Long-Acting Injectable Antiretroviral Agents (Apretude, Cabenuva, Sunlenca)

Coverage Summary & Scope

Defines UnitedHealthcare medical benefit coverage criteria for long-acting injectable antiretroviral agents Apretude (cabotegravir) for HIV-1 pre-exposure prophylaxis (PrEP), Cabenuva (cabotegravir/rilpivirine) for treatment of HIV-1 in virologically suppressed patients, and Sunlenca (lenacapavir) for treatment of multidrug-resistant HIV-1, plus applicable procedure and diagnosis codes and policy background (Policy Number IEXD0103.14). Coverage stance: mixed. Initial and continuation authorizations for these agents are limited to no more than 12 months per authorization.

Policy Thresholds (key values)

Virologic suppression thresholdHIV-1 RNA < 50 copies/mL

Apretude minimum weight>= 35 kg

Required pre-initiation viral suppression duration for Cabenuva>= 3 months (patient must have HIV-1 RNA < 50 copies/mL for at least 3 months prior to initiation)

Sunlenca CAPELLA enrollment viral load requirement>= 400 copies/mL (CAPELLA study enrollment criterion)

Apretude (cabotegravir) — Initial Therapy Criteria

Apretude (cabotegravir) - Initial Therapy

Apretude is proven and medically necessary to reduce the risk of sexually acquired HIV-1 infection in at-risk adults and adolescents ≥35 kg when ALL criteria are met:

Used for HIV-1 pre-exposure prophylaxis (PrEP)

Patient has a negative HIV-1 test

Provider confirms that the patient will be tested for HIV-1 infection with each subsequent injection

Dosing is in accordance with the United States Food and Drug Administration approved labeling

Initial authorization is for no more than 12 months

Authorization limited to no more than 12 months

Apretude — Continuation Therapy Criteria

Apretude (cabotegravir) - Continuation Therapy

Continuation is proven and medically necessary when ALL criteria are met:

Patient has previously received treatment with Apretude

Patient has a negative HIV-1 test

Provider confirms that the patient will be tested for HIV-1 infection with each subsequent injection

Dosing is in accordance with the United States Food and Drug Administration approved labeling

Authorization is for no more than 12 months

Authorization limited to no more than 12 months

Apretude — Unproven / Not Medically Necessary Uses

Apretude - Not Medically Necessary

Apretude is unproven and not medically necessary for:

Treatment of human immunodeficiency virus type-1 (HIV-1)

Cabenuva (cabotegravir/rilpivirine) — Initial Therapy Criteria

Cabenuva (cabotegravir/rilpivirine) - Initial Therapy

Cabenuva is proven and medically necessary for treatment of HIV-1 in patients who are virologically suppressed (HIV-1 RNA < 50 copies/mL) when ALL criteria are met:

Diagnosis of HIV-1 infection

Patient has no prior virologic failures or baseline resistance to either cabotegravir or rilpivirine

Patient is currently on a stable antiretroviral regimen

Treatment readiness attestation

Patient understands the risks of missed doses of Cabenuva

Cabenuva — Continuation Therapy Criteria

Cabenuva - Continuation Therapy

Continuation is proven and medically necessary when ALL criteria are met:

Patient has previously received treatment with Cabenuva

Provider confirms that the patient has achieved and maintained viral suppression (HIV-1 RNA < 50 copies/mL) while on Cabenuva therapyHIV-1 RNA < 50 copies/mL

Dosing is in accordance with the United States Food and Drug Administration approved labeling

Dosing per FDA labeling (monthly or every-2-month dosing and specified injection amounts)

Authorization is for no more than 12 months

Authorization limited to no more than 12 months

Cabenuva — Not Medically Necessary

Cabenuva - Not Medically Necessary

Cabenuva is unproven and not medically necessary for:

Treatment of HIV-1 in patients who are not currently virally suppressed (HIV-1 RNA < 50 copies/mL)HIV-1 RNA >= 50 copies/mL

Sunlenca (lenacapavir) — Initial Therapy Criteria

Sunlenca (lenacapavir) - Initial Therapy

Sunlenca is proven and medically necessary for treatment of multi-drug resistant HIV when ALL criteria are met:

Diagnosis and resistance: Both of the following: Diagnosis of HIV-1 infection; Provider attestation that the patient has multi-drug resistant HIV-1 infection

Provider confirms that the patient has been prescribed an optimized background antiretroviral regimen, containing at least one antiretroviral agent that demonstrates full viral sensitivity/susceptibility

Provider must document OBR with at least one fully active agent

Sunlenca initial and maintenance dosing is in accordance with the US Food and Drug Administration prescribing information

Dosing per FDA labeling

Initial authorization is for no more than 12 months

Sunlenca — Continuation Therapy Criteria

Sunlenca - Continuation Therapy

Continuation is proven and medically necessary when ALL criteria are met:

Patient has previously received treatment with Sunlenca

Provider confirms that the patient has achieved a clinically significant viral response to Sunlenca therapy

Provider confirms that the patient will continue to take an optimized background antiretroviral regimen, in combination with Sunlenca

Sunlenca maintenance dosing is in accordance with the US Food and Drug Administration prescribing information

Maintenance dosing per FDA labeling

Authorization is for no more than 12 months

Sunlenca — Not Medically Necessary / Unproven Uses

Sunlenca - Not Medically Necessary / Unproven Uses

Sunlenca is unproven and not medically necessary for the following uses:

Treatment of HIV-1 in patients who are virologically suppressed (HIV-1 RNA < 50 copies/mL)HIV-1 RNA < 50 copies/mL

Treatment in antiretroviral (ARV) naïve patients

HIV-1 pre-exposure prophylaxis (PrEP)

Applicable Codes

Drug J-codesHCPCS

J0739	Injection, cabotegravir, 1 mg, FDA-approved prescription, only for use as HIV pre-exposure prophylaxis (not for use as treatment for HIV).
J0741	Injection, cabotegravir and rilpivirine, 2mg/3mg.
J1961	Injection, lenacapavir, 1 mg

Relevant ICD-10 Diagnosis Codes (examples listed)ICD-10

B20	Human immunodeficiency virus (HIV) disease.
Z11.3	Encounter for screening for infections with a predominantly sexual mode of transmission.
Z11.4	Encounter for screening for human immunodeficiency virus (HIV).
Z16.33	Resistance to antiviral drug(s).
Z20.2	Contact with and (suspected) exposure to infections with a predominantly sexual mode of transmission.
Z20.6	Contact with and (suspected) exposure to human immunodeficiency virus (HIV).
Z21	Asymptomatic human immunodeficiency virus (HIV) infection status.
Z29.81	Encounter for HIV pre-exposure prophylaxis.
Z72.51	High risk heterosexual behavior.
Z72.52	High risk homosexual behavior.

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Provider Actions & Documentation Requirements

Prior Authorization

Authorization duration

Initial and continuation authorizations for Apretude, Cabenuva, and Sunlenca are limited to no more than 12 months per authorization.

Documentation Required

HIV testing before and during therapy

Apretude (cabotegravir) requires a negative HIV-1 test prior to initiation and confirmation that the patient will be tested for HIV-1 infection with each subsequent injection. For Cabenuva (cabotegravir/rilpivirine), providers must confirm and document viral suppression (HIV-1 RNA < 50 copies/mL) as required for initiation and continuation.

Apretude: negative HIV-1 test prior to initiation and testing with each injection.
Cabenuva: documentation of viral suppression (HIV-1 RNA < 50 copies/mL) for at least 3 months prior to initiation and confirmation of maintained suppression for continuation.

Clinical Evidence & Trial Highlights

66-69%HPTN 083: reduction in HIV-1 risk vs Truvada

88-90%HPTN 084: reduction in HIV-1 risk vs Truvada

2%ATLAS/FLAIR/ATLAS-2M: proportion with HIV-1 RNA ≥50 copies/mL (long-acting arms)

>=0.5 log10CAPELLA: primary endpoint ≥0.5 log10 HIV‑1 RNA reduction during functional monotherapy

Key supporting trials include HPTN 083 and HPTN 084 for Apretude (large randomized studies demonstrating superiority to oral Truvada for PrEP), the FLAIR, ATLAS, and ATLAS-2M Phase 3 trials supporting Cabenuva as a maintenance treatment option for virologically suppressed patients, and the CAPELLA study evaluating Sunlenca in heavily treatment-experienced, multidrug-resistant patients; FDA indications for each agent are described in the policy background.

Background & Definitions

Apretude (cabotegravir) is an integrase strand transfer inhibitor that binds the integrase active site and blocks the strand transfer step of retroviral DNA integration; it is FDA-indicated for HIV-1 PrEP in at-risk adults and adolescents weighing at least 35 kg with a negative HIV-1 test prior to initiation. Cabenuva (cabotegravir/rilpivirine) combines an INSTI (cabotegravir) and an NNRTI (rilpivirine); cabotegravir blocks integrase strand transfer and rilpivirine noncompetitively inhibits reverse transcriptase; Cabenuva is FDA-indicated as a complete regimen to replace a current antiretroviral regimen in adults who are virologically suppressed (HIV-1 RNA < 50 copies/mL) with no history of treatment failure or known/suspected resistance to either agent. Sunlenca (lenacapavir) is a multistage capsid inhibitor that binds the capsid protein interface and interferes with multiple steps of the viral lifecycle (nuclear import, assembly/release, and core formation); it is FDA-indicated in combination with other antiretrovirals for heavily treatment-experienced adults with multidrug-resistant HIV-1 failing their current regimen.

Definitions

Virologic suppression (definition)HIV-1 RNA less than 50 copies per mL (policy threshold for Cabenuva continuation/initiation)

Optimized background regimen (OBR)Background antiretroviral regimen containing at least one agent with demonstrated full viral sensitivity/susceptibility, used in combination with Sunlenca for multidrug resistant HIV-1.

Policy Revision History

2025-01-01material_revisionLatest

Revised Apretude initial therapy criteria: removed requirement that provider determine Apretude is preferred over lower-cost alternatives (e.g., generic emtricitabine/tenofovir disoproxil fumarate) and removed prior treatment‑readiness attestation language requiring the patient understand risks of missed doses and ability to adhere to every-2-month injection and testing appointments.

2025-01-01code_update

Removed ICD-10 diagnosis code Z20 from Applicable Codes.

2025-01-01administrative_update