HIV in the Era of Long-Acting Injectables: Redefining Adherence Without Abandoning Follow-Up

Introduction

For decades, adherence in HIV care has often been framed as daily pill-taking. That framework remains clinically important, but it is incomplete. It can underestimate the effects of stigma, treatment fatigue, privacy concerns, housing instability, pharmacy access, insurance interruptions, transportation barriers, competing illness, and clinic design.

Long-acting injectable medications are changing that model. Cabotegravir/rilpivirine provides a complete long-acting injectable treatment option for selected people with virologically suppressed HIV. Injectable cabotegravir and injectable lenacapavir provide long-acting options for HIV pre-exposure prophylaxis, or PrEP. Lenacapavir also has a separate treatment role, in combination with other active antiretroviral agents, for heavily treatment-experienced adults with multidrug-resistant HIV whose current regimen is failing.

For broader clinical background, GlobalRPh maintains resources addressing HIV management, HIV treatment and long-acting therapy, and commonly used HIV agents.

The central question is no longer whether adherence matters. It does. The more useful question is whether clinicians should define adherence only as pill-taking or more broadly as the ability of a patient and healthcare system to sustain therapeutic drug exposure, timely injections, appropriate laboratory surveillance, and rapid intervention when dosing is interrupted.

Why This Topic Matters Now

Long-acting HIV medications have emerged while substantial gaps remain in prevention uptake, PrEP persistence, viral suppression, retention in care, and equitable treatment access. These gaps are not distributed evenly.

People who may benefit most from a reduced pill burden may also face the greatest barriers to scheduled visits, transportation, insurance continuity, medication access, and appointment reminders. These barriers may be especially consequential for people experiencing unstable housing, substance use disorders, mental illness, geographic isolation, stigma, discrimination, or fragmented care.

Long-acting injectables can reduce one form of adherence burden while creating another. A patient may no longer need to remember a daily tablet but must still return for injections within product-specific dosing windows, complete appropriate testing, maintain medication access, and communicate promptly when appointments are delayed.

Implementation requires more than prescribing a different formulation. Clinics need scheduling systems, benefits investigation, medication procurement, inventory management, staff training, injection protocols, laboratory tracking, missed-dose procedures, and oral bridging plans when appropriate. The clinical value of long-acting medication therefore depends on both pharmacology and implementation.

Current Long-Acting Options in U.S. HIV Care

Long-acting injectable medications currently span three principal clinical domains:

1. Maintenance treatment for selected patients with virologically suppressed HIV

2. HIV PrEP for people without HIV who would benefit from prevention

3. Combination treatment for heavily treatment-experienced adults with multidrug-resistant HIV

Additional GlobalRPh resources include the HIV anti-agents reference and a general HIV clinical overview.

Table 1. Current Long-Acting Injectable HIV Options

Clinical use	Medication and dosing concept	Principal clinical cautions
Virologically suppressed HIV treatment	Cabotegravir/rilpivirine administered monthly or every 2 months after product-specific initiation	Relevant resistance, treatment-failure history, untreated HBV, major interactions, missed injections, and prolonged pharmacologic exposure
HIV PrEP	Intramuscular cabotegravir after initiation, then every 2 months	HIV testing before initiation and each injection, missed-dose management, interactions, and prolonged pharmacologic tail
HIV PrEP	Subcutaneous lenacapavir after oral and injectable initiation, then every 26 weeks	HIV testing, administration technique, persistent nodules, drug interactions, missed doses, and prolonged pharmacologic tail
Multidrug-resistant HIV treatment	Lenacapavir with an optimized background regimen every 6 months after initiation	Not a complete regimen, resistance with functional monotherapy, interactions, and injection-site reactions

Long-Acting Cabotegravir/Rilpivirine for HIV Treatment

Cabotegravir/rilpivirine should primarily be understood as a maintenance switch strategy rather than a universal replacement for oral antiretroviral therapy.

U.S. labeling indicates the regimen as a complete replacement for the current antiretroviral regimen in adults and adolescents aged 12 years or older who weigh at least 35 kg, are virologically suppressed with HIV-1 RNA below 50 copies/mL on a stable regimen, have no history of treatment failure, and have no known or suspected resistance to cabotegravir or rilpivirine.[3]

Current NIH guidance supports monthly or every-2-month dosing for people with sustained viral suppression, no documented or suspected resistance to either component, no active hepatitis B infection unless HBV-active therapy is continued, and no significant interacting medications.[11]

An oral lead-in with cabotegravir and rilpivirine may be used to assess tolerability, but it is optional under current U.S. labeling. Clinicians should follow product-specific initiation and dosing instructions.

Evidence from the pivotal treatment trials

The pivotal trials established noninferiority for maintaining viral suppression in carefully selected patients who were already suppressed on oral therapy:

• FLAIR supported monthly long-acting cabotegravir/rilpivirine after oral induction.[9]

• ATLAS supported switching from suppressive oral ART to monthly cabotegravir/rilpivirine.[18]

• ATLAS-2M supported every-2-month administration as noninferior to monthly dosing.[10]

• SOLAR supported switching from bictegravir/emtricitabine/tenofovir alafenamide to every-2-month cabotegravir/rilpivirine in appropriately selected adults with virologic suppression.[14]

Confirmed virologic failure was uncommon in these trials. When failure occurred, resistance to the integrase inhibitor class, the non-nucleoside reverse transcriptase inhibitor class, or both could emerge. This risk makes resistance history, prior treatment failure, dosing reliability, and prompt evaluation of virologic rebound clinically important.

The pivotal switch trials should not be generalized automatically to patients with uncontrolled viremia, uncertain resistance, or unstable follow-up because most participants were virologically suppressed, engaged in care, and screened for relevant resistance.

 

What LATITUDE adds

LATITUDE evaluated people with a history of adherence challenges, loss to follow-up, or viremia. Participants first received comprehensive adherence support for up to 24 weeks. Those who achieved HIV-1 RNA of 200 copies/mL or lower were eligible for randomization to monthly long-acting cabotegravir/rilpivirine or standard oral therapy.[15]

The study supports a potential role for long-acting cabotegravir/rilpivirine in a carefully selected and intensively supported population with prior adherence challenges. It should not be interpreted as evidence that cabotegravir/rilpivirine can be initiated routinely in any patient with uncontrolled viremia.

NIH guidelines permit case-by-case consideration of long-acting cabotegravir/rilpivirine for a small number of people with persistent virologic failure despite intensive adherence support, provided there is no evidence of resistance to cabotegravir or rilpivirine and close multidisciplinary follow-up is available. This is an off-label, low-certainty recommendation and should not replace efforts to construct a fully suppressive oral regimen whenever one is feasible.[11]

Injectable PrEP: Cabotegravir and Lenacapavir

Long-acting injectable PrEP expands prevention options for people who cannot or do not want to take daily oral PrEP, have difficulty sustaining oral adherence, have privacy concerns, have renal limitations affecting some tenofovir-based options, or prefer injection-based prevention.

Injectable PrEP should not be described as adherence-free prevention. It is visit-dependent prevention. The dosing task becomes less frequent, but injection attendance, HIV testing, interaction screening, and discontinuation planning remain clinically important.

Cabotegravir PrEP

Cabotegravir PrEP is administered intramuscularly. Following initiation injections 1 month apart, maintenance injections are given every 2 months. An optional oral lead-in may be used.[1]

HPTN 083 and HPTN 084 demonstrated superior HIV prevention efficacy compared with daily oral tenofovir disoproxil fumarate/emtricitabine in the studied populations.[5,8] The trial findings support cabotegravir as a highly effective PrEP option, but real-world effectiveness remains dependent on timely injections and appropriate HIV testing.

The APRETUDE label requires HIV testing before initiation and before every injection. A negative antigen-antibody test should be confirmed with an HIV-1 RNA assay according to labeling because long-acting single-agent exposure during unrecognized HIV infection can select integrase resistance.[1]

CDC guidance similarly recommends combined antigen-antibody and HIV-1 RNA testing during injectable cabotegravir follow-up.[4]

Lenacapavir PrEP

Lenacapavir PrEP is administered subcutaneously after an initiation regimen that includes oral dosing. Maintenance injections are administered every 26 weeks, with a permitted dosing window of 2 weeks before or after the scheduled date.[19]

PURPOSE 1 found no incident HIV infections among participants assigned to twice-yearly lenacapavir during the primary analysis and demonstrated superiority to background HIV incidence and daily oral comparators in the studied population.[2]

PURPOSE 2 found substantially lower HIV incidence with lenacapavir than estimated background incidence and lower incidence than with daily tenofovir disoproxil fumarate/emtricitabine in the studied population.[7] These trials supported FDA approval and a strong CDC recommendation for adults and adolescents weighing at least 35 kg who would benefit from PrEP.[13]

Cabotegravir and lenacapavir have not been compared directly in a randomized head-to-head trial. Cross-trial comparisons should therefore be avoided. Selection should account for patient preference, exposure pattern, pregnancy considerations, renal function, dosing interval, drug interactions, access, injection-site tolerability, and clinic capacity.

Redefining Adherence

Adherence in daily oral therapy usually means taking medication as prescribed. In long-acting injectable care, adherence encompasses a broader workflow:

• Confirming clinical eligibility

• Attending scheduled injection visits

• Completing HIV testing or viral-load monitoring appropriate to the indication

• Managing delayed or missed doses

• Using oral bridging or an alternative regimen when indicated

• Screening for drug interactions

• Transitioning safely to another regimen when injections are stopped

The distinction between treatment and prevention monitoring is essential.

For injectable PrEP, clinicians must exclude HIV before initiation and before ongoing injections. For cabotegravir/rilpivirine treatment, the relevant measure is HIV-1 RNA monitoring, including assessment after switching and prompt testing when injections are missed, delayed, or accompanied by concern for virologic rebound.

Adherence is not solely a patient behavior. It is also a clinical workflow. A motivated patient can still experience treatment interruption if authorization is delayed, medication is unavailable, an appointment cannot be scheduled, or transportation is inaccessible.

The practical question is therefore not simply whether a patient has previously been adherent. The more useful question is whether the patient and care system can sustain the dosing, monitoring, medication access, and contingency planning required for the selected regimen.

Patient Selection for Long-Acting HIV Treatment

For FDA-labeled cabotegravir/rilpivirine use, appropriate candidates generally have:

• Sustained virologic suppression

• No history of treatment failure

• No known or suspected resistance to cabotegravir or rilpivirine

• No untreated active hepatitis B infection

• No contraindicated drug interaction

• A reasonable pathway for receiving injections and managing interruptions

A careful treatment history remains essential. Clinicians should review previous virologic failure, all available genotype results, possible archived resistance, prior integrase inhibitor or NNRTI exposure, hepatitis B status, pregnancy considerations, and concurrent medications.

Long-acting treatment may be valuable for people with pill fatigue, dysphagia, privacy concerns, stigma related to medication storage, or difficulty maintaining daily routines. However, these advantages must be balanced against the need for reliable access to injections.

A person who cannot receive injections safely or predictably may be better served temporarily by a simplified oral regimen with a high genetic barrier to resistance, together with adherence and access support. Conversely, prior difficulty with daily oral medication should not automatically exclude someone from an injectable option.

Treatment selection should reflect the individual circumstances of people living with HIV rather than treating long-acting therapy as a reward for good adherence or withholding it reflexively after oral adherence difficulties.

Hepatitis B coinfection

Cabotegravir and rilpivirine do not treat hepatitis B virus infection. Switching away from tenofovir-containing ART in a patient with active HBV can create a risk of HBV reactivation or hepatitis flare if effective HBV therapy is not continued.

Patients with active HBV generally require continued TAF or TDF as part of a fully suppressive regimen. When tenofovir cannot be used, entecavir may be added to fully suppressive ART as clinically appropriate.[11]

HBV serologic status should be established before switching to a regimen without HBV activity. Patients susceptible to HBV should be offered vaccination when appropriate.

Patient Selection for Injectable PrEP

Injectable PrEP may be appropriate for people with ongoing risk of HIV acquisition who:

• Prefer injections

• Have difficulty with daily oral PrEP

• Have privacy or stigma concerns

• Have substantial pill burden

• Have renal or other limitations affecting selected oral PrEP options

• Prefer less frequent dosing

Existing HIV infection must be excluded before initiation. This is not a formality. Initiating or continuing long-acting PrEP in a person with undiagnosed HIV can delay diagnosis and select drug-resistant virus.

Assessment should include:

• A blood-based HIV antigen-antibody assay

• HIV-1 RNA testing as required by current labeling and guidance

• Review for symptoms or recent exposures compatible with acute HIV

• Confirmation that recent antiretroviral exposure has not complicated test interpretation

• Product-specific drug-interaction screening

• A plan for missed injections and discontinuation

If results are ambiguous or suggest possible acute infection, injectable PrEP should be deferred while HIV status is clarified.

Safety, Contraindications, and Monitoring

The safety profiles of long-acting HIV medications are generally manageable in appropriately selected patients, but the risks and interaction pathways differ by product. Class-wide statements should not substitute for review of the individual prescribing information.

Injection-site reactions

Injection-site reactions are common with long-acting products.

With cabotegravir/rilpivirine, injection-site pain, nodules, induration, swelling, erythema, pruritus, bruising, and warmth may occur. Most reactions are mild to moderate and decline with continued treatment, although discontinuation may occasionally be necessary.[3]

Serious post-injection reactions have occurred within minutes after rilpivirine-containing injections. Reported symptoms include dyspnea, bronchospasm, agitation, abdominal cramping, urticaria, dizziness, flushing, sweating, oral numbness, blood-pressure changes, and pain. Correct intramuscular administration is essential, and observation should follow current labeling and institutional protocols.

Cabotegravir PrEP can also cause injection-site reactions, most commonly pain. Patients should be counseled about expected reactions and symptoms that require evaluation.[1]

With lenacapavir PrEP, nodules, pain, erythema, induration, swelling, and other local reactions can occur. Nodules may persist for months and, in some cases, longer than 1 year. Incorrect intradermal rather than subcutaneous administration has been associated with serious reactions, including necrosis and ulceration. Proper subcutaneous technique is therefore essential.[19]

Hypersensitivity, hepatotoxicity, and neuropsychiatric effects

Hypersensitivity reactions, including severe cutaneous reactions, have been reported with cabotegravir-containing products. Treatment should be discontinued immediately when a hypersensitivity reaction is suspected, with appropriate clinical management and laboratory evaluation.[1,3]

Hepatotoxicity has also been reported. Patients with underlying liver disease, viral hepatitis, or other hepatic risk factors may require closer monitoring. Liver testing should be obtained when clinically indicated.

Depressive disorders have been reported with cabotegravir- and rilpivirine-containing products. Clinicians should assess new or worsening mood symptoms, particularly in patients with a psychiatric history.

Rilpivirine can prolong QTc at supratherapeutic exposures. Cabotegravir/rilpivirine should be used cautiously with medications known to create a risk of torsades de pointes.[3]

Product-specific drug interactions

Drug-interaction screening must be performed separately for CABENUVA, APRETUDE, YEZTUGO, and SUNLENCA.

CABENUVA is contraindicated with medications that may substantially reduce cabotegravir or rilpivirine exposure, including selected enzyme-inducing anticonvulsants, rifampin, rifapentine, rifabutin, systemic dexamethasone beyond a single dose, and St. John‘s wort.[3]

APRETUDE has a separate interaction profile involving inducers of UGT1A1 or UGT1A9. Clinicians should use the current APRETUDE interaction table rather than applying the CABENUVA list automatically.[1]

SUNLENCA is contraindicated with strong CYP3A inducers. Moderate CYP3A inducers and combined inhibitors of P-glycoprotein, UGT1A1, and strong CYP3A may also create clinically important concerns.[17]

Lenacapavir is a moderate CYP3A inhibitor. It may increase exposure to susceptible CYP3A substrates initiated within 9 months after the final injection. Interaction assessment must therefore continue after discontinuation.[17,19]

Related considerations in immunocompromised patients are reviewed in the GlobalRPh resource on HIV and infections.

Prolonged pharmacologic exposure

Long-acting injectable drugs do not disappear when injections are stopped. Residual cabotegravir, rilpivirine, or lenacapavir concentrations may persist for 12 months or longer, depending on the product and patient.[1,3,19]

During the declining pharmacologic tail, concentrations may eventually become insufficient for treatment or prevention but remain sufficient to exert selective pressure. This creates a potential pathway to viral replication and resistance.

Discontinuation planning should begin before the first injection. Patients stopping cabotegravir PrEP should transition promptly to another effective prevention option if exposure risk continues. Patients stopping cabotegravir/rilpivirine treatment should begin a fully suppressive oral regimen within the interval specified by the product label. Patients discontinuing lenacapavir PrEP should transition to an alternative PrEP strategy by the recommended deadline if HIV exposure risk continues.

Pregnancy and lactation

Pregnancy considerations differ between long-acting treatment and long-acting PrEP.

Initiation of long-acting cabotegravir/rilpivirine treatment is generally not recommended during pregnancy because pharmacokinetic and pregnancy-outcome data remain limited. If pregnancy occurs while a patient is virologically suppressed on the regimen, continuation versus transition to oral ART should be decided through shared decision-making with an HIV specialist.

When cabotegravir/rilpivirine is continued during pregnancy, current perinatal guidance recommends more frequent HIV-1 RNA monitoring, generally every 1 to 2 months. If the regimen is discontinued, a fully suppressive alternative should begin no later than 1 month after the final injection.[12]

For PrEP, current U.S. perinatal guidance recognizes TDF/FTC as the option with the most extensive pregnancy and breastfeeding experience. As of the March 2026 update, injectable lenacapavir is recommended as an available PrEP option during pregnancy and breastfeeding, while injectable cabotegravir may also be considered through shared decision-making.[12] Product labeling, exposure route, patient preference, dosing reliability, and the evolving evidence base should inform selection.

Additional patient-facing background is available in the GlobalRPh resource on HIV and pregnancy.

Table 2. Safety and Monitoring Priorities

Issue	Why it matters	Practical action
Undiagnosed HIV during PrEP	Can delay diagnosis and select resistance	Confirm HIV-negative status using product-specific testing before initiation and ongoing injections
Virologic rebound during treatment	Can lead to class resistance	Obtain HIV-1 RNA promptly and perform resistance testing when failure is suspected
Missed injections	Can reduce treatment or prevention reliability	Use the product-specific oral bridging, replacement, or re-initiation protocol
HBV coinfection	Cabotegravir/rilpivirine does not treat HBV	Continue effective HBV therapy and monitor when changing HBV-active ART
Drug interactions	May reduce efficacy or increase toxicity	Screen separately for each product before initiation and during follow-up
Pharmacologic tail	Drug persists after discontinuation	Plan alternative ART or PrEP before the final injection
Injection reactions	Common; rare serious reactions occur	Use correct technique and counsel patients about expected and urgent symptoms
Pregnancy	Recommendations differ by indication and product	Consult current perinatal guidance and use shared decision-making

Managing Missed or Delayed Injections

Missed-dose planning should be incorporated into treatment before the first injection. The allowable dosing window, oral bridging strategy, and re-initiation requirements differ by product and by the duration of the interruption.

Cabotegravir/rilpivirine treatment

When a planned cabotegravir/rilpivirine injection will be missed by more than the permitted window, oral cabotegravir plus rilpivirine may be used for up to 2 months to replace missed injection visits. Alternatively, another fully suppressive oral ART regimen may be used.[3]

The oral regimen replaces the missed injection interval. It should not be described as simple supplementation.

Patients returning after a prolonged interruption may require repeat initiation injections. The decision depends on whether the patient was receiving monthly or every-2-month injections and the time elapsed since the previous dose. HIV-1 RNA should be evaluated when clinically indicated, particularly after an unplanned interruption.

Cabotegravir PrEP

For a planned interruption, oral cabotegravir may be used for up to 2 months to replace a missed injection, or another effective oral PrEP regimen may be selected.[1]

After cabotegravir discontinuation, CDC recommends beginning another PrEP option within 8 weeks when HIV exposure is anticipated and continuing quarterly antigen-antibody and HIV-1 RNA testing for 12 months after the final injection.[4]

Lenacapavir PrEP

Lenacapavir maintenance injections are scheduled every 26 weeks with a 2-week dosing window. For a planned delay beyond that window, weekly oral lenacapavir may be used according to the prescribing information. Longer or unplanned interruptions require product-specific re-initiation and HIV-testing decisions.[19]

Practical Approach for Clinicians

A long-acting HIV workflow begins before the first injection.

For cabotegravir/rilpivirine treatment, clinicians should confirm:

1. The patient meets the labeled or carefully justified guideline-supported indication.

2. HIV-1 RNA is appropriately suppressed for labeled use.

3. There is no known or suspected resistance to either component.

4. Previous treatment failure has been reviewed.

5. HBV status and HBV therapy have been addressed.

6. Pregnancy and reproductive considerations have been discussed.

7. Drug interactions have been screened.

8. The clinic and patient have a workable injection and missed-dose plan.

For injectable PrEP, clinicians should confirm:

1. HIV infection has been confidently excluded.

2. The selected medication fits the patient preference and exposure pattern.

3. Drug interactions and product-specific precautions have been assessed.

4. Future injection visits and HIV testing are feasible.

5. A missed-dose and discontinuation plan has been documented.

6. Alternative PrEP can be started promptly if injections stop while exposure risk continues.

Table 3. Implementation Checklist

Step	Cabotegravir/rilpivirine treatment	Injectable PrEP
Confirm indication	Suppressed treatment switch, or rare specialist-managed exception	Prevention in a confirmed HIV-negative person
Review history	Treatment failure, resistance, prior ART, HBV	Previous PrEP, recent exposures, acute HIV symptoms
Check interactions	CABENUVA-specific interaction review	APRETUDE- or YEZTUGO-specific review
Plan monitoring	HIV-1 RNA and missed-dose follow-up	HIV testing before ongoing injections
Plan interruption	Oral CAB/RPV or another suppressive ART regimen	Oral bridging or alternative PrEP
Address pregnancy	Follow current treatment and perinatal guidance	Select PrEP using current perinatal guidance
Confirm operations	Medication access, injection scheduling, storage, and staffing	Medication access, testing, injection scheduling, and follow-up

Implementation and Health Equity

Long-acting therapy may reduce treatment fatigue, concerns about medication storage, disclosure risk, or daily reminders of HIV treatment and prevention. It may also be useful for some people who have difficulty sustaining daily oral dosing.

These potential advantages do not guarantee improved adherence or clinical outcomes. Real-world effectiveness is influenced by medication access, injection attendance, resistance, adverse effects, testing, transportation, payer policies, clinic capacity, and trust in the healthcare system.

Health systems should avoid using long-acting therapy only for patients perceived as reliably adherent. Such an approach may reproduce inequity and exclude people whose primary barrier is daily pill-taking rather than unwillingness to engage in care.

At the same time, long-acting therapy should not be used without a realistic plan for follow-up. The goal is to match the treatment or prevention strategy to the specific barriers affecting the patient and to the support the clinic can provide.

Useful implementation elements include:

• Flexible scheduling and reminder systems

• Rapid outreach after missed visits

• Transportation or patient-navigation support

• Pharmacy and benefits coordination

• Standardized laboratory and injection workflows

• Community-based or pharmacy-led administration when permitted and feasible

• Clear responsibility for tracking pharmacologic-tail follow-up

• Nonjudgmental communication about treatment interruptions

Long-acting therapy makes adherence a shared responsibility that extends beyond the individual patient to the healthcare delivery system.

Limitations of the Evidence

The pivotal cabotegravir/rilpivirine switch trials largely enrolled people who were already virologically suppressed and engaged in care. Their findings may not generalize fully to people with unstable housing, active substance use, severe mental illness, inconsistent insurance, uncertain resistance, or persistent viremia.

LATITUDE extends the evidence base to a population with previous adherence challenges, but participants received intensive adherence support and had to achieve HIV-1 RNA of 200 copies/mL or lower before randomization. Evidence remains insufficient to support routine initiation of cabotegravir/rilpivirine in people with uncontrolled viremia without those safeguards.

For PrEP, cabotegravir and lenacapavir have robust randomized evidence against their respective control strategies. No randomized head-to-head comparison between the two injectable options is available.

Pregnancy evidence continues to evolve and differs by medication and indication. Treatment recommendations for cabotegravir/rilpivirine should not be extrapolated directly to cabotegravir or lenacapavir PrEP.

Implementation evidence also remains incomplete. Outcomes may vary substantially with clinic staffing, medication-acquisition workflows, payer policies, transportation support, patient trust, and availability of community delivery models.

Future Directions

The next phase of long-acting HIV care will focus increasingly on implementation rather than efficacy alone.

Important questions include how to:

• Deliver injections safely outside traditional HIV clinics

• Manage missed visits at scale

• Integrate pharmacy-led or community-based administration

• Support people with unstable housing or transportation barriers

• Improve access without widening disparities

• Detect HIV promptly during injectable PrEP

• Prevent resistance when long-acting treatment or prevention is interrupted

• Incorporate future self-administered or extended-interval formulations

Additional research is needed in pregnancy, adolescents, people with HBV coinfection, patients with higher body mass index, people with complex psychiatric or substance-use comorbidity, and those with prior resistance.

Longer dosing intervals may reduce treatment burden further, but they will magnify the importance of durable monitoring systems and discontinuation planning.

 

References

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3. ViiV Healthcare Company. (2025). Cabenuva (cabotegravir and rilpivirine extended-release injectable suspensions) prescribing information. DailyMed. Updated November 26, 2025. Retrieved July 29, 2026, from https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1698baf3-f895-4c42-a1b1-e9ee3f20da36

4. Centers for Disease Control and Prevention. (2026). Clinical guidance for PrEP. HIV Nexus. Updated April 30, 2026. Retrieved July 29, 2026, from https://www.cdc.gov/hivnexus/hcp/prep/

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10. Overton, E. T., Richmond, G., Rizzardini, G., et al. (2021). Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection: 48-week results of ATLAS-2M, a randomized, multicenter, open-label, phase 3b noninferiority study. The Lancet, 396(10267), 1994-2005. https://doi.org/10.1016/S0140-6736(20)32666-0 PMID: 33308425

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13. Patel, R. R., Brooks, J. T., DeLuca, J. B., et al. (2025). Clinical recommendation for the use of injectable lenacapavir as HIV preexposure prophylaxis, United States, 2025. MMWR Morbidity and Mortality Weekly Report, 74(35), 541-549. https://doi.org/10.15585/mmwr.mm7435a1

14. Ramgopal, M. N., Castagna, A., Cazanave, C., et al. (2023). Efficacy, safety, and tolerability of switching to long-acting cabotegravir plus rilpivirine versus continuing fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed adults with HIV: 12-month results from SOLAR. The Lancet HIV, 10(9), e566-e577. https://doi.org/10.1016/S2352-3018(23)00136-4 PMID: 37567205

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