIV clinician.
- In three large trials, monthly or every-two-month cabotegravir-rilpivirine kept people suppressed about as well as daily pills. Everyone in those trials was already undetectable when they switched.
- Failures are rare but can come with drug resistance. A viral load test at your clinic shows whether injections are working; a home HIV antibody test cannot.
Published: October 2026 | Last updated: October 2026 | Editorial review and quality control: Martina N.
How well do long-acting HIV injections work?
For adults whose virus is already suppressed, about as well as daily pills. In the trials behind Cabenuva, 93–94% of people on monthly injections stayed below 50 copies/mL at 48 weeks, and about 2% or fewer had a viral load of 50 copies/mL or higher. Dosing every two months performed in the same range. The approval covers only people who are already suppressed.
A shot every one or two months can now stand in for daily HIV pills, and the first thing most people want to know is whether it holds the virus down as well. For people who are already undetectable, the trial evidence says yes. The caveats concern who qualifies, what happens in the small share of people whose virus breaks through, and the clinic visits injections require.
The question is in the news again because of a different pairing. On October 8, 2026, clinicians at the University of California, San Francisco, reported in JAMA Network Open that all 46 people who started lenacapavir plus cabotegravir at their clinic reached or kept viral suppression, including many who started with detectable virus and drug resistance. That combination is not approved for treatment, and it gets its own section below.
Our overview of what's new in HIV drugs, PrEP and cure research covers the wider field.
Which injections treat HIV, and which only prevent it
When people talk about injectable HIV treatment, they usually mean Cabenuva, which pairs two medicines, cabotegravir (an integrase inhibitor) and rilpivirine (an NNRTI). It is a complete regimen. Under its FDA prescribing information, it can replace the current regimen in adults and adolescents 12 and older who weigh at least 35 kg. They must be virologically suppressed (HIV-1 RNA below 50 copies/mL) on a stable regimen, with no history of treatment failure and no known or suspected resistance to either drug. A healthcare provider gives the two drugs as separate injections into the buttock muscles, every month or every two months.
Lenacapavir, sold for treatment as Sunlenca, is given under the skin every six months, but it does not work as a stand-alone treatment. Its label restricts it to heavily treatment-experienced adults with multidrug-resistant HIV whose current regimen is failing because of resistance, intolerance or safety concerns, and it is always combined with other HIV medicines.
The same molecule is also used in a prevention shot for people who do not have HIV. Our explainer on Yeztugo, the twice-yearly prevention shot, covers that use. Prevention dosing does not treat an existing infection.
Long-Acting HIV Treatment Options Compared
| Feature | Cabenuva | Sunlenca | Lenacapavir + cabotegravir |
|---|---|---|---|
| Medicines | Cabotegravir + rilpivirine | Lenacapavir | Lenacapavir + cabotegravir, with rilpivirine added for some people |
| Who it is for | People 12+ (at least 35 kg) already below 50 copies/mL, with no past treatment failure and no known or suspected resistance to either drug | Heavily treatment-experienced adults with multidrug-resistant HIV whose regimen is failing | Not approved for treatment; reported from one clinic, mostly in people with NNRTI resistance |
| How it is given | Two injections into the buttock muscles by a healthcare provider | Injection under the skin, alongside other HIV medicines | Varied between patients in the published case series |
| How often | Every month or every 2 months | Every 6 months | No single standard schedule yet |
| Complete regimen on its own? | Yes | No | Being studied as a two-drug long-acting regimen |
Eligibility comes from each product's FDA label; the third column describes a 2026 case series, not an approved use.
What the main trials found
Cabenuva's approval rests on two randomized trials published together in the New England Journal of Medicine in 2020. In FLAIR, people first reached suppression on daily dolutegravir-abacavir-lamivudine and were then randomized to keep taking pills or switch to monthly injections. ATLAS did the same with people who were already stable on a range of oral regimens.
Both trials measured failure, not success. The main outcome was the share of people whose viral load was 50 copies/mL or higher at week 48, and the injections had to come within 6 percentage points of pills to count as noninferior. Both trials met that test. The table below shows the results.
The success column does not add up to 100% because of a third group. Between 4% and 6% of each arm had no viral load result in the week-48 window, mostly because they had left the study or stopped treatment for other reasons. These people were not counted as failures, but they were not counted as successes either.
Noninferior does not mean better. For someone who takes pills reliably, injections offer a different routine, not stronger viral control.
| Trial (week 48) | People per arm | Below 50 copies/mL: injections vs pills | 50 copies/mL or higher: injections vs pills |
|---|---|---|---|
| FLAIR | 283 | 94% vs 93% | 2.1% vs 2.5% |
| ATLAS | 308 | 93% vs 95% | 1.6% vs 1.0% |
Every month or every two months?
The ATLAS-2M trial compared the two schedules directly in 522 people on every-two-month dosing and 523 on monthly dosing. At week 48, 94% in each arm were below 50 copies/mL, and 2% versus 1% had 50 copies or more, which met the noninferiority test, according to the Cabenuva label.
Confirmed failures were less evenly split. Nine people (1.7%) on the every-two-month schedule had confirmed virologic failure, against two (0.4%) on monthly dosing, and 8 of those 11 failures happened at or before the week-24 visit.
The practical difference is six clinic visits a year instead of twelve. Alongside it sits a small numerical difference in confirmed failures (9 vs 2 people), most early in the trial, that is one reason clinicians weigh resistance history before choosing the longer interval. The every-two-month schedule starts with two injection visits a month apart.
The Every-Two-Month Cabenuva Schedule
- Month 1 First injections
Initiation doses of cabotegravir and rilpivirine, given on the last day of current pills or of the oral lead-in
- Month 2 Second injections
A second set of initiation doses one month later
- Month 4 Every-two-month dosing begins
Continuation injections start
- Month 6 Ongoing
Injections continue every two months, with viral load checks set by the clinic
Based on the FDA label; an optional month of pills can come before the first injections.
When injections stop working
Failure is uncommon, but it has bigger consequences than a missed pill. When HIV breaks through on cabotegravir and rilpivirine, the virus often carries resistance mutations, and resistance to these drug classes can narrow the options for the next regimen. That is why the label requires no known or suspected resistance to cabotegravir or rilpivirine before the switch. The baseline factors it links to a higher risk of failure are listed below.
The drugs also leave the body slowly. Someone who stops injections without starting another full regimen in time has falling drug levels for months, which is when resistant virus has room to grow.
Body size comes up in these conversations too. The label does not list BMI as a risk factor for failure. Small subgroup tables show a few more people at or above 50 copies/mL at week 48 with a BMI of 30 or higher (3 of 40 in FLAIR's injection arm, against 3 of 243 with a lower BMI), but the numbers are too small to draw conclusions. A higher BMI can mean a longer needle is needed so the dose reaches the muscle.
Virologic Failure on Cabenuva: What the Label Reports
- In the label's pooled long-term analysis (FLAIR to week 124, ATLAS to week 96), confirmed virologic failure (two viral loads in a row of 200 copies/mL or higher) occurred in 8 of 591 people (1.4%) on monthly injections, the same count as in the daily-pill arms.
- Seven of those eight people had NNRTI resistance-associated mutations.
- Baseline factors linked to higher failure risk: HIV-1 subtype A1, the integrase L74I polymorphism, and archived NNRTI resistance mutations.
- Drug levels can remain for 12 months or longer after the last injection.
- After the final injections, a fully suppressive replacement regimen must start within 1 month on monthly dosing, or within 2 months on every-two-month dosing.
Can injections help people who miss pills?
FLAIR, ATLAS and ATLAS-2M all enrolled people who were already doing well on pills. The harder question is whether injections help people who struggle with daily pills. The LATITUDE trial, published in the New England Journal of Medicine in February 2026, enrolled 453 people with HIV and adherence challenges, defined as a viral load persistently above 200 copies/mL or loss to follow-up. Everyone first received 24 weeks of adherence support and conditional cash incentives on oral treatment. The 306 who reached 200 copies or lower were then randomized: 152 switched to monthly injections and 154 continued standard care.
By week 48, the estimated cumulative probability of regimen failure (virologic failure or stopping treatment) was 22.8% with injections and 41.2% with standard care. In the injection group, 24 of the 29 failures were people permanently stopping treatment, not virologic failure. The randomization was stopped early because injections had proved superior at a prespecified analysis. Two people in each group had confirmed failure with resistance mutations. The trial excluded people with hepatitis B coinfection and people with relevant rilpivirine or integrase-inhibitor resistance.
LATITUDE counted stopping treatment as well as viral breakthrough, so its failure figures cannot be set directly against the 2% in FLAIR and ATLAS. The people enrolled also had a much harder starting situation. LATITUDE does not change the FDA label, which still covers only people who are already suppressed. Whether someone outside the label is offered injections is a decision for their HIV clinician.
Monthly CAB+RPV long-acting injectable ART demonstrated superior efficacy in reducing regimen failure over SOC in PWH with adherence challenges.
The newest data: lenacapavir plus cabotegravir
The October 2026 report pairs cabotegravir with lenacapavir, in place of rilpivirine or alongside it. The idea is to give injectable treatment to people whose rilpivirine resistance rules out Cabenuva. The JAMA Network Open case series reviewed 46 people who started the combination at UCSF's Ward 86 HIV Clinic between March 2023 and May 2025. Nearly three-quarters had baseline NNRTI resistance, and 24 (52%) had a viral load of 200 copies/mL or higher at the start. Seventeen also received rilpivirine.
Over a median follow-up of 100 weeks, people who started suppressed stayed suppressed. Those who started with detectable virus all reached suppression by week 13, and no one had two viral loads in a row above 200 copies/mL. For a group that many clinics would struggle to treat, that is a strong early signal.
It was a retrospective review of one clinic's records in a small group. The authors note that Ryan White-funded clinics like theirs have higher suppression rates than the U.S. average, so results may not carry over to other settings. Regimens also differed between patients and there was no comparison group. The combination is not FDA-approved for HIV treatment. If you think you might be a candidate, ask your HIV clinician about clinical trials instead of asking to switch now.
What being on injections involves
Injections replace daily pills with a standing appointment. The NIH HIVinfo fact sheet notes that long-acting HIV medicines are given by a healthcare provider at regular visits. On the monthly schedule, the label allows each dose to be given up to 7 days before or after the scheduled date. If a visit has to be missed, tell the clinic ahead of time: the label has specific instructions that depend on how late the dose will be.
Sore injection sites are the norm. In FLAIR and ATLAS, 83% of people on monthly injections reported an injection-site reaction, most often pain or discomfort, and 4% had a severe (grade 3) reaction. Only 1% stopped treatment because of these reactions. In the two trials, injection-related side effects were common but rarely led people to stop.
Stopping takes planning too. Because the drugs fade slowly, ending injections means starting a full replacement regimen on the timeline in the fact list above, not just skipping the next visit.
How to tell whether injections are working
The test that answers this is a viral load test, an HIV RNA blood test processed by a lab and ordered by your HIV clinic on the schedule it sets. The CDC's page on treating HIV explains why the number matters: if you have an undetectable viral load, you will not transmit HIV through sex (Undetectable = Untransmittable), as long as it stays undetectable.
An HIV antibody test, including a home fingerstick kit, cannot do this job. Antibodies stay detectable in people living with HIV whether or not treatment is working, so an antibody result says nothing about how well injections are controlling the virus. Our article on HIV shots in older adults covers the difference between treatment monitoring and HIV testing in more depth.
HIV-negative partners have their own long-acting option. Our guide to the twice-yearly lenacapavir PrEP shot explains how it works for people who do not have HIV.
FAQs
- Do injections work as well for teenagers?
- Early data are encouraging but limited: in the label's adolescent study (MOCHA, no comparison group), 139 of 141 participants with available data remained below 50 copies/mL at week 24. Cabenuva is approved from age 12 for people who weigh at least 35 kg.
- Is every-two-month dosing easier on the injection sites?
- Not noticeably. In ATLAS-2M, 75% of people on each schedule reported an injection-site reaction, and pain was reported by 73% on every-two-month dosing and 71% on monthly dosing. The difference is fewer visits, not milder shots.
- Do I have to take pills before the first injection?
- Not for Cabenuva. The label calls the oral lead-in optional, to check tolerability: you and your provider can choose about a month (at least 28 days) of the same two drugs as tablets, or go straight to injections. The label's hypersensitivity warning notes that the lead-in can help identify people at risk of a reaction, so ask your clinician which they prefer.
- Can I give Cabenuva injections myself at home?
- No. The label says Cabenuva must be given by a healthcare provider as injections into the buttock muscles, with the two drugs placed at separate sites during the same visit.
This article summarizes current guidance from the U.S. National Institutes of Health (NIH), NIH HIVinfo and the U.S. Centers for Disease Control and Prevention (CDC). Each specific figure or recommendation links to the page that states it, and every page used is listed under Sources with what it supports. It is general health information written by our editorial staff, not a diagnosis or a treatment plan; how we choose topics and use sources is described in our editorial policy.
- ViiV Healthcare. CABENUVA (cabotegravir; rilpivirine) prescribing information, DailyMed, revised 11/2025. Indication and eligibility, dosing schedules, optional oral lead-in and hypersensitivity warning, ATLAS-2M results, confirmed virologic failure counts, baseline risk factors, BMI subgroup counts, injection-site reaction rates, residual drug levels, MOCHA adolescent data.
- Orkin C, et al. Long-Acting Cabotegravir and Rilpivirine after Oral Induction for HIV-1 Infection (FLAIR). N Engl J Med 2020;382:1124-1135. Week-48 failure rates of 2.1% vs 2.5% and the noninferiority margin.
- Swindells S, et al. Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 Suppression (ATLAS). N Engl J Med 2020;382:1112-1123. Week-48 failure rates of 1.6% vs 1.0%; injection-related events common but rarely led to withdrawal.
- Rana AI, et al. Cabotegravir plus Rilpivirine for Persons with HIV and Adherence Challenges (LATITUDE). N Engl J Med 2026;394:858-871. Trial design; estimated cumulative probability of regimen failure (virologic failure or treatment discontinuation) of 22.8% vs 41.2% by week 48, with most injection-arm failures being discontinuations; early stop for superiority; exclusions.
- Long-Acting Lenacapavir and Cabotegravir and Viral Suppression Among People With HIV. JAMA Netw Open 2026;9(10):e2638182. Single-clinic retrospective case series of 46 people: baseline viremia and resistance, 100-week median follow-up, suppression outcomes, limitations.
- Gilead Sciences. SUNLENCA (lenacapavir) prescribing information, DailyMed, revised 8/2026. Indication for heavily treatment-experienced adults with multidrug-resistant HIV-1 and every-six-month subcutaneous maintenance dosing.
- NIH HIVinfo. Long-Acting HIV Medicine fact sheet, last reviewed April 17, 2026. Long-acting HIV medicines are given by a healthcare provider at regular appointments; Cabenuva every one or two months.
- U.S. Centers for Disease Control and Prevention. Treating HIV. An undetectable viral load means HIV is not transmitted through sex (Undetectable = Untransmittable).