Skip to main content
SpringerLink
Log in

Molecular Diagnosis of HIV-1 Infections: Current State of the Art

  • Chapter
  • First Online:
Advanced Techniques in Diagnostic Microbiology

  • 4467 Accesses

Abstract

In the management of HIV infections, laboratorians or clinical microbiologists determine whether a patient is infected with HIV, evaluate the status of the HIV infection, and monitor antiretroviral therapy. Theoretically, an HIV infection can be diagnosed and monitored by any of five possible ways: (1) direct microscopic examination such as visualization of an HIV virion by electronic microscopy, (2) cultivation and identification of HIV by suspension lymphocyte culture, (3) detection of HIV viral antigens, (4) measurement of HIV-specific immune responses, and (5) detection and quantification of HIV-specific nucleic acids [1, 2]. Practically speaking, the diagnosis and monitoring of HIV infection is done by serologic and molecular methods. Molecular methods were first used by Ou et al. from the US Centers for Disease Control and Prevention in 1988 to directly amplify HIV-1 specific nucleic acids from peripheral blood mononuclear cells of HIV-1 seropositive individuals [3]. In this sentinel article, the authors concluded that “the method may therefore be used to complement or replace virus isolation as a routine means of determining HIV-1 infection [3].” This has certainly proven to be correct.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Tang YW, Persing DH (2009) Diagnostic microbiology. In: Schaechter M (ed) Encyclopedia of microbiology, 3rd edn. Elsevier, Oxford, pp 308–320

    Chapter  Google Scholar 

  2. Branson BM (2007) State of the art for diagnosis of HIV infection. Clin Infect Dis 45(Suppl 4):S221–S225

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  4. Owens DK, Holodniy M, McDonald TW, Scott J, Sonnad S (1996) A meta-analytic evaluation of the polymerase chain reaction for the diagnosis of HIV infection in infants. JAMA 275(17):1342–1348

    Article  PubMed  CAS  Google Scholar 

  5. 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  Google Scholar 

  6. Novitsky V, Gaolathe T, Woldegabriel E, Makhema J, Essex M (2007) A seronegative case of HIV-1 subtype C infection in Botswana. Clin Infect Dis 45(5):e68–e71

    Article  PubMed  CAS  Google Scholar 

  7. Sullivan PS, Schable C, Koch W et al (1999) Persistently negative HIV-1 antibody enzyme immunoassay screening results for patients with HIV-1 infection and AIDS: serologic, clinical, and virologic results. Seronegative AIDS Clinical Study Group. Aids 13(1):89–96

    Article  PubMed  CAS  Google Scholar 

  8. Fiebig EW, Wright DJ, Rawal BD et al (2003) Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection. AIDS 17(13):1871–1879

    Article  PubMed  Google Scholar 

  9. Giachetti C, Linnen JM, Kolk DP et al (2002) Highly sensitive multiplex assay for detection of human immunodeficiency virus type 1 and hepatitis C virus RNA. J Clin Microbiol 40(7):2408–2419

    Article  PubMed  CAS  Google Scholar 

  10. 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  PubMed  CAS  Google Scholar 

  11. Ren A, Louie B, Rauch L et al (2008) Screening and confirmation of human immunodeficiency virus type 1 infection solely by detection of RNA. J Med Microbiol 57(Pt 10):1228–1233

    Article  PubMed  Google Scholar 

  12. Kerr RJ, Player G, Fiscus SA, Nelson JA (2009) Qualitative human immunodeficiency virus RNA analysis of dried blood spots for diagnosis of infections in infants. J Clin Microbiol 47(1):220–222

    Article  PubMed  CAS  Google Scholar 

  13. Pilcher CD, McPherson JT, Leone PA et al (2002) Real-time, universal screening for acute HIV infection in a routine HIV counseling and testing population. JAMA 288(2):216–221

    Article  PubMed  Google Scholar 

  14. Ethridge SF, Hart C, Hanson DL et al (2010) Performance of the Aptima HIV-1 RNA qualitative assay with 16- and 32-member specimen pools. J Clin Microbiol 48(9):3343–3345

    Article  PubMed  Google Scholar 

  15. Stramer SL, Glynn SA, Kleinman SH et al (2004) Detection of HIV-1 and HCV infections among antibody-negative blood donors by nucleic acid-amplification testing. N Engl J Med 351(8):760–768

    Article  PubMed  CAS  Google Scholar 

  16. Nugent CT, Dockter J, Bernardin F et al (2009) Detection of HIV-1 in alternative specimen types using the APTIMA HIV-1 RNA Qualitative Assay. J Virol Methods 159(1):10–14

    Article  PubMed  CAS  Google Scholar 

  17. Kebe K, Ndiaye O, Ndiaye HD et al (2011) RNA versus DNA (NucliSENS EasyQ HIV-1 v1.2 versus Amplicor HIV-1 DNA Test v1.5) for Early Diagnosis of HIV-1 Infection in Infants in Senegal. J Clin Microbiol 49(7):2590–2593

    Article  PubMed  CAS  Google Scholar 

  18. Busch MP, Glynn SA, Wright DJ et al (2005) Relative sensitivities of licensed nucleic acid amplification tests for detection of viremia in early human immunodeficiency virus and hepatitis C virus infection. Transfusion 45(12):1853–1863

    Article  PubMed  CAS  Google Scholar 

  19. Cunningham CK, Charbonneau TT, Song K et al (1999) Comparison of human immunodeficiency virus 1 DNA polymerase chain reaction and qualitative and quantitative RNA polymerase chain reaction in human immunodeficiency virus 1-exposed infants. Pediatr Infect Dis J 18(1):30–35

    Article  PubMed  CAS  Google Scholar 

  20. Lambert JS, Harris DR, Stiehm ER et al (2003) Performance characteristics of HIV-1 culture and HIV-1 DNA and RNA amplification assays for early diagnosis of perinatal HIV-1 infection. J Acquir Immune Defic Syndr 34(5):512–519

    Article  PubMed  CAS  Google Scholar 

  21. Rouet F, Montcho C, Rouzioux C et al (2001) Early diagnosis of paediatric HIV-1 infection among African breast-fed children using a quantitative plasma HIV RNA assay. AIDS 15(14):1849–1856

    Article  PubMed  CAS  Google Scholar 

  22. Stevens W, Erasmus L, Moloi M, Taleng T, Sarang S (2008) Performance of a novel human immunodeficiency virus (HIV) type 1 total nucleic acid-based real-time PCR assay using whole blood and dried blood spots for diagnosis of HIV in infants. J Clin Microbiol 46(12):3941–3945

    Article  PubMed  CAS  Google Scholar 

  23. Sherman GG, Cooper PA, Coovadia AH et al (2005) Polymerase chain reaction for diagnosis of human immunodeficiency virus infection in infancy in low resource settings. Pediatr Infect Dis J 24(11):993–997

    Article  PubMed  Google Scholar 

  24. Dunn DT, Brandt CD, Krivine A et al (1995) The sensitivity of HIV-1 DNA polymerase chain reaction in the neonatal period and the relative contributions of intra-uterine and intra-partum transmission. AIDS 9(9):F7–F11

    Article  PubMed  CAS  Google Scholar 

  25. Kovacs A, Xu J, Rasheed S et al (1995) Comparison of a rapid nonisotopic polymerase chain reaction assay with four commonly used methods for the early diagnosis of human immunodeficiency virus type 1 infection in neonates and children. Pediatr Infect Dis J 14(11):948–954

    Article  PubMed  CAS  Google Scholar 

  26. Germer JJ, Gerads TM, Mandrekar JN, Mitchell PS, Yao JD (2006) Detection of HIV-1 proviral DNA with the AMPLICOR HIV-1 DNA Test, version 1.5, following sample processing by the MagNA Pure LC instrument. J Clin Virol 37(3):195–198

    Article  PubMed  CAS  Google Scholar 

  27. Ford N, Nachega JB, Engel ME, Mills EJ (2009) Directly observed antiretroviral therapy: a systematic review and meta-analysis of randomised clinical trials. Lancet 374:2064–2071

    Article  PubMed  Google Scholar 

  28. Mellors JW, Munoz A, Giorgi JV et al (1997) Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med 126(12):946–954

    PubMed  CAS  Google Scholar 

  29. O’Brien WA, Hartigan PM, Martin D et al (1996) Changes in plasma HIV-1 RNA and CD4+ lymphocyte counts and the risk of progression to AIDS. Veterans Affairs Cooperative Study Group on AIDS. N Engl J Med 334(7):426–431

    Article  PubMed  Google Scholar 

  30. Saag MS, Holodniy M, Kuritzkes DR et al (1996) HIV viral load markers in clinical practice. Nat Med 2(6):625–629

    Article  PubMed  CAS  Google Scholar 

  31. Hughes MD, Johnson VA, Hirsch MS et al (1997) Monitoring plasma HIV-1 RNA levels in addition to CD4+ lymphocyte count improves assessment of antiretroviral therapeutic response. ACTG 241 Protocol Virology Substudy Team. Ann Intern Med 126(12):929–938

    PubMed  CAS  Google Scholar 

  32. Kitchen CM, Kitchen SG, Dubin JA, Gottlieb MS (2001) Initial virological and immunologic response to highly active antiretroviral therapy predicts long-term clinical outcome. Clin Infect Dis 33(4):466–472

    Article  PubMed  CAS  Google Scholar 

  33. 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  PubMed  CAS  Google Scholar 

  34. Gross R, Bilker WB, Friedman HM, Strom BL (2001) Effect of adherence to newly initiated antiretroviral therapy on plasma viral load. AIDS 15(16):2109–2117

    Article  PubMed  CAS  Google Scholar 

  35. Wood E, Yip B, Hogg RS et al (2000) Full suppression of viral load is needed to achieve an optimal CD4 cell count response among patients on triple drug antiretroviral therapy. AIDS 14(13):1955–1960

    Article  PubMed  CAS  Google Scholar 

  36. Church D, Gregson D, Lloyd T et al (2011) Comparison of the RealTime HIV-1, COBAS TaqMan 48 v1.0, Easy Q v1.2, and Versant v3.0 assays for determination of HIV-1 viral loads in a cohort of Canadian patients with diverse HIV subtype infections. J Clin Microbiol 49(1):118–124

    Article  PubMed  Google Scholar 

  37. Lin HJ, Pedneault L, Hollinger FB (1998) Intra-assay performance characteristics of five assays for quantification of human immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol 36(3):835–839

    PubMed  CAS  Google Scholar 

  38. Martin D (2000) Appropriate laboratory monitoring of HIV. S Afr Med J 90(1):33–36

    PubMed  CAS  Google Scholar 

  39. Muyldermans G, Debaisieux L, Fransen K et al (2000) Blinded, multicenter quality control study for the quantification of human immunodeficiency virus type 1 RNA in plasma by the Belgian AIDS reference laboratories. Clin Microbiol Infect 6(4):213–217

    Article  PubMed  CAS  Google Scholar 

  40. Schuurman R, Descamps D, Weverling GJ et al (1996) Multicenter comparison of three commercial methods for quantification of human immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol 34(12):3016–3022

    PubMed  CAS  Google Scholar 

  41. Tang YW, Huong JT, Lloyd RM Jr, Spearman P, Haas DW (2000) Comparison of human immunodeficiency virus type 1 RNA sequence heterogeneity in cerebrospinal fluid and plasma. J Clin Microbiol 38(12):4637–4639

    PubMed  CAS  Google Scholar 

  42. Church D, Gregson D, Lloyd T et al (2011) Comparison of the RealTime HIV-1, COBAS TaqMan 48 v1.0, Easy Q v1.2, and Versant v3.0 assays for determination of HIV-1 viral loads in a cohort of Canadian patients with diverse HIV subtype infections. J Clin Microbiol 49(1):118–24

    Article  PubMed  Google Scholar 

  43. Sire JM, Vray M, Merzouk M et al (2011) Comparative RNA quantification of HIV-1 group M and non-M with the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 v2.0 and Abbott Real-Time HIV-1 PCR assays. J Acquir Immune Defic Syndr 56(3):239–243

    Article  PubMed  CAS  Google Scholar 

  44. Bourlet T, Signori-Schmuck A, Roche L et al (2011) HIV-1 load comparison using four commercial real-time assays. J Clin Microbiol 49(1):292–297

    Article  PubMed  Google Scholar 

  45. Griffith BP, Mayo DR (2006) Increased levels of HIV RNA detected in samples with viral loads close to the detection limit collected in Plasma Preparation Tubes (PPT). J Clin Virol 35(2):197–200

    Article  PubMed  CAS  Google Scholar 

  46. Rebeiro PF, Kheshti A, Bebawy SS et al (2008) Increased detectability of plasma HIV-1 RNA after introduction of a new assay and altered specimen-processing procedures. Clin Infect Dis 47(10):1354–1357

    Article  PubMed  Google Scholar 

  47. Salimnia H, Moore EC, Crane LR, Macarthur RD, Fairfax MR (2005) Discordance between viral loads determined by Roche COBAS AMPLICOR human immunodeficiency virus type 1 monitor (version 1.5) Standard and ultrasensitive assays caused by freezing patient plasma in centrifuged becton-dickinson vacutainer brand plasma preparation tubes. J Clin Microbiol 43(9):4635–4639

    Article  PubMed  CAS  Google Scholar 

  48. Stosor V, Palella FJ Jr, Berzins B et al (2005) Transient viremia in HIV-infected patients and use of plasma preparation tubes. Clin Infect Dis 41(11):1671–1674

    Article  PubMed  Google Scholar 

  49. Ayele W, Schuurman R, Messele T et al (2007) Use of dried spots of whole blood, plasma, and mother’s milk collected on filter paper for measurement of human immunodeficiency virus type 1 burden. J Clin Microbiol 45(3):891–896

    Article  PubMed  Google Scholar 

  50. Bourlet T, Cazorla C, Berthelot P et al (2001) Compartmentalization of HIV-1 according to antiretroviral therapy: viral loads are correlated in blood and semen but poorly in blood and saliva. AIDS 15(2):284–285

    Article  PubMed  CAS  Google Scholar 

  51. Lloyd RM Jr, Burns DA, Huong JT et al (2009) Dried-plasma transport using a novel matrix and collection system for human immunodeficiency virus and hepatitis C virus virologic testing. J Clin Microbiol 47(5):1491–1496

    Article  PubMed  Google Scholar 

  52. Shepard RN, Schock J, Robertson K et al (2000) Quantitation of human immunodeficiency virus type 1 RNA in different biological compartments. J Clin Microbiol 38(4):1414–1418

    PubMed  CAS  Google Scholar 

  53. Gil C, Garcia MT, Garcia F et al (2011) Evaluation of the Roche COBAS(R) TaqMan(R) HIV-1 test for quantifying HIV-1 RNA in infected cells and lymphoid tissue. J Virol Methods 174(1–2):69–76

    Article  PubMed  CAS  Google Scholar 

  54. Lofgren SM, Morrissey AB, Chevallier CC et al (2009) Evaluation of a dried blood spot HIV-1 RNA program for early infant diagnosis and viral load monitoring at rural and remote healthcare facilities. AIDS 23(18):2459–2466

    Article  PubMed  Google Scholar 

  55. Mbida AD, Sosso S, Flori P et al (2009) Measure of viral load by using the Abbott Real-Time HIV-1 assay on dried blood and plasma spot specimens collected in 2 rural dispensaries in Cameroon. J Acquir Immune Defic Syndr 52(1):9–16

    Article  PubMed  Google Scholar 

  56. van Deursen P, Oosterlaken T, Andre P et al (2010) Measuring human immunodeficiency virus type 1 RNA loads in dried blood spot specimens using NucliSENS EasyQ HIV-1 v2.0. J Clin Virol 47:120–125

    Article  PubMed  CAS  Google Scholar 

  57. Zhang Q, Wang L, Jiang Y et al (2008) Early infant human immunodeficiency virus type 1 detection suitable for resource-limited settings with multiple circulating subtypes by use of nested three-monoplex DNA PCR and dried blood spots. J Clin Microbiol 46(2):721–726

    Article  PubMed  CAS  Google Scholar 

  58. Nkenfou CN, Elong EL, Ouwe-Missi-Oukem-Boyer O et al (2012) Implementation of HIV Early Infant Diagnosis and HIV-1 RNA viral load determination on Dried Blood Spots in Cameroon: challenges and propositions. AIDS Res Hum Retroviruses 28:176–181

    Article  PubMed  CAS  Google Scholar 

  59. Driver GA, Patton JC, Moloi J, Stevens WS, Sherman GG (2007) Low risk of contamination with automated and manual excision of dried blood spots for HIV DNA PCR testing in the routine laboratory. J Virol Methods 146(1–2):397–400

    Article  PubMed  CAS  Google Scholar 

  60. Leelawiwat W, Young NL, Chaowanachan T et al (2009) Dried blood spots for the diagnosis and quantitation of HIV-1: stability studies and evaluation of sensitivity and specificity for the diagnosis of infant HIV-1 infection in Thailand. J Virol Methods 155(2):109–117

    Article  PubMed  CAS  Google Scholar 

  61. Mitchell C, Kraft K, Peterson D, Frenkel L (2010) Cross-contamination during processing of dried blood spots used for rapid diagnosis of HIV-1 infection of infants is rare and avoidable. J Virol Methods 163:489–491

    Article  PubMed  CAS  Google Scholar 

  62. Revets H, Marissens D, de Wit S et al (1996) Comparative evaluation of NASBA HIV-1 RNA QT, AMPLICOR-HIV monitor, and QUANTIPLEX HIV RNA assay, three methods for quantification of human immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol 34(5):1058–1064

    PubMed  CAS  Google Scholar 

  63. Damond F, Roquebert B, Benard A et al (2007) Human immunodeficiency virus type 1 (HIV-1) plasma load discrepancies between the Roche COBAS AMPLICOR HIV-1 MONITOR Version 1.5 and the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 assays. J Clin Microbiol 45(10):3436–3438

    Article  PubMed  CAS  Google Scholar 

  64. 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  PubMed  CAS  Google Scholar 

  65. Scott LE, Noble LD, Moloi J, Erasmus L, Venter WD, Stevens W (2009) Evaluation of the Abbott m2000 RealTime human immunodeficiency virus type 1 (HIV-1) assay for HIV load monitoring in South Africa compared to the Roche Cobas AmpliPrep-Cobas Amplicor, Roche Cobas AmpliPrep-Cobas TaqMan HIV-1, and BioMerieux NucliSENS EasyQ HIV-1 assays. J Clin Microbiol 47(7):2209–2217

    Article  PubMed  Google Scholar 

  66. Gueudin M, Plantier JC, Lemee V et al (2007) Evaluation of the Roche Cobas TaqMan and Abbott RealTime extraction-quantification systems for HIV-1 subtypes. J Acquir Immune Defic Syndr 44(5):500–505

    Article  PubMed  Google Scholar 

  67. Pas S, Rossen JW, Schoener D 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  PubMed  CAS  Google Scholar 

  68. Sizmann D, Glaubitz J, Simon CO et al (2011) Improved HIV-1 RNA quantitation by COBAS AmpliPrep/COBAS TaqMan HIV-1 Test, v2.0 using a novel dual-target approach. J Clin Virol 49(1):41–46

    Article  CAS  Google Scholar 

  69. Dewar RL, Highbarger HC, Sarmiento MD et al (1994) Application of branched DNA signal amplification to monitor human immunodeficiency virus type 1 burden in human plasma. J Infect Dis 170(5):1172–1179

    Article  PubMed  CAS  Google Scholar 

  70. Nolte FS, Boysza J, Thurmond C, Clark WS, Lennox JL (1998) Clinical comparison of an enhanced-sensitivity branched-DNA assay and reverse transcription-PCR for quantitation of human immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol 36(3):716–720

    PubMed  CAS  Google Scholar 

  71. Gleaves CA, Welle J, Campbell M et al (2002) Multicenter evaluation of the Bayer VERSANT HIV-1 RNA 3.0 assay: analytical and clinical performance. J Clin Virol 25(2):205–216

    Article  PubMed  CAS  Google Scholar 

  72. Berger A, Scherzed L, Sturmer M, Preiser W, Doerr HW, Rabenau HF (2005) Comparative evaluation of the Cobas Amplicor HIV-1 Monitor Ultrasensitive Test, the new Cobas AmpliPrep/Cobas Amplicor HIV-1 Monitor Ultrasensitive Test and the Versant HIV RNA 3.0 assays for quantitation of HIV-1 RNA in plasma samples. J Clin Virol 33(1):43–51

    Article  PubMed  CAS  Google Scholar 

  73. Holguin A, Lopez M, Molinero M, Soriano V (2008) Performance of three commercial viral load assays, Versant human immunodeficiency virus type 1 (HIV-1) RNA bDNA v3.0, Cobas AmpliPrep/Cobas TaqMan HIV-1, and NucliSens HIV-1 EasyQ v1.2, testing HIV-1 non-B subtypes and recombinant variants. J Clin Microbiol 46(9):2918–2923

    Article  PubMed  CAS  Google Scholar 

  74. van Gemen B, Kievits T, Schukkink R et al (1993) Quantification of HIV-1 RNA in plasma using NASBA during HIV-1 primary infection. J Virol Methods 43(2):177–187

    Article  PubMed  Google Scholar 

  75. Ginocchio CC, Kemper M, Stellrecht KA, Witt DJ (2003) Multicenter evaluation of the performance characteristics of the NucliSens HIV-1 QT assay used for quantitation of human immunodeficiency virus type 1 RNA. J Clin Microbiol 41(1):164–173

    Article  PubMed  CAS  Google Scholar 

  76. Weusten JJ, Wouters PA, van Zuijlen MC, van de Wiel PA (2002) Stochastic processes defining sensitivity and variability of internally calibrated quantitative NASBA-based viral load assays. Nucleic Acids Res 30(24):e137

    Article  PubMed  Google Scholar 

  77. Fiscus SA, Brambilla D, Coombs RW et al (2000) Multicenter evaluation of methods to quantitate human immunodeficiency virus type 1 RNA in seminal plasma. J Clin Microbiol 38(6):2348–2353

    PubMed  CAS  Google Scholar 

  78. Pyne MT, Konnick EQ, Phansalkar A, Hillyard DR (2009) Evaluation of the Abbott investigational use only realtime HIV-1 assay and comparison to the Roche Amplicor HIV-1 monitor test, version 1.5. J Mol Diagn 11(4):347–354

    Article  PubMed  Google Scholar 

  79. Schutten M, Fries E, Burghoorn-Maas C, Niesters HG (2007) Evaluation of the analytical performance of the new Abbott RealTime RT-PCRs for the quantitative detection of HCV and HIV-1 RNA. J Clin Virol 40(2):99–104

    Article  PubMed  CAS  Google Scholar 

  80. Swanson P, Huang S, Abravaya K et al (2007) Evaluation of performance across the dynamic range of the Abbott RealTime HIV-1 assay as compared to VERSANT HIV-1 RNA 3.0 and AMPLICOR HIV-1 MONITOR v1.5 using serial dilutions of 39 group M and O viruses. J Virol Methods 141(1):49–57

    Article  PubMed  CAS  Google Scholar 

  81. Huang S, Salituro J, Tang N et al (2007) Thermodynamically modulated partially double-stranded linear DNA probe design for homogeneous real-time PCR. Nucleic Acids Res 35(16):e101

    Article  PubMed  CAS  Google Scholar 

  82. Raboud JM, Seminari E, Rae SL et al (1998) Comparison of costs of strategies for measuring levels of human immunodeficiency virus type 1 RNA in plasma by using Amplicor and Ultra Direct assays. J Clin Microbiol 36(11):3369–3371

    PubMed  CAS  Google Scholar 

  83. Baxter JD, Mayers DL, Wentworth DN et al (2000) A randomized study of antiretroviral management based on plasma genotypic antiretroviral resistance testing in patients failing therapy. CPCRA 046 Study Team for the Terry Beirn Community Programs for Clinical Research on AIDS. AIDS 14(9):F83–F93

    Article  PubMed  CAS  Google Scholar 

  84. Cohen CJ, Hunt S, Sension M et al (2002) A randomized trial assessing the impact of phenotypic resistance testing on antiretroviral therapy. AIDS 16(4):579–588

    Article  PubMed  CAS  Google Scholar 

  85. Durant J, Clevenbergh P, Halfon P et al (1999) Drug-resistance genotyping in HIV-1 therapy: the VIRADAPT randomised controlled trial. Lancet 353(9171):2195–2199

    Article  PubMed  CAS  Google Scholar 

  86. Meynard JL, Vray M, Morand-Joubert L et al (2002) Phenotypic or genotypic resistance testing for choosing antiretroviral therapy after treatment failure: a randomized trial. AIDS 16(5):727–736

    Article  PubMed  Google Scholar 

  87. Tural C, Ruiz L, Holtzer C et al (2002) Clinical utility of HIV-1 genotyping and expert advice: the Havana trial. AIDS 16(2):209–218

    Article  PubMed  Google Scholar 

  88. Beddows S, Galpin S, Kazmi SH et al (2003) Performance of two commercially available sequence-based HIV-1 genotyping systems for the detection of drug resistance against HIV type 1 group M subtypes. J Med Virol 70(3):337–342

    Article  PubMed  CAS  Google Scholar 

  89. Sturmer M, Berger A, Doerr HW (2003) Modifications and substitutions of the RNA extraction module in the ViroSeq HIV-1 genotyping system version 2: effects on sensitivity and complexity of the assay. J Med Virol 71(4):475–479

    Article  PubMed  CAS  Google Scholar 

  90. Cunningham S, Ank B, Lewis D et al (2001) Performance of the applied biosystems ViroSeq human immunodeficiency virus type 1 (HIV-1) genotyping system for sequence-based analysis of HIV-1 in pediatric plasma samples. J Clin Microbiol 39(4):1254–1257

    Article  PubMed  CAS  Google Scholar 

  91. Sendi P, Gunthard HF, Simcock M, Ledergerber B, Schupbach J, Battegay M (2007) Cost-effectiveness of genotypic antiretroviral resistance testing in HIV-infected patients with treatment failure. PLoS One 2(1):e173

    Article  PubMed  Google Scholar 

  92. Weinstein MC, Goldie SJ, Losina E et al (2001) Use of genotypic resistance testing to guide hiv therapy: clinical impact and cost-effectiveness. Ann Intern Med 134(6):440–450

    PubMed  CAS  Google Scholar 

  93. Dunn DT, Coughlin K, Cane PA (2011) Genotypic resistance testing in routine clinical care. Curr Opin HIV AIDS 6(4):251–257

    Article  PubMed  Google Scholar 

  94. Hammer SM (2002) HIV drug resistance: implications for management. Top HIV Med 10(5):10–15

    PubMed  Google Scholar 

  95. Sturmer M, Berger A, Preiser W (2004) HIV-1 genotyping: comparison of two commercially available assays. Expert Rev Mol Diagn 4(3):281–291

    Article  PubMed  Google Scholar 

  96. Erali M, Page S, Reimer LG, Hillyard DR (2001) Human immunodeficiency virus type 1 drug resistance testing: a comparison of three sequence-based methods. J Clin Microbiol 39(6):2157–2165

    Article  PubMed  CAS  Google Scholar 

  97. Aghokeng AF, Mpoudi-Ngole E, Chia JE, Edoul EM, Delaporte E, Peeters M (2011) High failure rate of the ViroSeq HIV-1 genotyping system for drug resistance testing in Cameroon, a country with broad HIV-1 genetic diversity. J Clin Microbiol 49(4):1635–1641

    Article  PubMed  CAS  Google Scholar 

  98. Gunthard HF, Wong JK, Ignacio CC, Havlir DV, Richman DD (1998) Comparative performance of high-density oligonucleotide sequencing and dideoxynucleotide sequencing of HIV type 1 pol from clinical samples. AIDS Res Hum Retroviruses 14(10):869–876

    Article  PubMed  CAS  Google Scholar 

  99. Palmer S, Kearney M, Maldarelli F et al (2005) Multiple, linked human immunodeficiency virus type 1 drug resistance mutations in treatment-experienced patients are missed by standard genotype analysis. J Clin Microbiol 43(1):406–413

    Article  PubMed  CAS  Google Scholar 

  100. Servais J, Lambert C, Fontaine E et al (2001) Comparison of DNA sequencing and a line probe assay for detection of human immunodeficiency virus type 1 drug resistance mutations in patients failing highly active antiretroviral therapy. J Clin Microbiol 39(2):454–459

    Article  PubMed  CAS  Google Scholar 

  101. Stuyver L, Wyseur A, Rombout A et al (1997) Line probe assay for rapid detection of drug-selected mutations in the human immunodeficiency virus type 1 reverse transcriptase gene. Antimicrob Agents Chemother 41(2):284–291

    PubMed  CAS  Google Scholar 

  102. Vahey M, Nau ME, Barrick S et al (1999) Performance of the Affymetrix GeneChip HIV PRT 440 platform for antiretroviral drug resistance genotyping of human immunodeficiency virus type 1 clades and viral isolates with length polymorphisms. J Clin Microbiol 37(8):2533–2537

    PubMed  CAS  Google Scholar 

  103. Wilson JW, Bean P, Robins T, Graziano F, Persing DH (2000) Comparative evaluation of three human immunodeficiency virus genotyping systems: the HIV-GenotypR method, the HIV PRT GeneChip assay, and the HIV-1 RT line probe assay. J Clin Microbiol 38(8):3022–3028

    PubMed  CAS  Google Scholar 

  104. Halvas EK, Aldrovandi GM, Balfe P et al (2006) Blinded, multicenter comparison of methods to detect a drug-resistant mutant of human immunodeficiency virus type 1 at low frequency. J Clin Microbiol 44(7):2612–2614

    Article  PubMed  CAS  Google Scholar 

  105. Toni TA, Brenner BG, Asahchop EL, Ntemgwa M, Moisi D, Wainberg MA (2010) Development of an allele-specific PCR for detection of the K65R resistance mutation in patients infected with subtype C human immunodeficiency virus type 1. Antimicrob Agents Chemother 54(2):907–911

    Article  PubMed  CAS  Google Scholar 

  106. Van Laethem K, De Munter P, Schrooten Y et al (2007) No response to first-line tenofovir  +  lamivudine  +  efavirenz despite optimization according to baseline resistance testing: impact of resistant minority variants on efficacy of low genetic barrier drugs. J Clin Virol 39(1):43–47

    Article  PubMed  CAS  Google Scholar 

  107. Hedskog C, Mild M, Jernberg J et al (2010) Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. PLoS One 5(7):e11345

    Article  PubMed  CAS  Google Scholar 

  108. Simen BB, Simons JF, Hullsiek KH et al (2009) Low-abundance drug-resistant viral variants in chronically HIV-infected, antiretroviral treatment-naive patients significantly impact treatment outcomes. J Infect Dis 199(5):693–701

    Article  PubMed  Google Scholar 

  109. D’Aquila RT, Geretti AM, Horton JH et al (2011) Tenofovir (TDF)-selected or abacavir (ABC)-selected low-frequency HIV type 1 subpopulations during failure with persistent viremia as detected by ultradeep pyrosequencing. AIDS Res Hum Retroviruses 27(2):201–209

    Article  PubMed  CAS  Google Scholar 

  110. Delobel P, Saliou A, Nicot F et al (2011) Minor HIV-1 variants with the K103N resistance mutation during intermittent Efavirenz-containing antiretroviral therapy and virological failure. PLoS One 6(6):e21655

    Article  PubMed  CAS  Google Scholar 

  111. Varghese V, Wang E, Babrzadeh F et al (2010) Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. PLoS One 5(6):e10992

    Article  PubMed  CAS  Google Scholar 

  112. Gianella S, Delport W, Pacold ME et al (2011) Detection of minority resistance during early HIV-1 infection: natural variation and spurious detection rather than transmission and evolution of multiple viral variants. J Virol 85:8359–8367

    Article  PubMed  CAS  Google Scholar 

  113. Call SA, Saag MS, Westfall AO et al (2001) Phenotypic drug susceptibility testing predicts long-term virologic suppression better than treatment history in patients with human immunodeficiency virus infection. J Infect Dis 183(3):401–408

    Article  PubMed  CAS  Google Scholar 

  114. Dunne AL, Mitchell FM, Coberly SK et al (2001) Comparison of genotyping and phenotyping methods for determining susceptibility of HIV-1 to antiretroviral drugs. AIDS 15(12):1471–1475

    Article  PubMed  CAS  Google Scholar 

  115. Zhang M, Versalovic J (2002) HIV update. Diagnostic tests and markers of disease progression and response to therapy. Am J Clin Pathol 118(Suppl):S26–S32

    PubMed  Google Scholar 

  116. Hertogs K, de Bethune MP, Miller V et al (1998) A rapid method for simultaneous detection of phenotypic resistance to inhibitors of protease and reverse transcriptase in recombinant human immunodeficiency virus type 1 isolates from patients treated with antiretroviral drugs. Antimicrob Agents Chemother 42(2):269–276

    Article  PubMed  CAS  Google Scholar 

  117. Petropoulos CJ, Parkin NT, Limoli KL et al (2000) A novel phenotypic drug susceptibility assay for human immunodeficiency virus type 1. Antimicrob Agents Chemother 44(4):920–928

    Article  PubMed  CAS  Google Scholar 

  118. Qari SH, Respess R, Weinstock H et al (2002) Comparative analysis of two commercial phenotypic assays for drug susceptibility testing of human immunodeficiency virus type 1. J Clin Microbiol 40(1):31–35

    Article  PubMed  CAS  Google Scholar 

  119. Zhang J, Rhee SY, Taylor J, Shafer RW (2005) Comparison of the precision and sensitivity of the Antivirogram and PhenoSense HIV drug susceptibility assays. J Acquir Immune Defic Syndr 38(4):439–444

    Article  PubMed  CAS  Google Scholar 

  120. Munoz M, Carmona R, Perez-Alvarez L et al (2005) Analysis of discrepancies in the interpretation of antiretroviral drug resistance results in HIV-1 infected patients of Basque Country, Spain. J Clin Virol 33(3):224–229

    Article  PubMed  CAS  Google Scholar 

  121. Gallego O, Martin-Carbonero L, Aguero J, de Mendoza C, Corral A, Soriano V (2004) Correlation between rules-based interpretation and virtual phenotype interpretation of HIV-1 genotypes for predicting drug resistance in HIV-infected individuals. J Virol Methods 121(1):115–118

    Article  PubMed  CAS  Google Scholar 

  122. Perez-Elias MJ, Garcia-Arota I, Munoz V et al (2003) Phenotype or virtual phenotype for choosing antiretroviral therapy after failure: a prospective, randomized study. Antivir Ther 8(6):577–584

    PubMed  CAS  Google Scholar 

  123. Cooper DA, Steigbigel RT, Gatell JM et al (2008) Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med 359(4):355–365

    Article  PubMed  CAS  Google Scholar 

  124. Eshleman SH, Hudelson SE, Smith P et al (2009) Analysis of pol integrase sequences in diverse HIV type 1 strains using a prototype genotyping assay. AIDS Res Hum Retroviruses 25(3):343–345

    Article  PubMed  CAS  Google Scholar 

  125. Hearps AC, Greengrass V, Hoy J, Crowe SM (2009) An HIV-1 integrase genotype assay for the detection of drug resistance mutations. Sex Health 6(4):305–309

    Article  PubMed  Google Scholar 

  126. Hudelson SE, Marlowe N, Huang W et al (2009) Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. AIDS Res Hum Retroviruses 25(7):701–705

    Article  PubMed  CAS  Google Scholar 

  127. Coakley E, Petropoulos CJ, Whitcomb JM (2005) Assessing chemokine co-receptor usage in HIV. Curr Opin Infect Dis 18(1):9–15

    Article  PubMed  CAS  Google Scholar 

  128. Veazey RS, Ketas TA, Klasse PJ et al (2008) Tropism-independent protection of macaques against vaginal transmission of three SHIVs by the HIV-1 fusion inhibitor T-1249. Proc Natl Acad Sci U S A 105(30):10531–10536

    Article  PubMed  CAS  Google Scholar 

  129. Carmona R, Perez-Alvarez L, Munoz M et al (2005) Natural resistance-associated mutations to Enfuvirtide (T20) and polymorphisms in the gp41 region of different HIV-1 genetic forms from T20 naive patients. J Clin Virol 32(3):248–253

    Article  PubMed  CAS  Google Scholar 

  130. Smith RA, Anderson DJ, Pyrak CL, Preston BD, Gottlieb GS (2009) Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. J Infect Dis 199(9):1323–1326

    Article  PubMed  CAS  Google Scholar 

  131. Westby M, Lewis M, Whitcomb J et al (2006) Emergence of CXCR4-using human immunodeficiency virus type 1 (HIV-1) variants in a minority of HIV-1-infected patients following treatment with the CCR5 antagonist maraviroc is from a pretreatment CXCR4-using virus reservoir. J Virol 80(10):4909–4920

    Article  PubMed  CAS  Google Scholar 

  132. Recordon-Pinson P, Soulie C, Flandre P et al (2010) Evaluation of the genotypic prediction of HIV-1 coreceptor use versus a phenotypic assay and correlation with the virological response to maraviroc: the ANRS GenoTropism study. Antimicrob Agents Chemother 54(8):3335–3340

    Article  PubMed  CAS  Google Scholar 

  133. Low AJ, Swenson LC, Harrigan PR (2008) HIV coreceptor phenotyping in the clinical setting. AIDS Rev 10(3):143–151

    PubMed  Google Scholar 

  134. MacArthur RD, Novak RM (2008) Reviews of anti-infective agents: maraviroc: the first of a new class of antiretroviral agents. Clin Infect Dis 47(2):236–241

    Article  PubMed  CAS  Google Scholar 

  135. Whitcomb JM, Huang W, Fransen S et al (2007) Development and characterization of a novel single-cycle recombinant-virus assay to determine human immunodeficiency virus type 1 coreceptor tropism. Antimicrob Agents Chemother 51(2):566–575

    Article  PubMed  CAS  Google Scholar 

  136. Wilkin TJ, Goetz MB, Leduc R et al (2011) Reanalysis of coreceptor tropism in HIV-1-infected adults using a phenotypic assay with enhanced sensitivity. Clin Infect Dis 52(7):925–928

    Article  PubMed  CAS  Google Scholar 

  137. Lee-Lewandrowski E, Lewandrowski K (2009) Perspectives on cost and outcomes for point-of-care testing. Clin Lab Med 29(3):479–489

    Article  PubMed  Google Scholar 

  138. Blyth CC, Booy R, Dwyer DE (2011) Point of care testing: diagnosis outside the virology laboratory. Methods Mol Biol 665:415–433

    Article  PubMed  CAS  Google Scholar 

  139. Campbell S, Fedoriw Y (2009) HIV testing near the patient: changing the face of HIV testing. Clin Lab Med 29(3):491–501

    Article  PubMed  Google Scholar 

  140. Hsieh YH, Gaydos CA, Hogan MT et al (2011) What qualities are most important to making a point of care test desirable for clinicians and others offering sexually transmitted infection testing? PLoS One 6(4):e19263

    Article  PubMed  CAS  Google Scholar 

  141. Grant PR, Busch MP (2002) Nucleic acid amplification technology methods used in blood donor screening. Transfus Med 12(4):229–242

    Article  PubMed  CAS  Google Scholar 

  142. Scuracchio PS, Poli MC, Lemos MM et al (2007) Detection of HIV-1 infection in blood donors during the immunological window period using the nucleic acid-amplification technology. Transfus Med 17(3):200–204

    Article  PubMed  CAS  Google Scholar 

  143. An L, Tang W, Ranalli TA, Kim HJ, Wytiaz J, Kong H (2005) Characterization of a thermostable UvrD helicase and its participation in helicase-dependent amplification. J Biol Chem 280(32):28952–28958

    Article  PubMed  CAS  Google Scholar 

  144. Vincent M, Xu Y, Kong H (2004) Helicase-dependent isothermal DNA amplification. EMBO Rep 5(8):795–800

    Article  PubMed  CAS  Google Scholar 

  145. Goldmeyer J, Li H, McCormac M et al (2008) Identification of Staphylococcus aureus and determination of methicillin resistance directly from positive blood cultures by isothermal amplification and a disposable detection device. J Clin Microbiol 46(4):1534–1536

    Article  PubMed  CAS  Google Scholar 

  146. Tang W, Chow WH, Li Y, Kong H, Tang YW, Lemieux B (2010) Nucleic acid assay system for tier II labs and moderately complex clinics to detect HIV in low-resource settings. J Infect Dis 201:S46–S51

    Article  PubMed  CAS  Google Scholar 

  147. Spacek LA, Shihab HM, Lutwama F et al (2006) Evaluation of a low-cost method, the Guava EasyCD4 assay, to enumerate CD4-positive lymphocyte counts in HIV-infected patients in the United States and Uganda. J Acquir Immune Defic Syndr 41(5):607–610

    Article  PubMed  Google Scholar 

  148. Li X, Breukers C, Ymeti A et al (2010) Clinical evaluation of a simple image cytometer for CD4 enumeration on HIV-infected patients. Cytometry B Clin Cytom 78(1):31–36

    PubMed  Google Scholar 

  149. Rodriguez WR, Christodoulides N, Floriano PN et al (2005) A microchip CD4 counting method for HIV monitoring in resource-poor settings. PLoS Med 2(7):e182

    Article  PubMed  CAS  Google Scholar 

  150. Cheng X, Gupta A, Chen C, Tompkins RG, Rodriguez W, Toner M (2009) Enhancing the performance of a point-of-care CD4+ T-cell counting microchip through monocyte depletion for HIV/AIDS diagnostics. Lab Chip 9(10):1357–1364

    Article  PubMed  CAS  Google Scholar 

  151. Moon S, Keles HO, Ozcan A et al (2009) Integrating microfluidics and lensless imaging for point-of-care testing. Biosens Bioelectron 24(11):3208–3214

    Article  PubMed  CAS  Google Scholar 

  152. Jokerst JV, Floriano PN, Christodoulides N, Simmons GW, McDevitt JT (2008) Integration of semiconductor quantum dots into nano-bio-chip systems for enumeration of CD4+ T cell counts at the point-of-need. Lab Chip 8(12):2079–2090

    Article  PubMed  CAS  Google Scholar 

  153. Jani IV, Sitoe NE, Chongo PL et al (2011) Accurate CD4 T-cell enumeration and antiretroviral drug toxicity monitoring in primary healthcare clinics using point-of-care testing. AIDS 25(6):807–812

    Article  PubMed  Google Scholar 

  154. Tang YW, Procop GW, Persing DH (1997) Molecular diagnostics of infectious diseases. Clin Chem 43(11):2021–2038

    PubMed  CAS  Google Scholar 

  155. Jangam SR, Yamada DH, McFall SM, Kelso DM (2009) Rapid, point-of-care extraction of human immunodeficiency virus type 1 proviral DNA from whole blood for detection by real-time PCR. J Clin Microbiol 47(8):2363–2368

    Article  PubMed  CAS  Google Scholar 

  156. Guttikonda S, Wang W, Suresh M (2004) Molecular zipper assays: a simple homosandwich with the sensitivity of PCR. J Pharm Pharm Sci 7(4):7–16

    PubMed  CAS  Google Scholar 

  157. Panhotra BR, Hassan ZU, Joshi CS, Bahrani A (2005) Visual detection of multiple viral amplicons by dipstick assay: its application in screening of blood donors a welcome tool for the limited resource settings. J Clin Microbiol 43(12):6218, author reply -9

    Article  PubMed  CAS  Google Scholar 

  158. Raja S, Ching J, Xi L et al (2005) Technology for automated, rapid, and quantitative PCR or reverse transcription-PCR clinical testing. Clin Chem 51(5):882–890

    Article  PubMed  CAS  Google Scholar 

  159. Perrin A, Duracher D, Perret M, Cleuziat P, Mandrand B (2003) A combined oligonucleotide and protein microarray for the codetection of nucleic acids and antibodies associated with human immunodeficiency virus, hepatitis B virus, and hepatitis C virus infections. Anal Biochem 322(2):148–155

    Article  PubMed  CAS  Google Scholar 

  160. Hsia CC, Chizhikov VE, Yang AX et al (2007) Microarray multiplex assay for the simultaneous detection and discrimination of hepatitis B, hepatitis C, and human immunodeficiency type-1 viruses in human blood samples. Biochem Biophys Res Commun 356(4):1017–1023

    Article  PubMed  CAS  Google Scholar 

  161. Khodakov DA, Zakharova NV, Gryadunov DA, Filatov FP, Zasedatelev AS, Mikhailovich VM (2008) An oligonucleotide microarray for multiplex real-time PCR identification of HIV-1, HBV, and HCV. Biotechniques 44(2):241–246, 248

    Article  PubMed  CAS  Google Scholar 

  162. Burgess ST, Kenyon F, O’Looney N et al (2008) A multiplexed protein microarray for the simultaneous serodiagnosis of human immunodeficiency virus/hepatitis C virus infection and typing of whole blood. Anal Biochem 382(1):9–15

    Article  PubMed  CAS  Google Scholar 

  163. Miller MB, Tang YW (2009) Basic concepts of microarrays and potential applications in clinical microbiology. Clin Microbiol Rev 22(4):611–633

    Article  PubMed  CAS  Google Scholar 

  164. Lee SH, Kim SW, Kang JY, Ahn CH (2008) A polymer lab-on-a-chip for reverse transcription (RT)-PCR based point-of-care clinical diagnostics. Lab Chip 8(12):2121–2127

    Article  PubMed  CAS  Google Scholar 

  165. Edgar R, McKinstry M, Hwang J et al (2006) High-sensitivity bacterial detection using biotin-tagged phage and quantum-dot nanocomplexes. Proc Natl Acad Sci U S A 103(13):4841–4845

    Article  PubMed  CAS  Google Scholar 

  166. Kopp MU, Mello AJ, Manz A (1998) Chemical amplification: continuous-flow PCR on a chip. Science 280(5366):1046–1048

    Article  PubMed  CAS  Google Scholar 

  167. Liu RH, Lodes MJ, Nguyen T et al (2006) Validation of a fully integrated microfluidic array device for influenza A subtype identification and sequencing. Anal Chem 78(12):4184–4193

    Article  PubMed  CAS  Google Scholar 

  168. Michalet X, Pinaud FF, Bentolila LA et al (2005) Quantum dots for live cells, in vivo imaging, and diagnostics. Science 307(5709):538–544

    Article  PubMed  CAS  Google Scholar 

  169. Mokkapati VK, Sam Niedbala R, Kardos K et al (2007) Evaluation of UPlink-RSV: prototype rapid antigen test for detection of respiratory syncytial virus infection. Ann N Y Acad Sci 1098:476–485

    Article  PubMed  CAS  Google Scholar 

  170. Sista R, Hua Z, Thwar P et al (2008) Development of a digital microfluidic platform for point of care testing. Lab Chip 8(12):2091–2104

    Article  PubMed  CAS  Google Scholar 

  171. Rouet F, Rouzioux C (2007) The measurement of HIV-1 viral load in resource-limited settings: how and where? Clin Lab 53(3–4):135–148

    PubMed  CAS  Google Scholar 

  172. Calmy A, Ford N, Hirschel B et al (2007) HIV viral load monitoring in resource-limited regions: optional or necessary? Clin Infect Dis 44(1):128–134

    Article  PubMed  Google Scholar 

  173. Fiscus SA, Cheng B, Crowe SM et al (2006) HIV-1 viral load assays for resource-limited settings. PLoS Med 3(10):e417

    Article  PubMed  Google Scholar 

  174. Tanriverdi S, Chen L, Chen S (2010) A rapid and automated sample-to-result HIV load test for near-patient application. J Infect Dis 201(Suppl 1):S52–S58

    Article  PubMed  CAS  Google Scholar 

  175. Iqbal HS, Balakrishnan P, Cecelia AJ et al (2007) Use of an HIV-1 reverse-transcriptase enzyme-activity assay to measure HIV-1 viral load as a potential alternative to nucleic acid-based assay for monitoring antiretroviral therapy in resource-limited settings. J Med Microbiol 56(Pt 12):1611–1614

    Article  PubMed  Google Scholar 

  176. Labbett W, Garcia-Diaz A, Fox Z et al (2009) Comparative evaluation of the ExaVir Load version 3 reverse transcriptase assay for measurement of human immunodeficiency virus type 1 plasma load. J Clin Microbiol 47(10):3266–3270

    Article  PubMed  Google Scholar 

  177. Malmsten A, Shao XW, Aperia K et al (2003) HIV-1 viral load determination based on reverse transcriptase activity recovered from human plasma. J Med Virol 71(3):347–359

    Article  PubMed  CAS  Google Scholar 

  178. Greengrass V, Lohman B, Morris L et al (2009) Assessment of the low-cost Cavidi ExaVir Load assay for monitoring HIV viral load in pediatric and adult patients. J Acquir Immune Defic Syndr 52(3):387–390

    Article  PubMed  Google Scholar 

  179. Napravnik S, Cachafeiro A, Stewart P, Eron JJ Jr, Fiscus SA (2010) HIV-1 viral load and phenotypic antiretroviral drug resistance assays based on reverse transcriptase activity in comparison to amplification based HIV-1 RNA and genotypic assays. J Clin Virol 47(1):18–22

    Article  PubMed  CAS  Google Scholar 

  180. Fellay J, Shianna KV, Telenti A, Goldstein DB (2010) Host genetics and HIV-1: the final phase? PLoS Pathog 6(10):e1001033

    Article  PubMed  CAS  Google Scholar 

  181. Vannberg FO, Chapman SJ, Hill AV (2011) Human genetic susceptibility to intracellular pathogens. Immunol Rev 240(1):105–116

    Article  PubMed  CAS  Google Scholar 

  182. Telenti A, Goldstein DB (2006) Genomics meets HIV-1. Nat Rev Microbiol 4(11):865–873

    Article  PubMed  CAS  Google Scholar 

  183. Dean M, Carrington M, Winkler C et al (1996) Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study [see comments]. Science 273(5283):1856–1862

    Article  PubMed  CAS  Google Scholar 

  184. Samson M, Libert F, Doranz BJ et al (1996) Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene [see comments]. Nature 382(6593):722–725

    Article  PubMed  CAS  Google Scholar 

  185. Kostrikis LG (2000) Impact of natural chemokine receptor polymorphisms on perinatal transmission of human immunodeficiency virus type 1. Teratology 61(5):387–390

    Article  PubMed  CAS  Google Scholar 

  186. Marmor M, Hertzmark K, Thomas SM, Halkitis PN, Vogler M (2006) Resistance to HIV infection. J Urban Health 83(1):5–17

    Article  PubMed  CAS  Google Scholar 

  187. O’Brien SJ, Moore JP (2000) The effect of genetic variation in chemokines and their receptors on HIV transmission and progression to AIDS. Immunol Rev 177:99–111

    Article  PubMed  Google Scholar 

  188. Philpott S, Weiser B, Tarwater P et al (2003) CC chemokine receptor 5 genotype and susceptibility to transmission of human immunodeficiency virus type 1 in women. J Infect Dis 187(4):569–575

    Article  PubMed  CAS  Google Scholar 

  189. Reiche EM, Bonametti AM, Voltarelli JC, Morimoto HK, Watanabe MA (2007) Genetic polymorphisms in the chemokine and chemokine receptors: impact on clinical course and therapy of the human immunodeficiency virus type 1 infection (HIV-1). Curr Med Chem 14(12):1325–1334

    Article  PubMed  CAS  Google Scholar 

  190. Hendrickson SL, Jacobson LP, Nelson GW et al (2008) Host genetic influences on highly active antiretroviral therapy efficacy and AIDS-free survival. J Acquir Immune Defic Syndr 48(3):263–271

    Article  PubMed  CAS  Google Scholar 

  191. Pine SO, McElrath MJ, Bochud PY (2009) Polymorphisms in toll-like receptor 4 and toll-like receptor 9 influence viral load in a seroincident cohort of HIV-1-infected individuals. AIDS 23(18):2387–2395

    Article  PubMed  CAS  Google Scholar 

  192. Ramsuran V, Kulkarni H, He W et al (2011) Duffy-null-associated low neutrophil counts influence HIV-1 susceptibility in high-risk South African black women. Clin Infect Dis 52(10):1248–1256

    Article  PubMed  CAS  Google Scholar 

  193. Carrington M, O’Brien SJ (2003) The influence of HLA genotype on AIDS. Annu Rev Med 54:535–551

    Article  PubMed  CAS  Google Scholar 

  194. Gonzalez E, Kulkarni H, Bolivar H et al (2005) The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science 307(5714):1434–1440

    Article  PubMed  CAS  Google Scholar 

  195. Bleiber G, May M, Martinez R et al (2005) Use of a combined ex vivo/in vivo population approach for screening of human genes involved in the human immunodeficiency virus type 1 life cycle for variants influencing disease progression. J Virol 79(20):12674–12680

    Article  PubMed  CAS  Google Scholar 

  196. Fellay J, Marzolini C, Meaden ER et al (2002) Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study. Lancet 359(9300):30–36

    Article  PubMed  CAS  Google Scholar 

  197. Haas DW, Smeaton LM, Shafer RW et al (2005) Pharmacogenetics of long-term responses to antiretroviral regimens containing Efavirenz and/or Nelfinavir: an Adult Aids Clinical Trials Group Study. J Infect Dis 192(11):1931–1942

    Article  PubMed  CAS  Google Scholar 

  198. Tsuchiya K, Gatanaga H, Tachikawa N et al (2004) Homozygous CYP2B6 *6 (Q172H and K262R) correlates with high plasma efavirenz concentrations in HIV-1 patients treated with standard efavirenz-containing regimens. Biochem Biophys Res Commun 319(4):1322–1326

    Article  PubMed  CAS  Google Scholar 

  199. Pereyra F, Jia X, McLaren PJ et al (2010) The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 330(6010):1551–1557

    Article  PubMed  CAS  Google Scholar 

  200. Kerr JR, Kaushik N, Fear D, Baldwin DA, Nuwaysir EF, Adcock IM (2005) Single-nucleotide polymorphisms associated with symptomatic infection and differential human gene expression in healthy seropositive persons each implicate the cytoskeleton, integrin signaling, and oncosuppression in the pathogenesis of human parvovirus B19 infection. J Infect Dis 192(2):276–286

    Article  PubMed  CAS  Google Scholar 

  201. Pavy N, Pelgas B, Beauseigle S et al (2008) Enhancing genetic mapping of complex genomes through the design of highly-multiplexed SNP arrays: application to the large and unsequenced genomes of white spruce and black spruce. BMC Genomics 9:21

    Article  PubMed  CAS  Google Scholar 

  202. Chehab FF, Kan YW (1989) Detection of specific DNA sequences by fluorescence amplification: a color complementation assay. Proc Natl Acad Sci U S A 86(23):9178–9182

    Article  PubMed  CAS  Google Scholar 

  203. Saiki RK, Walsh PS, Levenson CH, Erlich HA (1989) Genetic analysis of amplified DNA with immobilized sequence-specific oligonucleotide probes. Proc Natl Acad Sci U S A 86(16):6230–6234

    Article  PubMed  CAS  Google Scholar 

  204. Kornher JS, Livak KJ (1989) Mutation detection using nucleotide analogs that alter electrophoretic mobility. Nucleic Acids Res 17(19):7779–7784

    Article  PubMed  CAS  Google Scholar 

  205. Alves AM, Carr FJ (1988) Dot blot detection of point mutations with adjacently hybridising synthetic oligonucleotide probes. Nucleic Acids Res 16(17):8723

    Article  PubMed  CAS  Google Scholar 

  206. Landegren U, Kaiser R, Sanders J, Hood L (1988) A ligase-mediated gene detection technique. Science 241(4869):1077–1080

    Article  PubMed  CAS  Google Scholar 

  207. Kwok PY (2000) Approaches to allele frequency determination. Pharmacogenomics 1(2):231–235

    Article  PubMed  CAS  Google Scholar 

  208. Shi MM (2002) Technologies for individual genotyping: detection of genetic polymorphisms in drug targets and disease genes. Am J Pharmacogenomics 2(3):197–205

    Article  PubMed  CAS  Google Scholar 

  209. Margulies M, Egholm M, Altman WE et al (2005) Genome sequencing in microfabricated high-density picolitre reactors. Nature 437(7057):376–380

    PubMed  CAS  Google Scholar 

  210. Douek DC, McFarland RD, Keiser PH et al (1998) Changes in thymic function with age and during the treatment of HIV infection. Nature 396(6712):690–695

    Article  PubMed  CAS  Google Scholar 

  211. Ribeiro RM, de Boer RJ (2008) The contribution of the thymus to the recovery of peripheral naive T-cell numbers during antiretroviral treatment for HIV infection. J Acquir Immune Defic Syndr 49(1):1–8

    Article  PubMed  Google Scholar 

  212. Zhang L, Lewin SR, Markowitz M et al (1999) Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy. J Exp Med 190(5):725–732

    Article  PubMed  CAS  Google Scholar 

  213. Dion ML, Bordi R, Zeidan J et al (2007) Slow disease progression and robust therapy-mediated CD4+ T-cell recovery are associated with efficient thymopoiesis during HIV-1 infection. Blood 109(7):2912–2920

    PubMed  CAS  Google Scholar 

  214. Hatzakis A, Touloumi G, Karanicolas R et al (2000) Effect of recent thymic emigrants on progression of HIV-1 disease. Lancet 355(9204):599–604

    Article  PubMed  CAS  Google Scholar 

  215. Marchetti G, Gori A, Casabianca A et al (2006) Comparative analysis of T-cell turnover and homeostatic parameters in HIV-infected patients with discordant immune-virological responses to HAART. AIDS 20(13):1727–1736

    Article  PubMed  Google Scholar 

  216. Saitoh A, Singh KK, Sandall S et al (2006) Association of CD4+ T-lymphocyte counts and new thymic emigrants in HIV-infected children during successful highly active antiretroviral therapy. J Allergy Clin Immunol 117(4):909–915

    Article  PubMed  CAS  Google Scholar 

  217. Haugaard SB, Andersen O, Pedersen SB et al (2005) Depleted skeletal muscle mitochondrial DNA, hyperlactatemia, and decreased oxidative capacity in HIV-infected patients on highly active antiretroviral therapy. J Med Virol 77(1):29–38

    Article  PubMed  CAS  Google Scholar 

  218. Swartz MN (1995) Mitochondrial toxicity—new adverse drug effects. N Engl J Med 333(17):1146–1148

    Article  PubMed  CAS  Google Scholar 

  219. Cote HC, Brumme ZL, Craib KJ et al (2002) Changes in mitochondrial DNA as a marker of nucleoside toxicity in HIV-infected patients. N Engl J Med 346(11):811–820

    Article  PubMed  CAS  Google Scholar 

  220. Casula M, Weverling GJ, Wit FW et al (2005) Mitochondrial DNA and RNA increase in peripheral blood mononuclear cells from HIV-1-infected patients randomized to receive stavudine-containing or stavudine-sparing combination therapy. J Infect Dis 192(10):1794–1800

    Article  PubMed  CAS  Google Scholar 

  221. Garrabou G, Moren C, Gallego-Escuredo JM et al (2009) Genetic and functional mitochondrial assessment of HIV-infected patients developing HAART-related hyperlactatemia. J Acquir Immune Defic Syndr 52(4):443–451

    Article  PubMed  CAS  Google Scholar 

  222. Miro O, Lopez S, Rodriguez de la Concepcion M et al (2004) Upregulatory mechanisms compensate for mitochondrial DNA depletion in asymptomatic individuals receiving stavudine plus didanosine. J Acquir Immune Defic Syndr 37(5):1550–1555

    Article  PubMed  CAS  Google Scholar 

  223. Lin CH, Sloan DD, Dang CH et al (2009) Assessment of mitochondrial toxicity by analysis of mitochondrial protein expression in mononuclear cells. Cytometry B Clin Cytom 76(3):181–190

    PubMed  Google Scholar 

  224. Wang Z, Trillo-Pazos G, Kim SY et al (2004) Effects of human immunodeficiency virus type 1 on astrocyte gene expression and function: potential role in neuropathogenesis. J Neurovirol 10(Suppl 1):25–32

    PubMed  Google Scholar 

  225. Giri MS, Nebozhyn M, Showe L, Montaner LJ (2006) Microarray data on gene modulation by HIV-1 in immune cells: 2000–2006. J Leukoc Biol 80(5):1031–1043

    Article  PubMed  CAS  Google Scholar 

  226. Rotger M, Dalmau J, Rauch A et al (2011) Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque. J Clin Invest 121(6):2391–2400

    Article  PubMed  CAS  Google Scholar 

  227. Wang Z, Gerstein M, Snyder M (2009) RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet 10(1):57–63

    Article  PubMed  CAS  Google Scholar 

  228. Cirulli ET, Singh A, Shianna KV et al (2011) Screening the human exome: a comparison of whole genome and whole transcriptome sequencing. Genome Biol 11(5):R57

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Laboratory Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, 37212, USA

    Yi-Wei Tang M.D., Ph.D.

Authors
  1. Yi-Wei Tang M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yi-Wei Tang M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Department of Laboratory Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, 10065, New York, USA

    Yi-Wei Tang

  2. Vanderbilt Clinic, Clinical Microbiology Laboratory, Vanderbilt University Medical Center, 22nd Avenue 1301, Nashville, 37232-5310, Tennessee, USA

    Charles W. Stratton

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Tang, YW. (2013). Molecular Diagnosis of HIV-1 Infections: Current State of the Art. In: Tang, YW., Stratton, C. (eds) Advanced Techniques in Diagnostic Microbiology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-3970-7_41

Download citation

Publish with us

Policies and ethics

Search

Navigation