Aetna modified CPB 0215 governing outpatient IV antibiotic therapy for Lyme disease, effective September 26, 2025. Here's what billing teams need to know.
Aetna, a CVS Health company, updated its Lyme disease and tick-borne illness coverage policy under CPB 0215 Aetna system. This policy sets strict medical necessity criteria for outpatient IV antibiotic therapy — including the specific lab tests required for diagnosis and the clinical conditions that justify a 4-week IV course. If your team bills CPT 96365, 96366, 96367, or home infusion codes like S9494 through S9498 for Lyme disease patients, this coverage policy change affects you directly.
Quick-Reference Table
| Field | Detail |
|---|---|
| Payer | Aetna, a CVS Health company |
| Policy | Lyme Disease and Other Tick-Borne Diseases |
| Policy Code | CPB 0215 |
| Change Type | Modified |
| Effective Date | September 26, 2025 |
| Impact Level | High |
| Specialties Affected | Infectious Disease, Internal Medicine, Neurology, Cardiology, Rheumatology, Home Infusion |
| Key Action | Audit open Lyme disease claims for IV antibiotic therapy against the two-tier serology and clinical criteria before billing CPT 96365 or S9494–S9498 |
Aetna Lyme Disease IV Antibiotic Coverage Criteria and Medical Necessity Requirements 2025
The core of this coverage policy is a two-gate entry system. To qualify for outpatient IV antibiotic therapy, a member must clear both a lab threshold and a clinical threshold. Neither alone is enough.
Gate one: Lab confirmation. Aetna requires a positive serologic or CSF titer using one of three methods — indirect immunofluorescence assay (IFA), the Prevue Borrelia burgdorferi antibody detection assay, or ELISA. That ELISA or IFA result must then be confirmed by a positive Western Blot (CPT 86617 or 84181/84182). This follows the CDC's 1995 two-tier approach: a sensitive EIA or IFA first, then Western Blot for any positive or equivocal result.
The Western Blot criteria are specific. For IgM immunoblot, two of three bands must be present: 21/22/23/24 kDa (OspC), 39 kDa (BmpA), or 41 kDa (Fla). For IgG immunoblot, five of ten specified bands must be present. One more thing your team needs to know: a positive IgM immunoblot alone does not establish active disease when illness has lasted more than one month. Aetna follows CDC guidance on this point. If you're billing based on IgM-only results for a patient more than 30 days into symptoms, expect a claim denial.
Gate two: Clinical indication. Once the lab criteria are satisfied, the member must also meet at least one of five clinical conditions to justify IV therapy. These are not interchangeable — each has its own documentation requirements.
Condition one is Lyme arthritis that has already failed a 4-week oral antibiotic course. Condition two is moderate-to-severe cardiac involvement: a first-degree heart block with P-R interval greater than 0.4 seconds, congestive heart failure, myopericarditis, or second-degree or higher AV block. Condition three is neuroborreliosis — encephalopathy, encephalomyelitis, meningitis confirmed by CSF showing lymphocytic pleocytosis with Borrelia antibody production, or sensory/motor radiculoneuropathy.
Condition four applies to all symptomatic pregnant members with either Stage II early disseminated Lyme disease (arthritic, cardiac, or neurologic organ manifestations) or Stage III late Lyme disease with arthritis or neurologic complications. Condition five governs a repeat 4-week IV course — and requires all three of the following: the member previously met criteria for an initial IV course using lab results from within the past three months, the member completed that initial IV course, and there is objective evidence of relapse, disease progression, or new organ involvement.
That three-part conjunctive test for repeat courses is where most billing disputes will land. All three criteria must be satisfied simultaneously. Document each one explicitly in your prior authorization request. If you're unsure whether your clinical documentation covers all three, loop in your compliance officer before submitting.
Aetna Lyme Disease Exclusions and Non-Covered Indications
This section is where the policy gets pointed. Aetna explicitly designates a long list of alternative or "integrative" Lyme disease treatments as not covered — and they're specific enough that your billing team needs to know them by name.
The following are not covered for Lyme disease diagnosis or treatment under this coverage policy: CPT 0316U (Borrelia burgdorferi OspA protein evaluation, urine), CPT 99183 (hyperbaric oxygen therapy), CPT 0232T (platelet rich plasma injections), CPT 96372 (subcutaneous or intramuscular injection for alternative therapies), radiation treatment delivery codes CPT 77401 through 77417, and PET imaging codes CPT 78608, 78609, and 78811 through 78816.
Also excluded: alpha lipoic acid or "healing" detox drip infusions, mycotoxin testing (CPT 87230), lymphocyte transformation testing (CPT 86353), lymphocyte marker panels (CPT 86355, 86357, 86359, 86360), complement testing (CPT 86160, 86161, 86162, 86171), immune complex assays (CPT 86332), cortisol (CPT 82533), DHEA (CPT 82626), histamine (CPT 83088), serotonin (CPT 84260), C-peptide (CPT 84681), and amino acid quantification (CPT 82136).
The real issue here is that alternative Lyme disease treatment is a high-fraud, high-audit category. Aetna has listed these codes explicitly because they appear in claims — and they're watching. If any of these codes appear on claims associated with Lyme disease diagnoses in your practice, audit those claims now.
Coverage Indications at a Glance
| Indication | Status | Relevant Codes | Notes |
|---|---|---|---|
| Outpatient IV antibiotics — Lyme arthritis after failed oral therapy | Covered | CPT 96365–96368, S9494–S9498 | Must document failed 4-week oral course first |
| Outpatient IV antibiotics — Moderate-to-severe cardiac involvement | Covered | CPT 96365–96368, S9494–S9498 | P-R interval >0.4s, CHF, myopericarditis, or 2nd+ degree AV block |
| Outpatient IV antibiotics — Neuroborreliosis | Covered | CPT 96365–96368, S9494–S9498 | CSF confirmation required for meningitis indication |
| Outpatient IV antibiotics — Pregnancy with Stage II or III Lyme | Covered | CPT 96365–96368, S9494–S9498 | All symptomatic pregnant members with documented dissemination |
| Repeat 4-week IV antibiotic course | Covered | CPT 96365–96368, 99601–99602 | All three conjunctive criteria must be met; labs within past 3 months |
| Serologic testing — ELISA + Western Blot confirmation | Covered | CPT 86617, 86618, 84181, 84182, 0041U, 0042U, 88346, 88350 | Two-tier CDC approach required |
| Tick-borne relapsing fever antibody testing | Covered | CPT 0043U, 0044U | Covered when selection criteria met |
| Other tick-borne disease testing (Ehrlichia, Rickettsia, Babesia, Tularensis) | Covered | CPT 86619, 86666, 86668, 86753, 86757 | Covered for appropriate organisms |
| Borrelia miyamotoi detection (CPT 87478) | Covered | CPT 87478 | Nucleic acid amplified probe |
| Hyperbaric oxygen therapy | Not Covered | CPT 99183 | Not medically necessary for Lyme disease |
| Urine OspA protein evaluation | Not Covered | CPT 0316U | Excluded |
| Platelet rich plasma injections | Not Covered | CPT 0232T | Excluded |
| Detox/alpha lipoic acid IV drips | Not Covered | CPT 96372, 83520 | Excluded |
| PET imaging for Lyme disease | Not Covered | CPT 78608, 78609, 78811–78816 | Excluded |
| Mycotoxin testing | Not Covered | CPT 87230 | Excluded |
| Lymphocyte/complement/immune panels | Not Covered | CPT 86160–86162, 86171, 86332, 86353, 86355, 86357, 86359, 86360 | Excluded |
| Hormone/metabolite testing (cortisol, DHEA, serotonin, etc.) | Not Covered | CPT 82533, 82626, 83088, 83497, 84260, 84681 | Excluded |
| Radiation treatment for Lyme disease | Not Covered | CPT 77401–77417 | Excluded |
Aetna Lyme Disease Billing Guidelines and Action Items 2025
| # | Action Item |
|---|---|
| 1 | Audit open claims before September 26, 2025. If you have claims pending for outpatient IV antibiotic therapy under Lyme disease diagnoses, check them against the updated two-tier serology requirement and clinical indication criteria now. Claims submitted after the effective date of September 26, 2025 will be evaluated under this updated policy. |
| 2 | Confirm your lab documentation before billing CPT 96365. Every IV antibiotic claim needs both a positive ELISA or IFA (CPT 86618 or 88346) and a positive Western Blot (CPT 86617, 84181, or 84182). One test without the other is insufficient. Build this dual-documentation check into your pre-billing workflow. |
| 3 | Stop billing CPT 0316U (urine OspA) in Lyme disease contexts. Aetna explicitly excludes this code. If your ordering clinicians use this test, flag it for your medical director. Claims including CPT 0316U alongside Lyme disease diagnoses will be denied — and repeated submissions could trigger a broader audit. |
| 4 | For repeat IV course requests, document all three conjunctive criteria explicitly. Your prior authorization request must show: (a) the member met initial IV criteria with labs from the past three months, (b) the member completed the initial IV course, and (c) there is objective evidence of relapse, progression, or new organ damage. Missing any one of these three collapses the authorization. Build a checklist into your PA workflow. |
| 5 | Verify home infusion billing codes are mapped correctly. HCPCS S9494 through S9498 and G0068 are covered when selection criteria are met. If you bill home infusion for Lyme disease patients, confirm your charge capture maps the appropriate antibiotic type to the correct S-code. Reimbursement depends on specificity here. |
| 6 | Flag any claims combining Lyme disease diagnoses with excluded codes. Run a report on any claims in the past 12 months that included both a Lyme disease diagnosis and CPT codes from the excluded group — 99183, 0232T, 77401–77417, 78608–78816, 86353, 86355, 86357, 86359, 86360, 82533, 82626, or 83088. If those claims were paid, you may have a refund liability. Talk to your compliance officer. |
| 7 | For tick-borne disease testing beyond Lyme, use the correct antibody codes. CPT 86619 (Borrelia relapsing fever), 86666 (Ehrlichia), 86668 (Francisella tularensis), 86753 (Babesiosis microti), and 86757 (Rickettsia) are covered when criteria are met. These are distinct from the Lyme-specific codes and require the appropriate clinical indication in your documentation. |
| Previous Version | Current Version |
|---|---|
| Coverage is considered experimental and investigational for all indications | Coverage is considered medically necessary when specific criteria are met |
| Prior authorization is not required | Prior authorization is required for initial treatment |
| Documentation must include clinical history | Documentation must include clinical history |
| Re-review every 24 months | Re-review every 12 months with updated clinical documentation |
CPT, HCPCS, and ICD-10 Codes for Lyme Disease Under CPB 0215
Covered CPT Codes (When Selection Criteria Are Met)
| Code | Type | Description |
|---|---|---|
| 0041U | CPT | Borrelia burgdorferi, antibody detection of 5 recombinant protein groups, by immunoblot, IgM |
| 0042U | CPT | Borrelia burgdorferi, antibody detection of 12 recombinant protein groups, by immunoblot, IgG |
| 0043U | CPT | Tick-borne relapsing fever Borrelia group, antibody detection to 4 recombinant protein groups, IgM |
| 0044U | CPT | Tick-borne relapsing fever Borrelia group, antibody detection to 4 recombinant protein groups, IgG |
| 84181 | CPT | Western Blot, with interpretation and report, blood or other body fluid |
| 84182 | CPT | Western Blot, with interpretation and report; immunological probe for band identification |
| 86617 | CPT | Borrelia burgdorferi (Lyme disease) confirmatory test (e.g., Western Blot or immunoblot) |
| 86618 | CPT | Borrelia burgdorferi (Lyme disease) antibody |
| 87478 | CPT | Borrelia miyamotoi, amplified probe technique, nucleic acid detection |
| 88346 | CPT | Immunofluorescence, per specimen; initial single antibody stain procedure |
| 88350 | CPT | Immunofluorescence, per specimen; each additional single antibody stain procedure |
| 96365 | CPT | Intravenous infusion for therapy, prophylaxis, or diagnosis; initial, up to 1 hour |
| +96366 | CPT | Each additional hour (add-on to 96365) |
| +96367 | CPT | Additional sequential infusion, up to 1 hour (add-on) |
| +96368 | CPT | Concurrent infusion (add-on) |
| 96369 | CPT | Subcutaneous infusion for therapy or prophylaxis; initial, up to 1 hour |
| +96370 | CPT | Each additional hour (add-on to 96369) |
| +96371 | CPT | Additional pump set-up with new subcutaneous infusion site (add-on) |
| 99601 | CPT | Home infusion/specialty drug administration, per visit (up to 2 hours) |
| +99602 | CPT | Each additional hour (add-on to 99601) |
Covered CPT Codes for Other Tick-Borne Disease Testing
| Code | Type | Description |
|---|---|---|
| 86619 | CPT | Antibody; Borrelia (relapsing fever) |
| 86666 | CPT | Antibody; Ehrlichia |
| 86668 | CPT | Antibody; Francisella tularensis |
| 86753 | CPT | Antibody; protozoa, not elsewhere specified (Babesiosis microti) |
| 86757 | CPT | Antibody; Rickettsia |
Not Covered / Experimental CPT Codes
| Code | Type | Description | Reason |
|---|---|---|---|
| 0232T | CPT | Injection(s), platelet rich plasma, any site | Alternative/unproven therapy for Lyme disease |
| 0316U | CPT | Borrelia burgdorferi (Lyme disease), OspA protein evaluation, urine | Excluded from coverage |
| 77401–77417 | CPT | Radiation treatment delivery (multiple codes) | Not medically necessary for Lyme disease |
| 78608 | CPT | Brain PET imaging; metabolic or perfusion evaluation | Excluded for Lyme disease |
| 78609 | CPT | Brain PET imaging; metabolic or perfusion evaluation | Excluded for Lyme disease |
| 78811–78816 | CPT | Positron emission tomography (PET), various | Excluded for Lyme disease |
| 82136 | CPT | Amino acids, 2 to 5 amino acids, quantitative | Excluded alternative testing |
| 82533 | CPT | Cortisol; total | Excluded alternative testing |
| 82626 | CPT | Dehydroepiandrosterone (DHEA) | Excluded alternative testing |
| 83088 | CPT | Histamine | Excluded alternative testing |
| 83497 | CPT | Hydroxyindolacetic acid, 5-(HIAA) | Excluded alternative testing |
| 83520 | CPT | Immunoassay for analyte other than infectious agent antibody; quantitative | Excluded alternative testing |
| 84260 | CPT | Serotonin | Excluded alternative testing |
| 84681 | CPT | C-peptide | Excluded alternative testing |
| 86160 | CPT | Complement; antigen, each component | Excluded alternative testing |
| 86161 | CPT | Complement; functional activity, each component | Excluded alternative testing |
| 86162 | CPT | Complement; total hemolytic (CH50) | Excluded alternative testing |
| 86171 | CPT | Complement fixation tests, each antigen | Excluded alternative testing |
| 86332 | CPT | Immune complex assay | Excluded alternative testing |
| 86353 | CPT | Lymphocyte transformation, mitogen or antigen induced blastogenesis | Excluded alternative testing |
| 86355 | CPT | B cells, total count | Excluded alternative testing |
| 86357 | CPT | Natural killer (NK) cells, total count | Excluded alternative testing |
| 86359 | CPT | T cells; total count | Excluded alternative testing |
| 86360 | CPT | T cells; absolute CD4 and CD8 count including ratio | Excluded alternative testing |
| 87230 | CPT | Toxin or antitoxin assay, tissue culture (mycotoxin testing) | Excluded alternative testing |
| 87449 | CPT | Infectious agent antigen detection by immunoassay technique | Excluded for Lyme disease |
| 96372 | CPT | Therapeutic, prophylactic, or diagnostic injection; subcutaneous or intramuscular | Excluded (alternative detox/alpha lipoic drips) |
| 99183 | CPT | Physician attendance and supervision of hyperbaric oxygen therapy, per session | Not medically necessary for Lyme disease |
Covered HCPCS Codes (When Selection Criteria Are Met)
| Code | Type | Description |
|---|---|---|
| G0068 | HCPCS | Professional services for the administration of anti-infective therapy |
| S9494 | HCPCS | Home infusion therapy, antibiotic, antiviral, or antifungal therapy |
| S9495 | HCPCS | Home infusion therapy, antibiotic, antiviral, or antifungal therapy |
| S9496 | HCPCS | Home infusion therapy, antibiotic, antiviral, or antifungal therapy |
| S9497 | HCPCS | Home infusion therapy, antibiotic, antiviral, or antifungal therapy |
| S9498 | HCPCS | Home infusion therapy, antibiotic, antiviral, or antifungal therapy |
Note: No ICD-10-CM codes were listed in the CPB 0215 policy data.
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