CurrentAetnaPolicy 0316

HIV Drug Susceptibility and Resistance Tests

Defines medical necessity, investigational indications, and coding guidance for HIV phenotypic and genotypic drug resistance and tropism testing for Aetna members.

Policy Summary

PayerAetna

PolicyHIV Drug Susceptibility and Resistance Tests

Policy CodePolicy 0316

Change TypeNo material change

Effective DateJan 22, 1999

Next Review DateMar 14, 2024

Key ActionOrder resistance or tropism testing only when documentation supports a listed medical necessity indication (e.g., acute infection, suboptimal suppression, or virologic failure) and for tropism testing ensure viral load ≥ 1,000 copies/ml.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

3medically necessary groups

1,000min viral load for tropism

11RCTs identified

81400-81408, 87900-87906, 0219UCPT/HCPCS referenced

Coverage Criteria for HIV Drug Resistance and Tropism Testing

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Medical necessity groups: 1) During acute (new onset) HIV infection to determine if a drug-resistant viral strain was transmitted and plan regimen accordingly; 2) Members with suboptimal suppression of viral load after initiation of antiretroviral therapy to determine the role of resistance and maximize the number of active drugs in the new regimen if indicated; 3) Members with virologic failure during highly active antiretroviral therapy (HAART) to determine the role of resistance in drug failure and maximize the number of active drugs in the new regimen if indicated.

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:

Concurrent phenotypic and genotypic testing: Performing both phenotypic and genotypic resistance tests at the same time is considered not medically necessary because it is duplicative.

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:

Evidence summaries: Resistance testing probably improved virological outcomes in people with virological failure in older trials; no evidence of benefit in treatment‑naive patients for mortality or progression to AIDS. NGS has greater sensitivity than Sanger sequencing and detects low‑frequency drug resistance mutations of uncertain clinical relevance.

Based on Cochrane review and multiple studies cited.

Sentosa SQ performance findings: Evaluations of the Sentosa SQ HIV‑1 genotyping assay reported high concordance with Sanger sequencing for predicted resistance in many samples (e.g., 80.5% identical interpretation reports in one study; similar predicted resistance in cohorts), detection of additional low‑frequency mutations by NGS, but also substantial technical and QC issues (e.g., 44% of Sentosa runs failed QC in one study) and need for further optimization. Sentosa reliably amplified PR/RT/IN in selected circumstances (e.g., high DNA load), with variable success rates across studies.

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.

Coding and Testing Thresholds

Covered CPT/HCPCS when selection criteria are metCPT/HCPCSCovered

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

CPT codes not covered for indications listed in the CPBCPTNot Covered

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

ICD-10 codes referencedICD-10

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

inv-11: Viral load threshold for tropism testing

Viral load threshold>= 1,000 copies/ml

PurposeMinimum plasma viral load required to reliably determine HIV co-receptor tropism (Trofile) for CCR5 vs CXCR4

Clinical implicationRequired documentation for tropism testing when considering CCR5 antagonist therapy (eg, maraviroc)

Provider Requirements, Billing and Operational Notes

Billing Rule

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.

Note

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

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).

Denial Risk

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.

Documentation Required

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.

Note

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.

Note

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

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

inv-25: Phenotypic test

DefinitionAssesses drug susceptibility by measuring the drug concentration that inhibits viral replication in vitro.

Clinical useUsed to guide selection of active agents for patients with treatment failure and complex prior therapy histories.

Relation to genotypingProvides complementary information to genotypic assays; no prospective data favoring one assay over the other in all settings.

inv-26: Genotypic test

DefinitionIdentifies mutations known to confer reduced susceptibility to antiretroviral drugs.

Clinical useCommonly used because results are more readily available and returned faster than phenotypic tests.

RoleRecommended to guide choice of new drugs after treatment failure and considered in acute infection to detect transmitted resistance.

inv-27: Tropism testing (Trofile)

DefinitionAssay determining HIV co-receptor usage (CCR5 vs CXCR4) to identify suitability for CCR5 antagonists like maraviroc.

Viral load requirementRequires plasma viral load >= 1,000 copies/ml for reliable amplification and tropism determination.

Clinical implicationUsed to identify patients who may benefit from maraviroc; dual/mixed or CXCR4-tropic results contraindicate maraviroc use.

inv-28: Next-generation sequencing (NGS)

DefinitionHigh-sensitivity sequencing method that can detect low-frequency HIV drug resistance mutations below the detection limit of Sanger sequencing.

Clinical noteNGS detects additional low-frequency DRMs of uncertain clinical relevance; larger studies are needed to define their impact.

PerformanceNGS showed higher sensitivity than Sanger and identified DRMs missed by Sanger in multiple evaluations.

inv-29: Sentosa SQ HIV-1 Genotyping Assay

PlatformSentosa SQ HIV-1 Genotyping Assay: a semi-automated Ion Torrent–based NGS platform evaluated for HIV-1 genotypic resistance testing.

Performance findingsStudies reported high concordance with Sanger for predicted resistance (eg, 80.5% identical interpretation in one study) but also substantial QC/run failures (44% of runs failed QC in another study).

Operational considerationsQC issues required additional runs and technical refinement; successful sequencing rates varied by region (PRO/RT/INT) and DNA/RNA load.

Policy Summary

PayerAetna

PolicyHIV Drug Susceptibility and Resistance Tests

Policy CodePolicy 0316

Change TypeNo material change

Effective DateJan 22, 1999

Next Review DateMar 14, 2024

SourceLink

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