Sierra Health and Life long‑acting ARV Coverage Update

Coverage Criteria for Long-Acting Injectable Antiretroviral Agents

Apretude (cabotegravir) - Initial and Continuation

Covered when ALL of the following are met

Apretude Initial Therapy: 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

Apretude is unproven and not medically necessary for treatment of HIV-1

Apretude Continuation Therapy: 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

Apretude is unproven and not medically necessary for treatment of HIV-1

Cabenuva (cabotegravir/rilpivirine) - Initial and Continuation

Covered when ALL of the following are met

Cabenuva Initial Therapy: 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; Provider attests that patient has achieved viral suppression (HIV-1 RNA less than 50 copies per mL) for at least 3 months prior to initiation of Cabenuva; Provider attests that patient demonstrates treatment readiness by both: patient understands the risks of missed doses of Cabenuva AND patient has the ability to adhere to the required monthly or every 2 months injection appointments; Dosing is in accordance with the United States Food and Drug Administration approved labeling; Initial authorization is for no more than 12 monthsHIV-1 RNA <50 copies/mL for ≥3 months

Continuation requires maintained viral suppression on Cabenuva

Cabenuva Continuation Therapy: Patient has previously received treatment with Cabenuva; Provider confirms that the patient has achieved and maintained viral suppression (HIV-1 RNA less than 50 copies per mL) while on Cabenuva therapy; Dosing is in accordance with the United States Food and Drug Administration approved labeling; Authorization is for no more than 12 monthsHIV-1 RNA <50 copies/mL

Cabenuva is not indicated for patients who are not currently virally suppressed

Sunlenca (lenacapavir) - Initial and Continuation

Covered when ALL of the following are met

Sunlenca Initial Therapy: 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 susceptibility; Sunlenca initial and maintenance dosing is in accordance with the United States Food and Drug Administration approved labeling; Initial authorization is for no more than 12 months

Continuation requires clinically significant viral response and continued optimized background regimen

Sunlenca Continuation Therapy: 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 United States Food and Drug Administration approved labeling; Authorization is for no more than 12 months

Sunlenca is unproven and not medically necessary for virologically suppressed patients, ARV‑naïve patients, and for PrEP

Yeztugo (lenacapavir) - Initial and Continuation

Covered when ALL of the following are met

Yeztugo Initial Therapy: 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

Yeztugo is unproven and not medically necessary for treatment of HIV-1

Yeztugo Continuation Therapy: Patient has previously received treatment with Yeztugo; 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

Yeztugo is unproven and not medically necessary for treatment of HIV-1

Initial Therapy — Yeztugo (PrEP)

Yeztugo (lenacapavir) injectable is considered medically necessary for HIV-1 pre-exposure prophylaxis when ALL of the following are met:

Yeztugo PrEP Initial: Used for HIV-1 pre-exposure prophylaxis (PrEP); Patient has a negative HIV-1 test prior to initiating; Provider confirms patient will be tested for HIV-1 infection with each subsequent injection; Dosing is in accordance with U.S. FDA approved labeling; Initial authorization is for no more than 12 months

Per policy revision: Yeztugo proven for PrEP in at‑risk individuals ≥35 kg; boxed warning for resistance if used in undiagnosed HIV-1 infection

Continuation Therapy — Yeztugo (PrEP)

Yeztugo continuation is considered medically necessary when ALL of the following are met:

Yeztugo PrEP Continuation: Patient has previously received treatment with Yeztugo; Patient has a negative HIV-1 test at time of continued authorization; Provider confirms ongoing HIV-1 testing with each subsequent injection; Dosing remains in accordance with U.S. FDA approved labeling; Authorization is for no more than 12 months

Continuation prior authorization requires documentation of prior Yeztugo receipt and negative HIV-1 test

Sunlenca — Treatment Indication

Sunlenca (lenacapavir) injectable is indicated for treatment of heavily treatment-experienced adults with multidrug resistant HIV-1 failing their current antiretroviral regimen.

Sunlenca treatment indication: Use in combination with other antiretroviral(s) for heavily treatment-experienced adults with multidrug-resistant HIV-1 failing current regimen due to resistance, intolerance, or safety considerations; CAPELLA trial required HIV-1 RNA ≥ 400 copies/mL, documented multiclass resistance (resistance to ≥2 agents from each of ≥3 of 4 ARV classes), and ≤2 fully active ARV medications remaining at baseline; demonstrated virologic activity during 14‑day functional monotherapy and favorable Week 26 and Week 52 outcomes in cohortsHIV-1 RNA ≥ 400 copies/mL (CAPELLA enrollment)

Continuation requires clinically significant viral response and ongoing optimized background regimen

Sunlenca (lenacapavir) is unproven and not medically necessary for use in patients who are virologically suppressed (HIV-1 RNA less than 50 copies/mL). The policy also specifies that Sunlenca is not medically necessary for antiretroviral (ARV)‑naïve patients and is not indicated for HIV‑1 pre‑exposure prophylaxis (PrEP).

Cabenuva (cabotegravir/rilpivirine) is considered unproven and not medically necessary for treatment of HIV‑1 in patients who are not currently virally suppressed (HIV‑1 RNA less than 50 copies/mL). Eligibility for Cabenuva requires documented viral suppression (HIV‑1 RNA <50 copies/mL) for at least 3 months prior to initiation; use in patients who do not meet that suppression threshold is excluded.

Apretude (cabotegravir) and Yeztugo (lenacapavir) are indicated for HIV‑1 pre‑exposure prophylaxis (PrEP) and are explicitly described in this policy as unproven and not medically necessary for treatment of HIV‑1 infection. The policy requires a documented negative HIV‑1 test prior to initiation and ongoing HIV‑1 testing with each subsequent injection when used for PrEP.

Yeztugo (lenacapavir) is stated in the policy as unproven and not medically necessary for the treatment of HIV‑1. The updated policy language added Yeztugo as an injectable PrEP product and clarifies that Yeztugo is not indicated for HIV‑1 treatment.

Apretude (cabotegravir) is described as unproven and not medically necessary for the treatment of human immunodeficiency virus type‑1 (HIV‑1); its covered indication in this policy is for HIV‑1 pre‑exposure prophylaxis (PrEP) only, with required negative HIV‑1 testing prior to and during therapy.

Cabenuva (cabotegravir/rilpivirine) is unproven and not medically necessary for treatment of HIV‑1 in patients who are not currently virally suppressed (HIV‑1 RNA less than 50 copies per mL). The policy requires virologic suppression and absence of prior virologic failures or baseline resistance before initiating Cabenuva.

Sunlenca (lenacapavir) is designated unproven and not medically necessary for patients who are virologically suppressed (HIV‑1 RNA less than 50 copies/mL). The policy limits Sunlenca’s treatment indication to heavily treatment‑experienced patients with multidrug resistance combined with an optimized background regimen.

Yeztugo (lenacapavir) is reiterated as unproven and not medically necessary for the treatment of HIV‑1 infection; the policy updates also clarify Yeztugo’s role as a long‑acting injectable for PrEP rather than for HIV‑1 treatment.

Use of Yeztugo for treatment of HIV‑1 infection (as opposed to its approved indication for PrEP) is explicitly considered unproven and not medically necessary in this policy. The revision history emphasizes that Yeztugo injection is covered under the medical benefit for PrEP and that Yeztugo is not authorized for HIV‑1 treatment.

Applicable Codes and Coding Details

Applicable HCPCS codesHCPCS

J0738	Injection, lenacapavir, 1 mg, FDA-approved prescription, only for use as HIV pre-exposure prophylaxis (PrEP) (not for use as treatment for HIV).
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, 2 mg/3 mg.
J1961	Injection, lenacapavir (only for use as HIV treatment), 1 mg.

Applicable ICD-10 CodesICD-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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Applicable HCPCS codes (updated)HCPCS

J0738	Added (description updated in policy)
J1961	Description revised (policy notes revision)

inv-20: Viral suppression threshold — HIV-1 RNA less than 50 copies per mL

Viral suppression thresholdHIV-1 RNA less than 50 copies per mL

Use for Cabenuva eligibilityPatient must have been virally suppressed (HIV-1 RNA <50 copies/mL) for at least 3 months prior to initiation

Continuation requirementPatient must maintain HIV-1 RNA less than 50 copies per mL while on therapy for continuation authorization

inv-21: Minimum weight for PrEP injections — At least 35 kg

Minimum weight for PrEP injectionsAt least 35 kg

Products referencing weight threshold

Provider Actions, Documentation, and Prior Authorization Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required with documentation that all specified clinical criteria are met. Initial and continuation authorizations are typically limited to no more than 12 months and must follow FDA-approved dosing.

Prior authorization required for initial and continuation therapy when applicable
Initial and continuation authorizations limited to ≤ 12 months unless otherwise specified

Prior Authorization

Yeztugo (lenacapavir) Prior Authorization

Yeztugo (lenacapavir) prior authorization is required when used for HIV-1 pre-exposure prophylaxis (PrEP). Initial authorization is for no more than 12 months; continuation requires documentation that prior treatment and testing requirements are met.

Yeztugo (lenacapavir) requires prior authorization for PrEP
Initial authorization limited to ≤ 12 months; continuation requires documentation of prior Yeztugo use and ongoing negative HIV-1 testing

Background and Clinical Context

Apretude and Yeztugo are long‑acting injectable formulations approved for HIV‑1 pre‑exposure prophylaxis (PrEP) in adults and adolescents weighing at least 35 kg. For PrEP indications, the policy requires a documented negative HIV‑1 test prior to initiation and confirmation that the patient will have HIV‑1 testing with each subsequent injection. The policy states these agents are not medically necessary when used to treat HIV‑1 infection.

Key Definitions and Mechanisms

inv-32: Lenacapavir mechanism — multistage selective inhibitor of HIV-1 capsid function

Mechanism of actionMultistage, selective inhibitor of HIV-1 capsid function that binds capsid protein interfaces and interferes with capsid-mediated nuclear uptake, virus assembly/release, and capsid core formation

Binding characteristicsDirectly binds the interface between capsid protein (p24) subunits in hexamers with high affinity (KD ~1.4 nM)

Lifecycle steps affectedInterferes with nuclear import of proviral DNA, Gag/Gag-Pol function (assembly/release), and capsid core formation

inv-33: Cabotegravir mechanism — integrase strand transfer inhibitor

Mechanism of actionIntegrase strand transfer inhibitor (INSTI) that binds the integrase active site and blocks strand transfer of viral DNA integration

Role in regimen

OpenPayer

Long-Acting Injectable Antiretroviral Agents for HIV

Coverage Criteria for Long-Acting Injectable Antiretroviral Agents

Applicable Codes and Coding Details

Provider Actions, Documentation, and Prior Authorization Requirements

Background and Clinical Context

Key Definitions and Mechanisms