CABOTEGRAVIR INJ,SUSP,SA
Clinical Criteria Summary
Document 326: HIV PrEP Clinical Recommendations for Use DEC 2025
Indications & Target Populations
- HIV preexposure prophylaxis (PrEP) for men who have sex with men (MSM), transgender women (TGW), cisgender men, and cisgender women at risk for HIV sexual acquisition.
- Patients at very high risk of transmission (e.g., frequent condom-less sexual encounters, partners with uncontrolled HIV infection).
Renal & Skeletal Considerations
- Alternative to oral PrEP for patients with renal dysfunction.
- Unlikely to impact renal function or bone mineral density.
- Appropriate alternative for patients with osteoporosis or osteopenia.
Adherence & Behavioral Factors
- Beneficial for patients unable to adhere to daily oral dosing due to unstable housing, stigma, cognitive difficulties, uncontrolled mental illness, or substance use disorders.
- Requires patient agreement to comply with a strict every-2-month injection and testing schedule.
- Long half-life may pose a risk if therapy is abruptly discontinued while continuing high-risk behaviors (subtherapeutic concentrations may persist for up to 1 year, increasing resistance risk).
Contraindications & Drug Interactions
- Should not be used in patients receiving strong CYP inducers.
- Indicated for patients with contraindications or intolerance to tenofovir or emtricitabine.
Monitoring & Testing Requirements
- HIV must be excluded at baseline and at least every 2 months while on therapy.
- Adherence counseling and support required; patients educated on side effects, particularly during the first month of therapy.
- Additional monitoring (e.g., sexually transmitted infections, serum lipids, weight) per CDC/USPSTF guidelines.
Administration & Prescribing Requirements
- Long-acting intramuscular injection formulation.
- Oral lead-in is optional but may be used to assess early tolerance prior to long-lasting injection; oral CAB must be procured from Theracom.
- Prior authorization (PA-F) on the VA National Formulary (VANF).
- Must be prescribed by Infectious Diseases, HIV, or other PrEP providers with training/experience in managing HIV PrEP patients.
Document 100: Cabotegravir Rilpivirine CABENUVA CFU Update Feb 2026
Exclusion Criteria
- Known hypersensitivity to any component of the treatment regimen
- Coadministration with strong UGT1A1 and/or CYP3A4 inducers (e.g., rifamycins, dexamethasone, anticonvulsants that induce UGT/CYP)
- Baseline resistance mutations to either CAB or RPV
- History of significant INSTI or NNRTI resistance associated mutations (with the exception of K103N)
- Pregnant or planning to become pregnant
- Active hepatitis B virus (HBV) infection not on active HBV therapy
- Unable to discontinue use of PPI therapy while on ORAL RPV induction/bridge therapy
Inclusion Criteria
- Prescribed and monitored by a VA/VA Community Care HIV/ID provider or locally designated expert
- A specific indication for CAB/RPV injection exists, SUCH AS difficulty managing oral medication (e.g., cognitive deficits, homelessness), concern for oral absorption of antiretrovirals, or concern for severe stigma with discovery of oral medications
- Documented history of adherence to HIV-related clinic appointments for at least 3 months
- Provider documents that the patient agrees to show up for clinic injections and understands that failure to do so will impact clinic schedules, increase risk of treatment failure and MAY result in changing back to an oral and potentially salvage regimen
Additional Inclusion Criteria (ONE must be selected)
- Virologically controlled (HIV-1 RNA<50 copies/mL) on a stable oral standard antiretroviral regimen for ≥ 3 months
- Detectable viremia (HIV-1 RNA >50 copies/mL) with a high risk of HIV disease progression and its complications (CD4 count <200 /uL or AIDS-defining illness) and documented adherence issues to oral ART despite reinforcement efforts and clinical support
Document 309: Cabotegravir APRETUDE Jun2022
Patient Eligibility & Inclusion Criteria
- • Prescribed by or in collaboration with a provider experienced or trained in PrEP administration (designated facility providers)
- • Substantial risk of HIV acquisition: sex without condoms, recent or frequent sexually transmitted infections (STIs), sexual relationship with an HIV-infected partner, injection drug abuse with equipment sharing
- • Must also meet at least one additional criterion:
- Intolerance to Truvada or Descovy
- CrCl <60 mL/min or multiple risk factors for significant renal dysfunction
- Patient-specific factors impacting adherence to daily oral PrEP (cognitive difficulties, gastrointestinal dysfunction, unstable housing, stigma, or fear of discovery)
- Very high-risk for HIV acquisition (MSM engaging in frequent condom-less receptive anal intercourse, repeated STIs, or high-risk sexual activity with partners known/likely to be HIV-infected)
Exclusion Criteria
- • Significant noncompliance with follow-up appointments unless barriers to compliance have been significantly addressed by the provider
- • Drug interactions that preclude administration of CAB (UGT1A1 inducers, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifamycin derivatives, St. John’s Wort)
Dosing & Administration Criteria
- • Dosing: 600mg IM monthly for 2 months, then every 2 months
- • Administration site: Gluteal muscle (absorption from other sites can be unpredictable)
Pre-Administration & Monitoring Criteria
- • HIV must be excluded prior to administration of CAB
- • Clinical recommendations for monitoring should be consulted
Document 310: MON Cabotegravir APRETUDE Jun 2022
Indication & Patient Population
- Indicated for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in at-risk adults and adolescents.
- Recommended for individuals reporting sexual behaviors placing them at substantial ongoing risk of HIV acquisition, and persons who inject drugs (PWID) with injection practices placing them at ongoing risk.
- Particularly beneficial for patients unable to adhere to oral daily dosing due to cognitive dysfunction impacting adherence, unstable housing or homelessness, gastrointestinal dysfunction impairing absorption, previous medication non-adherence despite regular clinic visit adherence, mental illness or substance abuse impacting compliance, or concerns about stigma/discovery of PrEP use by family or friends.
- May be considered on a case-by-case basis for those at highest risk of HIV infection (e.g., frequent condom-less or unprotected sexual encounters with partners known/at high risk for HIV, frequent needle/equipment sharing with IDU).
Dosing & Administration Requirements
- Dosage form: 600mg extended-release injectable suspension for intramuscular (IM) administration.
- Dosing schedule: 600mg IM repeated 4 weeks later, then every 8 weeks. Can be administered up to 7 days before or after the due date.
- Oral lead-in (30mg daily by mouth for 28 days) is OPTIONAL; if used, injection should start on the last day of oral therapy or within 3 days thereafter.
- Injectable must be administered by a healthcare professional.
- If a scheduled dose is missed by >7 days, clinical reassessment is required to ensure resumption remains appropriate; dosing schedule may need adjustment (e.g., restarting with 2 monthly doses prior to resuming every-2-month schedule).
- Oral cabotegravir (30mg daily for up to 2 months) can be used to replace one scheduled every-2-month injection if a patient is known/scheduled to miss an injection.
Testing & Monitoring Requirements
- A negative HIV-1 test MUST be completed and confirmed negative prior to initiating therapy AND with each subsequent injection (at least every 2 months).
- Testing should be repeated upon diagnosis of other STIs.
- For patients with recent high-risk behaviors, evaluate for clinical symptoms compatible with acute HIV infection; if present, use an FDA-cleared/approved test for acute HIV diagnosis.
- Patients must agree to required injection dosing and testing schedules; adherence counseling and support are required.
Contraindications & Warnings/Precautions
- Contraindicated in patients with unknown or positive HIV status.
- Contraindicated with previous hypersensitivity to cabotegravir.
- Contraindicated with co-administration of moderate-strong inducers of UGT1A1 due to potential loss of efficacy from decreased plasma concentrations.
- Boxed Warning: Risk of drug resistance if used as PrEP in undiagnosed HIV infection; monotherapy in undiagnosed HIV-1 may result in INSTI resistance. Patients found HIV-positive must immediately transition to a full antiretroviral regimen.
- Long-acting properties: Residual concentrations may remain for up to 12 months or longer. If discontinued, alternative PrEP should be considered for those remaining at high risk beginning within 2 months of the last injection; additional oral PrEP should be started within 4 weeks after the last dose in those continuing to engage in high-risk behaviors. Patients must reliably attend clinic visits.
- Hepatotoxicity: Clinical and lab monitoring should be considered; discontinue if suspected.
- Depressive disorders: Reported (including depression, suicide ideation/attempt).
- Hypersensitivity reactions: Oral lead-in may help identify risk prior to long-acting injection.
Special Populations & Organ Function Considerations
- Renal insufficiency: No dosage adjustment for mild/moderate impairment. Increased monitoring recommended for severe impairment (CrCl 15-29 mL/min) or ESRD (CrCl <15 mL/min). Dialysis not expected to alter exposures. Particularly beneficial for patients with CrCl <30 mL/min or multiple risk factors for nephrotoxicity.
- Hepatic insufficiency: No dose adjustment for mild-moderate impairment (CTP A or B). Impact of severe impairment unknown.
- Pregnancy: Insufficient data; neural tube defects associated with other INSTIs. Animal studies showed delayed parturition, increased stillbirths/neonatal deaths at >28x RHD. Pregnancy registry exists. Consider prolonged concentrations in women of childbearing potential.
- Lactation: Unknown if present in human milk. Recommended to breastfeed only if benefits outweigh risks given potential persistence >12 months. Present in rat milk.
- Geriatric: No dose adjustment required; very limited data in patients ≥65 years.