Lenacapavir - Revision history

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	Lenacapavir is a first-in-class [[HIV]] capsid inhibitor ~~developed by Gilead Sciences~~. It is the first antiretroviral that targets the HIV-1 capsid protein (p24), interfering with multiple stages of viral replication rather than a single enzyme.<ref name="Paik2022">Paik J. Lenacapavir: first approval. ''Drugs''. 2022;82(14):1499-1504. doi:10.1007/s40265-022-01786-0</ref> It is available as an oral tablet and subcutaneous injection, with the injectable formulation designed for twice-yearly (every 6 months) administration.		Lenacapavir is a first-in-class [[HIV]] capsid inhibitor. It is the first antiretroviral that targets the HIV-1 capsid protein (p24), interfering with multiple stages of viral replication rather than a single enzyme.<ref name="Paik2022">Paik J. Lenacapavir: first approval. ''Drugs''. 2022;82(14):1499-1504. doi:10.1007/s40265-022-01786-0</ref> It is available as an oral tablet and subcutaneous injection, with the injectable formulation designed for twice-yearly (every 6 months) administration.

	==Background==		==Background==

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Lenacapavir is a first-in-class [[HIV]] capsid inhibitor developed by Gilead Sciences. It is the first antiretroviral that targets the HIV-1 capsid protein (p24), interfering with multiple stages of viral replication rather than a single enzyme.<ref name="Paik2022">Paik J. Lenacapavir: first approval. ''Drugs''. 2022;82(14):1499-1504. doi:10.1007/s40265-022-01786-0</ref> It is available as an oral tablet and subcutaneous injection, with the injectable formulation designed for twice-yearly (every 6 months) administration.

==Background==
*Approved by the FDA in December 2022 (as Sunlenca) for [[HIV - AIDS (main)|HIV-1]] treatment in heavily treatment-experienced adults with multidrug-resistant (MDR) HIV-1<ref name="FDA2022">U.S. Food and Drug Administration. FDA approves new HIV drug for adults with limited treatment options. December 2022.</ref>
*Approved by the FDA in June 2025 (as Yeztugo) for HIV pre-exposure prophylaxis ([[HIV post-exposure prophylaxis|PrEP]]) to reduce the risk of sexually acquired HIV-1 in adults and adolescents ≥35 kg<ref name="Gilead2025">Gilead Sciences. Yeztugo (lenacapavir) is now the first and only FDA-approved HIV prevention option offering 6 months of protection. June 2025.</ref>
*Named "2024 Breakthrough of the Year" for its efficacy in HIV prevention trials<ref name="Wiki2024">Lenacapavir. ''Wikipedia''. Accessed 2025.</ref>

==Administration==
*Type: First-in-class HIV-1 capsid inhibitor (antiretroviral)
*Dosage Forms: 300 mg oral tablets; 463.5 mg/1.5 mL (309 mg/mL) subcutaneous injection solution (single-dose vials)<ref name="SunlencaPI">Sunlenca (lenacapavir) [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; 2024.</ref>
*Routes of Administration: Oral (tablets); Subcutaneous injection (abdomen preferred; thigh as alternate site)
**Do '''NOT''' administer intradermally — intradermal injection has been associated with serious injection site reactions including necrosis and ulcer<ref name="SunlencaPI"/>
*Common Trade Names: Sunlenca (HIV treatment), Yeztugo (HIV PrEP)

==Adult Dosing==

===HIV-1 Treatment (Sunlenca) — used with other antiretroviral(s)===
'''Initiation Option 1:'''<ref name="SunlencaPI"/>
*Day 1: 927 mg SC injection + 600 mg PO (2 × 300 mg tablets)
*Day 2: 600 mg PO (2 × 300 mg tablets)

'''Initiation Option 2:'''
*Day 1: 600 mg PO (2 × 300 mg tablets)
*Day 2: 600 mg PO (2 × 300 mg tablets)
*Day 8: 300 mg PO (1 tablet)
*Day 15: 927 mg SC injection

'''Maintenance:''' 927 mg SC injection every 26 weeks (±2 weeks) from the date of last injection<ref name="SunlencaPI"/>

===HIV PrEP (Yeztugo)===
'''Initiation:'''<ref name="YeztugoPI">Yeztugo (lenacapavir) [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; 2025.</ref>
*Day 1: 927 mg SC injection + 600 mg PO (2 × 300 mg tablets)
*Day 2: 600 mg PO (2 × 300 mg tablets)

'''Continuation:''' 927 mg SC injection every 26 weeks (±2 weeks)
*Individuals '''must''' be confirmed HIV-1 negative before each injection<ref name="CDC2025">CDC. Clinical Recommendation for the Use of Injectable Lenacapavir as HIV Preexposure Prophylaxis — United States, 2025. ''MMWR''. 2025;74(35).</ref>

===Missed Doses===
*'''Treatment (Sunlenca):''' If >28 weeks since last injection, restart the full initiation regimen if clinically appropriate<ref name="SunlencaPI"/>
*If discontinuing, begin an alternative suppressive ARV regimen no later than 28 weeks after last injection to avoid resistance development<ref name="SunlencaPI"/>
*'''PrEP (Yeztugo):''' If >28 weeks since last injection and oral tablets not taken, restart with initiation dosing<ref name="YeztugoPI"/>

==Pediatric Dosing==
*'''PrEP:''' Approved for adolescents ≥35 kg; same dosing as adults<ref name="YeztugoPI"/>
*'''Treatment:''' Not established in pediatric patients

==Special Populations==

===[[Drug pregnancy categories|Pregnancy Rating]]===
*No adequate, well-controlled studies in pregnant women<ref name="SunlencaPI"/>
*Animal studies showed no adverse developmental effects at exposures ≥16 times the human dose (AUC)
*Antiretroviral Pregnancy Registry (APR) has been established — report exposures at 1-800-258-4263
*'''PrEP use:''' May be used in pregnancy after shared decision-making, considering HIV risk without PrEP<ref name="CDC2025"/>

===Lactation risk===
*Lenacapavir is present in human milk<ref name="YeztugoPI"/>
*Individuals with HIV-1 infection should be counseled regarding the risks of breastfeeding (risk of HIV transmission)
*For PrEP: consider risks and benefits; limited data suggest no increased drug-associated risks for infant outcomes<ref name="CDC2025"/>

===Renal Dosing===
*Adult: No dose adjustment required for mild, moderate, or severe renal impairment (CrCl ≥15 mL/min)<ref name="RenalHepatic">Shaik N, et al. Pharmacokinetics of long-acting lenacapavir in participants with hepatic or renal impairment. ''Antimicrob Agents Chemother''. 2024;68(4):e01344-23. doi:10.1128/aac.01344-23</ref>
**Not studied in ESRD (CrCl <15 mL/min); use with caution
**Highly protein bound (≥99.8%); hemodialysis not expected to significantly affect levels<ref name="RenalHepatic"/>
*Pediatric: Not established

===Hepatic Dosing===
*Adult: No dose adjustment for mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment<ref name="RenalHepatic"/>
**Not studied in severe hepatic impairment (Child-Pugh C)
*Pediatric: Not established

==Contraindications==
*Allergy to lenacapavir or any component of the formulation
*'''Treatment (Sunlenca):''' Coadministration with strong CYP3A inducers is contraindicated (may reduce lenacapavir concentrations, risking treatment failure and resistance)<ref name="SunlencaPI"/>
*'''PrEP (Yeztugo):''' Use in individuals with HIV-1 infection or unknown HIV status is contraindicated<ref name="YeztugoPI"/>

==Adverse Reactions==

===Serious===
*[[Immune reconstitution syndrome|Immune reconstitution inflammatory syndrome (IRIS)]] (when used for HIV treatment)<ref name="SunlencaPI"/>
*Serious injection site reactions (necrosis, ulcer — associated with improper intradermal administration)<ref name="SunlencaPI"/>
*Risk of drug-resistant HIV if used for PrEP in undiagnosed HIV infection (Boxed Warning on Yeztugo)<ref name="YeztugoPI"/>
*Hepatitis B reactivation flares may occur in patients with pre-existing chronic hepatitis B

===Common===
*Injection site reactions (65% in treatment trials): swelling, pain, erythema, subcutaneous nodules, induration, pruritus<ref name="ISR">Sunlenca HCP. Safety and Tolerability. Gilead Sciences, 2024.</ref>
**Nodules may persist for months (median ~183 days in PrEP trials)<ref name="NYSDOH">NYSDOH AI. Interim Guideline on the Use of Twice-Yearly Lenacapavir for HIV Prevention. 2025.</ref>
**Most ISRs are mild (Grade 1) or moderate (Grade 2); median time to resolution (excluding nodules/indurations) is ~5 days<ref name="ISR"/>
*Nausea (4% in treatment; common in PrEP trials)<ref name="SunlencaPI"/>
*Headache (common in PrEP trials)<ref name="YeztugoPI"/>

==Drug Interactions==
===Key interactions for the ED physician===
*'''Strong CYP3A inducers''' — Contraindicated (treatment) or require supplemental dosing (PrEP). Remember the mnemonic '''COPPER''': '''C'''arbamazepine, '''O'''xcarbazepine, '''P'''henobarbital (and primidone), '''P'''henytoin, '''E'''nzalutamide, '''R'''ifampin (also rifabutin, rifapentine)<ref name="NYSDOH"/>
*'''St. John's wort''' — Avoid; significantly decreases lenacapavir levels<ref name="SunlencaPI"/>
*Lenacapavir is a '''moderate CYP3A inhibitor''' and '''P-gp inhibitor''' — may increase levels of CYP3A substrates for up to 9 months after last SC dose<ref name="SunlencaPI"/>
**Be aware of interactions with common ED medications metabolized by CYP3A (e.g., midazolam, fentanyl, certain statins)
*Lenacapavir is a substrate of CYP3A, P-gp, and UGT1A1<ref name="SunlencaPI"/>

==Pharmacology==
*Half-life: 10–12 days (oral); 8–12 weeks (subcutaneous — due to slow depot release/flip-flop kinetics)<ref name="Paik2022"/>
*Protein Binding: ≥99.8%<ref name="RenalHepatic"/>
*Metabolism: Minor metabolism via CYP3A and UGT1A1; unchanged drug is the predominant species in plasma (~69% of total radioactivity after IV dose)<ref name="SunlencaPI"/>
*Excretion: 76% in feces (33% as unchanged drug); <1% in urine<ref name="Paik2022"/>

==Mechanism of Action==
Lenacapavir binds directly to the interface between HIV-1 capsid protein (p24) subunits within capsid hexamers.<ref name="DvorySobol2022">Dvory-Sobol H, et al. Lenacapavir: a first-in-class HIV-1 capsid inhibitor. ''Curr Opin HIV AIDS''. 2022;17(1):15-21. doi:10.1097/COH.0000000000000713</ref> This binding interferes with multiple stages of the HIV lifecycle:<ref name="Paik2022"/>
*'''Early stages:''' Over-stabilizes the capsid, causing premature brittle fracture before the virus reaches the nucleus — the exposed genetic material is degraded in the cytoplasm<ref name="eLife">Walsh J, et al. Lenacapavir molecular mechanisms. ''eLife''. 2024.</ref>
*'''Late stages:''' Disrupts Gag/Gag-Pol polyprotein function, reduces capsid subunit production, and accelerates capsid assembly leading to malformed, non-functional virions<ref name="DvorySobol2022"/>

Because it targets a structural protein rather than an enzyme, mutations conferring resistance to other antiretroviral classes do not affect lenacapavir activity.<ref name="Paik2022"/>

==ED Relevance==
*Emergency physicians may encounter patients on lenacapavir in two contexts: as part of MDR-HIV treatment or as twice-yearly PrEP
*If a patient on lenacapavir PrEP presents to the ED with concern for acute HIV exposure or seroconversion symptoms:
**Confirm whether they are up-to-date on their injection schedule
**Send HIV Ag/Ab and HIV-1 RNA viral load testing
**Patients who acquire HIV while on lenacapavir must be transitioned to a complete HIV treatment regimen<ref name="CDC2025"/>
*Lenacapavir does '''not''' protect against other sexually transmitted infections
*When prescribing medications in the ED for patients on lenacapavir, be mindful of CYP3A interactions — the inhibitory effect may persist up to 9 months after the last SC dose<ref name="SunlencaPI"/>
*There is no known antidote for overdose; management is supportive. Hemodialysis is unlikely to be effective due to high protein binding<ref name="SunlencaPI"/>
*If a patient receiving lenacapavir for treatment is admitted or has their ARV regimen disrupted, consult [[HIV - AIDS (main)|HIV/ID service]] promptly — nonadherence risks virologic failure and resistance development<ref name="SunlencaPI"/>

===Clinical Pearls===
*PURPOSE 1 trial: 100% efficacy in preventing HIV in cisgender women; PURPOSE 2: ~96% efficacy in men and gender-diverse individuals<ref name="Bekker2024">Bekker LG, et al. Twice-yearly lenacapavir or daily F/TAF for HIV prevention in cisgender women. ''N Engl J Med''. 2024;391(13):1179-1192. doi:10.1056/NEJMoa2407001</ref><ref name="Kelley2025">Kelley CF, et al. Twice-yearly lenacapavir for HIV prevention in men and gender-diverse persons. ''N Engl J Med''. 2025;392(14):1261-1276. doi:10.1056/NEJMoa2411858</ref>
*Resistance mutations (e.g., M66I, Q67H, N74D) alter capsid binding sites; no cross-resistance to other ARV classes<ref name="SciDirect">Segal-Maurer S, et al. Lenacapavir: a novel injectable HIV-1 capsid inhibitor. ''Int J Antimicrob Agents''. 2023;62(6):107003. doi:10.1016/j.ijantimicag.2023.107003</ref>
*Lenacapavir has not been associated with significant nephrotoxicity or hepatotoxicity; no routine liver or kidney function monitoring is required for PrEP use<ref name="WHO2025">World Health Organization. Guidelines on lenacapavir for HIV prevention. Geneva: WHO; 2025.</ref>

==See Also==
*[[HIV - AIDS (main)]]
*[[HIV post-exposure prophylaxis]]
*[[Immune reconstitution syndrome]]
*[[Emtricitabine/tenofovir]]

==References==
{{reflist|2}}
[[Category:Pharmacology]]

← Older revision		Revision as of 09:12, 22 March 2026
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	*Dosage Forms: 300 mg oral tablets; 463.5 mg/1.5 mL (309 mg/mL) subcutaneous injection solution (single-dose vials)<ref name="SunlencaPI">Sunlenca (lenacapavir) [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; 2024.</ref>		*Dosage Forms: 300 mg oral tablets; 463.5 mg/1.5 mL (309 mg/mL) subcutaneous injection solution (single-dose vials)<ref name="SunlencaPI">Sunlenca (lenacapavir) [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; 2024.</ref>
	*Routes of Administration: Oral (tablets); Subcutaneous injection (abdomen preferred; thigh as alternate site)		*Routes of Administration: Oral (tablets); Subcutaneous injection (abdomen preferred; thigh as alternate site)
	**Do ~~'''~~NOT~~'''~~ administer intradermally — intradermal injection has been associated with serious injection site reactions including necrosis and ulcer<ref name="SunlencaPI"/>		**Do NOT administer intradermally — intradermal injection has been associated with serious injection site reactions including necrosis and ulcer<ref name="SunlencaPI"/>
	*Common Trade Names: Sunlenca (HIV treatment), Yeztugo (HIV PrEP)		*Common Trade Names: Sunlenca (HIV treatment), Yeztugo (HIV PrEP)

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	===HIV-1 Treatment (Sunlenca) — used with other antiretroviral(s)===		===HIV-1 Treatment (Sunlenca) — used with other antiretroviral(s)===
	~~'''~~Initiation Option 1:~~'''~~<ref name="SunlencaPI"/>		Initiation Option 1:<ref name="SunlencaPI"/>
	*Day 1: 927 mg SC injection + 600 mg PO (2 × 300 mg tablets)		*Day 1: 927 mg SC injection + 600 mg PO (2 × 300 mg tablets)
	*Day 2: 600 mg PO (2 × 300 mg tablets)		*Day 2: 600 mg PO (2 × 300 mg tablets)

	~~'''~~Initiation Option 2:~~'''~~		Initiation Option 2:
	*Day 1: 600 mg PO (2 × 300 mg tablets)		*Day 1: 600 mg PO (2 × 300 mg tablets)
	*Day 2: 600 mg PO (2 × 300 mg tablets)		*Day 2: 600 mg PO (2 × 300 mg tablets)
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	*Day 15: 927 mg SC injection		*Day 15: 927 mg SC injection

	~~'''~~Maintenance:~~'''~~ 927 mg SC injection every 26 weeks (±2 weeks) from the date of last injection<ref name="SunlencaPI"/>		Maintenance: 927 mg SC injection every 26 weeks (±2 weeks) from the date of last injection<ref name="SunlencaPI"/>

	===HIV PrEP (Yeztugo)===		===HIV PrEP (Yeztugo)===
	~~'''~~Initiation:~~'''~~<ref name="YeztugoPI">Yeztugo (lenacapavir) [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; 2025.</ref>		Initiation:<ref name="YeztugoPI">Yeztugo (lenacapavir) [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; 2025.</ref>
	*Day 1: 927 mg SC injection + 600 mg PO (2 × 300 mg tablets)		*Day 1: 927 mg SC injection + 600 mg PO (2 × 300 mg tablets)
	*Day 2: 600 mg PO (2 × 300 mg tablets)		*Day 2: 600 mg PO (2 × 300 mg tablets)

	~~'''~~Continuation:~~'''~~ 927 mg SC injection every 26 weeks (±2 weeks)		Continuation: 927 mg SC injection every 26 weeks (±2 weeks)
	*Individuals ~~'''~~must~~'''~~ be confirmed HIV-1 negative before each injection<ref name="CDC2025">CDC. Clinical Recommendation for the Use of Injectable Lenacapavir as HIV Preexposure Prophylaxis — United States, 2025. ''MMWR''. 2025;74(35).</ref>		*Individuals must be confirmed HIV-1 negative before each injection<ref name="CDC2025">CDC. Clinical Recommendation for the Use of Injectable Lenacapavir as HIV Preexposure Prophylaxis — United States, 2025. ''MMWR''. 2025;74(35).</ref>

	===Missed Doses===		===Missed Doses===
	*~~'''~~Treatment (Sunlenca):~~'''~~ If >28 weeks since last injection, restart the full initiation regimen if clinically appropriate<ref name="SunlencaPI"/>		*Treatment (Sunlenca): If >28 weeks since last injection, restart the full initiation regimen if clinically appropriate<ref name="SunlencaPI"/>
	*If discontinuing, begin an alternative suppressive ARV regimen no later than 28 weeks after last injection to avoid resistance development<ref name="SunlencaPI"/>		*If discontinuing, begin an alternative suppressive ARV regimen no later than 28 weeks after last injection to avoid resistance development<ref name="SunlencaPI"/>
	*~~'''~~PrEP (Yeztugo):~~'''~~ If >28 weeks since last injection and oral tablets not taken, restart with initiation dosing<ref name="YeztugoPI"/>		*PrEP (Yeztugo): If >28 weeks since last injection and oral tablets not taken, restart with initiation dosing<ref name="YeztugoPI"/>

	==Pediatric Dosing==		==Pediatric Dosing==
	*~~'''~~PrEP:~~'''~~ Approved for adolescents ≥35 kg; same dosing as adults<ref name="YeztugoPI"/>		*PrEP: Approved for adolescents ≥35 kg; same dosing as adults<ref name="YeztugoPI"/>
	*~~'''~~Treatment:~~'''~~ Not established in pediatric patients		*Treatment: Not established in pediatric patients

	==Special Populations==		==Special Populations==
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	*Animal studies showed no adverse developmental effects at exposures ≥16 times the human dose (AUC)		*Animal studies showed no adverse developmental effects at exposures ≥16 times the human dose (AUC)
	*Antiretroviral Pregnancy Registry (APR) has been established — report exposures at 1-800-258-4263		*Antiretroviral Pregnancy Registry (APR) has been established — report exposures at 1-800-258-4263
	*~~'''~~PrEP use:~~'''~~ May be used in pregnancy after shared decision-making, considering HIV risk without PrEP<ref name="CDC2025"/>		*PrEP use: May be used in pregnancy after shared decision-making, considering HIV risk without PrEP<ref name="CDC2025"/>

	===Lactation risk===		===Lactation risk===
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	===Key interactions for the ED physician===		===Key interactions for the ED physician===
	*'''Strong CYP3A inducers''' — Contraindicated (treatment) or require supplemental dosing (PrEP). Remember the mnemonic '''COPPER''': '''C'''arbamazepine, '''O'''xcarbazepine, '''P'''henobarbital (and primidone), '''P'''henytoin, '''E'''nzalutamide, '''R'''ifampin (also rifabutin, rifapentine)<ref name="NYSDOH"/>		*'''Strong CYP3A inducers''' — Contraindicated (treatment) or require supplemental dosing (PrEP). Remember the mnemonic '''COPPER''': '''C'''arbamazepine, '''O'''xcarbazepine, '''P'''henobarbital (and primidone), '''P'''henytoin, '''E'''nzalutamide, '''R'''ifampin (also rifabutin, rifapentine)<ref name="NYSDOH"/>
	*~~'''~~St. John's wort~~'''~~ — Avoid; significantly decreases lenacapavir levels<ref name="SunlencaPI"/>		*St. John's wort — Avoid; significantly decreases lenacapavir levels<ref name="SunlencaPI"/>
	*Lenacapavir is a ~~'''~~moderate CYP3A inhibitor~~'''~~ and ~~'''~~P-gp inhibitor~~'''~~ — may increase levels of CYP3A substrates for up to 9 months after last SC dose<ref name="SunlencaPI"/>		*Lenacapavir is a moderate CYP3A inhibitor and P-gp inhibitor — may increase levels of CYP3A substrates for up to 9 months after last SC dose<ref name="SunlencaPI"/>
	**Be aware of interactions with common ED medications metabolized by CYP3A (e.g., midazolam, fentanyl, certain statins)		**Be aware of interactions with common ED medications metabolized by CYP3A (e.g., midazolam, fentanyl, certain statins)
	*Lenacapavir is a substrate of CYP3A, P-gp, and UGT1A1<ref name="SunlencaPI"/>		*Lenacapavir is a substrate of CYP3A, P-gp, and UGT1A1<ref name="SunlencaPI"/>
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	==Mechanism of Action==		==Mechanism of Action==
	Lenacapavir binds directly to the interface between HIV-1 capsid protein (p24) subunits within capsid hexamers.<ref name="DvorySobol2022">Dvory-Sobol H, et al. Lenacapavir: a first-in-class HIV-1 capsid inhibitor. ''Curr Opin HIV AIDS''. 2022;17(1):15-21. doi:10.1097/COH.0000000000000713</ref> This binding interferes with multiple stages of the HIV lifecycle:<ref name="Paik2022"/>		Lenacapavir binds directly to the interface between HIV-1 capsid protein (p24) subunits within capsid hexamers.<ref name="DvorySobol2022">Dvory-Sobol H, et al. Lenacapavir: a first-in-class HIV-1 capsid inhibitor. ''Curr Opin HIV AIDS''. 2022;17(1):15-21. doi:10.1097/COH.0000000000000713</ref> This binding interferes with multiple stages of the HIV lifecycle:<ref name="Paik2022"/>
	*~~'''~~Early stages:~~'''~~ Over-stabilizes the capsid, causing premature brittle fracture before the virus reaches the nucleus — the exposed genetic material is degraded in the cytoplasm<ref name="eLife">Walsh J, et al. Lenacapavir molecular mechanisms. ''eLife''. 2024.</ref>		*Early stages: Over-stabilizes the capsid, causing premature brittle fracture before the virus reaches the nucleus — the exposed genetic material is degraded in the cytoplasm<ref name="eLife">Walsh J, et al. Lenacapavir molecular mechanisms. ''eLife''. 2024.</ref>
	*~~'''~~Late stages:~~'''~~ Disrupts Gag/Gag-Pol polyprotein function, reduces capsid subunit production, and accelerates capsid assembly leading to malformed, non-functional virions<ref name="DvorySobol2022"/>		*Late stages: Disrupts Gag/Gag-Pol polyprotein function, reduces capsid subunit production, and accelerates capsid assembly leading to malformed, non-functional virions<ref name="DvorySobol2022"/>

	Because it targets a structural protein rather than an enzyme, mutations conferring resistance to other antiretroviral classes do not affect lenacapavir activity.<ref name="Paik2022"/>		Because it targets a structural protein rather than an enzyme, mutations conferring resistance to other antiretroviral classes do not affect lenacapavir activity.<ref name="Paik2022"/>
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	**Send HIV Ag/Ab and HIV-1 RNA viral load testing		**Send HIV Ag/Ab and HIV-1 RNA viral load testing
	**Patients who acquire HIV while on lenacapavir must be transitioned to a complete HIV treatment regimen<ref name="CDC2025"/>		**Patients who acquire HIV while on lenacapavir must be transitioned to a complete HIV treatment regimen<ref name="CDC2025"/>
	*Lenacapavir does ~~'''~~not~~'''~~ protect against other sexually transmitted infections		*Lenacapavir does not protect against other sexually transmitted infections
	*When prescribing medications in the ED for patients on lenacapavir, be mindful of CYP3A interactions — the inhibitory effect may persist up to 9 months after the last SC dose<ref name="SunlencaPI"/>		*When prescribing medications in the ED for patients on lenacapavir, be mindful of CYP3A interactions — the inhibitory effect may persist up to 9 months after the last SC dose<ref name="SunlencaPI"/>
	*There is no known antidote for overdose; management is supportive. Hemodialysis is unlikely to be effective due to high protein binding<ref name="SunlencaPI"/>		*There is no known antidote for overdose; management is supportive. Hemodialysis is unlikely to be effective due to high protein binding<ref name="SunlencaPI"/>