HIV Drug Susceptibility and Resistance Tests
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Defines medical necessity, investigational indications, and coding guidance for HIV phenotypic and genotypic drug resistance and tropism testing for Aetna members.
No material clinical or coverage changes in this revision.
Coverage Criteria for HIV Drug Resistance and Tropism Testing
inv-01: Medically Necessary Indications — Covered when ANY of the following are met
Covered when ANY of the following are met:
Supportive documentation should demonstrate the indicated clinical scenario.
inv-02: Concurrent Testing Policy — Covered with restrictions / Not routinely covered
Covered with restrictions / Not routinely covered:
An alternate type of resistance assay (phenotypic or genotypic) may be authorized on an exception basis for members with virologic failure despite adequate therapy when other causes have been excluded and one assay shows no resistance.
inv-03: Evidence and assay performance — Evidence summary and performance characteristics for resistance testing and Sentosa SQ NGS
Evidence summary and performance characteristics for resistance testing and Sentosa SQ NGS:
Based on Cochrane review and multiple studies cited.
See individual study findings for concordance, additional mutations detected by NGS, QC failure rates, and amplification success thresholds.
Drug resistance testing is not covered for members who have discontinued antiretroviral therapy because resistance mutations may revert to low-level or minor species that current assays may not detect. Testing is also considered experimental/investigational and may be denied for members with an HIV viral load of <1,000 copies/ml, as available assays cannot reliably detect resistance at that low level. In addition, resistance and susceptibility testing is excluded for indications not explicitly listed as medically necessary, for tropism testing for indications not listed (including repeat tropism testing during or after CCR5 antagonist therapy), and for use of the Sentosa SQ HIV-1 genotyping assay for phenotype prediction.
A cited systematic review reported no evidence of important patient benefits from resistance testing among treatment‑naive people: resistance testing did not demonstrate important benefits in terms of risk of death or progression to AIDS in treatment‑naive individuals.
Performing both phenotypic and genotypic resistance tests simultaneously is considered not medically necessary as duplicative. An exception may be considered when virologic failure persists despite one assay showing no resistance, but routine concurrent ordering of both assay types is not supported.
In randomized trials included in the cited review, resistance testing in treatment‑naive individuals did not show important patient‑level benefits: there was no demonstrated reduction in mortality or progression to AIDS attributable to resistance testing in this population.
Coding and Testing Thresholds
| 81400-81408 | Molecular pathology |
| 87900 | Infectious agent drug susceptibility phenotype prediction using regularly updated genotypic bioinformatics |
| 87901 | Infectious agent genotype analysis by nucleic acid (DNA or RNA); HIV 1, reverse transcriptase and protease |
| 87903 | Infectious agent phenotype analysis by nucleic acid (DNA or RNA) with drug resistance tissue culture analysis, HIV 1; first through 10 drugs tested |
| 87904 | Each additional drug tested (List separately in addition to code for primary procedure) |
| 87906 | Infectious agent genotype analysis by nucleic acid (DNA or RNA); HIV-1, other region(e.g. integrase, fusion) |
| 0219U | Infectious agent (human immunodeficiency virus), targeted viral next-generation sequence analysis (ie, protease [PR], reverse transcriptase [RT], integrase [INT]), algorithm reported as prediction of antiviral drug susceptibility |
| 0219U | Infectious agent (human immunodeficiency virus), targeted viral next-generation sequence analysis (ie, protease [PR], reverse transcriptase [RT], integrase [INT]), algorithm reported as prediction of antiviral drug susceptibility |
| B20 | Human immunodeficiency virus [HIV] disease |
| B97.35 | Human immunodeficiency virus, type 2 [HIV-2], as the cause of diseases classified elsewhere |
| Z21 | Asymptomatic human immunodeficiency virus [HIV] infection status |
Provider Requirements, Billing and Operational Notes
Coverage tied to listed codes
Coverage for the listed CPT/HCPCS and ICD-10 codes is tied to meeting the policy selection and medical necessity criteria. Tests represented by the codes below are covered only when documentation supports one of the medically necessary indications in this policy (acute/new-onset infection, suboptimal suppression after ART initiation, or virologic failure) and when other policy requirements are satisfied.
- Only the CPT/HCPCS and ICD-10 codes listed in the policy are eligible for coverage when selection criteria are met.
- Tests billed with codes listed as not covered or experimental (e.g., 0219U) are not eligible except as stated under experimental/investigational exclusions.
- Ensure coding matches the clinical indication and documentation submitted.
Payer policy notice
This Clinical Policy Bulletin is maintained by Aetna to assist in administering plan benefits. It does not itself guarantee coverage for a specific member — providers should verify member-specific benefits and follow payer-specific requirements for prior authorization and claims submission.
- Policy maintained as a Clinical Policy Bulletin by Aetna.
- Providers must verify member benefits and eligibility prior to ordering/testing.
Prior authorization note
Refer to the main policy document and the member's plan for prior authorization requirements. When prior authorization is required by the member's plan, submit clinical documentation that demonstrates the test meets the medical necessity criteria in this policy.
- Prior authorization requirements vary by plan — check the member's benefit plan for PA rules and submission instructions.
- If PA is required, include supporting clinical documentation (see Required clinical documentation callout).
Low viral load
Testing is considered not medically necessary (and may be denied) for members with an HIV viral load < 1,000 copies/mL because available tests cannot reliably detect resistance or determine tropism at low viral loads.
- Do not order resistance or tropism testing for members with HIV RNA <1,000 copies/mL unless an exception is documented and justified.
- Document the viral load value and rationale if requesting testing near this threshold.
Required clinical documentation
Document clinical indication and relevant clinical data demonstrating that the test is necessary. Required documentation should be submitted with the prior authorization request and with claims when applicable.
- Clinical indication: acute/new-onset HIV infection, suboptimal suppression after ART initiation, or virologic failure during HAART.
- Recent plasma HIV-1 RNA (viral load) values with dates (showing viral load >=1,000 copies/mL when applicable).
- Antiretroviral treatment history, including prior and current regimens and dates of therapy.
- Evidence of virologic failure or lack of suppression (rising viral load despite adherence and adequate dosing) when applicable.
- Prior resistance testing results, if available, and rationale for repeat or alternative testing.
Supportive references
Include relevant guideline and evidence references when ordering or interpreting tests; these support clinical justification and may be requested during review.
- Key supportive references are listed in the policy References section and should be available to support clinical rationale.
- Studies noting limitations of newer assays (e.g., Sentosa SQ quality control issues) should be considered when interpreting results.
Documentation and resources
Refer to the Clinical Policy Bulletin and linked Aetna resources for plan-specific operational requirements, submission portals, and contact information. The CPB contains additional administrative notes and links to definitions, review history, and glossary resources.
- Use the CPB Additional Information links for definitions, review history, and plan notices.
- Verify prior authorization process, submission requirements, and appeal instructions via payer resources.
Step therapy
No step therapy requirements are specified in this portion of the policy. If a plan imposes step therapy or other utilization management controls, follow plan-specific rules.
- Policy does not define any step therapy sequences for HIV resistance/tropism testing.
- Check member’s benefit plan for any step therapy or prerequisite testing requirements.
Background on Resistance Testing
Phenotypic assays assess in‑vitro drug susceptibility by measuring the drug concentration required to inhibit viral replication, while genotypic assays identify mutations associated with reduced antiretroviral susceptibility. Resistance testing is used to guide selection of active drugs after treatment failure and to detect transmitted resistance in acute infection. Tropism testing (eg, Trofile) determines HIV co‑receptor usage (CCR5 versus CXCR4) to assess suitability for CCR5 antagonists and requires a viral load of >= 1,000 copies/ml for reliable results. Genotypic testing is more widely available and faster; next‑generation sequencing (NGS) methods can detect low‑frequency resistance mutations below Sanger sequencing limits, though the clinical significance of such low‑frequency variants is uncertain.
Definitions and Test Descriptions
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