Human Immunodeficiency Virus (HIV)
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Defines coverage, limitations, and clinical background for HIV screening, confirmatory testing, nucleic acid testing, viral load monitoring, and genotypic/phenotypic resistance assays for affected individuals and providers.
Addition of new CC9: '9) Screening for HIV-1 and HIV-2 using an antibody test that does not provide rapid results and does not incorporate antigen testing DOES NOT MEET COVERAGE CRITERIA.'
Removed CPT code 86689.
New CC3 and CC4 clarifying PrEP-related screening and antibody differentiation assay coverage: screening with antigen/antibody combination assay or rapid antibody test for PrEP populations meets criteria; HIV-1/HIV-2 antibody differentiation assay meets criteria if initial screening positive.
Frequency limits and test-type clarifications moved into new Note 1 and Note 2 describing repeat testing intervals and lists of risk factors; antigen testing alone does not meet criteria.
Coverage Criteria — Screening, Diagnostic, and Resistance Testing
inv-01: Screening and Diagnostic Testing
Covered when the following conditions are met:
See Note 1 for frequency limits
See Note 2 for risk factors and Note 1 for frequency limits
inv-02: Confirmatory and Nucleic Acid Testing
Covered when ANY of the following apply:
See Note 1 for frequency limits
NAT repeat interval: not more often than once every month; collect new specimen to confirm before initiating ART when indicated
Antibody tests may be confounded by maternal antibodies in this age group
inv-03: Genotyping and Phenotyping (Resistance Testing)
Genotypic or phenotypic testing meets coverage criteria for any of the following situations:
Phenotyping specifically required per policy
Genotypic testing preferred; add phenotypic testing for suspected multidrug resistance or complex patterns
Do not delay ART initiation for results; modify regimen once results available
Genotypic testing recommended at entry to care in pregnancy; include integrase testing when INSTI exposure or concern
Phenotypic testing added to genotypic when complex resistance patterns are suspected
inv-04: DHHS-aligned coverage criteria
Covered when ALL of the following DHHS-recommended conditions are met
Do not delay ART initiation for resistance results
Follow DHHS monitoring intervals
Strength of evidence stronger for >1,000 copies/mL; testing may be unsuccessful at some VL levels but should still be attempted
If positive in labor, initiate intrapartum zidovudine prophylaxis and perform infant NAT
Consider HIV DNA testing when diagnostic testing inconclusive
inv-05: Resistance testing for virologic failure
Covered when ALL of the following are met
Order INSTI assays separately if needed; perform testing while on ART or within 4 weeks of stopping non‑long‑acting agents; for long‑acting agents test regardless of time since discontinuation
inv-06: Diagnostic testing
Covered when ALL of the following are met
Rapid testing may be used when expedited results are needed (e.g., PrEP initiation); collect new specimen to confirm diagnosis before initiating ART when indicated
inv-07: Resistance testing modality
Covered when ALL of the following are met
Review prior and current resistance tests when constructing new regimens; proviral DNA genotyping may be useful in select circumstances but is not routinely recommended
inv-08: HIV-2 monitoring
Covered when ALL of the following are met
Repeat viral load and perform resistance testing if viral load becomes repeatedly detectable after maximal suppression
Per BHIVA and policy guidance
inv-09: Testing and monitoring criteria
Covered when testing and monitoring follow evidence-based timing and indications
Document investigation and include PCR for HIV‑2 proviral DNA as indicated
Follow DHHS and other society guidance for intervals; document timing of measurements
Review prior resistance results when changing therapy and document in the medical record
inv-10: Summary of recently added/changed coverage criteria
Policy coverage changes described in revision history — select highlights:
Added as CC3 in revision history
Added as CC4 in revision history
Added as CC9 in revision history; removed outdated antibody-only screening methods
Consolidated into Note 1 per revision history
Routine simultaneous ordering of both genotypic and phenotypic resistance assays is not supported by the evidence and DOES NOT MEET COVERAGE CRITERIA. The policy specifically states that routine use of combined genotyping and phenotyping does not meet coverage criteria, and that drug-susceptibility phenotype prediction using genotypic comparison to databases does not meet coverage criteria (lack of sufficient published literature demonstrating clinical benefit). Providers should order genotypic or phenotypic testing only when indicated by the covered clinical scenarios (e.g., treatment failure, pre-doravirine evaluation, suspected multidrug resistance), and document the clinical rationale when phenotypic testing is requested for complex resistance patterns.
A modeled economic evaluation referenced in the policy found that using point-of-care HIV RNA testing to guide mode of delivery for women without prenatal care was associated with higher costs and more HIV-infected neonates compared with routine cesarean delivery for all. The analysis concluded point-of-care viral-load–guided delivery increased cost and decreased effectiveness under most modeled assumptions, and therefore routine use of point-of-care RNA testing for mode-of-delivery decision-making is not supported by this evidence.
Per International Antiviral Society guidance cited in the policy, proviral (proviral DNA) resistance testing is not required prior to switching to two‑drug therapy unless there is a documented or suspected history of treatment failure. The guidance also supports switching virologically suppressed patients from long-acting cabotegravir plus rilpivirine back to daily oral therapy without proviral DNA testing when suppression has been maintained; document prior treatment history and any concerns for archived resistance when considering testing.
The policy references the European AIDS Clinical Society statement that routine proviral DNA genotyping is currently not recommended. Proviral DNA assays can fail to detect prior resistance mutations and may detect archived mutations of uncertain clinical significance; therefore proviral testing should be reserved for specific circumstances (for example, multiple prior virologic failures, unavailable resistance history, or low-level viremia at the time of switch) and results interpreted cautiously.
HIV antigen testing ordered alone (separate from an antigen/antibody combination assay) is explicitly noncovered in this policy: HIV antigen testing independent of antigen/antibody testing DOES NOT MEET COVERAGE CRITERIA. In addition, the policy clarifies that screening with antibody-only tests that are non-rapid and lack antigen detection DOES NOT MEET COVERAGE CRITERIA for initial screening, and providers should use an antigen/antibody combination assay or an appropriate rapid antibody test per the coverage criteria.
The policy reiterates that routine combined genotyping and phenotyping does not meet coverage criteria and that computational phenotype prediction from genotypic comparisons to databases is not an accepted substitute for clinically indicated testing. Genotypic testing is preferred for most clinical situations; phenotypic assays are covered only when clinically justified (for example, suspected multidrug resistance or complex mutation patterns) and should be ordered with documentation of the specific clinical indication.
When considering mode-of-delivery decisions, the policy cites modeling and guideline context indicating limited value for routine point-of-care viral-load testing compared with established delivery strategies. The referenced modeling found point-of-care RNA-guided delivery increased costs and neonatal infections versus routine cesarean delivery, and professional guidance (e.g., SMFM/ACOG context) supports third-trimester viral-load assessment and a cesarean-planning threshold of ≥1000 copies/mL rather than relying on point-of-care RNA testing as a universal delivery decision tool.
For intrapartum or peripartum decision-making, rapid diagnostic pathways are available when maternal HIV status is undocumented, but the policy notes that modelling and guideline evidence do not support routine point-of-care viral-load testing to change mode of delivery for all patients. When viral-load measurement is used in delivery planning, follow established thresholds and timing (for example, third-trimester assessment and the ≥1000 copies/mL threshold informing cesarean recommendations) rather than routine point-of-care RNA testing for every case.
The policy aligns with international guidance that proviral resistance testing is not required when switching virologically suppressed patients back to oral therapy from long-acting injectables (e.g., cabotegravir plus rilpivirine) provided suppression has been maintained and there is no documented or suspected treatment failure. Proviral DNA genotyping may be considered in complex cases (multiple prior failures, unavailable resistance history), but it is not a routine pre-switch requirement.
Echoing EACS recommendations cited in the policy, routine proviral DNA genotyping for virologically suppressed persons is not recommended. Proviral assays can miss previous resistance or identify archived mutations of unclear significance; their use should be limited to select clinical situations and interpreted in context of prior resistance history and treatment course.
Procedure and Billing Codes
| 87390 | Infectious agent antigen detection by immunoassay technique; HIV-1 antigen(s) with HIV-1 and HIV-2 antibodies, single result. |
| 87391 | Infectious agent antigen detection by immunoassay technique; HIV-2. |
| 87534 | Infectious agent detection by nucleic acid (DNA or RNA); HIV-1, direct probe technique. |
| 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). |
| 87901 | Infectious agent phenotype analysis by nucleic acid with drug resistance tissue culture analysis, HIV-1; first through 10 drugs tested. |
| 87903 | Tissue culture analysis, HIV-1; first through 10 drugs tested (phenotype). |
| 87904 | Infectious agent genotype analysis by nucleic acid (DNA or RNA); HIV-1, other region (eg, integrase, fusion). |
| 87906 | Infectious agent (HIV), targeted viral next-generation sequence analysis (PR, RT, INT), algorithm reported as prediction of antiviral drug susceptibility. |
| 0219U | Proprietary test: Sentosa® SQ HIV-1 Genotyping Assay. |
| G0432 | Infectious agent antibody detection by enzyme immunoassay (EIA) technique, HIV-1 and/or HIV-2, screening. |
| G0433 | Infectious agent antibody detection by enzyme-linked immunosorbent assay (ELISA). |
| 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. |
| 86689 | CPT code removed from policy |
| No codes listed |
Actions for Providers — Documentation, Ordering, and Resistance Testing
Obtain genotyping/phenotyping for specified indications
HIV genotyping or phenotyping meets coverage criteria for specified situations; providers must obtain genotypic and phenotypic testing prior to initiating doravirine and when indicated for treatment-experienced or failing regimens (e.g., suboptimal viral load reduction, noncompliance, acute/recent infection, ARV‑naïve entering care, pregnant individuals prior to ART or with detectable RNA).
- Required prior to initiating doravirine therapy (genotyping and phenotyping is required).
- Phenotyping meets coverage for treatment‑experienced individuals on failing regimens thought to have multidrug resistance.
Order genotypic resistance testing for initial care and virologic failure
Order genotypic resistance testing at entry into care to guide initial ART and when virologic failure occurs (HIV‑RNA >200 copies/mL), and include integrase genotyping when INSTI resistance is suspected or prior CAB‑LA exposure occurred.
- Genotypic testing recommended at entry into care (to guide selection of initial ART).
- Perform resistance testing for virologic failure (>200 copies/mL; stronger evidence at >1,000 copies/mL).
- Include INSTI genotyping if INSTI resistance is suspected or prior CAB‑LA exposure occurred.
Include INSTI genotyping (and phenotyping when complex)
When ordering resistance testing for virologic failure or to guide regimen selection, ensure genotypic assays include INSTI sequencing when indicated; providers may need to order INSTI‑specific assays separately and consider adding phenotypic testing for complex resistance patterns.
- Reverse transcriptase and protease genotypic testing should be performed for everyone with virologic failure; order integrase testing for INSTI‑based regimen failures.
- Add phenotypic testing when complex mutation patterns are known or suspected.
Use referenced procedure codes and follow PA rules
Refer to the listed CPT/HCPCS and proprietary codes when submitting claims; follow payer prior authorization policies for advanced assays or phenotypic testing as applicable.
Do not use removed CPT code 86689 on claims
The policy removed CPT code 86689; do not bill using this removed code — claims using 86689 may be denied or require recoding to current covered codes.
- 86689 was removed from the policy's listed codes and may trigger denial or need recoding.
- Use current covered CPT/HCPCS codes from the policy when submitting claims.
Perform genotyping/phenotyping before doravirine
Obtain genotyping and phenotyping prior to initiating doravirine; document genotypic testing and use phenotyping when treatment‑experienced patients are on failing regimens suspected to have multidrug resistance.
- Genotyping and phenotyping are required prior to doravirine initiation.
- Phenotyping meets coverage for treatment‑experienced individuals on failing regimens thought to have multidrug resistance.
Start ART immediately for PrEP patients with RNA ≥200 copies/mL
If HIV is suspected in a person on PrEP with HIV RNA ≥200 copies/mL, initiate an effective HIV treatment regimen immediately while awaiting confirmation of diagnosis.
- Immediate initiation of effective ART is recommended for persons on PrEP with RNA ≥200 copies/mL while confirming diagnosis (AIII).
- Very low‑positive RNA (<200 copies/mL) requires confirmatory testing before initiating ART.
Do not require proviral testing for routine switches without failure
Do not routinely require proviral (proviral DNA) resistance testing prior to switching suppressed patients to 2‑drug therapy unless there is documented or suspected treatment failure; switching from long‑acting CAB+rPV back to oral therapy does not require proviral testing if suppression maintained.
- Proviral resistance testing is not required prior to switching to 2‑drug therapy unless documented/suspected treatment failure.
- Switching from long‑acting cabotegravir plus rilpivirine back to daily oral therapy can be done without proviral DNA resistance testing in patients who have maintained suppression.
Initiate ART without waiting for resistance results
Do not delay ART initiation while awaiting resistance test results; start ART promptly and modify the regimen later if resistance results indicate a change is needed.
- ART initiation should not be delayed for resistance testing results; regimens can be modified once results are reported.
- EACS and DHHS guidance support starting ART promptly and using resistance results to adjust therapy.
Follow recent policy revisions and Change Log
(See policy notes and revision history) Recent revisions added and clarified provider actions and testing criteria — review policy Change Log and Notes for details when ordering tests or performing prior authorization.
- Revision history documents additions (CC3, CC4, CC9), frequency guidance moved into Note 1, and removal of CPT 86689.
- Ensure claims and orders adhere to updated test‑type criteria and new notes.
Adhere to testing frequency limits
Antibody and antigen/antibody testing should not be repeated more often than once every 90 days; nucleic acid testing (qualitative or quantitative) should not be repeated more often than once every month.
- Antibody/antigen retest interval: not more often than every 90 days (Note 1).
- Nucleic acid testing retest interval: not more often than once every month (Note 1).
Document viral load and CD4 timing/results in the record
Document timing and results of viral load and CD4 testing in the medical record at entry into care, at ART initiation, and at recommended monitoring intervals to support medical necessity and coverage.
- Document viral load and CD4 at entry into care and per DHHS monitoring schedule (e.g., 4–8 weeks after ART start, then every 3–4 months or up to 6 months if stable).
- Document genotypic resistance testing performed before ART initiation and when virologic failure occurs.
Review and document prior resistance results
Review and document all prior and current drug‑resistance test results when designing a new antiretroviral regimen; include evidence of reviewed prior tests in the medical record when changing therapy after virologic failure.
- All prior and current resistance results should be reviewed and considered when constructing a new regimen.
- Documentation of reviewed prior tests should be included in the medical record when changing therapy after virologic failure.
Document investigations for indeterminate serology and monitoring
For indeterminate serology or inconclusive diagnostic testing, document investigation including PCR for HIV‑2 proviral DNA when indicated; document timing of viral load measurements and any resistance testing performed.
- Investigate indeterminate HIV‑1 or HIV‑2 serology with PCR for HIV‑2 proviral DNA.
- Document viral load monitoring per schedule and document resistance testing when viral load thresholds are met.
Document risk factors and indication when ordering tests
When ordering tests such as PrEP initiation/maintenance screening or testing after suspected exposure, document the patient's risk factors and specific indication (see Note 2) to support medical necessity.
- Document elevated‑risk factors (e.g., MSM, multiple partners, injection drug use, transactional sex, prior/concurrent STI/hepatitis/TB) per Note 2.
- Include the indication (PrEP initiation/maintenance, suspected recent exposure, positive/indeterminate screen) on the order and in the medical record.
Avoid non‑rapid antibody‑only screening tests
Screening with an antibody test that is non‑rapid and lacks an antigen component DOES NOT MEET COVERAGE CRITERIA; ordering such tests risks denial of coverage.
- Explicit policy statement: antibody test that does not provide rapid results and does not incorporate antigen testing does not meet coverage criteria (CC9).
- Antigen testing alone is also noncovered per revision history; use antigen/antibody combination assays or rapid antibody tests where indicated.
Attempt and document resistance testing even if VL >500 copies/mL
Even if HIV‑RNA is >500 copies/mL (where genotyping may be unsuccessful), attempt drug‑resistance testing and document inability to obtain a genotype if unsuccessful; failure to attempt recommended testing may affect coverage of regimen changes.
- Drug‑resistance testing may be unsuccessful when HIV‑RNA levels are >500 copies/mL but should still be considered.
- If testing is unsuccessful, document attempts and rationale in the medical record to support subsequent treatment decisions.
Order resistance testing at virologic failure threshold (>200 copies/mL)
Order resistance testing for patients on combination ART with confirmed HIV‑RNA >200 copies/mL (AI); consider testing at 201–500 copies/mL and recognize evidence is stronger at >1,000 copies/mL.
- Recommended trigger: HIV‑RNA >200 copies/mL for virologic failure; AI strength for >1,000 copies/mL; consider testing at 201–500 copies/mL.
- Perform resistance testing while patient is on ART or within 4 weeks of stopping non‑long‑acting agents.
Perform resistance testing for HIV‑2 at ≥500 copies/mL
Perform resistance testing at diagnosis, prior to treatment initiation, and at virological failure for HIV‑2 when viral load meets or exceeds ≥500 copies/mL; omission when indicated may risk denial.
- HIV‑2 resistance testing threshold: ≥500 copies/mL for testing at diagnosis, prior to treatment initiation, and at virological failure.
- Document testing and results in the chart to support medical necessity.
Do not order antigen‑only tests for screening
Ordering HIV antigen testing alone (independent of antigen/antibody testing) does not meet coverage and will trigger noncoverage; use an antigen/antibody combination assay or rapid antibody test per policy.
- Antigen‑alone testing is explicitly stated as not meeting coverage criteria.
- Use approved antigen/antibody combination assays or rapid antibody tests for screening where indicated.
Claims using removed CPT 86689 may be denied
Claims submitted using removed CPT code 86689 may be denied or require recoding; update billing to current listed CPT/HCPCS codes in the policy.
- 86689 was removed from the policy's applicable procedure codes and may trigger claim denial.
- Ensure claims use current CPT/HCPCS codes listed in the policy (see code table).
Clinical Background and Rationale
Background: Human immunodeficiency virus (HIV) is an RNA retrovirus that targets CD4+ lymphocytes and, if untreated, can progress to acquired immunodeficiency syndrome (AIDS). The policy notes that HIV-1 is the dominant global subtype with widely available quantitative RNA assays, whereas HIV-2 is less common and often associated with lower viremia and different diagnostic considerations. Viral load measurement (HIV-1 RNA) is central to diagnosis and management, and consistent use of assay platforms is recommended because inter-assay variability can affect comparability of results.
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