Cabenuva vs. Apretude

Published on: June 7, 2025June 7, 2025Author: Bestie Paws

When it comes to HIV management in 2025, two heavyweight injectables are changing the game: Cabenuva and Apretude. But beyond the buzzwords and pharma brochures, what are the real-world differences that matter to patients, clinicians, and public health decision-makers? Whether you’re managing HIV or preventing it, understanding when, why, and how to use these long-acting treatments can be the key to better outcomes — or serious mistakes.

🔑 Key Takeaways at a Glance

Question	Fast Answer
Which one treats HIV?	Cabenuva 🩺
Which one prevents HIV?	Apretude 🛡️
Do both use cabotegravir?	Yes – it’s the shared core ingredient. 🔁
Is rilpivirine in both?	No – only in Cabenuva. ⚠️
How often are injections?	Every 2 months (after initiation) 💉
Can drug levels linger post-injection?	Yes – up to 12+ months 🕒
Biggest safety concern for Apretude?	Using it in undiagnosed HIV ➡️ resistance risk ❌
Biggest safety concern for Cabenuva?	Post-injection reactions (rare, but serious) 🚨
Is oral lead-in mandatory?	Optional for both, but helps assess tolerability ✔️
Who administers the injections?	Healthcare professionals only 🏥

🤔 “Can I Use Cabenuva or Apretude Interchangeably?”

Absolutely not. Despite the shared ingredient (cabotegravir), these medications serve opposite clinical purposes. Cabenuva is for treating HIV-positive patients who are already stable and suppressed on ART. Apretude is for preventing HIV infection in HIV-negative individuals at risk.

📌 What happens if you give Apretude to someone with undiagnosed HIV?
You risk creating drug-resistant HIV strains, because Apretude is not a full treatment regimen — it’s monotherapy. That’s why every single injection requires an HIV test with an FDA-approved method that can catch acute infections.

🧬 “How Do These Drugs Actually Work Inside the Body?”

Here’s a look under the hood of both drugs:

Mechanism	Cabenuva ⚕️	Apretude 🛡️
Core Drug	Cabotegravir + Rilpivirine	Cabotegravir only
Targets	HIV integrase and reverse transcriptase	HIV integrase
Function	Stops HIV from multiplying & infecting cells	Blocks virus from taking hold if exposed
Therapeutic Goal	Maintain viral suppression (HIV+)	Prevent infection (HIV-)

💡 Pro Tip: Apretude’s strength lies in prevention. But if infection sneaks through, it’s not strong enough to suppress — hence the resistance risk.

🗓️ “How Often Do I Need Injections?”

Phase	Cabenuva 💉	Apretude 💉
Initiation	One injection monthly for 2 months	One injection monthly for 2 months
Maintenance	Every 1 or 2 months	Every 2 months
Oral Lead-in	Optional (30 days)	Optional (30 days)

📆 Both treatments offer less frequent dosing than daily pills, but clinic visit commitment is non-negotiable. You miss an injection? You may be left with lingering drug levels and suboptimal protection.

🧪 “What Are the Most Critical Safety Concerns?”

Shared Risks (Both Drugs):

Injection Site Reactions (ISRs) 😣 – pain, swelling, bruising.
Liver Problems 🟡 – monitor for jaundice, dark urine, nausea.
Depression or Mood Changes 😞 – screening and support are essential.

Unique to Apretude:

🚫 HIV Resistance – if used in someone already infected, the virus could mutate.
🧪 Rigorous HIV Testing – before every injection.

Unique to Cabenuva:

💥 Post-Injection Reactions – rare, but may include sudden allergic-like responses (especially rilpivirine-related).

🧠 “What If I Stop Injections or Miss a Dose?”

This is one of the biggest risks — and least understood.

Both Cabenuva and Apretude linger in your system for up to a year after the last shot. That means:

🔄 Cabenuva Users (HIV-positive):
If you stop without transitioning to oral ART within 1–2 months, you risk viral rebound and resistance.

🛡️ Apretude Users (HIV-negative):
If you miss a dose and get exposed to HIV during the drug “tail,” you could get infected AND develop resistance.

⚠️ Bottom Line: These drugs aren’t “fire and forget.” You need a solid exit plan if stopping.

👥 “Who Are These Injections Really For?”

Here’s who benefits most — and who might need to think twice:

Population	Best Fit For	Considerations
Adherent HIV+ patients	Cabenuva users tired of daily pills	Must be virologically suppressed
At-risk HIV-negative individuals	Apretude users wanting less stigma & better privacy	Must be HIV-1 negative at every dose
Teens (≥12 yrs)	Both drugs are approved	Weight ≥35 kg required
Pregnant individuals	Use with caution	Drug can linger for a year postpartum

👨‍⚕️ Expert Insight: Always assess lifestyle, travel, clinic access, and mental health history. Long-acting isn’t “set it and forget it” — it’s commitment in a different form.

💊 “What About Side Effects — Will I Feel Sick?”

Here’s a rapid breakdown:

Side Effect	Cabenuva	Apretude
Injection pain	✅ Very common	✅ Very common
Fatigue / fever	✅ Occasional	✅ Occasional
Mood changes	⚠️ Reported	⚠️ Reported
Liver effects	⚠️ Possible	⚠️ Possible
Diarrhea / GI upset	😐 Less common	✅ Noted

🎯 What to Expect: Most side effects fade with time. ISRs usually improve within 3–5 days. Counseling upfront makes all the difference for long-term adherence.

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🔄 “What’s the Real Clinical Takeaway?”

These two injectables mark a paradigm shift in HIV care — but they are not interchangeable, and not risk-free. They offer convenience, discretion, and better adherence for the right patients — but they demand careful screening, education, and follow-up.

✅ Cabenuva is a maintenance weapon for those already winning the viral suppression battle.
✅ Apretude is a prevention shield — but it’s only as strong as your HIV testing protocol.

🧭 Final Thoughts: Choose Wisely, Commit Fully

These are high-impact tools, but they require precision. Long-acting injectables are not casual switch-outs for forgetful pill takers. They’re clinical commitments that pay off when matched to the right patient, at the right time, with the right monitoring.

📌 Summary: Top 7 Expert Tips

Never use Apretude without confirming HIV-negative status — every time.
Educate about the “tail” – the drug stays in the system for up to a year.
Use oral lead-ins when possible to test for tolerability.
For Cabenuva, always switch to oral ART within 1–2 months if discontinuing.
Expect ISRs. Manage them. Don’t let them derail treatment.
Check for drug interactions – especially seizure meds, rifampin, St. John’s wort.
Adherence doesn’t disappear — it just becomes a calendar problem instead of a daily one.

💬 Comment Section

❓“If both drugs have a long ‘tail,’ what happens if a patient misses their injection window?”

Missing your scheduled injection isn’t just a logistical hiccup — it’s a pharmacological time bomb.

With Cabenuva, sub-therapeutic drug levels begin shortly after the end of the dosing window (1 or 2 months depending on the schedule). This allows HIV replication to resume without sufficient antiretroviral coverage, risking viral rebound and resistance development — especially dangerous if rilpivirine resistance emerges, as treatment options narrow.

For Apretude, the stakes shift: if HIV exposure occurs during the “tail” period, when drug levels are low but still present, the virus is more likely to develop integrase resistance mutations due to inadequate suppression. Unlike daily PrEP, there’s no “forgiveness buffer” — the injectable either works or it doesn’t.

Missed Dose Impact	Cabenuva 🩸	Apretude 🛡️
Viral Rebound	✅ High risk	❌ Not applicable (if still HIV-)
Resistance Development	⚠️ Especially rilpivirine	🚨 High risk if infected
Management	Restart oral ART ASAP	Restart oral PrEP or alternative form
Protection Lost?	Yes – virus replicates again	Yes – risk of infection and resistance

❓“Why is rilpivirine included in Cabenuva but not in Apretude?”

Because treatment and prevention require fundamentally different pharmacodynamic strategies.

HIV treatment targets an actively replicating virus already integrated into host cells. To suppress it effectively, Cabenuva pairs cabotegravir (INSTI) with rilpivirine (NNRTI). This dual-targeted mechanism blocks HIV at both reverse transcription and integration stages, mimicking the standard triple-therapy principle by attacking two unique enzymes.

In contrast, prevention (PrEP) doesn’t deal with active infection — it aims to block establishment of infection after exposure. For this, cabotegravir alone is potent enough. By saturating integrase binding sites early, it halts the virus before it integrates. Adding rilpivirine wouldn’t significantly enhance prevention but would increase toxicity and complexity unnecessarily.

Feature	Cabenuva ⚕️	Apretude 🛡️
Requires dual therapy?	✅ Yes – virus is replicating	❌ No – goal is to prevent entry
Rilpivirine use	Essential for suppression	Irrelevant for prevention
Targets	Reverse transcriptase + integrase	Integrase only
Clinical Rationale	Mimics combo ART	Focused monotherapy for PrEP

❓“How does Cabenuva’s dosing flexibility affect adherence and outcomes?”

Dual-frequency dosing was a design masterstroke — and a clinical turning point.

Cabenuva’s approval with monthly and every-2-month dosing options gives clinicians a valuable tool to customize therapy based on patient lifestyle, virologic stability, and behavioral patterns. Monthly dosing allows for closer monitoring in early months, especially for those transitioning from oral ART or with marginal adherence histories. Once stability is confirmed, patients can switch to the more convenient bi-monthly injections, improving satisfaction and reducing clinic burden.

Outcomes-wise, studies like SOLAR showed non-inferiority to top-tier oral regimens (like BIKTARVY), even with 2-month intervals. Real-world cohorts report >95% viral suppression at 12 months, confirming sustained efficacy.

Dosing Option	Ideal For	Benefits
Monthly	Recent ART switchers, patients needing monitoring	Frequent touchpoints, tight control
Every 2 Months	Stable, virologically suppressed individuals	Reduced burden, better satisfaction
Transition Flexibility	Start monthly → move to bi-monthly	Enhances long-term engagement 💉

❓“Is Apretude effective in women and adolescent girls? Most PrEP data is from men.”

Yes — and its real-world efficacy in women is not just theoretical, it’s proven.

HPTN 084, the landmark trial for Apretude in cisgender women, showed that long-acting cabotegravir was 89% more effective than daily oral Truvada (emtricitabine/tenofovir). This matters because adherence to daily PrEP is often lower in women due to social stigma, partner dynamics, and privacy concerns. The ability to “protect silently” through bi-monthly injections can profoundly shift the risk landscape.

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In adolescent girls and young women (AGYW) — the demographic most vulnerable in sub-Saharan Africa — Apretude offers a revolutionary tool to close the adherence gap. Early implementation science shows high acceptability, low discontinuation, and better persistence than oral PrEP.

Population	Apretude Effectiveness ✅
Cisgender women	89% more effective than daily oral PrEP
AGYW (12–24 yrs)	Strong uptake, minimal drop-off
Injection adherence	Higher vs. daily pills
Unique advantage	Discreet, stigma-proof protection 🌍

❓“What’s the risk of resistance with Apretude if someone gets HIV anyway?”

Extremely high — and that’s what keeps infectious disease physicians up at night.

Because Apretude is monotherapy, if someone acquires HIV while on suboptimal levels (e.g., missed injection, late dose), the virus is exposed to a single antiretroviral — cabotegravir — without backup. That’s a perfect storm for integrase mutation selection.

In trials, integrase resistance mutations (e.g., Q148R, G140S) were observed in breakthrough infections, especially in people who were actually HIV-positive at baseline (but missed during screening). These variants reduce future treatment options, making subsequent ART more complex and less durable.

That’s why the boxed warning exists — not to scare clinicians, but to demand meticulous HIV testing at every injection.

Resistance Trigger	Risk Level 🚨	Prevention Strategy
Pre-existing undetected HIV	Very high	Use acute infection-sensitive tests
Delayed injection with new exposure	High	Educate on timing, offer backup oral PrEP
Unrecognized seroconversion post-injection	Moderate	Routine symptom check, prompt retesting

❓“How do I counsel a patient switching from oral ART to Cabenuva?”

Switching isn’t just a script — it’s a structured clinical process with precision checkpoints.

First, confirm at least 3–6 months of undetectable viral load on a stable oral regimen. Next, assess for resistance mutations (especially to rilpivirine). If there’s any past virologic failure or inconsistent adherence, delay the switch — Cabenuva is maintenance therapy, not a rescue option.

Offer an oral lead-in (30 days of cabotegravir + rilpivirine) to catch hypersensitivity or tolerance issues. Once injections begin, reinforce the new form of adherence: clinic punctuality, not daily pill-taking. Finally, explain discontinuation logistics — if they ever stop, they must resume oral ART within 30–60 days to avoid resistance.

Step	Clinical Action ✔️
Viral suppression ≥6 months	Confirm before switch
Resistance check	No known cabotegravir/rilpivirine resistance
Oral lead-in (optional)	Helps screen for AEs 🧪
Adherence counseling	Shift from daily pill → visit schedule
Backup plan	Oral ART if Cabenuva stopped ❗

❓“What makes Apretude a better option than oral PrEP for some populations?”

Three words: discretion, freedom, and biological forgiveness.

Daily oral PrEP (like Truvada or Descovy) requires consistent daily intake. That’s feasible for some, but for many — especially adolescents, people in unstable housing, or individuals fearing stigma — the routine becomes a burden. Apretude decouples protection from daily habits, making it easier to stay covered even during travel, life disruptions, or periods of low sexual activity.

It also offers biological forgiveness: if one injection is slightly delayed (by days, not weeks), therapeutic levels often persist, preventing a protection lapse — something that’s unforgiving in oral PrEP missed doses, particularly in rectal tissue.

Feature	Apretude Advantage 🌟
Doesn’t rely on daily pill memory	✅ Yes
Reduced stigma (no pill bottle)	✅ Yes
Steady drug levels in tissues	✅ Longer half-life
Useful in mobile/displaced populations	✅ Excellent fit
Better for episodic risk behavior	✅ Long-lasting protection

❓“How should clinicians handle patients who develop ISRs and want to discontinue injections?”

Injection site reactions (ISRs) are common but rarely dangerous — yet they can erode adherence if not proactively managed.

Clinicians must distinguish between transient discomfort and psychological intolerance. Most ISRs (e.g., pain, erythema, induration) are Grade 1–2, resolve in 2–5 days, and decrease in frequency over time. However, for patients with low pain thresholds, anxiety around injections, or underlying neuropathies, these symptoms may feel disproportionately severe.

Rather than discontinuing immediately, consider behavioral pain management, topical anesthetics, or pre-injection analgesics (e.g., acetaminophen or NSAIDs if not contraindicated). A clinical reassessment after 3–4 injection cycles often reveals that tolerance improves naturally.

If the patient insists on stopping:

For Cabenuva, transition to oral ART within 4 weeks of the last dose.
For Apretude, initiate alternative PrEP (e.g., Truvada or Descovy) within 8 weeks to avoid vulnerability during the “drug tail.”

Management Strategy	Intervention 💉	Purpose 🎯
Symptom Relief	Ice packs, analgesics, lidocaine cream	Alleviate acute pain
Education	Normalize ISR trajectory	Reduce anxiety and anticipation
Schedule Adjustment	Rotate injection sites	Distribute localized trauma
Transition Protocol	Oral ART or PrEP initiation	Maintain coverage post-discontinuation

❓“How does the pharmacokinetic tail affect pregnancy planning?”

Planning pregnancy on long-acting cabotegravir requires foresight due to its prolonged elimination curve.

Both Cabenuva and Apretude remain detectable in plasma for 12 months or longer post-final injection. The slow depot-release mechanism creates a pharmacokinetic tail, during which drug levels gradually decline but remain biologically active.

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In Apretude users who become pregnant, cabotegravir may be present throughout early fetal development — a window critical for organogenesis. Although no definitive teratogenic effects have been observed to date, safety data in pregnancy remain limited, making pre-conception counseling essential.

For Cabenuva, the scenario is more layered. Women with HIV should not breastfeed, and if pregnancy is anticipated or confirmed, clinicians must assess:

Virologic stability
Alternative ART options with established pregnancy data (e.g., dolutegravir-based regimens)
Patient preference and perinatal care access

Reproductive Scenario	Clinical Action Plan 🤰
Desire to conceive post-Apretude	Delay pregnancy ≥12 months after last dose
Pregnancy confirmed on Apretude	Initiate close fetal monitoring; consult perinatology
Cabenuva + early pregnancy	Evaluate ART switch; ensure viral suppression
Breastfeeding	Discouraged in HIV+ mothers, regardless of regimen

❓“Why is testing for acute HIV so critical before Apretude initiation?”

Because early HIV infection is the Achilles heel of injectable PrEP — and the leading cause of resistance emergence.

During acute seroconversion, standard antibody tests may return false negatives, missing early infection despite high viral replication. If Apretude is initiated during this silent window, the virus is exposed to cabotegravir monotherapy, leading to rapid mutation of the integrase gene, especially at codons like Q148, N155, or G140.

That’s why guidelines demand 4th-generation antigen/antibody tests or HIV-1 RNA assays pre-injection. Moreover, clinicians should perform a symptom screen to detect signs like fever, myalgia, rash, or pharyngitis — subtle but diagnostically rich clues of acute retroviral syndrome.

Diagnostic Factor	Action Needed 🔬	Rationale 🧠
HIV-1 antibody only	Insufficient	May miss acute cases
HIV-1/2 antigen/antibody combo	Preferred baseline test	Detects earlier infection stages
HIV-1 RNA PCR	Ideal if acute infection suspected	Direct viral load detection
Flu-like symptoms	Defer Apretude, test RNA	Rule out seroconversion risk

❓“How should providers address long-term adherence to bi-monthly injection schedules?”

Long-acting regimens shift the burden from daily memory to logistical consistency. It’s a different muscle — but still adherence.

High efficacy hinges on timely injection cycles. For Cabenuva, a grace period of ±7 days is built in. For Apretude, the window is tighter, especially in high-risk exposure periods.

To support adherence:

Use clinic appointment synchronization tools (e.g., injection calendars, text reminders)
Implement community-based administration (mobile vans, peer-led pop-ups)
Offer “buffer” oral supplies (30-day supply of oral PrEP/ART) for missed visits or travel
Integrate injection appointments with other routine health care visits

High persistence rates (e.g., 85% at 6 months for Apretude, >89% timely injection rate for Cabenuva) suggest success is possible — but requires system-level scaffolding.

Adherence Strategy	Implementation 🗓️	Benefit 💡
Appointment syncing	Digital tools, SMS	Prevent missed doses
Decentralized injection delivery	Pharmacies, community hubs	Improve access for rural or mobile patients
Missed-dose plans	Temporary oral coverage	Avoid resistance & viral rebound
Bundled care	Combine with STI screening, mental health visits	Normalize and integrate HIV care

❓“Can patients with mental health disorders safely use these injectables?”

Yes — but only with proactive psychiatric screening and support, given the known risk of mood disturbances.

Both Apretude and Cabenuva have reported associations with depression, anxiety, dysphoria, and suicidality — particularly in individuals with pre-existing mental health conditions. The mechanism is unclear but likely linked to central nervous system penetration of cabotegravir and possibly pharmacodynamic interactions at serotonin or dopamine-related pathways.

Screen all patients for:

History of major depressive episodes
Current mood disorder symptoms
Suicidal ideation or behaviors

Do not withhold treatment based on mental health history alone. Instead, co-manage with psychiatric providers, schedule frequent mental health check-ins, and consider delaying initiation during periods of psychological instability.

Psychiatric Risk Factor	Clinical Response 🧠
Past suicidal ideation	Delay initiation, involve psychiatry
Mild to moderate depression	Proceed with monitoring
Active psychiatric treatment	Coordinate interdisciplinary care
Sudden mood changes post-injection	Discontinue drug, evaluate immediately

❓“How do I explain the risk of resistance in simple terms to patients?”

Use metaphors — science is strongest when it’s relatable.

“Imagine trying to trap a wild animal with only one kind of cage. If that animal escapes, it learns how to avoid that trap forever.”

That’s what happens when cabotegravir is used alone in someone who’s already HIV-positive — the virus adapts, mutates, and develops resistance, meaning fewer medication options in the future.

Stress that:

For treatment (Cabenuva): missing or delaying injections allows the virus to “break free.”
For prevention (Apretude): starting while secretly infected gives the virus a head start against the drug.

Use visual aids or analogies to reinforce the idea that resistance is permanent, prevents future options, and is completely avoidable with proper testing and adherence.

Analogy	Explanation 🎯
“Virus in a cage”	Resistance = escape and learning
“Expired passport”	Sub-therapeutic drug = blocked access
“Broken umbrella”	Drug without coverage = ineffective barrier
“Silent alarm”	Resistance may develop without visible warning 🚨

❓“Can Cabenuva be used in people with prior treatment failure or drug resistance?”

Only under very specific conditions — and with extreme caution.

Cabenuva is not intended for individuals with a history of virologic failure or documented resistance to either cabotegravir or rilpivirine. Its mechanism relies on the assumption that the virus is fully suppressed and susceptible to both drugs, which are individually potent but vulnerable to resistance if the viral barrier is already compromised.

Rilpivirine, in particular, has a low genetic barrier. Resistance can occur from single mutations (e.g., E138K, K101E, Y181C), often seen in archived virus from past suboptimal NNRTI use. Even if a patient is currently suppressed, past resistance tests and treatment history must be scrutinized.

Risk Factor	Action Plan 🔍
Prior NNRTI failure	Avoid Cabenuva unless full susceptibility confirmed
Integrase resistance history	Do not use cabotegravir
No genotyping available	Exercise caution; oral lead-in + suppression history critical
Past adherence issues	Consider enhanced support or retain oral therapy 🧠

❓“How do these injectables perform in patients with high BMI?”

Pharmacokinetics are influenced — but not always compromised.

Long-acting cabotegravir and rilpivirine are injected deep intramuscularly, typically into the gluteus medius. In patients with elevated body mass index (BMI) — particularly those with ≥30 kg/m² — the standard 1.5-inch needle may not penetrate adequately into the muscle, risking subcutaneous delivery. This can delay absorption, create erratic plasma levels, and increase injection site complications (e.g., nodules or abscesses).

Clinical studies, such as ATLAS and FLAIR, included participants with varying body compositions, and efficacy remained consistent overall. However, data on extreme obesity (>40 BMI) remain limited, and customized injection techniques are often necessary.

Consideration	Recommendation 🧵
BMI >30	Consider 2-inch needle for full IM delivery
Gluteal fat >35 mm	Use ultrasound guidance if available
Injection issues	Switch to ventrogluteal site; avoid dorsogluteal
Plasma monitoring	Consider drug level testing in select cases 📊

❓“Do Cabenuva or Apretude affect hormonal contraceptives or gender-affirming hormone therapy?”

No clinically significant interactions — but still worth discussing.

Cabotegravir and rilpivirine are not known to reduce the efficacy of estrogen or progestin-based contraceptives, nor do they impact testosterone or estradiol levels used in gender-affirming care. Unlike some protease inhibitors or older NNRTIs (e.g., efavirenz), they are not hepatic enzyme inducers, meaning the risk of contraceptive failure is negligible.

However, rilpivirine has been associated with mild interactions via CYP3A4, and individual metabolism may vary in transgender patients undergoing hormone therapy. Thus, clinicians should:

Encourage dual protection (e.g., barrier methods) when appropriate.
Discuss bleeding pattern changes openly.
Monitor gender-affirming therapy efficacy via hormone levels and clinical signs, not assumptions.

Medication	Effect on Hormones ⚖️	Clinical Guidance 📍
Cabotegravir	No known effect	Safe with all contraceptives
Rilpivirine	Mild CYP3A4 involvement	Monitor breakthrough bleeding
Estradiol/Testosterone	No impact from either	No dosage adjustment needed
Clinical Tip	Always ask about gender goals	Tailor communication respectfully 🧬

❓“Are there equity concerns around injectable PrEP and ART access?”

Absolutely — and failing to address them risks widening health disparities.

Access to long-acting injectables is unequally distributed, particularly in rural areas, low-resource clinics, and underinsured populations. While injectables remove the daily pill burden, they create new barriers:

Need for cold-chain storage
Healthcare personnel to administer doses
Travel costs and scheduling challenges
Institutional stigma in certain regions

Moreover, the populations that may benefit most — Black MSM, transgender women, young adults in high-incidence zip codes — often face structural barriers to consistent care engagement.

Barrier	Impact 🛑	Possible Solutions 🌍
Geographic location	Limited injection centers	Mobile units, telehealth-linked delivery
Insurance gaps	High out-of-pocket cost	Patient assistance programs, 340B clinics
Mistrust of institutions	Poor retention	Peer navigation, culturally congruent messaging
Incarcerated individuals	Missed doses	Prison-based injectables rollout pilot 📦

❓“How do we handle patients who wish to stop PrEP after several injections?”

Stopping isn’t immediate — it’s a managed descent, not a hard stop.

Due to Apretude’s long terminal half-life, discontinuation doesn’t equal “drug out of system.” Residual cabotegravir remains active — but declining — in plasma and tissues for up to a year. This pharmacologic tail creates a window of vulnerability where the patient is unprotected, but still partially exposed to the drug, which could facilitate resistance if HIV is acquired.

The gold-standard exit strategy:

Start oral PrEP (Truvada or Descovy) within 2 months of the final Apretude injection.
Continue daily for at least 12 weeks.
Educate on symptom monitoring, and re-test for HIV if symptoms arise.

Discontinuation Element	Timeframe 🕒	Purpose 🎯
Last injection	Day 0	Start of tail
Oral PrEP start	Day 30–60	Maintain protection during tail
Oral PrEP duration	≥12 weeks	Ensure complete drug clearance
Final HIV re-test	Post-PrEP	Rule out late seroconversion ⚠️

❓“Is Apretude suitable for people with infrequent or episodic risk?”

Yes — in fact, it may be better than daily oral PrEP for that population.

For individuals whose HIV exposure risk is sporadic (e.g., seasonal work-related, relationship-based, or circumstantial), daily oral PrEP is often psychologically burdensome or non-intuitive. It requires commitment during months of no actual exposure, which erodes motivation and adherence.

Apretude, given every 2 months, aligns better with episodic risk profiles. Patients remain protected continuously, even if their risk fluctuates. The “invisible coverage” effect is particularly valuable for:

College students
Migrant workers
Individuals leaving incarceration
People with cyclical sexual activity (e.g., due to travel, relationships)

Risk Pattern	Apretude Suitability 📌
Consistent high-risk	Excellent fit
Seasonal/circumstantial	Better than daily PrEP
Unpredictable behavior	Offers steady coverage
Sexually active, but irregular	Ideal match for low-burden adherence 🎯

❓“Could Apretude be self-administered in the future?”

Technologically possible — logistically and medically complex.

Currently, Apretude is an intramuscular gluteal injection, requiring trained administration to ensure proper depth, sterility, and site rotation. Self-injection poses challenges:

Risk of subcutaneous delivery (reduced efficacy)
Improper technique → abscesses or tissue damage
Cold-chain integrity must be preserved until use

However, research is ongoing into:

Auto-injector devices
Alternative injection sites (e.g., thigh or deltoid)
Subcutaneous formulations with modified pharmacokinetics

Until then, community-based injectable delivery and task-shifting to pharmacists may serve as middle-ground innovations.

Self-Use Challenge	Barrier 🚧	Possible Innovation 💡
Technique control	Risk of improper injection	Auto-injector development
Storage	Cold chain required	Shelf-stable formulations
Site complexity	Gluteal muscle difficult to access solo	Alt-site dosing studies (thigh)
Patient training	Extensive education needed	ARV delivery kiosks/pilot programs 🧪