Coverage Policy Manual
Policy #: 2022003
Category: Pharmacy
Initiated: January 2022
Last Review: January 2025
  Cabotegravir ER (e.g., Apretude)
Description:
Cabotegravir ER (e.g., Apretude) is an integrase strand transfer inhibitor (INSTI). INSTIs inhibit HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T-cells).
 
Cabotegravir extended-release is indicated in at-risk adults and adolescents weighing at least 35 kg for PrEP to reduce the risk of sexually acquired HIV-1 infection. Individuals must have a negative HIV-1 test prior to initiating cabotegravir extended-release (with or without an oral lead-in with oral cabotegravir) for HIV-1 PrEP.
 
Regulatory
 
On December 21, 2021, the U.S. Food and Drug Administration approved cabotegravir extended-release injectable suspension (e.g., Apretude) for use in at-risk adults and adolescents weighing at least 35 kg (77#) for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV. Cabotegravir ER is given first as two initiation injections administered one month apart, and then every two months thereafter. Individuals can either start their treatment with Cabotegravir ER or take oral cabotegravir (Vocabria) for four weeks to assess how well they tolerate the drug.
 
Coding
 
See CPT/HCPCS Code section below.
Policy/
Coverage:
Effective January 2025
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Cabotegravir ER (e.g., Apretude) meets member benefit certificate primary coverage criteria that there be scientific effectiveness in improving health outcomes when the following criteria are met:
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
1. Cabotegravir extended-release (e.g., Apretude) will be used in at risk adults and adolescents for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection; AND
2. Individual weighs at least 35 kg; AND
3. Individual is at high risk for sexually acquiring HIV infection; AND
4. Documentation of non-reactive/negative HIV test result prior to treatment; AND
5. Must be dosed in accordance with the FDA label.
 
CONTINUED APPROVAL for 1 year:
 
1. Individual meets all the above criteria; AND
2. Individual is compliant with Cabotegravir (defined as receiving >80% of doses in the past 12 months).
 
Dosage and Administration
Dosing per FDA Guidelines
 
Screen individual for HIV-1 infection immediately prior to initiating cabotegravir extended-release for HIV-1 PrEP and prior to each injection while taking cabotegravir extended-release.
 
Prior to initiating cabotegravir extended-release, an oral lead-in dosing may be used for approximately 1 month with the recommended dosage to assess the tolerability of cabotegravir extended-release.
 
For gluteal intramuscular injection only.
 
The recommended dosing schedule for Cabotegravir extended-release (e.g., Apretude): initiate cabotegravir extended release with a single 600 mg (3 mL) injection given 1 month apart for 2 consecutive months on the last day of an oral lead-in if used or within 3 days and continue with injections every 2 months thereafter.
 
Cabotegravir extended-release (e.g., Apretude) is available in a single-dose vial of 600 mg/3 mL (200 mg/mL) extended-release injectable suspension.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Cabotegravir extended-release (e.g., Apretude), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for any indication or circumstance including an individual with unknown or positive HIV-1 status.
 
For members with contracts without primary coverage criteria, Cabotegravir extended release (e.g., Apretude), for any indication or circumstance not described above including an individual with unknown or positive HIV-1 status is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective August 9, 2023 to December 2024
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of cabotegravir extended-release meets member benefit certificate primary coverage criteria that there be scientific effectiveness in improving health outcomes in at-risk adults and adolescents for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection when the following criteria are met:
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
    1. Individual weighs at least 35 kg; AND
    2. Individual is at high risk for sexually acquiring HIV infection; AND
    3. Documentation of non-reactive/negative HIV test result prior to treatment; AND
    4. Must be dosed in accordance with the FDA label.
 
CONTINUED APPROVAL for 1 year:
 
    1. Individual meets all the above criteria; AND
    2. Individual is compliant with Cabotegravir (defined as receiving >80% of doses in the past 12 months).
 
Dosage and Administration
Dosing per FDA Guidelines
 
Screen individual for HIV-1 infection immediately prior to initiating cabotegravir extended-release for HIV-1 PrEP and prior to each injection while taking cabotegravir extended-release.
 
Prior to initiating cabotegravir extended-release, an oral lead-in dosing may be used for approximately 1 month with the recommended dosage to assess the tolerability of cabotegravir extended-release.
 
For gluteal intramuscular injection only.
 
Recommended dosing schedule: initiate cabotegravir extended release with a single 600 mg (3 mL) injection given 1 month apart for 2 consecutive months on the last day of an oral lead-in if used or within 3 days and continue with injections every 2 months thereafter.
 
Cabotegravir is available in a single-dose vial of 600 mg/3 mL (200 mg/mL) extended-release injectable suspension.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Cabotegravir extended-release, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for any indication or circumstance including an individual with unknown or positive HIV-1 status.
 
For members with contracts without primary coverage criteria, Cabotegravir extended release, for any indication or circumstance not described above including an individual with unknown or positive HIV-1 status is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective January 02, 2023 to August 8, 2023
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of cabotegravir extended-release meets member benefit certificate primary coverage criteria that there be scientific effectiveness in at-risk adults and adolescents for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection when the following criteria are met:
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
  1. Individual weighs at least 35 kg AND
  2. Individual is at high risk for sexually acquiring HIV infection AND
  3. Documentation of non-reactive/negative HIV test result prior to treatment AND
  4. Individual must have documentation of one of the following:
a.  Non-compliance to available oral products (i.e., emtricitabine; tenofovir alafenamide, emtricitabine; tenofovir disoproxil fumarate); OR
b.  Inadequate response, intolerance, or contraindication to available oral products (i.e., emtricitabine; tenofovir alafenamide, emtricitabine; tenofovir disoproxil fumarate).
 
Continued Approval (1 year):
  • Individual meets all the above criteria.
  • Member is compliant with Cabotegravir (no missed doses in the past 12 months).
 
Dosage and Administration
  1.  Screen individual for HIV-1 infection immediately prior to initiating cabotegravir extended-release for HIV-1 PrEP and prior to each injection while taking cabotegravir extended-release.
  2.  Prior to initiating cabotegravir extended-release, an oral lead-in dosing may be used for approximately 1 month with the recommended dosage to assess the tolerability of cabotegravir extended-release.
  3.  For gluteal intramuscular injection only.
  4.  Recommended dosing schedule: initiate cabotegravir extended release with a single 600 mg (3 mL) injection given 1 month apart for 2 consecutive months on the last day of an oral lead-in if used or within 3 days and continue with injections every 2 months thereafter.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Cabotegravir extended-release does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for any indication or circumstance other than those listed above including an Individual with unknown or positive HIV-1 status.
 
For members with contracts without primary coverage criteria, Cabotegravir extended release is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective January 26, 2022
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of cabotegravir extended-release meets member benefit certificate primary coverage criteria that there be scientific effectiveness in at-risk adults and adolescents for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection when the following criteria are met:
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
    1. Must have evidence of non-compliance AND
    2. Individual weighs at least 35 kg AND
    3. Individual is at high risk for sexually acquiring HIV infection AND
    4. Documentation of non-reactive/negative HIV test result prior to treatment AND
    5. If of reproductive potential (defined as pre-menopausal women who have not had a sterilization procedure per self-report, such as hysterectomy, bilateral oophorectomy, tubal ligation, or salpingectomy), individual must have a negative beta human chorionic gonadotropin (HCG) pregnancy test AND
    6. Have documented evidence of surgical sterilization OR must agree to use a reliable form of long-acting contraception, during and after stopping the long acting injectable from the list below:
        1. Intrauterine device (IUD) or intrauterine system (IUS) that meets less than 1% failure rate as stated in the product label.
        2. Hormone-based contraceptive that meets less than 1% failure rate when used consistently and correctly as stated in the product label (implants or injectables only; this excludes combined oral contraception)
    7. Must have tolerated 30 mg oral Cabotegravir lead-in dosing for approximately 1 month (FDA, 2021)
    8. Must have had an inadequate response, intolerance, or contraindication to oral tenofovir disoproxil fumarate and emtricitabine combination.
 
Continued Approval (1 year):
    1. Individual meets all of the above criteria.
    2. Member is compliant with Cabotegravir (no missed doses in the past 12 months).
 
Dosage and Administration
 
    • Screen individual for HIV-1 infection immediately prior to initiating cabotegravir extended-release for HIV-1 PrEP and prior to each injection while taking cabotegravir extended-release.
    • Prior to initiating cabotegravir extended-release, an oral lead-in dosing may be used for approximately 1 month with the recommended dosage to assess the tolerability of cabotegravir extended-release.
    • For gluteal intramuscular injection only.
    • Recommended dosing schedule: initiate cabotegravir extended-release with a single 600 mg (3 mL) injection given 1 month apart for 2 consecutive months on the last day of an oral lead-in if used or within 3 days and continue with injections every 2 months thereafter.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Cabotegravir extended-release does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for any indication or circumstance other than those listed above including an Individual with unknown or positive HIV-1 status.
 
For members with contracts without primary coverage criteria, Cabotegravir extended-release is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Rationale:
A randomized, double-blind, double-dummy, noninferiority trial was conducted to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate–emtricitabine (TDF–FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection.
 
The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF–FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF–FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified.
 
CAB-LA was superior to daily oral TDF–FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Landovitz RJ, Donnell D, Clement ME, 2021)
 
2023 Update  
A literature search conducted through January 2023 did not reveal any new information that would prompt a change in the coverage statement.
 
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2024. No new literature was identified that would prompt a change in the coverage statement.
 
2025 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2025. No new literature was identified that would prompt a change in the coverage statement.
CPT/HCPCS:
J0739Injection, cabotegravir, 1 mg
J3490Unclassified drugs
References: Cabotegravir extended-release injectable suspension (Apretude) [prescribing information]; ViiV Healthcare, 2021.

Landovitz RJ, Donnell D, Clement ME, et.al.,(2021) Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women. N Engl J Med. 2021 Aug 12;385(7):595-608. doi: 10.1056/NEJMoa2101016. PMID: 34379922; PMCID: PMC8448593.
Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2025 American Medical Association.