mp-322 - Medical Policies - Alabama
Laboratory Testing for HIV Tropism
Policy Number: MP-322
Latest Review Date: January 2021
Policy Grade: Effective January 31, 2019: Active Policy but no longer scheduled for regular literature reviews and updates
HIV tropism testing with either the phenotypic assay or V3 population (via Sanger or V3 deep sequencing method) genotyping may be considered medically necessary for selecting patients for treatment with HIV co-receptor antagonists, such as maraviroc (Selzentry), when there is an immediate plan to prescribe a co-receptor antagonist.
HIV tropism testing without immediate plans to prescribe HIV co-receptor antagonists, such as maraviroc (Selzentry), is considered not medically necessary.
Repeat HIV tropism testing during co-receptor antagonist treatment or after failure with co-receptor antagonists is considered not medically necessary.
HIV tropism testing to predict disease progression (irrespective of co-receptor antagonist treatment) is considered not medically necessary.
*Refer also to medical policy #264: HIV Genotyping and Phenotyping for additional information.
DESCRIPTION OF PROCEDURE OR SERVICE:
HIV tropism testing can determine the predominant co-receptor protein used by the human immunodeficiency virus (HIV) to infect target cells. Tropism testing can help select patients for treatment with HIV co-receptor antagonists, such as Maraviroc, which block specific co-receptor proteins.
The 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. Dual or mixed (D/M) tropic viruses can bind to either receptor type. It is estimated that around 85% of treatment-naive patients harbor CCR5-tropic virus only, around 15% harbor D/M virus, and less than 1% are infected with CXCR4-tropic virus alone. CXCR4-tropic virus is associated with immunosuppression and later stages of disease. Co-receptor antagonists have been designed to interfere with the interaction between HIV-1 and its co-receptors.
HIV Co-receptor Antagonists
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. According to the drug’s original label, Maraviroc, in combination with other antiretroviral agents, is indicated for adult patients who are infected with only CCR5-tropic detectable HIV-1, who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents.
The currently-approved maraviroc label indicates that maraviroc is indicated for combination antiretroviral treatment for adults infected with only CCR5-tropic HIV-1, without discussion of the presence of viral replication. The FDA-approved full prescribing information states “Tropism testing must be conducted on a current sample with a highly sensitive tropism assay that has demonstrated the ability to identify patients appropriate for use of SELZENTRY.” 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.
Other HIV co-receptor antagonists are in the drug development pipeline. Cenicriviroc (Tobira Therapeutics) is a small-molecule antagonist of both CCR5 and CCR2, a receptor involved in a number of inflammatory diseases that is currently being investigated for treatment of CCR5-tropic HIV. In January 2015, cenicriviroc was granted fast track designation by FDA for the treatment of nonalcoholic steatohepatitis in patients with liver fibrosis, but the drug does not yet have FDA approval.
HIV Tropism Testing
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 TrofileTM assay (Monogram Biosciences, South San Francisco, CA) assay (ESTA). 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. Genotypic tropism testing is based on sequencing the third variable (V3) loop of the HIV glycoprotein 120 gene, because the V3 loop interacts with the HIV co-receptor, and mutations in V3 are associated with measurable changes in HIV tropism. Tropism assignment is derived from the sequence data using a bio-informatic algorithm such as geno2pheno (G2P). In the U.S., the only commercially available genotypic HIV co-receptor tropism assay is available from Quest Diagnostics, which uses triplicate population sequencing with reflex to ultra-deep sequencing if only CCR5-tropic virus is detected. Quest Diagnostics also offers a pro-viral DNA tropism test (Trofile DNA) which sequences the tropism of HIV-1 DNA that has integrated into the host genome of infected T-lymphocytes via triplicate population sequencing, without the use of ultra-deep sequencing.
This policy was updated with the literature available through January 4, 2021.
Summary of Evidence
For individuals who have HIV infection who are being considered for HIV co-receptor antagonist therapy who receive HIV tropism testing, the evidence includes RCTs. Relevant outcomes are overall survival, disease-specific survival, morbid events, quality of life, hospitalizations, medication use, and treatment-related morbidity. RCTs on treatment-naive and treatment-experienced HIV-infected patients have provided evidence that selection of candidates for HIV co-receptor antagonist therapy using HIV tropism testing results in higher rates of treatment success compared with HIV co-receptor antagonist therapy without HIV tropism testing. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.
For individuals with HIV infection receiving HIV co-receptor antagonist therapy or who have failed co-receptor antagonist therapy who receive HIV tropism testing, the evidence includes post hoc analysis of RCTs and observational studies. Relevant outcomes are overall survival, disease-specific survival, morbid events, quality of life, hospitalizations, medication use, and treatment-related mortality and morbidity. Current evidence does not indicate improved outcomes with additional tropism monitoring during treatment. The evidence is insufficient to determine the effects of the technology on health outcomes.
For individuals with HIV infection who are undergoing tests to predict disease progression who receive HIV tropism testing, the evidence includes observational studies. Relevant outcomes are overall survival, disease-specific survival, morbid events, quality of life, hospitalizations, and medication use. Current evidence is inconsistent in as relates to whether HIV tropism testing independently predicts disease progression among HIV-infected patients. The evidence is insufficient to determine the effects of the technology on health outcomes.
Practice Guidelines and Position Statements
HIV Medicine Association of the Infectious Disease society of North America
The HIV Medicine Association of the Infectious Disease Society of North America released updated guidelines on the on the management of persons infected with HIV in 2013. These guidelines state that tropism testing should be performed if the use of a CCR5 antagonist is being considered (strong recommendation, high quality evidence). The guidelines also state that “routine tropism testing is not recommended prior to initiation of other regimens because of cost and lack of demonstrated benefit.” The guidelines do not specify the preferred method of tropism testing.
European Consensus Group
The European Consensus Group on clinical management of tropism testing states that tropism testing is indicated for patients who fail treatment or have unacceptable toxicity and a CCR5 inhibitor is being considered. In the absence of evidence, the group provides no guidance regarding tropism testing for newly diagnosed patients whose immediate treatment plan does not include a CCR5 inhibitor. In the absence of adequate data, the group could provide no guidance regarding the question of testing treatment-naïve patients prior to the start of a regimen not including a CCR5 inhibitor, in anticipation of need for a fast change to a CCR5 inhibitor due to the toxicity of the initial treatment regimen. For patients with a plasma HIV RNA load >1,000 copies/mL, tropism testing can be done by Trofile ESTA or by population genotypic analysis of the V3 loop, indicating for both a moderate level of evidence based on well-designed, nonrandomized trials or cohort studies with long-term clinical outcomes. For patients with a plasma HIV RNA load <1,000 copies/mL, genotyping is the preferred method.
Department of Health and Human Services
The U.S. DHHS Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV (DHHS, 2018) recommends the use of co-receptor tropism assays (including a phenotypic tropism assay) in clinical practice as follows:
- A co-receptor tropism assay should be performed whenever the use of a CCR5 co-receptor antagonist is being considered (Level of Evidence AI);
- Co-receptor tropism testing is also recommended for patients who exhibit virologic failure on a CCR5 antagonist (Level of Evidence BIII);
- A phenotypic tropism assay is preferred to determine HIV-1 co-receptor usage (A1);
- A proviral DNA tropism assay can be utilized for patients with undetectable HIV-1 RNA when CCR5 antagonist is considered for use in a new regimen (e.g., as part of a regimen switch or simplification) (BII).
- Rating of Recommendations: A = Strong; B = Moderate; C = Optional
- Rating of Evidence: I = data from randomized controlled trials; II = data from well-designed nonrandomized trials or observational cohort studies with long-term clinical outcomes; III = expert opinion.
In addition, the DHHS guidelines state:
A tropism assay may potentially be used in clinical practice for prognostic purposes or to assess tropism before starting ART if future use of a CCR5 antagonist is anticipated (e.g., a regimen change for toxicity). Currently, sufficient data do not exist to support these uses.
International Antiviral Society
The Antiretroviral Drug for Treatment and Prevention of HIV Infection in Adults - 2018 Recommendations of the International Antiviral Society-USA Panel (Saag, 2018) states that CCR5 tropism testing results must be confirmed prior to initiating ART that includes maraviroc and at time of virologic failure.
U.S. Preventive Services Task Force Recommendations
Maraviroc (Selzentry™, Pfizer), Trofile™ (Monogram Biosciences, South San Francisco, CA) assay, SensiTrop assay, HIV-1 Coreceptor Tropism, Tropism testing, Genotypic tropism testing, tropism assay, V3 genotyping, HIV V3, ESTA, antiretroviral drug resistance testing
APPROVED BY GOVERNING BODIES:
The FDA-approved full prescribing information for maraviroc (Selzentry™, Pfizer) 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.”
Currently-available HIV tropism tests are performed as laboratory developed tests (LDTs). Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; LDTs must meet the general regulatory standards of the Clinical Laboratories Improvement Act (CLIA). HIV tropism tests are is available under the auspices of the Clinical Laboratory Improvement Amendments. Laboratories that offer laboratory-developed tests must be licensed by the Clinical Laboratory Improvement Amendments for high-complexity testing. To date, the FDA has chosen not to require any regulatory review of this test.
Coverage is subject to member’s specific benefits. Group specific policy will supersede this policy when applicable.
ITS: Home Policy provisions apply
FEP contracts: Special benefit consideration may apply. Refer to member’s benefit plan. FEP does not consider investigational if FDA approved and will be reviewed for medical necessity.
Unlisted microbiology procedure
- Aberg JA, Gallant JE, Ghanem KG et al. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2014; 58(1):1-10.
- Almeida FJ, Zaparoli MS, Moreira DH, et al. Association of X4 tropism with disease progression in antiretroviral-treated children and adolescents living with HIV/AIDS in Sao Paulo, Brazil. Braz J Infect Dis. May-Jun 2014; 18(3):300-307.
- Archer J, Weber J, Henry K et al. Use of four next-generation sequencing platforms to determine HIV-1 coreceptor tropism. PloS One 2012; 7(11):e49602.
- Bartlett AD, MaCartney MJ, Conibear TC, et al. The utility of different bioinformatics algorithms for genotypic HIV-1 tropism testing in a large clinical cohort with multiple subtypes. AIDS. Jul 17 2014; 28(11):1611-1617.
- Brown J, Burger H, Weiser B, et al. A genotypic HIV-1 proviral DNA coreceptor tropism assay: characterization in viremic subjects. AIDS Res Ther. 2014; 11:14.
- Cardona L, Ana G, Luisa B et al. Thrombus formation on a left atrial appendage closure device. Circulation 2011; 124(14):1595-6.
- Casadella M, Cozzi-Lepri A, Phillips A, et al. Plasma HIV-1 Tropism and the Risk of Short-Term Clinical Progression to AIDS or Death. PLoS One. 2017; 12(1):e0166613.
- Castagna A, Monno L, Carta S, et al. Switch of predicted HIV-1 tropism in treated subjects and its association with disease progression. Medicine (Baltimore). Nov 2016; 95(44):e5222
- Ceresola ER, Nozza S, Sampaolo M, et al. Performance of commonly used genotypic assays and comparison with phenotypic assays of HIV-1 coreceptor tropism in acutely HIV-1-infected patients. J Antimicrob Chemother. Jan 20 2015.
- Ceresola ER, Nozza S, Sampaolo M, et al. Performance of commonly used genotypic assays and comparison with phenotypic assays of HIV-1 coreceptor tropism in acutely HIV-1-infected patients. J Antimicrob Chemother. May 2015; 70(5):1391-1395.
- Cooper DA, Heera J, Goodrich J et al. Maraviroc versus efavirenz, both in combination with zidovudine-lamivudine, for the treatment of antiretroviral-naive subjects with CCR5-tropic HIV-1 infection. J Infect Dis 2010; 201(6):803-13.
- Daar ES, Kesler KL, Petropoulos CJ et al. Baseline HIV type 1 coreceptor tropism predicts disease progression. Clin Infect Dis 2007; 45(5):643-9.
- Department of Health and Human Services. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. 2014;//aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/21/hiv-infected-adolescents-and-young-adults. Accessed November 2017.
- Diez-Fuertes F, Delgado E, Vega Y et al. Improvement of HIV-1 coreceptor tropism prediction by employing selected nucleotide positions of the env gene in a Bayesian network classifier. J Antimicrob Chemother 2013; 68(7):1471-85.
- Dolin R. A new class of anti-HIV therapy and new challenges. NEJM, October 2008; 359(14): 1509-1511.
- Efficacy, Safety, and Tolerability of Cenicriviroc (CVC) in Combination with Truvada or Sustiva Plus Truvada in HIV 1-infected, Antiretroviral Treatment-naïve, Adult Patients Infected With Only CCR5-tropic Virus. 2013; clinicaltrials.gov/ct2/show/NCT01338883?term=NCT01338883&rank=1.
- Fatkenheuer G, Nelson M, Lazzarin A, et al. Subgroup analyses of maraviroc in previously treated R5 HIV-1 infection. NEJM, October 2008; 359(14): 1441-1455.
- Fontdevila MC, Cozzi-Lepri A, Phillips A, et al. Plasma HIV-1 tropism and risk of short-term clinical progression to AIDS or death. J Int AIDS Soc. 2014; 17(4 Suppl 3):19685.
- Garcia F, Poveda E, Perez-Elias MJ, et al. Genotypic tropism testing in proviral DNA to guide maraviroc initiation in aviremic subjects: 48-week analysis of the PROTEST study. J Int AIDS Soc. 2014; 17(4 Suppl 3):19520.
- Gibson RM, Meyer AM, Winner D, et al. Sensitive deep-sequencing-based HIV-1 genotyping assay to simultaneously determine susceptibility to protease, reverse transcriptase, integrase, and maturation inhibitors, as well as HIV-1 coreceptor tropism. Antimicrob Agents Chemother. 2014; 58(4):2167-2185.
- Gonzalez-Serna A, McGovern RA, Harrigan PR et al. Correlation of the virological response to short-term Maraviroc monotherapy with standard and deep sequencing-based genotypic tropism methods. Antimicrob Agents Chemother 2012; 56(3):1202-07.
- Gulick RM, Fatkenheuer G, Burnside R et al. Five-Year Safety Evaluation of Maraviroc in HIV-1- Infected Treatment-Experienced Patients. J Acquir Immune Defic Syndr 2014; 65(1):78-81.
- Gulick RM, Lalezari J, Goodrich J, et al. Maraviroc for previously treated patients with R5 HIV-1 infection. NEJM, October 2008, Vol., 359, No. 14, pp. 1429-1441.
- Hardy WD, Gulick RM, Mayer H et al. Two-year safety and virologic efficacy of maraviroc in treatment-experienced patients with CCR5-tropic HIV-1 infection: 96-week combined analysis of MOTIVATE 1 and 2. J Acquir Immune Defic Syndr 2010; 55(5):558-64.
- Harrigan PR. MOTIVATE tropism study group. Optimization of clinical cutoffs for determining HIV co-receptor use by population and “deep” sequencing methods. Infectious Diseases Society of America, Philadelphia, PA 2009.
- Harrigan PR, McGovern R, Dong W et al. Screening for HIV tropism using population-based V3 genotypic analysis: a retrospective virological outcome analysis using stored plasma screening samples from MOTIVATE-1. 5th International AIDS Symposium, 2009, Cape Town, S. Africa: Abstract WELBA101.
- Heera J, Valluri S, Craig C, et al. First prospective comparison of genotypic vs phenotypic tropism assays in predicting virologic responses to Maraviroc (MVC) in a phase 3 study: MODERN. J Int AIDS Soc. 2014;17(4 Suppl 3):19519
- Hirsch MS, Günthard HF, Schapiro JM, et al. Antiretroviral drug resistance testing in adult HIV-1 infection: 2008 recommendations of an International AIDS Society-USA panel. Top HIV Med, Aug-Sept 2008; 16(3): 266-285.
- Huang W, Toma J, Stawiski E et al. Characterization of human immunodeficiency virus type 1 populations containing CXCR4-using variants from recently infected individuals. AIDS Res Hum Retroviruses 2009; 25(8):795-802.
- Jensen MA, Li FS, van 't Wout AB et al. Improved coreceptor usage prediction and genotypic monitoring of R5-to-X4 transition by motif analysis of human immunodeficiency virus type 1 env V3 loop sequences. J Virol 2003; 77(24):13376-88.
- Kagan RM, Johnson EP, Siaw M et al. A genotypic test for HIV-1 tropism combining Sanger sequencing with ultradeep sequencing predicts virologic response in treatment-experienced patients. PloS One 2012; 7(9):e46334.
- Kanters S, Vitoria M, Doherty M, et al. Comparative efficacy and safety of first-line antiretroviral therapy for the treatment of HIV infection: a systematic review and network meta-analysis. Lancet HIV. 2016; 3(11):e510-e520.
- Kaplan SS, Mounzer KC. Antiretroviral therapy in HIV-infected patients with multidrug-resistant virus: applying the guidelines to practice. AIDS Patient Care STDS. 2008; 22(12):931-940.
- Katzenstein DA, Hammer SM, Hughes MD et al. The relation of virologic and immunologic markers to clinical outcomes after nucleoside therapy in HIV-infected adults with 200 to 500 CD4 cells per cubic millimeter. AIDS Clinical Trials Group Study 175 Virology Study Team. N Engl J Med 1996; 335(15):1091-8.
- Lengauer T, Sander O, Sierra S et al. Bioinformatics prediction of HIV coreceptor usage. Nat Biotechnol 2007; 25(12):1407-10.
- Lin NH, Kuritzkes DR. Tropism testing in the clinical management of HIV-1 infection. Curr Opin HIV AIDS. 2009; 4(6):481-487.
- Low AJ, Dong W, Chan D, Sing T, et al. Current V3 genotyping algorithms are inadequate for predicting X4 co-receptor usage in clinical isolates. AIDS, Sept 2007; 21(14): F17-24.
- Low AJ, Swenson LC and Harrigan PR. HIV coreceptor phenotyping in the clinical setting. AIDS Rev, Jul-Sept 2008; 10(3): 143-151.
- Max Planck Institut Informatik. Geno2pheno [coreceptor] 2.5. 2014; coreceptor.bioinf.mpi-inf.mpg.de/index.php. Accessed November 28, 2017.
- McGovern RA, Dong W, Mo T et al. Optimization of clinically relevant cut-points for the determination of HIV co-receptor usage to predict maraviroc responses in treatment experienced (TE) patients using population V3 genotyping. 12th European AIDS Conference. Cologne, Germany 2009: Abstract PE3.4/8.
- McGovern RA, Thielen A, Mo T et al. Population-based V3 genotypic tropism assay: a retrospective analysis using screening samples from the A4001029 and MOTIVATE studies. AIDS 2010; 24(16):2517-25.
- McGovern RA, Thielen A, Portsmouth S et al. Population-based sequencing of the V3-loop can predict the virological response to maraviroc in treatment-naive patients of the MERIT trial. J Acquir Immune Defic Syndr 2012; 61(3):279-86.
- Mellors JW, Munoz A, Giorgi JV, et al. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med. Jun 15 1997; 126(12):946-954.
- Mellors JW, Rinaldo CR, Jr., Gupta P, et al. Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science. May 24 1996; 272(5265):1167-1170.
- Misbah M, Roy G, Shahid M, et al. Comparative analysis of drug resistance mutations in the human immunodeficiency virus reverse transcriptase gene in patients who are non-responsive, responsive and naive to antiretroviral therapy. Arch Virol. 2016; 161(5):1101-1113.
- Mortier V, Dauwe K, Vancoillie L, et al. Frequency and predictors of HIV-1 co-receptor switch in treatment naive patients. PLoS One. 2013; 8(11):e80259.
- Moyle GJ, Wildfire A, Mandalia S, et al. Epidemiology and predictive factors for chemokine receptor use in HIV-1 infection. J Infect Dis 2005; 191(6):866-72.
- Mullins Lab, University of Washington. Web PSSM. 2009; https://indra.mullins.microbiol.washington.edu/webpssm/. Accessed November 28, 2017.
- Nanfack AJ, Takou D, Fokam J, et al. HIV-1 drug susceptibility to potential second- and third-line antiretroviral regimens among Cameroonian patients: Evidence from a cross-sectional design. Curr HIV Res. 2017; 15(1):66-73.
- Nozza S, Pignataro AR, Galli L, et al. 48 week outcomes of maraviroc-containing regimens following the genotypic or Trofile assay in HIV-1 failing subjects: the OSCAR Study. New Microbiol. Jul 2016; 39(3):192-196.
- Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Updated March 2012. Accessible at aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?GuidelineID=7&ClassID=1http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf. Accessed November 28, 2017.
- Perez-Olmeda M, Alcami J. Determination of HIV tropism and its use in the clinical practice. Expert Rev Anti Infect Ther. 2013; 11(12):1291-1302.
- Pfizer, Inc. Selzentry TM, (maroviroc) prescribing information. 2009; www.accessdata.fda.gov/drugsatfda_docs/label/2009/022128s002lbl.pdf. Accessed November 28, 2017.
- Philpott SM. HIV-1 coreceptor usage, transmission, and disease progression. Curr HIV Res 2003; 1(2):217-27.
- Pou C, Cabrera C, Dalmau J et al. Co-Receptor Tropism Prediction in Chronically HIV-1-Infected Subjects with Suppressed Viremia. 7th European HIV Drug Resistance Workshop, Stockholm, Sweden; March 27–29, 2009: Abstract 82.
- Poveda E, Paredes R, Moreno S et al. Update on clinical and methodological recommendations for genotypic determination of HIV tropism to guide the usage of CCR5 antagonists. AIDS Reviews 2012; 14(3):208-17.
- Prosperi MC, Bracciale L, Fabbiani M et al. Comparative determination of HIV-1 co-receptor tropism by Enhanced Sensitivity Trofile, gp120 V3-loop RNA and DNA genotyping. Retrovirology 2010; 7:56.
- Raymond S, Maillard A, Amiel C, et al. Virological failure of patients on maraviroc-based antiretroviral therapy. J Antimicrob Chemother. Feb 2015; 70(6):1858-1864.
- Reeves JD, Coakley E, Petropoulos CJ et al. An enhanced-sensitivity Trofile HIV coreceptor tropism assay for selecting patients for therapy with entry inhibitors targeting CCR5: A review of analytical and clinical studies. J Viral Entry 2009; 3:94-102.
- Saag M, Goodrich J, Fatkenheuer G et al. A double-blind, placebo-controlled trial of maraviroc in treatment-experienced patients infected with non-R5 HIV-1. J Infect Dis 2009; 199(11):1638-47.
- Saliou A, Delobel P, Dubois M et al. Concordance between two phenotypic assays and ultradeep pyrosequencing for determining HIV-1 tropism. Antimicrob Agents Chemother 2011; 55(6):2831-6.
- Sanchez V, Masia M, Robledano C et al. Performance of genotypic algorithms for predicting HIV-1 tropism measured against the enhanced-sensitivity Trofile coreceptor tropism assay. J Clin Microbiol 2010; 48(11):4135-9.
- Saracino A, Bruno G, Scudeller L, et al. Does HIV-1 co-receptor tropism correlate with fibrosis progression in HIV/HCV co-infected patients? J Clin Virol. Mar 2014; 59(3):167-171.
- Sierra-Madero J, Di Perri G, Wood R, et al. Efficacy and safety of maraviroc versus efavirenz, both with zidovudine/lamivudine: 96-week results from the MERIT study. HIV Clin Trials. 2010; 11(3):125-132.
- Strang AL, Cameron J, Booth CL et al. Genotypic prediction of viral co-receptor tropism: correlation with enhanced Trofile. 15th Annual Conference of the British HIV Association 1-3 April 2009, Liverpool, UK: Abstract P95.
- Svicher V, Alteri C, Montano M, et al. Genotypic testing on HIV-1 DNA as a tool to assess HIV-1 co-receptor usage in clinical practice: results from the DIVA study group. Infection. Feb 2014; 42(1):61-71.
- Svicher V, Alteri C, Montano M, et al. Performance of genotypic tropism testing on proviral DNA in clinical practice: results from the DIVA study group. New Microbiol. Jan 2012; 35(1):17-25.
- Svicher V, D'Arrigo R, Alteri C et al. Performance of genotypic tropism testing in clinical practice using the enhanced sensitivity version of Trofile as reference assay: results from the OSCAR Study Group. New Microbiol 2010; 33(3):195-206.
- Swenson LC, Mo T, Dong WW et al. Deep sequencing to infer HIV-1 co-receptor usage: application to three clinical trials of maraviroc in treatment-experienced patients. J Infect Dis 2011; 203(2):237-45.
- Swenson LC, Mo T, Dong WW et al. Deep V3 sequencing for HIV type 1 tropism in treatment-naive patients: a reanalysis of the MERIT trial of maraviroc. Clin Infect Dis 2011; 53(7):732-42.
- Swenson LC, Moores A, Low AJ et al. Improved detection of CXCR4-using HIV by V3 genotyping: application of population-based and "deep" sequencing to plasma RNA and proviral DNA. J Acquir Immune Defic Syndr 2010; 54(5):506-10.
- Tobira Therapeutics Inc. Efficacy, Safety, and Tolerability of Cenicriviroc (CVC) in Combination With Truvada or Sustiva Plus Truvada in HIV 1-infected, Antiretroviral Treatment-naïve, Adult Patients Infected With Only CCR5-tropic Virus. 2013; clinicaltrials.gov/ct2/show/NCT01338883?term=NCT01338883&rank=1. Accessed November 28, 2017.
- Tsibris AM, Korber B, Arnaout R et al. Quantitative deep sequencing reveals dynamic HIV-1 escape and large population shifts during CCR5 antagonist therapy in vivo. PLoS One 2009; 4(5):e5683.
- U.S. Food and Drug Administration. Full Prescribing Information: SELZENTRY. 2007; www.accessdata.fda.gov/drugsatfda_docs/label/2007/022128lbl.pdf. Accessed November 28, 2017.
- U.S. Food and Drug Administration. Full Prescribing Information: SELZENTRY. 2014; www.accessdata.fda.gov/drugsatfda_docs/label/2014/022128s012lbl.pdf. Accessed November 28, 2017.
- Vandekerckhove LP, Wensing AM, Kaiser R et al. European guidelines on the clinical management of HIV-1 tropism testing. Lancet Infect Dis 2011; 11(5):394-407.
- Visseaux B, Charpentier C, Rouard C, et al. HIV-2 X4 tropism is associated with lower CD4+ cell count in treatment-experienced patients. AIDS. Sep 10 2014; 28(14):2160-2162.
- Weber J, Piontkivska H and Quinones-Mateu ME. HIV type 1 tropism and inhibitors of viral entry: clinical implications. AIDS Rev 2006; 8(2):60-77.
- Whitcomb JM, Huang W, Fransen S et al. Development and characterization of a novel single-cycle recombinant-virus assay to determine human immunodeficiency virus type 1 coreceptor tropism. Antimicrob Agents Chemother 2007; 51(2):566-575.
- Wilkin TJ, Goetz MB, Leduc R et al. Reanalysis of coreceptor tropism in HIV-1-infected adults using a phenotypic assay with enhanced sensitivity. Clin Infect Dis 2011; 52(7):925-8.
- Wilkin TJ, Gulick RM. CCR5 Antagonism in HIV Infection: Current Concepts and Future Opportunities. Annu Rev Med 2012; 63:81-93.
Medical Policy Group, July 2008 (3)
Medical Policy Administration Committee, July 2008
Available for comment July 15-August 28, 2008
Medical Policy Group, July 2010 (1): Policy statement update, Key Points updated
Medical Policy Administration Committee, June 2010
Available for comment June 18-August 2, 2010
Medical Policy Group, December 2010 (1): Coding update, Added new CPT code, and updated verbiage
Medical Policy Group, July 2011 (2): Key Words update
Medical Policy Group, March 2012 (1): Update to Descriptions, Policy, Key Points and References related to addition of coverage criteria for V3 population genotyping per MPP update
Medical Policy Administration Committee, May 2012
Medical Policy Panel, March 2013
Medical Policy Group, April 2013 (1) Updates to Key Points and References; no change to policy statement
Medical Policy Panel, March 2014
Medical Policy Group, March 2014 (1): Update to Description, Policy, Key Points, Key Words and References related to removal of V3 deep sequencing non-coverage statement
Medical Policy Administration Committee, April 2014
Available for comment April 4 through May 19, 2014
Medical Policy Panel, March 2015
Medical Policy Group, May 2015 (3): Updates to Description, Policy statement (removed patient indications for testing), Key Points, Approved by Governing Bodies, Coding, and References; no change in policy intent.
Available for comment May 16 through June 29, 2015
Medical Policy Panel, December 2017
Medical Policy Group, January 2018 (3): 2017 Updates to Description, Key Points, and References; no changes to current policy statements. Removed policy statements that were effective for dates of service prior to March 1, 2014
Medical Policy Panel, January 2019
Medical Policy Group, January 2019 (3): Updates to Key Points and References. No change to policy statement or intent. Active policy but no longer scheduled for regular reviews and updates.
Medical Policy Group, January 2021 (9): Updates to Key Points, Description, References. Removed policy statements for dates March 1, 2014 through April 30, 2015, removed dates descriptor "on or after May 1, 2015" from current policy criteria. Removed the word “investigational” from applicable policy statements that included the wording "investigational and not medically necessary" (for consistency). Added common brand name to generic name maraviroc (Selzentry) in policy statement for clarification purposes. No change to policy statement intent. Active policy but no longer scheduled for regular reviews and updates.
This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.
This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.
The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.
As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.
The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:
1. The technology must have final approval from the appropriate government regulatory bodies;
2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;
3. The technology must improve the net health outcome;
4. The technology must be as beneficial as any established alternatives;
5. The improvement must be attainable outside the investigational setting.
Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:
1. In accordance with generally accepted standards of medical practice; and
2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and
3. Not primarily for the convenience of the patient, physician or other health care provider; and
4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.