Modifiedmedical mutual - ohioPolicy AHS - M2116 - Human Immunodeficiency Virus (HIV), 1

Human Immunodeficiency Virus (HIV)

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Coverage criteria for laboratory testing related to diagnosis, monitoring, and resistance assessment of Human Immunodeficiency Virus (HIV) for covered individuals; describes which HIV assays and circumstances meet or do not meet coverage.

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Modifiedmedical mutual - ohioPolicy AHS - M2116 - Human Immunodeficiency Virus (HIV), 1

Human Immunodeficiency Virus (HIV)

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Policy Summary

Payermedical mutual - ohio

PolicyHuman Immunodeficiency Virus (HIV)

Policy CodePolicy AHS - M2116 - Human Immunodeficiency Virus (HIV), 1

Change TypeAdded coverage criteria and testing frequency clarifications

Effective DateFeb 1, 2026

Last ReviewSep 4, 2025

Next Review DateSep 4, 2025

Key ActionOrder HIV antigen/antibody screening for individuals starting or receiving PrEP and document risk factors per Note 2; do not order standalone HIV antigen testing.

SourceLink

POLICY UPDATE CHANGES

New coverage criteria CC3, CC4, and CC9 were added regarding screening for individuals beginning or receiving PrEP and that HIV antigen testing independent of antigen/antibody testing does not meet coverage criteria.

Frequency limits for antigen/antibody and NAAT testing were moved into a new Note 1 with specific repeat-interval recommendations.

A new Note 2 lists explicit risk factors for HIV infection to guide screening decisions.

every 3 monthsCDC PrEP testing interval

doravirineResistance test required prior to

monthlyNAT repeat limit

≥90 daysAg/Ab repeat interval

≥1000Pregnancy VL threshold

Coverage Criteria for HIV Testing and Resistance

inv-01: Covered tests and indications

Covered when ALL of the following are met (per specified situations):

Screening (initial): For individuals 11 to 65 years of age, initial screening for HIV infection with an antigen/antibody combination assay is covered.age 11-65

See Note 1 for repeat intervals.

Screening (repeat): For individuals 11 to 65 years of age, repeat antigen/antibody screening for HIV infection meets coverage criteria (antibody/antigen testing should not be repeated more often than once every 90 days - Note 1).>=90 days between tests

See Note 1 for frequency limits.

PrEP and elevated risk screening: Individuals who will begin pre-exposure prophylaxis (PrEP), individuals receiving PrEP, or individuals with elevated risk factors for HIV infection may be screened with an antigen/antibody combination assay or with a rapid antibody test.

Risk factors listed in Note 2.

Confirmatory differentiation assay: For individuals with an initial positive screening, the HIV-1/HIV-2 antibody differentiation assay meets coverage criteria.

See Note 1 for timing/frequency considerations.

Nucleic acid testing (NAT): Qualitative or quantitative NAT for HIV-1 and HIV-2 meets coverage criteria for: a) initial positive screening; b) indeterminate initial screening; c) suspected or recent exposure.>=1 month between NATs

NAT should not be repeated more often than once every month (Note 1).

Genotype/phenotype testing: HIV genotyping or phenotyping meets coverage criteria for prior to initiating doravirine (required), treatment failure, suboptimal viral load reduction, noncompliance, acute/recent infection (within 6 months), antiretroviral-naïve individuals entering treatment, and specified situations in pregnant individuals (before ART initiation or if detectable RNA).

Phenotyping is specifically covered for suspected multidrug resistance or failing regimens.

Viral load monitoring: Plasma quantification of HIV-1 or HIV-2 RNA meets coverage criteria for monitoring disease progression, monitoring response to antiretroviral therapy, infants <18 months born to HIV-positive mothers, and predicting maternal-fetal transmission.

Use the same analytical method for serial measurements when possible (see clinical guidance).

inv-02: Coverage criteria for monitoring and resistance testing

Covered when criteria below (DHHS guidance) are met:

Viral load monitoring for patients on ART: Measure plasma viral load before ART initiation, within 4-8 weeks after initiation, then every 3-4 months for suppressed patients; interval may be extended to every 6 months for stable, adherent patients suppressed >1 year.timing-based

Repeat at 4-8 week intervals until level falls below detection after regimen changes or virologic failure.

When to perform resistance testing: Perform genotypic resistance testing for persons entering care to guide initial ART; for persons with virologic failure; for pregnant persons prior to initiating ART or entering pregnancy with detectable RNA; and for persons with suboptimal viral suppression.HIV-RNA >200 to >1,000 copies/mL depending on context

Include integrase gene testing if INSTI resistance is suspected; testing may be unsuccessful at lower VLs but should still be considered.

Resistance testing timing relative to ART:

inv-03: Indications for resistance testing

Covered when ALL of the following are met (situations recommending resistance testing):

Resistance testing at diagnosis: Drug-resistance testing is recommended at time of diagnosis and before initiation of therapy in ART-naïve patients (genotypic assay generally preferred).

Treatment should not be delayed while awaiting results for most patients, including pregnant persons when ART initiation is urgent.

Resistance testing for virologic failure: Drug-resistance testing is recommended in patients on combination ART with HIV-RNA levels >200 copies/mL (AI for >1,000; AIII for 501-1,000) and in suboptimal suppression after ART initiation.>200 copies/mL (AI for >1,000; AIII for 501-1,000)

Testing should be done while on ART or within 4 weeks after stopping non-long-acting ARVs; add phenotypic testing for complex resistance patterns.

Resistance testing in pregnancy: Genotypic resistance testing is recommended for all pregnant people before initiation of ART and for those entering pregnancy with detectable HIV-RNA on therapy.

inv-04: Viral load monitoring indications and intervals

Covered when ALL of the following are met (viral load monitoring intervals and purposes):

Initial viral load assessment: Obtain a quantitative HIV RNA (viral load) at entry into care to establish baseline and characterize stage of infection.

CDC and other societies recommend baseline viral load assessment prior to ART initiation.

Early on-ART viral load monitoring: Measure HIV RNA within 2-4 weeks (IDSA) or within 6 weeks (International Antiviral Society) of ART initiation to assess adherence and tolerability; monitor every 4-8 weeks until suppression is achieved.

If HIV RNA has not declined by 2 log10 within 12 weeks, consider genotype based on regimen.

Maintenance viral load monitoring: For stable, suppressed patients, monitor HIV RNA every 3 months until suppressed for at least 1 year, then every 6 months (International Antiviral Society); BHIVA recommends routine testing every 6 months and possibly up to 12 months for stable patients.

Follow society-specific schedules for patients with different stability and risk profiles.

inv-05: New/Updated Coverage Criteria (CC3, CC4, CC9)

Coverage criteria updates added (CC3, CC4, CC9) and testing frequency notes (Note 1 and Note 2).

CC3: For individuals who will begin pre-exposure prophylaxis (PrEP), individuals receiving PrEP, or individuals with elevated risk factors for HIV infection (see Note 2), screening with an antigen/antibody combination assay or with a rapid antibody test MEETS COVERAGE CRITERIA.

See Note 1 for frequency limits and Note 2 for listed risk factors.

CC4: For individuals with an initial positive screening for HIV infection, the HIV-1/HIV-2 antibody differentiation assay MEETS COVERAGE CRITERIA.

Referenced frequency constraints moved to Note 1 (antibody/antigen tests no more often than every 90 days; NAT no more often than monthly).

CC9: HIV antigen testing independent of antigen/antibody combination testing DOES NOT MEET COVERAGE CRITERIA.

Standalone antigen testing is explicitly excluded from coverage.

HIV antigen testing performed on its own — that is, independent of an antigen/antibody combination assay — does not meet coverage criteria. This exclusion reflects the policy determination that standalone antigen assays lack sufficient supporting literature to be considered required and beneficial for diagnosis or management in covered individuals.

The policy states that the routine, concurrent use of genotyping and phenotyping for an individual patient does not meet coverage criteria. Phenotypic testing may still meet criteria in specific complex resistance scenarios, but combined routine use as a default strategy is not covered.

Prediction of phenotypic drug susceptibility solely by comparing genotypic results to a genotypic/phenotypic database is not considered to meet coverage criteria due to insufficient published evidence supporting that approach as definitively required for patient care.

Within the scope of the document portion cited, there are no additional explicit procedural exclusions identified beyond those listed (for example, exclusions for standalone antigen testing or routine combined genotype/phenotype use).

The policy follows society guidance noting that routine proviral DNA resistance testing is not required prior to switching to two‑drug regimens when there is no documented or suspected history of treatment failure. For patients who have maintained viral suppression (including when switching from long‑acting injectable cabotegravir plus rilpivirine back to oral therapy), proviral resistance testing is not routinely required; genotypic testing is recommended when virologic failure is confirmed or suspected.

The policy explicitly excludes HIV antigen testing performed independently of antigen/antibody combination testing from coverage. This noncoverage is reiterated in the revision history and in the exclusions list and may result in denial if billed as a standalone antigen assay.

The policy summarizes that certain tests or routine combinations lack sufficient published evidence and therefore do not meet coverage criteria (for example, standalone antigen testing and routine combined genotype/phenotype). A referenced cost‑effectiveness analysis is discussed in the evidence section but does not by itself establish additional NMN exclusions in this portion of the document.

There are no standalone 'not medically necessary' (NMN) statements beyond the exclusions listed; the document references a cost‑effectiveness study (Avram et al., 2019) in the clinical utility section but does not convert that economic model into a separate NMN policy statement in this section.

Proviral DNA genotyping is described as a useful option in limited circumstances — for example, when plasma HIV‑RNA genotyping is unlikely to succeed (undetectable or very low viremia) or when prior resistance history is unavailable — but it is not routinely recommended for all regimen switches. The policy notes limitations of proviral assays and that they may miss or detect mutations of uncertain clinical relevance.

Standalone HIV antigen testing is specifically identified in the policy as not meeting coverage criteria and therefore is treated as not medically necessary when ordered independent of an antigen/antibody combination assay.

Procedure and Billing Codes, Thresholds

No codes present in this document portionmixed

No codes listed

Covered CPT Codes - Antibody testingCPTCovered

86689	Antibody; HTLV or HIV antibody, confirmatory test (e.g., Western Blot).
86701	Antibody; HIV-1.
86702	Antibody; HIV-2.
86703	Antibody; HIV-1 and HIV-2, single result.

Covered CPT Codes - Antigen, NAAT, Genotype/PhenotypeCPTCovered

87389	Infectious agent antigen detection by immunoassay technique; HIV-1 antigen(s), with HIV-1 and HIV-2 antibodies, single result.
87390	Immunoassay; HIV-1.
87391	Immunoassay; HIV-2.
87534	Infectious agent detection by nucleic acid (DNA or RNA); HIV-1, direct probe.
87535	Infectious agent detection by nucleic acid (DNA or RNA); HIV-1, amplified probe technique, includes reverse transcription when performed.
87536	Infectious agent detection by nucleic acid (DNA or RNA); HIV-1, quantification, includes reverse transcription when performed.
87537	Infectious agent detection by nucleic acid (DNA or RNA); HIV-2, direct probe technique.
87538	Infectious agent detection by nucleic acid (DNA or RNA); HIV-2, amplified probe technique, includes reverse transcription when performed.
87539	Infectious agent detection by nucleic acid (DNA or RNA); HIV-2, quantification, includes reverse transcription when performed.
87806	Infectious agent antigen detection by immunoassay with direct optical observation; HIV-1 antigen(s), with HIV-1 and HIV-2 antibodies.

1–10 of 11

1/2

HCPCS/G-codes/S-codes - Screening assaysHCPCSCovered

G0433	Infectious agent antibody detection by enzyme-linked immunosorbent assay (ELISA) technique, HIV-1 and/or HIV-2, screening.
G0435	Infectious agent antibody detection by rapid antibody test, HIV-1 and/or HIV-2, screening.
G0475	HIV antigen/antibody, combination assay, screening.
S3645	HIV-1 antibody testing of oral mucosal transudate.

inv-20: Virologic failure threshold — 200 copies/mL

Virologic failure threshold200 copies/mL

ContextAgreement between assays improved using a 200-copies/mL threshold consistent with treatment guidelines' definition of virological failure.

Use in resistance testing guidanceDHHS recommends resistance testing for virologic failure in patients with HIV-RNA levels >200 copies/mL (with stronger recommendations at higher VLs).

inv-21: Significant change in HIV-1 RNA — ≥0.5 log10 (threefold) change

Significant change definition≥0.5 log10 (threefold) change in HIV-1 RNA

Clinical note

Provider Action Items, Prior Authorization, and Denial Risks

Prior Authorization

Order genotype/phenotype when specified clinical indications are present

HIV genotyping or phenotyping meets coverage criteria when clinically indicated, including prior to initiating doravirine therapy (genotyping and phenotyping required), for individuals who have failed antiviral therapy, those with suboptimal viral load reduction, noncompliance, to guide treatment in acute/recent infection (within 6 months), antiretroviral‑naïve individuals entering treatment, and specified pregnancy indications (before ART initiation or for those with detectable HIV RNA).

Required prior to doravirine therapy (genotype & phenotype).
Indicated for treatment failure, suboptimal viral load reduction, noncompliance, acute/recent infection (≤6 months), and ARV‑naïve entry into care.
Recommended for pregnant individuals before ART initiation and for those with detectable HIV RNA.

Prior Authorization

Obtain genotypic resistance testing at entry to care and for virologic failure

Perform genotypic resistance testing at entry into HIV care and for virologic failure; include protease and reverse transcriptase testing routinely and add integrase testing when INSTI resistance is a concern or suspected (may need a separate INSTI assay).

Background and Clinical Context

HIV is an RNA retrovirus that infects CD4+ T lymphocytes and, if untreated, leads to progressive immune dysfunction and acquired immunodeficiency syndrome. HIV‑1 is the predominant global subtype; HIV‑2 is less common and generally has a milder clinical course with more limited availability of quantitative assays. Viral load (HIV‑1 RNA) testing is central to diagnosis in select situations and to monitoring response to antiretroviral therapy; differences among assay platforms can affect absolute values and serial monitoring is best performed using the same analytical method when possible.

Definitions and Assay Descriptions

inv-44: HIV-1 — dominant subtype; viral load quantification widely available and used for monitoring

Dominant subtypeHIV-1 is the predominant subtype globally and the primary target for viral load quantification and monitoring.

Viral load monitoringHIV-1 RNA quantification is widely available and used for diagnosis in select situations and for monitoring response to therapy; use the same platform for serial measurements when possible.

Clinical implicationMonitoring HIV-1 viral load guides ART effectiveness and detection of virologic failure.

inv-45: HIV-2 — less common, milder course, intrinsic resistance to some drug classes; limited quantitative testing availability

HIV-2 characteristicsHIV-2 is less common, often milder clinically, with longer asymptomatic period and lower plasma viremia compared to HIV-1.

Resistance and treatment

Policy Summary

Payermedical mutual - ohio

PolicyHuman Immunodeficiency Virus (HIV)

Policy CodePolicy AHS - M2116 - Human Immunodeficiency Virus (HIV), 1

Change TypeAdded coverage criteria and testing frequency clarifications

Effective DateFeb 1, 2026

Last ReviewSep 4, 2025

Next Review DateSep 4, 2025

Key ActionOrder HIV antigen/antibody screening for individuals starting or receiving PrEP and document risk factors per Note 2; do not order standalone HIV antigen testing.

SourceLink

On This Page

When possible, perform resistance testing while the patient is still taking non-long-acting ART or within 4 weeks after discontinuation; for long-acting injectables, perform testing regardless of time since discontinuation if virologic failure occurred.

If ART is initiated before results are available, modify regimen based on results.

Special contexts: In acute/recent infection and when ART will be started immediately, do not delay ART for resistance results; in persons on PrEP with ambiguous tests consider HIV DNA testing; for pregnant persons initiate ART promptly and modify based on resistance results.clinical-context

Providers should review prior and current resistance results when designing new regimens.

If ART will be initiated immediately, treatment can begin prior to resistance results and be modified when results are available.

Proviral DNA resistance testing: Proviral DNA resistance assays may be useful for persons with undetectable or low-level viremia when HIV-RNA genotyping is unlikely to be successful, and in persons with multiple prior virologic failures or unavailable resistance history.

Proviral DNA genotyping has limitations and may miss or detect clinically irrelevant mutations.

Changes smaller than 0.5 log10 may represent assay variability or transient rises; consider repeat testing if clinically indicated.

ImplicationUse this threshold to interpret biologically relevant changes in viral replication when monitoring therapy.

inv-22: Viral load thresholds for resistance testing — >200 to 1,000 copies/mL (varies by context: >200, >500, 501-1,000, >1,000 per DHHS)

Range of thresholds>200 to 1,000 copies/mL (varies by context; DHHS: >200 to 1,000 copies/mL)

Lower-limit considerationsFor confirmed HIV RNA >200 but <1,000 copies/mL, testing may be unsuccessful but should still be considered.

Pregnancy-specific thresholdsDHHS pregnancy guidance references thresholds of >500 to 1,000 copies/mL for some recommendations.

Historical noteOlder guidance proposed <3,000 copies/mL as a threshold for early assays, but modern assays detect lower levels reliably; repeat low-positive results to confirm.

inv-23: Resistance testing viral load thresholds — general virologic failure testing recommended for HIV-RNA >200 copies/mL; AI for >1,000; AIII for 501-1,000; BHIVA notes

General recommendationPerform resistance testing for virologic failure at HIV-RNA >200 copies/mL (DHHS).

Strength by viral loadDHHS: AI recommendation for >1,000 copies/mL; AIII for 501–1,000 copies/mL; CIII for 201–500 copies/mL confirmed.

BHIVA (HIV-2) guidanceBHIVA recommends resistance testing for HIV-2 when viral load meets a threshold of ≥500 copies/mL.

Practical noteTesting may be unsuccessful at lower viral loads but should still be considered; include integrase genotyping when INSTI resistance is suspected.

inv-24: Peripartum viral load threshold for cesarean delivery — ≥1000 copies/mL

Peripartum cesarean threshold≥1000 copies/mL

ACOG recommendationOffer scheduled prelabor cesarean at 38 0/7 weeks if viral load is over 1000 copies/mL at or near delivery to reduce mother-to-child transmission risk.

SMFM practice pointAssess viral load at 34–36 weeks; if ≥1000 copies/mL at 37–38 weeks, schedule cesarean at 38 weeks.

inv-25: Aptima HIV-1 Quant assay range — 30 to 10,000,000 copies/mL

Aptima Quant range30 to 10,000,000 copies/mL

Regulatory statusFDA-approved for dual use (diagnosis and viral load monitoring) for HIV-1 groups M, N, and O (approval Nov 20, 2020).

Platform noteRun on the automated Panther® system as described by the manufacturer and FDA materials.

Genotypic testing recommended at entry to guide initial ART (preferred over phenotypic testing).
In virologic failure, perform genotypic testing for RT and protease on everyone; order integrase genotyping for INSTI‑based regimen failures or suspected INSTI resistance.
When possible, test while patient remains on non‑long‑acting ART or within 4 weeks of stopping; for long‑acting injectables, test regardless of time since discontinuation if virologic failure occurred.

Note

No payer-specific prior authorization; labs may use FDA assays or validated LDTs

No payer-specific prior authorization requirement is stated in this policy; laboratories may use FDA‑approved assays or validated laboratory‑developed tests (LDTs) under CLIA guidance for clinical use.

Policy does not specify a prior‑authorization process for resistance assays.
LDTs are regulated as high‑complexity tests under CLIA '88 and may be used if validated in‑house; FDA approval is not required for clinical use.

Billing Rule

Bill using the policy’s referenced CPT/HCPCS procedure codes

Use the listed CPT/HCPCS codes when billing HIV antibody/antigen, nucleic acid, and genotype/phenotype tests; these codes are provided for reference and remain subject to the policy's coverage criteria and frequency limits.

Antibody codes: 86689, 86701, 86702, 86703.
Antigen/NAAT/genotype codes include 87389, 87390, 87391, 87534–87539, 87806, 87901, etc.
Screening HCPCS/G‑codes: G0433, G0435, G0475, S3645.

Step Therapy

Obtain resistance testing when therapy selection triggers it (e.g., doravirine)

Perform genotyping and/or phenotyping before initiating therapies when specifically required by guidance (e.g., prior to doravirine) or when clinical response suggests resistance; document prior therapies and viral load trend.

Doravirine initiation: genotyping and phenotyping required prior to therapy.
When clinical response suggests resistance (treatment failure or suboptimal suppression), obtain resistance testing to guide regimen selection.

Prior Authorization

Start ART promptly in pregnancy; adapt regimen after resistance results

If initiating ART in pregnancy before resistance results are available, start ART promptly and then modify the regimen as needed based on subsequent resistance assay results.

Initiate ART immediately in pregnant persons; modify regimen if resistance testing later indicates changes are needed (AII/AIII).
For pregnant persons on ART who enter pregnancy with detectable RNA, perform genotypic resistance testing to guide regimen changes.

Documentation Required

Do not routinely require proviral resistance testing before regimen switches without failure

Do not require proviral DNA resistance testing routinely before switching to two‑drug therapy in patients without documented or suspected treatment failure; switching from long‑acting CAB+rilpivirine back to oral therapy does not require proviral DNA testing in suppressed patients.

Proviral resistance testing is not required prior to 2‑drug therapy switches unless there is documented or suspected treatment failure.
Suppressed patients switching from long‑acting CAB+rilpivirine to oral therapy do not need proviral DNA resistance testing.

Note

No step‑therapy requirements specified

The policy does not specify any step‑therapy program requirements for antiviral selection or testing in this document portion.

No step‑therapy rules are detailed in this policy section.

Documentation Required

Follow repeat‑testing intervals and document clinical indications

Adhere to the policy’s repeat‑testing frequency limits: antibody/antigen testing should not be repeated more often than every 90 days; nucleic acid testing (qualitative or quantitative) should not be repeated more often than once per month. Document clinical indications (e.g., initial positive/indeterminate screening, recent exposure, PrEP status, pregnancy, treatment failure) to justify repeat testing.

Antibody/Ag: ≥90 days between tests (Note 1).
NAT (qualitative/quantitative): ≥1 month between tests (Note 1).
Record indication such as suspected acute infection, PrEP, pregnancy, or virologic failure.

Documentation Required

Repeat quantitative HIV RNA testing to confirm acute infection

Repeat quantitative HIV RNA testing on a new specimen to confirm suspected acute infection when antibody differentiation is negative or indeterminate; obtain verification before initiating ART when possible.

Low‑positive quantitative HIV RNA (<3,000 copies/mL) in context of negative/indeterminate antibody should be repeated on a new specimen to confirm acute infection.
Collect a new blood specimen to verify diagnosis before initiating treatment when possible; in certain PrEP contexts immediate ART may be recommended while confirming.

Documentation Required

Review prior and current resistance results before selecting a regimen

Review and consider all prior and current drug‑resistance test results when designing a new antiretroviral regimen; perform repeat resistance testing as indicated for acute/early infection, entry to care, virologic failure, pregnancy, pediatric patients, or when changing therapy.

Incorporate historical and current genotype/phenotype results into regimen construction.
Repeat testing may be considered if therapy was deferred or when starting new ART.

Documentation Required

Ensure LDTs are validated and CLIA‑regulated before clinical use

Laboratory‑developed tests (LDTs) used clinically must be validated and performed in‑house and are regulated as high‑complexity tests under CLIA '88; FDA clearance is not required for clinical use but labs must follow CLIA validation requirements.

LDTs are regulated by CMS under CLIA '88 as high‑complexity tests.
Labs must validate and perform these assays in‑house before clinical use.

Prior Authorization

Initiate ART promptly when indicated; modify therapy after resistance results

Start ART without waiting for resistance results when clinically indicated (e.g., pregnant patients or urgent initiation), but obtain resistance testing and modify the regimen as necessary once results are available.

Do not delay ART initiation when rapid suppression is needed; adjust therapy based on subsequent resistance assay findings.
Document rationale for immediate ART and subsequent modifications.

Documentation Required

Order proviral DNA testing selectively before regimen changes when RNA genotyping unlikely

Before switching regimens, ensure appropriate testing per guidance: proviral DNA resistance assays may be useful when RNA genotyping is unlikely (e.g., undetectable or low viremia), but are not routinely required before switching to two‑drug therapy in patients without suspected failure.

Consider proviral DNA assays for patients with undetectable or low‑level viremia or unavailable resistance history.
Do not require proviral testing routinely for 2‑drug switches absent documented/suspected failure.

Denial Risk

Avoid ordering standalone HIV antigen tests (non‑covered)

Ordering standalone HIV antigen testing (independent of an antigen/antibody combination assay) does not meet coverage criteria and may be denied; do not order antigen‑only assays for screening separate from Ag/Ab combo testing.

Standalone HIV antigen testing DOES NOT MEET COVERAGE CRITERIA and may be denied.
Use antigen/antibody combination assays (or rapid antibody tests) per screening guidance instead.

Denial Risk

Combined genotype+phenotype is not routinely covered; justify phenotyping

Do not routinely order combined genotyping plus phenotyping for all patients; routine combined use is not covered and may be denied—reserve phenotypic testing for suspected complex or multidrug resistance.

Routine combined genotype+phenotype DOES NOT MEET COVERAGE CRITERIA.
Phenotyping meets criteria for suspected multidrug resistance or failing regimens; document clinical justification when ordering phenotypic testing.

HIV-2 is intrinsically resistant to non-nucleoside reverse transcriptase inhibitors and enfuvirtide; no FDA-approved genotypic or phenotypic resistance assays currently available.

Testing availabilityQuantitative HIV-2 RNA assays are limited commercially; many labs offer only qualitative HIV-2 testing, limiting monitoring utility.

inv-46: Ag/Ab assay — combination immunoassays that detect HIV-1/2 antibodies and p24 antigen used in initial algorithms

DefinitionCombination immunoassays that detect HIV-1 and HIV-2 antibodies and HIV p24 antigen used in initial HIV testing algorithms to improve acute infection detection.

Algorithm roleReactive Ag/Ab specimens should be tested with an HIV-1/HIV-2 antibody differentiation immunoassay; negative or indeterminate differentiation results warrant HIV RNA testing.

Clinical utilityAg/Ab assays enhance early detection by identifying p24 antigen prior to antibody seroconversion.

inv-47: Genotypic resistance testing — identifies mutations in HIV genes (reverse transcriptase, protease, integrase) to guide ART selection

Genotypic testing purposeIdentifies mutations in HIV genes (reverse transcriptase, protease, and integrase when indicated) to guide antiretroviral therapy selection.

Preferred useGenotypic resistance testing is generally preferred over phenotypic testing for initial and many clinical scenarios; add phenotypic testing for complex or multidrug-resistant patterns.

INSTI considerationIf INSTI resistance is suspected, include integrase gene sequencing (may need separate order).

inv-48: Fourth-generation HIV Ag/Ab assay — detects p24 antigen and HIV antibodies allowing earlier identification than antibody-only assays

Fourth-generation assayDetects both p24 antigen and HIV antibodies (IgM/IgG), allowing earlier identification of infection than antibody-only assays.

Initial testing roleRecommended as the initial diagnostic test in current algorithms; reactive results require follow-up antibody differentiation and possibly NAT if indeterminate.

Window period benefitImproves detection within the early window period by identifying p24 antigen prior to seroconversion.

inv-49: NAT — detects HIV viral RNA; used for earlier detection and acute infection diagnosis

NAT definitionNucleic Acid Test (NAT) detects HIV viral RNA and can identify infection sooner than antigen/antibody tests (typically 10–33 days after exposure).

Diagnostic usesUsed to confirm acute infection when Ag/Ab differentiation is negative or indeterminate and to quantify viral load for monitoring.

LimitationsHIV-1 RNA tests do not detect HIV-2; FDA has not approved HIV-2 RNA or DNA tests for viral load quantification.

inv-50: Aptima HIV-1 Quant Dx Assay — FDA-approved NAAT for quantitation of HIV-1 RNA (30–10,000,000 copies/mL), approved for diagnosis and monitoring

Assay identityAptima HIV-1 Quant Dx Assay — FDA-approved NAAT for quantitation of HIV-1 RNA (groups M, N, O).

Reportable rangeReportable range: 30 to 10,000,000 copies/mL; approved for diagnosis and viral load monitoring.

Regulatory noteFDA approval (Nov 20, 2020) permits dual diagnostic and monitoring use per manufacturer/FDA documentation.

inv-51: Geenius HIV-1/2 Supplemental Assay — single-use immunochromatographic assay for confirmation and differentiation of HIV-1/2 antibodies read with dedicated reader/software

Assay purposeGeenius HIV-1/2 Supplemental Assay — single-use immunochromatographic assay for confirmation and differentiation of HIV-1 and HIV-2 antibodies.

Operational noteIntended for use as an additional confirmatory test for repeatedly reactive screening results; results are interpreted with the Geenius Reader and dedicated software.

Performance dataFDA summary: classified known HIV-2 samples with some cross-reactivity; used for differentiation after reactive Ag/Ab screening.