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DESCRIPTIONThe human immunodeficiency virus (HIV-1), which causes acquired immunodeficiency syndrome, uses co-receptor proteins (either CCR5 or CXCR4) on the surface of target cells to enter and infect the cells. The most commonly transmitted strains of HIV-1 bind to CCR5 and are said to have “tropism” for CCR5-expressing cells. Over the course of infection, CXCR4-tropic HIV-1 clones emerge in some infected individuals. New, experimental drugs, termed co-receptor antagonists, have been designed to interfere with the interaction between HIV-1 and its co-receptors.
Maraviroc (Selzentry™, Pfizer) is the first co-receptor antagonist to be approved by the U.S. Food and Drug Administration (FDA). Maraviroc is a selective, slowly reversible, small-molecule antagonist of the interaction between human cell surface CCR5 and HIV-1 gp120, necessary for HIV-1 cell infection. Blocking this interaction prevents CCR5-tropic HIV-1 entry into cells. However, CXCR4-tropic HIV-1 entry is not prevented. Maraviroc, in combination with other antiretroviral agents, is indicated for adult patients who:
The FDA-approved full prescribing information states that “Tropism testing must be conducted with a highly sensitive and specific tropism assay that has demonstrated the ability to identify patients appropriate for [maraviroc] use.” This is because efficacy was not demonstrated in a phase II study of maraviroc in patients with dual/mixed or CXCR4-tropic HIV-1. Due to potential adverse effects (hepatic and cardiotoxicity), maraviroc should only be used in indicated patients.
HIV tropism testing is available by either phenotypic or genotypic methods. Tropism testing with a phenotypic assay, a cellular-based assay that functionally determines tropism, is available with the enhanced sensitivity Trofile™ (Monogram Biosciences, South San Francisco, CA) assay. This phenotypic assay uses virus stocks pseudotyped with envelope sequences derived from patient plasma to infect cell lines engineered to express CCR5 or CXCR4 HIV-2 co-receptors. Other phenotypic assays have been developed (e.g., in Europe) but commercial availability in the United States is uncertain. Genotypic tropism testing, which infers tropism on the basis of sequencing data, was first available with the SensiTrop assay. However, the SensiTrop assay has been discontinued and replaced by assays from other commercial and laboratory sources. For example, Quest Diagnostics Inc. offers the HIV-1 Coreceptor Tropism test, which is based on heteroduplex analysis of PCR-amplified and sequenced regions of the HIV-1 envelope V3 loop.
POLICYHIV tropism testing with either the phenotypic assay or V3 population genotyping may be considered medically necessary for selecting patients for treatment with HIV co-receptor antagonists such as maraviroc. Patients indicated for testing:
HIV V3 deep sequencing (synonyms: ultra-deep sequencing; pyrosequencing; next generation sequencing) for selecting patients for treatment with HIV co-receptor antagonists is considered investigational.
HIV tropism testing without immediate plans to prescribe HIV co-receptor antagonists such as maraviroc) is not medically necessary.
Repeat HIV tropism testing during co-receptor antagonist treatment or after failure with co-receptor antagonists is investigational.
HIV tropism testing to predict disease progression (irrespective of co-receptor antagonist treatment) is investigational.
POLICY EXCEPTIONSFederal Employee Program (FEP) may dictate that all FDA-approved devices, drugs or biologics may not be considered investigational and thus these devices may be assessed only on the basis of their medical necessity.
POLCIY GUIDELINESTesting should be conducted immediately prior to intended prescribed use of maraviroc to obtain the most accurate prediction of tropism at the start of treatment.
Either phenotypic or V3 population genotypic testing may be used to determine HIV tropism; both are not necessary.
Investigative service is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized by certifying boards and/or approving or licensing agencies or published peer review criteria as standard, effective medical practice for the treatment of the condition being treated and as such therefore is not considered medically necessary.
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
POLICY HISTORY1/11/2008: Policy added
1/24/2008: Added "see POLICY section" to Code Reference section for CPT 87999
3/27/2008: Reviewed and approved by the Medical Policy Advisory Committee (MPAC)
04/21/2010: Policy description updated regarding testing availability and indications. The first policy statement was revised to include treatment-naïve patients as one of the indications that may be considered medically necessary. The third policy statement was revised to replace “in advance of multiple antiretroviral treatment failures” with “without immediate plans.” FEP verbiage added to the Policy Exceptions section.
04/26/2012: Policy statement revised to indicate that HIV V3 genotyping is medically necessary for tropism testing. Deleted the following policy statement: HIV tropism testing using other assay techniques is considered investigational. Added the following policy statement: HIV V3 deep sequencing (synonyms: ultra-deep sequencing; pyrosequencing; next generation sequencing) for selecting patients for treatment with HIV co-receptor antagonists is considered investigational. Policy guidelines updated regarding testing protocol.
SOURCES(S)Blue Cross & Blue Shield Association Policy # 2.04.49
CODE REFERENCEThis is not intended to be a comprehensive list of codes. Some covered procedure codes have multiple descriptions. Coverage will only be made for covered codes when used for services outlined within the policy statement section.