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Nucleic acid testing and molecular characterization of HIV infections

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Abstract

Significant advances have been made in the molecular assays used for the detection of human immunodeficiency virus (HIV), which are crucial in preventing HIV transmission and monitoring disease progression. Molecular assays for HIV diagnosis have now reached a high degree of specificity, sensitivity and reproducibility, and have less operator involvement to minimize risk of contamination. Furthermore, analyses have been developed for the characterization of host gene polymorphisms and host responses to better identify and monitor HIV-1 infections in the clinic. Currently, molecular technologies including HIV quantitative and qualitative assays are mainly based on the polymerase chain reaction (PCR), transcription-mediated amplification (TMA), nucleic acid sequence-based amplification (NASBA), and branched chain (b) DNA methods and widely used for HIV detection and characterization, such as blood screening, point-of-care testing (POCT), pediatric diagnosis, acute HIV infection (AHI), HIV drug resistance testing, antiretroviral (AR) susceptibility testing, host genome polymorphism testing, and host response analysis. This review summarizes the development and the potential utility of molecular assays used to detect and characterize HIV infections.

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References

  1. (2018) HIV/AIDS Fact sheets, http://www.who.int/en/news-room/fact-sheets/detail/hiv-aids

  2. UNAIDS DATA 2017 http://www.unaids.org/en/resources/documents/2017/2017_data_book

  3. Branson B, Owen SM, Bennett B, Werner BG, Pentella MA, Wesolowski LG (2014) Laboratory testing for the diagnosis of HIV infection: updated recommendations. Algorithms

  4. Earl LA, Lifson JD, Subramaniam S (2013) Catching HIV ‘in the act’ with 3D electron microscopy. Trends Microbiol 21(8):397–404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Viana IFT, Coelho DF, Palma ML, Nascimento EJM, Gu G, Lima LFO et al (2018) Detection of IgG3 antibodies specific to the human immunodeficiency virus type 1 (HIV-1) p24 protein as marker for recently acquired infection. Epidemiol Infect 146(10):1293–1300

    Article  CAS  PubMed  Google Scholar 

  6. Ou CY, Kwok S, Mitchell SW, Mack DH, Sninsky JJ, Krebs JW et al (1988) DNA amplification for direct detection of HIV-1 in DNA of peripheral blood mononuclear cells. Science 239(4837):295–297

    Article  CAS  PubMed  Google Scholar 

  7. Brauer M, De Villiers JC, Mayaphi SH (2013) Evaluation of the determine fourth generation HIV rapid assay. J Virol Methods 189(1):180–183

    Article  CAS  PubMed  Google Scholar 

  8. Ly TD, Laperche S, Brennan C, Vallari A, Ebel A, Hunt J et al (2004) Evaluation of the sensitivity and specificity of six HIV combined p24 antigen and antibody assays. J Virol Methods 122(2):185–194

    Article  CAS  PubMed  Google Scholar 

  9. Zhao Y, Gou Y, Li D, Wang T, Huang X, Shi M et al (2018) Performance evaluation of a new automated fourth-generation HIV Ag/Ab combination chemiluminescence immunoassay. Clin Chem Lab Med 56(5):e115–e117

    Article  CAS  PubMed  Google Scholar 

  10. Delaney KP, Wesolowski LG, Owen SM (2017) The evolution of HIV testing continues. Sex Transm Dis 44(12):747–749

    Article  PubMed  Google Scholar 

  11. (2018) Advantages and disadvantages of FDA-approved HIV assays used for screening, by test category, https://www.cdc.gov/hiv/pdf/testing/hiv-tests-advantages-disadvantages_1.pdf

  12. (2014) Laboratory testing for the diagnosis of hiv infection updated recommendations, https://stacks.cdc.gov/view/cdc/23447

  13. Branson BM, Stekler JD (2012) Detection of acute HIV infection: we can’t close the window. J Infect Dis 205(4):521–524

    Article  PubMed  Google Scholar 

  14. Weber B (2006) Screening of HIV infection: role of molecular and immunological assays. Expert Rev Mol Diagn 6(3):399–411

    Article  CAS  PubMed  Google Scholar 

  15. Galel SA, Simon TL, Williamson PC, AuBuchon JP, Waxman DA, Erickson Y et al (2018) Sensitivity and specificity of a new automated system for the detection of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus nucleic acid in blood and plasma donations. Transfusion 58(3):649–659

    Article  CAS  PubMed  Google Scholar 

  16. Pas S, Rossen JW, Schoener D, Thamke D, Pettersson A, Babiel R et al (2010) Performance evaluation of the new Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test version 2.0 for quantification of human immunodeficiency virus type 1 RNA. J Clin Microbiol 48(4):1195–1200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Schmidt M, Korn K, Nubling CM, Chudy M, Kress J, Horst HA et al (2009) First transmission of human immunodeficiency virus type 1 by a cellular blood product after mandatory nucleic acid screening in Germany. Transfusion 49(9):1836–1844

    Article  CAS  PubMed  Google Scholar 

  18. Müller B, Nübling CM, Kress J, Roth WK, De Zolt S, Pichl L (2013) How safe is safe: new human immunodeficiency virus type 1 variants missed by nucleic acid testing. Transfusion 53(10pt2):2422–2430

    Article  CAS  PubMed  Google Scholar 

  19. Complete list of donor screening assays for infectious agents and HIV diagnostic assays, https://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/BloodDonorScreening/InfectiousDisease/ucm080466.htm#HIV1_NucleicAcid_Assays

  20. Human immunodeficiency virus, type 1 (HIV-1) REVERSE TRANSCRIPTION (RT) polymerase chain reaction (PCR) assay, https://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/BloodDonorScreening/InfectiousDisease/ucm093501.htm

  21. UltraQual HIV-1 RT-PCR Assay, https://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/BloodDonorScreening/InfectiousDisease/ucm172937.htm

  22. COBAS AmpliScreen HIV-1 Test, https://www.fda.gov/downloads/BiologicsBloodVaccines/Blood-BloodProducts/ApprovedProducts/LicensedProductsBLAs/BloodDonorScreening/InfectiousDisease/UCM093531.pdf

  23. APTIMA HIV-1 RNA Qualitative Assay, https://www.fda.gov/downloads/BiologicsBloodVaccines-/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/BloodDonorScreening/InfectiousDisease/UCM149927.pdf

  24. Aptima HIV-1 Quant Assay, https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/PremarketApprovalsPMAs/UCM534609.pdf

  25. cobas HIV-1 Quantitative nucleic acid test for use on the cobas 6800/8800 Systems, https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/PremarketApprovalsPMAs/UCM478438.pdf

  26. Roche Amplicor HIV-1 Monitor Test, https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/PremarketApprovalsPMAs/UCM093317.pdf

  27. COBAS AmpliPrep/COBAS TaqMan HIV-1 Test, 48 Tests; COBAS AmpliPrep/COBAS TaqMan Wash Reagent, 5.1 L, https://www.fda.gov/downloads/ BiologicsBloodVaccines/BloodBloodProducts/Approv-edProducts/PremarketApprovalsPMAs/UCM092878.pdf

  28. Abbott RealTime HIV-1 Amplification Reagent Kit, Abbott RealTime HIV-1 Calibrator Kit, Abbott RealTime HIV-1 Control Kit, https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/PremarketApprovalsPMAs/UCM091193.pdf

  29. Gomes P, Palma AC, Cabanas J, Abecasis A, Carvalho AP, Ziermann R et al (2006) Comparison of the COBAS TAQMAN HIV-1 HPS with VERSANT HIV-1 RNA 3.0 assay (bDNA) for plasma RNA quantitation in different HIV-1 subtypes. J Virol Methods 135(2):223–228

    Article  CAS  PubMed  Google Scholar 

  30. VERSANT HIV-1 RNA 3.0 Assay (bDNA), https://www.fda.gov/downloads/BiologicsBloodVaccines-/BloodBloodProducts/ApprovedProducts/PremarketApprovalsPMAs/UCM091276.pdf

  31. Eshleman SH, John H, Priscilla S, Cunningham SP, Birgit D, Catherine B et al (2004) Performance of the Celera Diagnostics ViroSeq HIV-1 Genotyping System for sequence-based analysis of diverse human immunodeficiency virus type 1 strains. J Clin Microbiol 42(6):2711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. ViroSeq HIV-1 Genotyping System, https://www.molecular.abbott/us/en/products/infectious-disease/viroseq-hiv-1-genotyping-system

  33. Robert MG, Daniel RK, Victoria AJ, John WM, John LS, Ronald S et al (2003) Accuracy of the TRUGENE HIV-1 genotyping kit. J Clin Microbiol 41(4):1586

    Article  CAS  Google Scholar 

  34. COBAS TaqScreen MPX Test, https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloo-dProducts/ApprovedProducts/LicensedProductsBLAs/BloodDonorScreening/InfectiousDisease/UCM176443.pdf

  35. cobas TaqScreen MPX Test, version 2.0 for use with the cobas s 201 system, https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/BloodDonorScreening/InfectiousDisease/UCM427750.pdf

  36. cobas MPX Test, for use on the cobas 6800/8800 Systems, https://www.fda.gov/downloads/Biol-ogicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/BloodDonorScreening/InfectiousDisease/UCM614913.pdf

  37. Procleix Ultrio Assay, https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProd-ucts/ApprovedProducts/LicensedProductsBLAs/BloodDonorScreening/InfectiousDisease/UCM335285.pdf

  38. Procleix Ultrio Plus Assays, https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBlood-Products/ApprovedProducts/LicensedProductsBLAs/BloodDonorScreening/InfectiousDisease/UCM092120.pdf

  39. Procleix Ultrio Elite Assay, https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBlood-Products/ApprovedProducts/LicensedProductsBLAs/BloodDonorScreening/InfectiousDisease/UCM606730.pdf

  40. NGI UltraQual Multiplex PCR Assay for HCV, HIV-1, HIV-2 and HBV, https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/BloodDonorScreening/InfectiousDisease/UCM609997.pdf

  41. Bourlet T, Memmi M, Saoudin H, Pozzetto B (2013) Molecular HIV screening. Expert Rev Mol Diagn 13(7):693–705

    Article  CAS  PubMed  Google Scholar 

  42. Stevens WS, Noble L, Berrie L, Sarang S, Scott LE (2009) Ultra-high-throughput, automated nucleic acid detection of human immunodeficiency virus (HIV) for infant infection diagnosis using the Gen-Probe Aptima HIV-1 screening assay. J Clin Microbiol 47(8):2465–2469

    Article  PubMed  PubMed Central  Google Scholar 

  43. Simonds RJ, Brown TM, Thea DM, Orloff SL, Steketee RW, Lee FK et al (1998) Sensitivity and specificity of a qualitative RNA detection assay to diagnose HIV infection in young infants. Perinatal AIDS Collaborative Transmission Study. Aids 12(12):1545–1549

    Article  CAS  PubMed  Google Scholar 

  44. Dubrow R, Qin L, Lin H, Hernandez-Ramirez RU, Neugebauer RS, Leyden W et al (2017) Association of CD4+ T-cell count, HIV-1 RNA viral load, and antiretroviral therapy with Kaposi sarcoma risk among HIV-infected persons in the United States and Canada. J Acquir Immune Defic Syndr 75(4):382–390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. May MT, Gompels M, Delpech V, Porter K, Orkin C, Kegg S et al (2014) Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy. Aids 28(8):1193–1202

    Article  PubMed  Google Scholar 

  46. Mellors JW, Rinaldo CR Jr, Gupta P, White RM, Todd JA, Kingsley LA (1996) Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science 272(5265):1167–1170

    Article  CAS  PubMed  Google Scholar 

  47. Cozzi LA, Katzenstein TL, Ullum H, Phillips AN, Skinhøj P, Gerstoft J et al (1998) The relative prognostic value of plasma HIV RNA levels and CD4 lymphocyte counts in advanced HIV infection. Aids 12(13):1639–1643

    Article  Google Scholar 

  48. Abbott MA, Poiesz BJ, Byrne BC, Kwok S, Sninsky JJ, Ehrlich GD (1988) Enzymatic gene amplification: qualitative and quantitative methods for detecting proviral DNA amplified in vitro. J Infect Dis 158(6):1158–1169

    Article  CAS  PubMed  Google Scholar 

  49. Malek L, Sooknanan R, Compton J (1994) Nucleic acid sequence-based amplification (NASBA). Methods Mol Biol 28(28):253

    CAS  PubMed  Google Scholar 

  50. Horn T, Chang CA, Urdea MS (1997) Chemical synthesis and characterization of branched oligodeoxyribonucleotides (bDNA) for use as signal amplifiers in nucleic acid quantification assays. Nucleic Acids Res 25(23):4842–4849

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Sloma CR, Germer JJ, Gerads TM, Mandrekar JN, Mitchell PS, Yao JD (2009) Comparison of the Abbott realtime human immunodeficiency virus type 1 (HIV-1) assay to the Cobas AmpliPrep/Cobas TaqMan HIV-1 test: workflow, reliability, and direct costs. J Clin Microbiol 47(4):889–895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Schumacher W, Frick E, Kauselmann M, Maier-Hoyle V, van der Vliet R, Babiel R (2007) Fully automated quantification of human immunodeficiency virus (HIV) type 1 RNA in human plasma by the COBAS AmpliPrep/COBAS TaqMan system. J Clin Virol 38(4):304–312

    Article  CAS  PubMed  Google Scholar 

  53. Korn K, Weissbrich B, Henke-Gendo C, Heim A, Jauer CM, Taylor N et al (2009) Single-point mutations causing more than 100-fold underestimation of human immunodeficiency virus type 1 (HIV-1) load with the Cobas TaqMan HIV-1 real-time PCR assay. J Clin Microbiol 47(4):1238–1240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Tung YC, Ke LY, Lu PL, Lin KH, Lee SC, Lin YY et al (2015) Comparison of the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 test V1.0 with V2.0 in HIV-1 viral load quantification. Kaohsiung J Med Sci 31(4):188–193

    Article  PubMed  Google Scholar 

  55. Mourez T, Delaugerre C, Vray M, Lemee V, Simon F, Plantier JC (2015) Comparison of the bioMerieux NucliSENS EasyQ HIV-1 V2.0-HIV-1 RNA quantification assay versus Abbott RealTime HIV-1 and Roche Cobas TaqMan HIV-1 V2.0 on current epidemic HIV-1 variants. J Clin Virol 71:76–81

    Article  CAS  PubMed  Google Scholar 

  56. Manak MM, Hack HR, Nair SV, Worlock A, Malia JA, Peel SA et al (2016) Evaluation of Hologic Aptima HIV-1 Quant Dx assay on the Panther System on HIV subtypes. J Clin Microbiol 54(10):2575–2581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Loetscher P (2017) Performance evaluation of Cobas® HIV-1, a quantitative nucleic acid test for use on the Cobas® 6800/8800 systems. Journal of HIV and AIDS 3(1)

  58. Wiesmann F, Ehret R, Naeth G, Daumer M, Fuhrmann J, Kaiser R et al (2018) Multicenter evaluation of two next-generation HIV-1 quantitation assays, Aptima Quant Dx and Cobas 6800, in comparison to the RealTime HIV-1 reference assay. J Clin Microbiol 56(10)

  59. Elbeik T, Loftus RA, Beringer S (2014) Health care industries perspective of viral load assays: the VERSANT HIV-1 RNA 3.0 assay. Expert Rev Mol Diagn 2(3):275–285

    Article  Google Scholar 

  60. Zhang L, Jin C, Jiang Z, Tang T, Jiang Y, Pan PL (2017) Comparison of commercial HIV-1 viral load tests by using proficiency test results in China, 2013–2015. Zhonghua Liu Xing Bing Xue Za Zhi 38(9):1231–1235

    CAS  PubMed  Google Scholar 

  61. Baumeister MA, Zhang N, Beas H, Brooks JR, Canchola JA, Cosenza C et al (2012) A sensitive branched DNA HIV-1 signal amplification viral load assay with single day turnaround. PLoS One 7(3):e33295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Xu S, Song A, Nie J, Li X, Wang Y (2010) Performance of NucliSens HIV-1 EasyQ Version 2.0 compared with six commercially available quantitative nucleic acid assays for detection of HIV-1 in China. Mol Diagn Ther 14(5):305

    Article  CAS  PubMed  Google Scholar 

  63. (2016) BioMerieux SA alerts customers about potential inaccurate test results when using NucliSENS® easyMAG® magnetic silica for nucleic acid extraction, https://www.fda.gov/MedicalDevice-s/Safety/ListofRecalls/ucm516437.htm

  64. Roth WK, Weber M, Seifried E (1999) Feasibility and efficacy of routine PCR screening of blood donations for hepatitis C virus, hepatitis B virus, and HIV-1 in a blood-bank setting. Lancet 353(9150):359

    Article  CAS  PubMed  Google Scholar 

  65. Susan AF, Takesha M, Julie AEN, William CM (2013) Validation of the gen-probe Aptima qualitative HIV-1 RNA assay for diagnosis of human immunodeficiency virus infection in infants. J Clin Microbiol 51(12):4137–4140

    Article  CAS  Google Scholar 

  66. Lelie PN, van Drimmelen HA, Cuypers HT, Best SJ, Stramer SL, Hyland C et al (2010) Sensitivity of HCV RNA and HIV RNA blood screening assays. Transfusion 42(5):527–536

    Article  Google Scholar 

  67. (2010) WHO Guidelines Approved by the Guidelines Review Committee. WHO Recommendations on the Diagnosis of HIV Infection in Infants and Children. World Health Organization World Health Organization., Geneva

  68. Hamlyn E, Jones V, Porter K, Fidler S (2010) Antiretroviral treatment of primary HIV infection to reduce onward transmission. Curr Opin HIV AIDS 5(4):283–290

    Article  PubMed  Google Scholar 

  69. Dodd RY (2015) Transfusion-transmitted infections: testing strategies and residual risk. Isbt Science 9(1):1–5

    Google Scholar 

  70. Shyamala V (2015) Nucleic acid technology (NAT) testing for blood screening: impact of individual donation and Mini Pool-NAT testing on analytical sensitivity, screening sensitivity and clinical sensitivity. Isbt Science 9(2):315–324

    Article  CAS  Google Scholar 

  71. Van Laethem K, Beuselinck K, Van Dooren S, De Clercq E, Desmyter J, Vandamme AM (1998) Diagnosis of human immunodeficiency virus infection by a polymerase chain reaction assay evaluated in patients harbouring strains of diverse geographical origin. J Virol Methods 70(2):153–166

    Article  PubMed  Google Scholar 

  72. Chudy M, Weber-Schehl M, Pichl L, Jork C, Kress J, Heiden M et al (2012) Blood screening nucleic acid amplification tests for human immunodeficiency virus type 1 may require two different amplification targets. Transfusion 52(2):431–439

    Article  CAS  PubMed  Google Scholar 

  73. Margaritis AR, Brown SM, Seed CR, Kiely P, D'Agostino B, Keller AJ (2007) Comparison of two automated nucleic acid testing systems for simultaneous detection of human immunodeficiency virus and hepatitis C virus RNA and hepatitis B virus DNA. Transfusion 47(10):1783–1793

    Article  CAS  PubMed  Google Scholar 

  74. Assal A, Barlet V, Deschaseaux M, Dupont I, Gallian P, Guitton C et al (2009) Comparison of the analytical and operational performance of two viral nucleic acid test blood screening systems: Procleix Tigris and cobas s 201. Transfusion 49(2):289–300

    Article  PubMed  Google Scholar 

  75. Assal A, Barlet V, Deschaseaux M, Dupont I, Gallian P, Guitton C et al (2009) Sensitivity of two hepatitis B virus, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) nucleic acid test systems relative to hepatitis B surface antigen, anti-HCV, anti-HIV, and p24/anti-HIV combination assays in seroconversion panels. Transfusion 49(2):301–310

    Article  PubMed  Google Scholar 

  76. Grabarczyk P, van Drimmelen H, Kopacz A, Gdowska J, Liszewski G, Piotrowski D et al (2013) Head-to-head comparison of two transcription-mediated amplification assay versions for detection of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus type 1 in blood donors. Transfusion 53(10 Pt 2):2512–2524

    Article  CAS  PubMed  Google Scholar 

  77. Grabarczyk P, Koppelman M, Boland F, Sauleda S, Fabra C, Cambie G et al (2015) Inclusion of human immunodeficiency virus type 2 (HIV-2) in a multiplex transcription-mediated amplification assay does not affect detection of HIV-1 and hepatitis B and C virus genotypes: a multicenter performance evaluation study. Transfusion 55(9):2246–2255

    Article  CAS  PubMed  Google Scholar 

  78. Heim A (2016) Evaluation of the Procleix Ultrio Elite Assay and the Panther-System for individual NAT screening of blood, hematopoietic stem cell, tissue and organ donors. Transfus Med Hemother 43(3):177–182

    Article  PubMed  PubMed Central  Google Scholar 

  79. Le Corfec E, Le Pont F, Tuckwell HC, Rouzioux C, Costagliola D (1999) Direct HIV testing in blood donations: variation of the yield with detection threshold and pool size. Transfusion 39(10):1141–1144

    Article  PubMed  Google Scholar 

  80. Ha J, Park Y, Kim HS (2017) Evaluation of clinical sensitivity and specificity of hepatitis B virus (HBV), hepatitis C virus, and human immunodeficiency Virus-1 by cobas MPX: detection of occult HBV infection in an HBV-endemic area. J Clin Virol 96:60–63

    Article  CAS  PubMed  Google Scholar 

  81. Migueles SA, Connors M (2010) Long-term nonprogressive disease among untreated HIV-infected individuals: clinical implications of understanding immune control of HIV. Jama 304(2):194–201

    Article  CAS  PubMed  Google Scholar 

  82. Mendoza D, Johnson SA, Peterson BA, Natarajan V, Salgado M, Dewar RL et al (2012) Comprehensive analysis of unique cases with extraordinary control over HIV replication. Blood 119(20):4645–4655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Cock KMD, Fowler MG, Mercier E, Vincenzi ID, Saba J, Hoff E et al (2000) Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice. Jama 283(9):1175–1182

    Article  PubMed  Google Scholar 

  84. Luzuriaga K, Mofenson LM (2016) Challenges in the elimination of pediatric HIV-1 infection. N Engl J Med 374(8):761–770

    Article  CAS  PubMed  Google Scholar 

  85. Canals F, Masia M, Gutierrez F (2018) Developments in early diagnosis and therapy of HIV infection in newborns. Expert Opin Pharmacother 19(1):13–25

    Article  PubMed  Google Scholar 

  86. Stevens W, Sherman G, Downing R, Parsons LM, Ou CY, Crowley S et al (2008) Role of the laboratory in ensuring global access to ARV treatment for HIV-infected children: consensus statement on the performance of laboratory assays for early infant diagnosis. Open AIDS J 2:17–25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Ou C-Y, Fiscus S, Ellenberger D, Parekh B, Korhonen C, Nkengasong J et al (2012) Early diagnosis of HIV infection in the breastfed infant. Adv Exp Med Biol 743(743):51–65

    Article  PubMed  Google Scholar 

  88. Pierce VM, Neide B, Hodinka RL (2011) Evaluation of the Gen-Probe Aptima HIV-1 RNA qualitative assay as an alternative to Western blot analysis for confirmation of HIV infection. J Clin Microbiol 49(4):1642–1645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Alvarez P, Prieto L, Martin L, Obiang J, Avedillo P, Vargas A et al (2017) Evaluation of four commercial virological assays for early infant HIV-1 diagnosis using dried blood specimens. Pediatr Res 81(1–1):80–87

    Article  PubMed  Google Scholar 

  90. Ceffa S, Luhanga R, Andreotti M, Brambilla D, Erba F, Jere H et al (2016) Comparison of the Cepheid GeneXpert and Abbott M2000 HIV-1 real time molecular assays for monitoring HIV-1 viral load and detecting HIV-1 infection. J Virol Methods 229:35–39

    Article  CAS  PubMed  Google Scholar 

  91. Hsiao NY, Dunning L, Kroon M, Myer L (2016) Laboratory evaluation of the Alere q point-of-care system for early infant HIV diagnosis. PLoS One 11(3):e0152672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Koopman JS, Jacquez JA, Welch GW, Simon CP, Foxman B, Pollock SM et al (1997) The role of early HIV infection in the spread of HIV through populations. J Acquir Immune Defic Syndr Hum Retrovirol 14(3):249–258

    Article  CAS  PubMed  Google Scholar 

  93. Brenner BG, Roger M, Routy JP, Moisi D, Ntemgwa M, Matte C et al (2007) High rates of forward transmission events after acute/early HIV-1 infection. J Infect Dis 195(7):951–959

    Article  CAS  PubMed  Google Scholar 

  94. Bassett IV, Chetty S, Giddy J, Reddy S, Bishop K, Lu Z et al (2015) Screening for acute HIV infection in South Africa: finding acute and chronic disease. HIV Med 12(1):46–53

    Article  Google Scholar 

  95. Martin EG, Salaru G, Mohammed D, Coombs RW, Paul SM, Cadoff EM (2013) Finding those at risk: acute HIV infection in Newark, NJ. J Clin Virol 58:E24–E28

    Article  PubMed  PubMed Central  Google Scholar 

  96. Emerson B, Plough K (2013) Detection of acute HIV-1 infections utilizing NAAT technology in Dallas, Texas. J Clin Virol 58(Suppl 1):e48–e53

    Article  PubMed  Google Scholar 

  97. Drancourt M, Michellepage A, Boyer S, Raoult D (2016) The point-of-care laboratory in clinical microbiology. Clin Microbiol Rev 29(3):429

    Article  PubMed  PubMed Central  Google Scholar 

  98. Engel N, Pant PN (2015) Qualitative research on point-of-care testing strategies and programs for HIV. Expert Rev Mol Diagn 15(1):71

    Article  CAS  PubMed  Google Scholar 

  99. Chang M, Steinmetzer K, Raugi DN, Smith RA, Ba S, Sall F et al (2017) Detection and differentiation of HIV-2 using the point-of-care Alere q HIV-1/2 detect nucleic acid test. J Clin Virol 97:22–25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Jani IV, Meggi B, Vubil A, Sitoe NE, Bhatt N, Tobaiwa O et al (2016) Evaluation of the whole-blood Alere Q NAT point-of-care RNA assay for HIV-1 viral load monitoring in a primary health care setting in Mozambique. J Clin Microbiol 54(8):2104–2108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Scott L, Gous N, Carmona S, Stevens W (2015) Laboratory evaluation of the Liat HIV Quant (IQuum) whole-blood and plasma HIV-1 viral load assays for point-of-care testing in South Africa. J Clin Microbiol 53(5):1616–1621

    Article  PubMed  PubMed Central  Google Scholar 

  102. Murtagh M (2013) HIV / AIDS diagnostic technology landscape. 3rd edition

  103. Pironti A, Walter H, Pfeifer N, Knops E, Lübke N, Büch J et al (2017) Determination of phenotypic resistance cutoffs from routine clinical data. J Acquir Immune Defic Syndr 74(5):e129–e137

    Article  PubMed  PubMed Central  Google Scholar 

  104. Tsai HC, Chen IT, Lee SS, Chen YS (2018) HIV-1 genotypic drug resistance in patients with virological failure to single-tablet antiretroviral regimens in southern Taiwan. Infection & Drug Resistance 11:1061

    Article  Google Scholar 

  105. Mayers DL, Baxter JD (2017) Clinical implications of HIV-1 drug resistance. In: Mayers DL, Sobel JD, Ouellette M, Kaye KS, Marchaim D (eds) Antimicrobial drug resistance: clinical and epidemiological aspects, Volume 2. Springer International Publishing, Cham, pp 1213–1225

  106. Pattery T, Verlinden Y, De Wolf H, Nauwelaers D, Van Baelen K, Van Houtte M et al (2012) Development and performance of conventional HIV-1 phenotyping (Antivirogram(R)) and genotype-based calculated phenotyping assay (virco(R)TYPE HIV-1) on protease and reverse transcriptase genes to evaluate drug resistance. Intervirology 55(2):138–146

    Article  CAS  PubMed  Google Scholar 

  107. Cahn P, Pozniak AL, Mingrone H, Shuldyakov A, Brites C, Andrade-Villanueva JF et al (2013) Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet 382(9893):700–708

    Article  CAS  PubMed  Google Scholar 

  108. Westen GJPV, Hendriks A, Wegner JK, Ijzerman AP, Vlijmen HWTV, Bender A (2013) Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. PLoS Comput Biol 9(2(2013-2-21)):e1002899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Mohamed S, Penaranda G, Gonzalez D, Camus C, Khiri H, Boulmé R et al (2014) Clinical impact of ultra deep versus Sanger sequencing detection of minority mutations on HIV-1 drug resistance genotype interpretation after virological failure. Aids 14(S2):1–1

    Google Scholar 

  110. Mekue MLC, Hélène P, Angélique NM, Donato K, Dieu LJD, François-Xavier MK et al (2015) LETTER TO THE EDITOR Performance of the ViroSeq® HIV-1 genotyping system V2.0 in Central Africa. Open Aids Journal 9(1):9–13

    Article  Google Scholar 

  111. Paraschiv S, Otelea D, Baicus C, Tinischi M, Costache M, Neaga E (2009) Nucleoside reverse transcriptase inhibitor resistance mutations in subtype F1 strains isolated from heavily treated adolescents in Romania. Int J Infect Dis 13(1):81–89

    Article  CAS  PubMed  Google Scholar 

  112. Stelzl E, Proll J, Bizon B, Niklas N, Danzer M, Hackl C et al (2011) Human immunodeficiency virus type 1 drug resistance testing: evaluation of a new ultra-deep sequencing-based protocol and comparison with the TRUGENE HIV-1 genotyping kit. J Virol Methods 178(1–2):94–97

    Article  CAS  PubMed  Google Scholar 

  113. Duarte HA, Panpradist N, Beck IA, Lutz B, Lai J, Kanthula RM et al (2017) Current status of point-of-care testing for human immunodeficiency virus drug resistance. J Infect Dis 216(suppl_9):S824–s828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Metzner KJ, Rauch P, Braun P, Knechten H, Ehret R, Korn K et al (2011) Prevalence of key resistance mutations K65R, K103N, and M184V as minority HIV-1 variants in chronically HIV-1 infected, treatment-naive patients. J Clin Virol 50(2):156–161

    Article  CAS  PubMed  Google Scholar 

  115. Grant RM, Liegler T, Defechereux P, Kashuba AD, Taylor D, Abdelmohsen M et al (2015) Drug resistance and plasma viral RNA level after ineffective use of oral pre-exposure prophylaxis in women. Aids 29(3):331

    Article  CAS  PubMed  Google Scholar 

  116. Zhang G, Cai F, de Rivera IL, Zhou Z, Zhang J, Nkengasong J et al (2016) Simultaneous detection of major drug resistance mutations of HIV-1 subtype B viruses from dried blood spot specimens by multiplex allele-specific assay. J Clin Microbiol 54(1):220–222

    Article  CAS  PubMed  Google Scholar 

  117. Clutter DS, Rojas Sanchez P, Rhee SY, Shafer RW (2016) Genetic variability of HIV-1 for drug resistance assay development. Viruses 8(2)

  118. Quinones-Mateu ME, Avila S, Reyes-Teran G, Martinez MA (2014) Deep sequencing: becoming a critical tool in clinical virology. J Clin Virol 61(1):9–19

    Article  PubMed  PubMed Central  Google Scholar 

  119. Thiam M, Diop-Ndiaye H, Kebe K, Vidal N, Diakhate-Lô R, Diouara AA et al (2013) Performance of the ViroSeq HIV-1 genotyping system V2.0 on HIV-1 strains circulating in Senegal. J Virol Methods 188(1–2):97–103

    Article  CAS  PubMed  Google Scholar 

  120. Van Laethem K, Theys K, Vandamme AM (2015) HIV-1 genotypic drug resistance testing: digging deep, reaching wide? Curr Opin Virol 14:16–23

    Article  CAS  PubMed  Google Scholar 

  121. Johnson EO, Hancock DB, Gaddis NC, Levy JL, Page G, Novak SP et al (2015) Novel genetic locus implicated for HIV-1 acquisition with putative regulatory links to HIV replication and infectivity: a genome-wide association study. PLoS One 10(3):e0118149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. McLaren PJ, Pulit SL, Gurdasani D, Bartha I, Shea PR, Pomilla C et al (2017) Evaluating the impact of functional genetic variation on HIV-1 control. J Infect Dis 216(9):1063–1069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Skerlj RT, Bridger GJ, Kaller A, Mceachern EJ, Crawford JB, Zhou Y et al (2010) Discovery of novel small molecule orally bioavailable C-X-C chemokine receptor 4 antagonists that are potent inhibitors of T-tropic (X4) HIV-1 replication. J Med Chem 53(8):3376–3388

    Article  CAS  PubMed  Google Scholar 

  124. Tsukamoto T (2018) Transcriptional gene silencing limits CXCR4-associated depletion of bone marrow CD34+ cells in HIV-1 infection. Aids 32(13):1737–1747

    Article  CAS  PubMed  Google Scholar 

  125. Liu Z, Chen S, Jin X, Wang Q, Yang K, Li C et al (2017) Genome editing of the HIV co-receptors CCR5 and CXCR4 by CRISPR-Cas9 protects CD4 + T cells from HIV-1 infection. Cell Biosci 7(1):47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. D'Antoni ML, Paul RH, Mitchell BI, Kohorn L, Fischer L, Lefebvre E et al (2018) Improved cognitive performance and reduced monocyte activation in virally suppressed chronic HIV following dual CCR2 and CCR5 antagonism. J Acquir Immune Defic Syndr 79(1):1

    Article  CAS  Google Scholar 

  127. Ioannidis JPA, Rosenberg PS, Goedert JJ, Ashton LJ, Benfield TL, Buchbinder SP et al (2001) Effects of CCR5-Δ 32, CCR2-64I, and SDF-1 3′a alleles on HIV-1 disease progression: an international meta-analysis of individual-patient data. Ann Intern Med 135(9):782–795

    Article  CAS  PubMed  Google Scholar 

  128. Verheyen J, Thielen A, Lübke N, Dirks M, Widera M, Dittmer U, et al (2018) Rapid rebound of a preexisting CXCR4-tropic HIV variant after allogeneic transplantation with CCR5 delta32 homozygous stem cells. Clinical Infectious Diseases An Official Publication of the Infectious Diseases Society of America

  129. Mori M, Wichukchinda N, Miyahara R, Rojanawiwat A, Pathipvanich P, Maekawa T et al (2014) HLA-B*35: 05 is a protective allele with a unique structure among HIV-1 CRF01_AE-infected Thais, in whom the B*57 frequency is low. Aids 28(7):959–967

    Article  CAS  PubMed  Google Scholar 

  130. Ragoussis J (2009) Genotyping technologies for genetic research. Annu Rev Genomics Hum Genet 10(1):117–133

    Article  CAS  PubMed  Google Scholar 

  131. Dumoulin A, Hirsch HH (2011) Reevaluating and optimizing polyomavirus BK and JC real-time PCR assays to detect rare sequence polymorphisms. J Clin Microbiol 49(4):1382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Komninakis S, Fukumori L, Alcalde R, Cortina M, Abdala L, Brito A et al (2007) Techniques used to identify the Brazilian variant of HIV-1 subtype B. Braz J Med Biol Res 40(3):301

    Article  CAS  PubMed  Google Scholar 

  133. Devadas K, Biswas S, Haleyurgirisetty M, Wood O, Ragupathy V, Lee S et al (2016) Analysis of host gene expression profile in HIV-1 and HIV-2 infected T-cells. PLoS One 11(1):e0147421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Lynch HE, Sempowski GD (2013) Molecular measurement of T cell receptor excision circles. Methods Mol Biol 979(979):147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Julia D, Nienke V, Tendai M, Bregje DBA, Otto SA, Hazenberg MD et al (2016) Reconciling longitudinal naive T-cell and TREC dynamics during HIV-1 infection. PLoS One 11(3):e0152513

    Article  CAS  Google Scholar 

  136. Touloumi G, Pantazis N, Karafoulidou A, Mandalaki T, Goedert JJ, Kostrikis LG et al (2004) Changes in T cell receptor excision DNA circle (TREC) levels in HIV type 1-infected subjects pre- and post-highly active antiretroviral therapy. Aids Research & Human Retroviruses 20(1):47–54

    Article  CAS  Google Scholar 

  137. Vogelstein B, Kinzler KW (1999) Digital PCR. Proc Natl Acad Sci U S A 96(16):9236–9241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Jones RB, Mueller S, O'Connor R, Rimpel K, Sloan DD, Karel D et al (2016) A subset of latency-reversing agents expose HIV-infected resting CD4+ T-cells to recognition by cytotoxic T-lymphocytes. PLoS Pathog 12(4):e1005545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Yucha RW, Hobbs KS, Hanhauser E, Hogan LE, Nieves W, Ozen MO et al (2017) High-throughput characterization of HIV-1 reservoir reactivation using a single-cell-in-droplet PCR assay. Ebiomedicine 20(C):217–229

    Article  PubMed  PubMed Central  Google Scholar 

  140. Hancock G, Morónlópez S, Kopycinski J, Puertas MC, Giannoulatou E, Rose A et al (2017) Evaluation of the immunogenicity and impact on the latent HIV-1 reservoir of a conserved region vaccine, MVA.HIVconsv, in antiretroviral therapy-treated subjects. Journal of the International Aids Society 20(1):1

    Article  Google Scholar 

  141. Mothe B, Climent N, Plana M, Rosà M, Luis J, Nez J et al (2015) Safety and immunogenicity of a modified vaccinia Ankara-based HIV-1 vaccine (MVA-B) in HIV-1-infected patients alone or in combination with a drug to reactivate latent HIV-1. J Antimicrob Chemother 70(6):1833–1842

    CAS  PubMed  Google Scholar 

  142. Goo L, Jalalianlechak Z, Richardson BA, Overbaugh J (2012) A combination of broadly neutralizing HIV-1 monoclonal antibodies targeting distinct epitopes effectively neutralizes variants found in early infection. J Virol 86(19):10857–10861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Mccoy LE, Weiss RA (2013) Neutralizing antibodies to HIV-1 induced by immunization. J Exp Med 210(2):209–223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Stahl T, Böhme MU, Kröger N, Fehse B (2015) Digital PCR to assess hematopoietic chimerism after allogeneic stem cell transplantation. Exp Hematol 43(6):462–468.e461

    Article  CAS  PubMed  Google Scholar 

  145. Rosas-Umbert M, Mothe B, Noguera-Julian M, Bellido R, Puertas MC, Carrillo J et al (2017) Virological and immunological outcome of treatment interruption in HIV-1-infected subjects vaccinated with MVA-B. PLoS One 12(9):e0184929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Maria JB, Enrique M-G, Florencia P, Zhengyu O, Hong S, Jonathan ZL et al (2014) Long-term antiretroviral treatment initiated at primary HIV-1 infection affects the size, composition, and decay kinetics of the reservoir of HIV-1-infected CD4 T cells. J Virol 88(17):10056–10065

    Article  CAS  Google Scholar 

  147. Chaillon A, Gianella S, Lada SM, Perez-Santiago J, Jordan P, Ignacio C et al (2017) Size, composition, and evolution of HIV DNA populations during early antiretroviral therapy and intensification with Maraviroc. J Virol 92(3):JVI.01589–JVI.01517

    Article  Google Scholar 

  148. Bosman KJ, Nijhuis M, van Ham PM, Wensing AM, Vervisch K, Vandekerckhove L et al (2015) Comparison of digital PCR platforms and semi-nested qPCR as a tool to determine the size of the HIV reservoir. Sci Rep 5(2):13811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Rutsaert S, Bosman K, Trypsteen W, Nijhuis M, Vandekerckhove L (2018) Digital PCR as a tool to measure HIV persistence. Retrovirology 15(1):16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Strain MC, Lada SM, Luong T, Rought SE, Gianella S, Terry VH et al (2013) Highly precise measurement of HIV DNA by droplet digital PCR. PLoS One 8(4):e55943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Henrich TJ, Gallien S, Li JZ, Pereyra F, Kuritzkes DR (2012) Low-level detection and quantitation of cellular HIV-1 DNA and 2-LTR circles using droplet digital PCR. J Virol Methods 186(1–2):68–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Ho Y, Shan L, Hosmane Nina N, Wang J, Laskey Sarah B, Rosenbloom Daniel IS et al (2013) Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure. Cell 155(3):540–551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Samson M, Labbe O, Mollereau C, Vassart G, Parmentier M (1996) Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry 35(11):3362–3367

    Article  CAS  PubMed  Google Scholar 

  154. Hutter G, Nowak D, Mossner M, Ganepola S, Mussig A, Allers K et al (2009) Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med 360(7):692–698

    Article  PubMed  Google Scholar 

  155. Soriano V (2017) Hot news: gene therapy with CRISPR/Cas9 coming to age for HIV cure. AIDS Rev 19(3):167–172

    PubMed  Google Scholar 

  156. Zulfiqar HF, Javed A, Sumbal, Afroze B, Ali Q, Akbar K et al (2017) HIV diagnosis and treatment through advanced technologies. Front Public Health 5:32

    Article  PubMed  PubMed Central  Google Scholar 

  157. Zhu W, Lei R, Duff YL, Li J, Guo F, Wainberg MA et al (2015) The CRISPR/Cas9 system inactivates latent HIV-1 proviral DNA. Retrovirology 12(1):22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Wang Z, Pan Q, Gendron P, Zhu W, Guo F, Cen S et al (2016) CRISPR/Cas9-derived mutations both inhibit HIV-1 replication and accelerate viral escape. Cell Rep 15(3):481–489

    Article  CAS  PubMed  Google Scholar 

  159. Hütter G, Bodor J, Ledger S, Boyd M, Millington M, Tsie M et al (2015) CCR5 targeted cell therapy for HIV and prevention of viral escape. Viruses 7(8):4186–4203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Zhao, J., Chang, L. & Wang, L. Nucleic acid testing and molecular characterization of HIV infections. Eur J Clin Microbiol Infect Dis 38, 829–842 (2019). https://doi.org/10.1007/s10096-019-03515-0

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