medigraphic.com
ISSN 1527-3172 (Electronic)

2021, Number 3-4

<< Back Next >>

MEDICC Review 2021; 23 (3-4)

Subtype-Dependent Co-receptor Tropism in Cuban HIV-1–Infected Patients: Implications for Maraviroc Treatment

Martínez-Montesino Y, Kourí-Cardellá V, Pérez-Santos L, Han R, Pintos-Saavedra Y, Alemán-Campos Y, Soto-Brito Y, Baños-Morales Y, Caturla-Fernández Y

Language: English
References: 36
Page: 29-36
PDF size: 399.82 Kb.


ABSTRACT

INTRODUCTION Unlike most high-income countries where subtype B viruses predominate, the Cuban HIV-1 epidemic is characterized by a great diversity of subtypes and circulating recombinant forms. Some studies have shown that HIV variants exhibiting a preference for the CXCR4 co-receptor (X4-tropic) could have impacts on disease pathogenesis, with clinical implications for antiviral treatment plans. Determination of HIV co-receptor tropism is crucial for clinicians in deciding whether maraviroc is an appropriate antiviral.
OBJECTIVE Characterize V3 sequence variability and its relation to viral tropism across different subtypes circulating in Cuba and explore how this may affect treatment success with maraviroc.
METHODS We designed a cross-sectional study that included 72 plasma samples obtained at the Pedro Kourí Tropical Medicine Institute in Havana, Cuba. We sequenced the C2V3 env region and assessed subtype based both on env and pol sequences; tropism was predicted by Geno2pheno analysis. Additionally, 35 V3-loop Cuban sequences, obtained from a previous study, were incorporated into the analysis. Statistical associations among virological, clinical and epidemiological variables were assessed by a chi-square test.
RESULTS Tropism prediction for 72 variants revealed that CRF19_cpx was associated with dual-tropic R5X4 viruses (p = 0.034). Moreover, when 35 sequences from a former study were added, the association was significant not only for R5X4 (p = 0.019) but also for X4-tropic variants (p = 0.044). Alignment of 107 V3-loop sequences showed wide diversity among the different HIV-1 subtypes circulating in Cuba.
CONCLUSIONS In accordance with G2P, CRF19_cpx is a genetic variant with a high proportion of X4 and R5X4-tropic viruses. The results from the present study suggest that the Cuban recombinant could be a more pathogenic variant and that maraviroc may not be suitable for patients infected with CRF19_cpx.


REFERENCES

  1. Riemenschneider M, Cashin KY, Budeus B,Sierra S, Shirvani-Dastgerdi E, BayanolhaghS, et al. Genotypic Prediction of Co-receptorTropism of HIV-1 Subtypes A and C. Sci Rep[Internet]. 2016 [cited 2020 Dec 3];6:24883.Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850382/pdf/srep24883.pdf

  2. Pérez-Álvarez L, Delgado E, Vega Y, MonteroV, Cuevas T, Fernández-García A, et al.Predominance of CXCR4 tropism in HIV-1 CRF14_BG strains from newly diagnosedinfections. J Antimicrob Chemother [Internet].2014 Jan [cited 2020 Dec 2];69(1):246–53.Available at: https://pdfs.semanticscholar.org/3ada/c6787c3af51dfa8b2b51764550cfe6f57608.pdf?_ga=2.176869410.60519488.1608083556-726339794.1548872336

  3. Soulie C, Morand-Joubert L, Cottalorda J,Charpentier C, Bellecave P, Le Guen L, et al.Performance of genotypic algorithms for predictingtropism for HIV-1 CRF01_AE recombinant. J ClinVirol [Internet]. 2018 Feb–Mar [cited 2020 Dec2];99–100:57–60. Available at: https://linkinghub.elsevier.com/retrieve/pii/S1386-6532(17)30354-2

  4. Panos G, Watson DC. Effect of HIV-1 subtype andtropism on treatment with chemokine coreceptorentry inhibitors; overview of viral entry inhibition.Crit Rev Microbiol [Internet]. 2015 [cited 2020Dec 2];41(4):473–87. Available at: https://www.tandfonline.com/doi/full/10.3109/1040841X.2013.867829?scroll=top&needAccess=true

  5. Woollard SM, Kanmogne GD. Maraviroc: a reviewof its use in HIV infection and beyond. Drug DesDevel Ther [Internet]. 2015 Oct 1 [cited 2020 Dec2];9:5447–68. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26491256/

  6. Schuitemaker H, van ‘t Wout AB, Lusso P.Clinical signifi cance of HIV-1 coreceptor usage.J Transl Med [Internet]. 2011 Jan 27 [cited 2020Dec 15];9 Suppl 1 (Suppl 1):S5. Available at:https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-9-S1-S5

  7. Mild M, Esbjornsson J, Fenyo EM, MedstrandP. Frequent intrapatient recombination betweenhuman immunodefi ciency virus type 1 R5 andX4 envelopes: implications for coreceptor switch.J Virol [Internet]. 2007 Apr [cited 2020 Dec16];81(7):3369–76. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1866041/pdf/1295-06.pdf

  8. Phuphuakrat A, Phawattanakul S, Pasomsub E,Kiertiburanakul S, Chantratita W, SungkanuparphS. Coreceptor tropism determined by genotypicassay in HIV-1 circulating in Thailand, whereCRF01_AE predominates. HIV Med [Internet].2014 May [cited 2020 Dec 15];15(5):269–75.Available at: https://onlinelibrary.wiley.com/doi/epdf/10.1111/hiv.12108

  9. Asin-Milan O, Chamberland A, Wei Y, HaidaraA, Sylla M, Tremblay CL. Mutations in variabledomains of the HIV-1 envelope gene can havea signifi cant impact on maraviroc and vicrivirocresistance. AIDS Res Ther [Internet]. 2013 Jun 7[cited 2020 Dec 20];10(1):15. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700831/pdf/1742-6405-10-15.pdf

  10. Recordon-Pinson P, Soulie C, Flandre P, DescampsD, Lazrek M, Charpentier C, et al. Evaluation ofthe genotypic prediction of HIV-1 coreceptor useversus a phenotypic assay and correlation withthe virological response to maraviroc: the ANRSGenoTropism study. Antimicrob Agents Chemother[Internet]. 2010 Aug [cited 2020 Dec 3];54(8):3335–40. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916345/pdf/0148-10.pdf

  11. Poveda E, Alcami J, Paredes R, CórdobaJ, Gutiérrez F, Llibre JM, et al. Genotypicdetermination of HIV tropism - clinical andmethodological recommendations to guide thetherapeutic use of CCR5 antagonists. AIDS Rev[Internet]. 2010 [cited 2020 Dec18];12(3):135–48. Available at: https://www.researchgate.net/publication/230569071_Genotypic_Determination_of_HIV_TropismClinical_and_methodological_recommendations_to_guide_the_therapeutic_use_of_CCR5_antagonists/link/00b4952ea736ab0cf1000000/download

  12. Dina J, Raymond S, Maillard A, Le Guillou-Guillemette H, Rodalec A, Beby-Defaux A, etal. Algorithm-based prediction of HIV-1 subtypeD coreceptor use. J Clin Microbiol [Internet].2013 Sep [cited 2020 Dec 15];51(9):3087–9.Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754628/pdf/zjm3087.pdf

  13. Angel JB, Saget BM, Walsh SP, Greten TF,Dinarello CA, Skolnik PR, et al. Rolipram, aspecifi c type IV phosphodiesterase inhibitor,is a potent inhibitor of HIV-1 replication. AIDS[Internet]. 1995 Oct [cited 2020 Dec 16];9(10):1137–44. Available at: https://journals.lww.com/AIDSonline/Abstract/1995/10000/Rolipram,_a_specifi c_type_IV_phosphodiesterase.4.aspx

  14. Borthwick NJ, Bofi ll M, Gombert WM, Akbar AN,Medina E, Sagawa K, et al. Lymphocyte activationin HIV-1 infection. II. Functional defects of CD28-T cells. AIDS [Internet]. 1994 Apr [cited 2020Dec 2];8(4):431–42. Available at: https://journals.lww.com/AIDSonline/Abstract/1994/04000/Lymphocyte_activation_in_HIV_1_infection__II_.4.aspx

  15. Kourí V, Khouri R, Alemán Y, Abrahantes Y,Vercauteren J, Pineda-Pena AC, et al. CRF19_cpx is an evolutionary fi t HIV-1 variant stronglyassociated with rapid progression to AIDS inCuba. EBioMedicine [Internet]. 2015 Jan 28[cited 2020 Dec 16];2(3):244–54. Availableat: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4484819/pdf/main.pdf

  16. Pérez L, Kouri V, Alemán Y, Abrahantes Y,Correa C, Aragones C, et al. Antiretroviral drugresistance in HIV-1 therapy-naive patients inCuba. Infect Genet Evol [Internet]. 2013 Jun[cited 2020 Dec 15];16:144–50. Available at:https://www.sciencedirect.com/science/article/abs/pii/S1567134813000361

  17. Fenyö EM, Esbjörnsson J, Medstrand P,Jansson M. Human immunodefi ciency virustype 1 biological variation and coreceptoruse: from concept to clinical signifi cance. JIntern Med [Internet]. 2011 Dec [cited 2020Dec 17];270(6):520–31. Available at: https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1365-2796.2011.02455.x

  18. Kourí V, Alemán Y, Díaz D, Pérez L, Limia CM,Soto Y, et al. Co-receptor tropism determinedby genotypic assay in HIV-1 circulating inCuba. J AIDS Clin Res [Internet]. 2016 [cited2020 Dec 2];7(7):592. Available at: https://www.hilarispublisher.com/open-access/coreceptor-tropism-determined-by-genotypic-assay-in-hiv1-circulating-in-cuba-2155-6113-1000592.pdf

  19. Kourí V, Alemán Y, Pérez L, Pérez J, FonsecaC, Correa C, et al. High frequency of antiviraldrug resistance and non-B subtypes in HIV-1patients failing antiviral therapy in Cuba. J ClinVirol [Internet]. 2012 Dec 5 [cited 2020 Dec2];55(4):348–55. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225368/pdf/JIAS-17-19754.pdf

  20. Pineda-Pena AC, Faria NR, Imbrechts S, LibinP, Abecasis AB, Deforche K, et al. Automatedsubtyping of HIV-1 genetic sequences for clinicaland surveillance purposes: performance evaluationof the new REGA version 3 and seven other tools.Infect Genet Evol [Internet]. 2013 Oct [cited 2020Dec 14];19:337–48. Available at: https://reader.elsevier.com/reader/sd/pii/S1567134813001810?token=224CF28032AD88B452AD006B04DDF3EEA3E86330D469FD9040A10BEC8BE99E5839D54348182D867AB69D2307C8D37009

  21. de Oliveira T, Deforche K, Cassol S, SalminenM, Paraskevis D, Seebregts C, et al. Anautomated genotyping system for analysisof HIV-1 and other microbial sequences.Bioinformatics [Internet]. 2005 Oct 1 [cited 2020Dec 16];21(19):3797–800. Available at: https://www.researchgate.net/publication/7682559_An_automated_genotyping_system_for_analysis_of_HIV-1_and_other_microbial_sequences

  22. Lemoine F, Correia D, Lefort V, Doppelt-Azeroual O, Mareuil F, Cohen-Boulakia S, et al.NGPhylogeny.fr: new generation phylogeneticservices for non-specialists. Nucleic AcidsRes [Internet]. 2019 Apr 27 [cited 2020 Dec3];47(W1):W260–W5. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602494/pdf/gkz303.pdf

  23. Alemán Y, Vinken L, Kouri V, Pérez L, ÁlvarezA, Abrahantes Y, et al. Performance of anin-house human immunodefi ciency virus type1 genotyping system for assessment of drugresistance in Cuba. PLoS One [Internet]. 2015Feb 11 [cited 2020 Dec 14];10(2):e0117176.Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324769/pdf/pone.0117176.pdf

  24. Lengauer T, Sander O, Sierra S, Thielen A, KaiserR. Bioinformatics prediction of HIV coreceptorusage. Nat Biotechnol [Internet]. 2007 Dec[cited 2020 Dec 4];25(12):1407–10. Available at:https://www.nature.com/articles/nbt1371

  25. Jensen MA, van ‘t Wout AB. Predicting HIV-1 coreceptor usage with sequence analysis.AIDS Rev [Internet]. 2003 Apr–Jun [cited2020 Dec 4];5(2):104–12. Available at: https://www.researchgate.net/publication/10648055_Predicting_HIV1_coreceptor_usage_with_sequence_analysis

  26. Seclén E, Garrido C, González M M, González-Lahoz J, de Mendoza C, Soriano V, et al. Highsensitivity of specifi c genotypic tools for detectionof X4 variants in antiretroviral-experiencedpatients suitable to be treated with CCR5antagonists. J Antimicrob Chemother [Internet].2010 Jul [cited 2020 Dec 16];65(7):1486–92.Available at: https://www.researchgate.net/publication/43351431_High_sensitivity_of_specific_genotypic_tools_for_detection_of_X4_variants_in_antiretroviralexperienced_patients_suitable_to_be_treated_with_CCR5_antagonists

  27. Fogel GB, Lamers SL, Liu ES, Salemi M,McGrath MS. Identifi cation of dual-tropic HIV-1 using evolved neural networks. Biosystems[Internet]. 2015 Nov [cited 2020 Dec 3];137:12–9.Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921197/pdf/nihms730074.pdf

  28. Matume ND, Tebit DM, Gray LR, HammarskjoldML, Rekosh D, Bessong PO. Next generationsequencing reveals a high frequency of CXCR4utilizing viruses in HIV-1 chronically infecteddrug experienced individuals in South Africa. JClin Virol [Internet]. 2018 Jun [cited 2020 Dec17];103:81–7. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229640/pdf/nihms-1584881.pdf

  29. Hayashida T, Tsuchiya K, Kikuchi Y, Oka S,Gatanaga H. Emergence of CXCR4-tropicHIV-1 variants followed by rapid diseaseprogression in hemophiliac slow progressors.PLoS One [Internet]. 2017 May 4 [cited 2020 Dec16];12(5):e0177033. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5417636/pdf/pone.0177033.pdf

  30. Gupta S, Neogi U, Srinivasa H, Banerjea AC,Shet A. HIV-1 coreceptor tropism in India: increasing proportion of X4-tropism in subtypeC strains over two decades. J Acquir ImmuneDefi c Syndr [Internet]. 2014 Apr 1 [cited 2020 Dec17];65(4):397–404. Available at: https://journals.lww.com/jAIDS/Fulltext/2014/04010/HIV_1_Coreceptor_Tropism_in_India Increasing.3.aspx

  31. Guo JL, Yan Y, Zhang JF, Ji JM, Ge ZJ, GeR, et al. Co-receptor tropism and geneticcharacteristics of the V3 regions in variantsof antiretroviral-naive HIV-1 infected subjects[Internet]. Epidemiol Infect. 2019 Jan [cited 2020Dec 18];147:e181. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518647/pdf/S0950268819000700a.pdf

  32. Morgado MG, Guimaraes ML, Gripp CB,Neves Junior I, Costa CI, dos Santos VG, et al.Polymorphism of the predictive antigenic sites onthe V3 loop of Brazilian HIV-1 subtype B strains.HEC/FIOCRUZ AIDS Clinical Research Group.Mem Inst Oswaldo Cruz [Internet]. 1996 May–Jun [cited 2020 Dec 18];91(3):339–42. Availableat: https://www.scielo.br/pdf/mioc/v91n3/15.pdf

  33. Milich L, Margolin BH, Swanstrom R. Patternsof amino acid variability in NSI-like and SI-likeV3 sequences and a linked change in theCD4-binding domain of the HIV-1 Env protein.Virology [Internet]. 1997 Dec 8 [cited 2020Dec 18];239(1):108–18. Available at: https://linkinghub.elsevier.com/retrieve/pii/S0042-6822(97)98821-8

  34. Heera J, Valluri SR, Craig C, Fang A, ThomasN, Meyer RD, et al. First prospective comparisonof genotypic versus phenotypic tropism assays inpredicting virologic responses to maraviroc in aphase 3 study. New Microbiol [Internet]. 2019 Apr[cited 2020 Dec 19];41(2):101–7. Available at:http://www.newmicrobiologica.org/PUB/allegati_pdf/2019/2/101.pdf

  35. Esbjörnsson J, Månsson F, Martínez-Arias W,Vincic E, Biague AJ, da Silva ZJ, et al. FrequentCXCR4 tropism of HIV-1 subtype A and CRF02_AG during late-stage disease--indication of anevolving epidemic in West Africa. Retrovirology[Internet]. 2010 Mar 22 [cited 2020 Dec 18];7:23.DOI: 10.1186/1742-4690-7-23. Available at:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855529/pdf/1742-4690-7-23.pdf

  36. Church JD, Huang W, Mwatha A, Toma J, Stawiski E,Donnell D, et al. HIV-1 tropism and survival in verticallyinfected Ugandan infants. J Infect Dis [Internet].2008 May 15 [cited 2020 Dec 18];197(10):1382–8.Available at: https://pdfs.semanticscholar.org/be30/beae653aaaea6cd4305dd42ae01d7232364d.pdf?_ga=2.8524978.60519488.1608083556-726339794.1548872336




2020     |     www.medigraphic.com