Evolutionary Dynamics of HIV-1 and the Control of AIDS

  • J. I. Mullins
  • M. A. Jensen
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 299)


Human immunodeficiency viruses (HIV) have exhibited an extraordinary capacity for genetic change, exploring new evolutionary space after each transmission to a new host. This presents a great challenge to the prevention and management of HIV-1 infection. At the same time, the relentless diversification of HIV-1, developing as it does under the constraints imposed by the human immune system and other selective forces, contains within it information useful for understanding HIV epidemiology and pathogenesis. Comparing the sheer mutational potential of HIV with actual data representing viral lineages that can survive selection suggests that HIV does not have unlimited capacity for change. Rather, clinical and bioinformatic data suggest that, even in the most diverse gene of the most highly variable organism, natural selection places severe limits on the portion of amino acid sequence space that ensures viability. This suggests some optimism for those attempting to identify sets of antigens that can generate effective humoral and cellular immune responses against HIV.


Coreceptor Usage Latent Reservoir Structure Treatment Interruption 
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  1. Achaz G, Palmer S, Kearney M, Maldarelli F, Mellors JW, Coffin JM, Wakeley J (2004) A robust measure of HIV-1 population turnover within chronically infected individuals. Mol Biol Evol 21:1902–1912PubMedGoogle Scholar
  2. Aldrovandi GM (1999) Natural history of pediatric HIV disease. Lippincott Williams and Wilkins, PhiladelphiaGoogle Scholar
  3. Allen TM, Altfeld M, Yu XG, O’Sullivan KM, Lichterfeld M, Le Gall S, John M, Mothe BR, Lee PK, Kalife ET, Cohen DE, Freedberg KA, Strick DA, Johnston MN, Sette A, Rosenberg ES, Mallal SA, Goulder PJ, Brander C, Walker BD (2004) Selection, transmission, and reversion of an antigen-processing cytotoxic T-lymphocyte escape mutation in human immunodeficiency virus type 1 infection. J Virol 78:7069–7078PubMedGoogle Scholar
  4. Altfeld M, Walker BD (2001) Less is more? STI in acute and chronic HIV-1 infection. Nat Med 7:881–884CrossRefPubMedGoogle Scholar
  5. Altfeld M, Allen TM, Yu XG, Johnston MN, Agrawal D, Korber BT, Montefiori DC, O’Connor DH, Davis BT, Lee PK, Maier EL, Harlow J, Goulder PJ, Brander C, Rosenberg ES, Walker BD (2002) HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus. Nature 420:434–439CrossRefPubMedGoogle Scholar
  6. Arts EJ, Quinones-Mateu ME (2003) Sorting out the complexities of HIV-1 fitness. Aids 17:780–781CrossRefPubMedGoogle Scholar
  7. Bickel PJ, Cosman PC, Olshen RA, Spector PC, Rodrigo AR, Mullins JI (1996) Covariability of V3 loop amino acids. AIDS Res Human Retrovir 12:1401–1411Google Scholar
  8. Bienzle D, MacDonald KS, Smaill FM, Kovacs C, Baqi M, Courssaris B, Luscher MA, Walmsley SL, Rosenthal KL (2000) Factors contributing to the lack of human immunodeficiency virus type 1 (HIV-1) transmission in HIV-1-discordant partners. J Infect Dis 182:123–132CrossRefPubMedGoogle Scholar
  9. Birk M, Svedhem V, Sonnerborg A (2001) Kinetics of HIV-1 RNA and resistance-associated mutations after cessation of antiretroviral combination therapy. Aids 15:1359–1368CrossRefPubMedGoogle Scholar
  10. Björndal A, Deng H, Jansson M, Fiore JR, Colognesi C, Karlsson A, Albert J, Scarlatti G, Littman DR, Fenyö EM (1997) Coreceptor usage of primary human immunodeficiency virus type 1 isolates varies according to biological phenotype. J Virol 71:7478–7487PubMedGoogle Scholar
  11. Brenner BG, Routy JP, Petrella M, Moisi D, Oliveira M, Detorio M, Spira B, Essabag V, Conway B, Lalonde R, Sekaly RP, Wainberg MA (2002) Persistence and fitness of multidrug-resistant human immunodeficiency virus type 1 acquired in primary infection. J Virol 76:1753–1761CrossRefPubMedGoogle Scholar
  12. Bretscher MT, Althaus CL, Muller V, Bonhoeffer S (2004) Recombination in HIV and the evolution of drug resistance: for better or for worse? Bioessays 26:180–188CrossRefPubMedGoogle Scholar
  13. Brumme ZL, Dong WWY, Yip B, Wynhoven B, Hoffman NG, Swanstrom R, Jensen MA, Mullins JI, Hogg RS, Montaner JSG, Harrigan PR (2004) Clinical and immunological impact of HIV envelope V3 sequence variation after starting initial triple antiretroviral therapy. Aids 18:F1–F9PubMedGoogle Scholar
  14. Casartelli N, Di Matteo G, Potesta M, Rossi P, Doria M (2003) CD4 and major histocompatibility complex class I downregulation by the human immunodeficiency virus type 1 nef protein in pediatric AIDS progression. J Virol 77:11536–11545CrossRefPubMedGoogle Scholar
  15. Chen R, Quinones-Mateu ME, Mansky LM (2004) Drug resistance, virus fitness and HIV-1 mutagenesis. Curr Pharm Des 10:4065–4070PubMedGoogle Scholar
  16. Chen R, Quinones-Mateu ME, Mansky LM (2005) HIV-1mutagenesis during antiretroviral therapy: implications for successful drug treatment. Front Biosci 10:743–750PubMedGoogle Scholar
  17. Chun TW, Stuyver L, Mizell SB, Ehler LA, Mican JA, Baseler M, Lloyd AL, Nowak MA, Fauci AS (1997) Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci U S A 94:13193–13197CrossRefPubMedGoogle Scholar
  18. Chun TW, Davey RT Jr, Ostrowski M, Shawn Justement J, Engel D, Mullins JI, Fauci AS (2000) Relationship between pre-existing viral reservoirs and the re-emergence of plasma viremia after discontinuation of highly active anti-retroviral therapy. Nat Med 6:757–761CrossRefPubMedGoogle Scholar
  19. Connor RI, Sheridan KE, Ceradini D, Choe S, Landau NR (1997) Change in coreceptor use correlates with disease progression in HIV-1-infected individuals. J Exp Med 185:621–628CrossRefPubMedGoogle Scholar
  20. Cooper DA, Imrie AA, Penney R (1987) Antibody response to human immunodeficiency virus after primary infection. J Infect Dis 155:1113–1118PubMedGoogle Scholar
  21. Daar ES, Moudgil T, Meyer RD, Ho DD (1991) Transient high levels of viremia in patients with primary HIV-1 infection. N Engl J Med 324:961–964PubMedGoogle Scholar
  22. De Jong JJ, Goudsmit J, Keulen W, Klaver B, Krone W, Tersmette M, de Ronde A (1992) Human immunodeficiency virus type 1 clones chimeric for the envelope V3 domain differ in syncytium formation and replication capacity. J Virol 66:757–765PubMedGoogle Scholar
  23. Deeks SG, Barbour JD, Martin JN, Swanson MS, Grant RM (2000) Sustained CD4+ T cell response after virologic failure of protease inhibitor-based regimens in patients with human immunodeficiency virus infection. J Infect Dis 181:946–953CrossRefPubMedGoogle Scholar
  24. Deeks SG, Wrin T, Liegler T, Hoh R, Hayden M, Barbour JD, Hellmann NS, Petropoulos CJ, McCune JM, Hellerstein MK, Grant RM (2001) Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia. N Engl J Med 344:472–480CrossRefPubMedGoogle Scholar
  25. Deeks SG, Grant RM, Wrin T, Paxinos EE, Liegler T, Hoh R, Martin JN, Petropoulos CJ (2003) Persistence of drug-resistant HIV-1 after a structured treatment interruption and its impact on treatment response. Aids 17:361–370CrossRefPubMedGoogle Scholar
  26. Delwart EL, Sheppard HW, Walker BD, Goudsmit J, Mullins JI (1994) Human immunodeficiency virus type 1 evolution in vivo tracked by DNA heteroduplex mobility assays. J Virol 68:6672–6683PubMedGoogle Scholar
  27. Derdeyn CA, Decker JM, Bibollet-Ruche F, Mokili JL, Muldoon M, Denham SA, Heil ML, Kasolo F, Musonda R, Hahn BH, Shaw GM, Korber BT, Allen S, Hunter E (2004) Envelope-constrained neutralization-sensitive HIV-1 after heterosexual transmission. Science 303:2019–2022CrossRefPubMedGoogle Scholar
  28. Desrosiers RC (2004) Prospects for an AIDS vaccine. Nat Med 10:221–223CrossRefPubMedGoogle Scholar
  29. Di Mascio M, Markowitz M, Louie M, Hurley A, Hogan C, Simon V, Follmann D, Ho DD, Perelson AS (2004) Dynamics of intermittent viremia during highly active antiretroviral therapy in patients who initiate therapy during chronic versus acute and early human immunodeficiency virus type 1 infection. J Virol 78:10566–10573PubMedGoogle Scholar
  30. Domingo E, Menendez-Arias L, Quinones-Mateu ME, Holguin A, Gutierrez-Rivas M, Martinez MA, Quer J, Novella IS, Holland JJ (1997) Viral quasispecies and the problem of vaccine-escape and drug-resistant mutants. Prog Drug Res 48:99–128PubMedGoogle Scholar
  31. Dybul M, Chun TW, Yoder C, Hidalgo B, Belson M, Hertogs K, Larder B, Dewar RL, Fox CH, Hallahan CW, Justement JS, Migueles SA, Metcalf JA, Davey RT, Daucher M, Pandya P, Baseler M, Ward DJ, Fauci AS (2001) Short-cycle structured intermittent treatment of chronic HIV infection with highly active antiretroviral therapy: effects on virologic, immunologic, and toxicity parameters. Proc Natl Acad Sci U S A 98:15161–15166CrossRefPubMedGoogle Scholar
  32. Dybul M, Daucher M, Jensen MA, Hallahan CW, Chun TW, Belson M, Hidalgo B, Nickel DC, Yoder C, Metcalf JA, Davey RT, Ehler L, Kress-Rock D, Nies-Kraske E, Liu S, Mullins JI, Fauci AS (2003) Genetic characterization of rebounding human immunodeficiency virus type 1 in plasma during multiple interruptions of highly active antiretroviral therapy. J Virol 77:3229–3237CrossRefPubMedGoogle Scholar
  33. Finzi D, Blankson J, Siliciano JD, Margolick JB, Chadwick K, Pierson T, Smith K, Lisziewicz J, Lori F, Flexner C, Quinn TC, Chaisson RE, Rosenberg E, Walker B, Gange S, Gallant J, Siliciano RF (1999) Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med 5:512–517PubMedGoogle Scholar
  34. Fouchier RAM, Groenink M, Kootstra NA, Tersmette M, Huisman HG, Miedema F, Schuitemaker H (1992) Phenotype-associated sequence variation in the third variable domain (V3) of the human immunodeficiency virus type 1 gp120 molecule. J Virol 66:3183–3187PubMedGoogle Scholar
  35. Fowke KR, Nagelkerke NJ, Kimani J, Simonsen JN, Anzala AO, Bwayo JJ, MacDonald KS, Ngugi EN, Plummer FA (1996) Resistance to HIV-1 infection among persistently seronegative prostitutes in Nairobi, Kenya. Lancet 348:1347–1351CrossRefPubMedGoogle Scholar
  36. Frenkel LM, Mullins JI (2001) Should patients with drug-resistant HIV-1 continue to receive antiretroviral Therapy? N Engl J Med 344:520–522CrossRefPubMedGoogle Scholar
  37. Frenkel LM, Wang Y, Learn GH, McKernan JL, Ellis GM, Mohan KM, Holte SE, De Vange SM, Pawluk DM, Melvin AJ, Lewis PF, Heath LM, Beck IA, Mahalanabis M, Naugler WE, Tobin NH, Mullins JI (2003) Multiple viral genetic analyses detecting low-level HIV-1 replication during effective HAART. J Virol 77:5721–5730CrossRefPubMedGoogle Scholar
  38. Friedrich TC, Dodds EJ, Yant LJ, Vojnov L, Rudersdorf R, Cullen C, Evans DT, Desrosiers RC, Mothe BR, Sidney J, Sette A, Kunstman K, Wolinsky S, Piatak M, Lifson J, Hughes AL, Wilson N, O’Connor DH, Watkins DI (2004) Reversion of CTL escape-variant immunodeficiency viruses in vivo. Nat Med 10:275–281CrossRefPubMedGoogle Scholar
  39. Goudsmit J, De Ronde A, Ho DD, Perelson AS (1996) Human immunodeficiency virus fitness in vivo: calculations based on a single zidovudine resistance mutation at codon 215 of reverse transcriptase. J Virol 70:5662–5664PubMedGoogle Scholar
  40. Grobler J, Gray CM, Rademeyer C, Seoighe C, Ramjee G, Abdool Karim S, Morris L, Williamson C (2004) Incidence of HIV-1 dual infection and its association with increased viral load set point in a cohort of HIV-1 subtype C-infected female sex workers. J Infect Dis 190:1355–1359CrossRefPubMedGoogle Scholar
  41. Gunthard HF, Frost SD, Leigh-Brown AJ, Ignacio CC, Kee K, Perelson AS, Spina CA, Havlir DV, Hezareh M, Looney DJ, Richman DD, Wong JK (1999) Evolution of envelope sequences of human immunodeficiency virus type1 in cellular reservoirs in the setting of potent antiviral therapy. J Virol 73:9404–9412PubMedGoogle Scholar
  42. Hatano H, Vogel S, Yoder C, Metcalf JA, Dewar R, Davey RT Jr, Polis MA (2000) Pre-HAART HIV burden approximates post-HAART viral levels following interruption of therapy in patients with sustained viral suppression. Aids 14:1357–1363PubMedGoogle Scholar
  43. Ho DD (1998) Toward HIV eradication or remission: the tasks ahead. Science 280:1866–1867CrossRefPubMedGoogle Scholar
  44. Ho DD, Sarngadharan MG, Resnick L, Dimarzoveronese F, Rota TR, Hirsch MS (1985) Primary human T-lymphotropic virus type III infection. Ann Intern Med 103:880–883PubMedGoogle Scholar
  45. Hoffman NG, Seillier-Moiseiwitsch F, Ahn J, Walker JM, Swanstrom R (2002) Variability in the human immunodeficiency virus type 1 gp120 Env protein linked to phenotype-associated changes in the V3 loop. J Virol 76:3852–3864CrossRefPubMedGoogle Scholar
  46. Huang Y, Paxton WA, Wolinsky SM, Neumann AU, Zhang L, He T, Kang S, Ceradini D, Jin Z, Yazdanbakhsh K, Kunstman K, Erickson D, Dragon E, Landau NR, Phair J, Ho DD, Koup RA (1996) The role of a mutant CCR5 allele in HIV-1 transmission and disease progression [see comments]. Nat Med 2:1240–1243CrossRefPubMedGoogle Scholar
  47. Jain RG, Furfine ES, Pedneault L, White AJ, Lenhard JM (2001) Metabolic complications associated with antiretroviral therapy. Antiviral Res 51:151–177CrossRefPubMedGoogle Scholar
  48. Jensen MA, van’ t Wout AB (2003) Predicting HIV-1 coreceptor usage with sequence analysis. AIDS Rev 5:104–112PubMedGoogle Scholar
  49. Jensen MA, Li F-S, van’ t Wout AB, Nickle DC, Shriner D, He H, McLaughlin S, Shankarappa R, Margolick JB, Mullins JI (2003) Improved coreceptor usage prediction and genotypic monitoring of R5-to-X4 transition by motif analysis of human immunodeficiency virus type 1 env V3 loop sequences. J Virol 77:13376–13388PubMedGoogle Scholar
  50. Jost S, Bernard MC, Kaiser L, Yerly S, Hirschel B, Samri A, Autran B, Goh LE, Perrin L (2002) A patient with HIV-1 superinfection. N Engl J Med 347:731–736CrossRefPubMedGoogle Scholar
  51. Karlsson I, Antonsson L, Shi Y, Karlsson A, Albert J, Leitner T, Olde B, Owman C, Fenyo EM (2003) HIV biological variability unveiled: frequent isolations and chimeric receptors reveal unprecedented variation of coreceptor use. Aids 17:2561–2569PubMedGoogle Scholar
  52. Kaufmann DE, Lichterfeld M, Altfeld M, Addo MM, Johnston MN, Lee PK, Wagner BS, Kalife ET, Strick D, Rosenberg ES, Walker BD (2004) Limited durability of viral control following treated acute HIV infection. Plos Med 1:e36CrossRefPubMedGoogle Scholar
  53. Kaul R, Rowland-Jones SL, Kimani J, Dong T, Yang HB, Kiama P, Rostron T, Njagi E, Bwayo JJ, MacDonald KS, McMichael AJ, Plummer FA (2001) Late seroconversion in HIV-resistant Nairobi prostitutes despite pre-existing HIV-specific CD8+ responses. J Clin Invest 107:341–349PubMedGoogle Scholar
  54. Kiepiela P, Leslie AJ, Honeyborne I, Ramduth D, Thobakgale C, Chetty S, Rathnavalu P, Moore C, Pfafferott KJ, Hilton L, Zimbwa P, Moore S, Allen T, Brander C, Addo MM, Altfeld M, James I, Mallal S, Bunce M, Barber LD, Szinger J, Day C, Klenerman P, Mullins J, Korber B, Coovadia HM, Walker BD, Goulder PJ (2004) Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA. Nature 432:769–775CrossRefPubMedGoogle Scholar
  55. Kijak GH, Simon V, Balfe P, Vanderhoeven J, Pampuro SE, Zala C, Ochoa C, Cahn P, Markowitz M, Salomon H (2002) Origin of human immunodeficiency virus type 1 quasispecies emerging after antiretroviral treatment interruption in patients with therapeutic failure. J Virol 76:7000–7009CrossRefPubMedGoogle Scholar
  56. Koot M, Keet I, Vos A, deGoede R, Roos M, Coutinho R, Miedema F, Schellekens P, Tersmette M (1993) Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS. Ann Intern Med 118:681–688PubMedGoogle Scholar
  57. Korber BT, Farber RM, Wolpert DH, Lapedes AS (1993) Covariation of mutations in the V3 loop of human immunodeficiency virus type 1 envelope protein: an information theoretic analysis. Proc Natl Acad Sci U S A 90:7176–7180PubMedGoogle Scholar
  58. Koup RA, Safrit JT, Cao Y, Andrews CA, McLeod G, Borkowsky W, Farthing C, Ho DD (1994) Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J Virol 68:4650–4655PubMedGoogle Scholar
  59. Learn GH, Muthui D, Brodie SJ, Zhu T, Diem K, Mullins JI, Corey L (2002) Virus population homogenization following acute human immunodeficiency virus type 1 infection. J Virol 76:11953–11959CrossRefPubMedGoogle Scholar
  60. Leigh-Brown AJ (1997) Analysis of HIV-1 env gene sequences reveals evidence for a low effective number in the viral population. Proc Natl Acad Sci U S A 94:1862–1865Google Scholar
  61. Leslie AJ, Pfafferott KJ, Chetty P, Draenert R, Addo MM, Feeney M, Tang Y, Holmes EC, Allen T, Prado JG, Altfeld M, Brander C, Dixon C, Ramduth D, Jeena P, Thomas SA, John AS, Roach TA, Kupfer B, Luzzi G, Edwards A, Taylor G, Lyall H, Tudor-Williams G, Novelli V, Martinez-Picado J, Kiepiela P, Walker BD, Goulder PJ (2004) HIV evolution: CTL escape mutation and reversion after transmission. Nat Med 10:282–289CrossRefPubMedGoogle Scholar
  62. Liu S-L, Mittler JE, Nickel DC, Mulvania TM, Shriner D, Rodrigo AG, Kosloff B, He X, Corey L, Mullins JI (2002) Selection for human immunodeficiency virus type 1 recombinants in a patient with rapid progression to AIDS. J Virol 76:10674–10684PubMedGoogle Scholar
  63. Long EM, Martin HL Jr, Kreiss JK, Rainwater SM, Lavreys L, Jackson DJ, Rakwar J, Mandaliya K, Overbaugh J (2000) Gender differences in HIV-1 diversity at time of infection. Nat Med 6:71–75PubMedGoogle Scholar
  64. Malaspina A, Moir S, Nickle DC, Donoghue ET, Ogwaro KM, Ehler LA, Liu S, Mican JA, Dybul M, Chun TW, Mullins JI, Fauci AS (2002) Human immunodeficiency virus type 1 bound to B cells: relationship to virus replicating in CD4(+) T cells and circulating in plasma. J Virol 76:8855–8863CrossRefPubMedGoogle Scholar
  65. Mallon PW, Carr A, Cooper DA (2002) HIV-associated lipodystrophy: description, pathogenesis, and molecular pathways. Curr Diab Rep 2:116–124PubMedGoogle Scholar
  66. Margolick JB, Donnenberg AD, Munoz A (1994) T lymphocyte homeostasis after HIV seroconversion. J Acquir Immune Defic Syndr 7:415–416PubMedGoogle Scholar
  67. Margolick JB, Munoz A, Donnenberg AD et al (1995) Failure of T-cell homeostasis preceding AIDS in HIV-1 infection. Nat Med 1:674–680CrossRefPubMedGoogle Scholar
  68. Mellors JW, Munoz A, Giorgi JV, Margolick JB, Tassoni CJ, Gupta P, Kingsley LA, Todd JA, Saah AJ, Detels R, Phair JP, Rinaldo CR Jr (1997) Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med 126:946–954PubMedGoogle Scholar
  69. Menzo S, Monachetti A, Balotta C, Corvasce S, Rusconi S, Paolucci S, Baldanti F, Bagnarelli P, Clementi M (2003) Processivity and drug-dependence of HIV-1 protease: determinants of viral fitness in variants resistant to protease inhibitors. Aids 17:663–671CrossRefPubMedGoogle Scholar
  70. Michael NL, Chang G, Louie LG, Mascola JR, Dondero D, Birx DL, Sheppard HW (1997) The role of viral phenotype and CCR-5 gene defects in HIV-1 transmission and disease progression. Nat Med 3:338–340PubMedGoogle Scholar
  71. Milich L, Margolin B, Swanstrom R (1993) V3 loop of the human immunodeficiency virus type 1 Env protein: interpreting sequence variability. J Virol 67:5623–5634PubMedGoogle Scholar
  72. Miller V (2001) Structured treatment interruptions in antiretroviral management of HIV-1. Curr Opin Infect Dis 14:29–37PubMedGoogle Scholar
  73. Moore CB, John M, James IR, Christiansen FT, Witt CS, Mallal SA (2002) Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level. Science 296:1439–1443CrossRefPubMedGoogle Scholar
  74. Mullins JI (1997) Curtailing the AIDS pandemic (letter). Science 276:1955–1957CrossRefPubMedGoogle Scholar
  75. Mullins JI, Hoover EA, Quackenbush SL, Donahue PR (1991) Disease progression and viral genome variants in experimental feline leukemia virus-induced immunodeficiency syndrome (published erratum appears in J Acquir Immune Defic Syndr 1991;4:925). J Acquir Immune Defic Syndr 4:547–557PubMedGoogle Scholar
  76. Mullins JI, Nickle DC, Heath L, Rodrigo AG, Learn GH (2004) Immunogen sequence: the fourth tier of AIDS vaccine design. Expert Rev Vaccines 3[Suppl 1]: S151–S159PubMedGoogle Scholar
  77. Muñoz A, Sabin CA, Phillips AN (1997) The incubation period of AIDS. AIDS 11:S69–S76PubMedGoogle Scholar
  78. Nickle DC, Jensen MA, Shriner D, Brodie SJ, Frenkel LM, Mittler JE, Mullins JI (2003a) Evolutionary indicators of human immunodeficiency virus type 1 reservoirs and compartments. J Virol 77:5540–5546CrossRefPubMedGoogle Scholar
  79. Nickle DC, Shriner D, Mittler JE, Frenkel LM, Mullins JI (2003b) Importance and detection of virus reservoirs and compartments of HIV infection. Curr Opin Microbiol 6:410–416CrossRefPubMedGoogle Scholar
  80. Nijhuis M, Deeks S, Boucher C (2001) Implications of antiretroviral resistance on viral fitness. Curr Opin Infect Dis 14:23–28PubMedGoogle Scholar
  81. O’Brien SJ, Nelson GW (2004) Human genes that limit AIDS. Nat Genet 36:565–574PubMedGoogle Scholar
  82. O’Brien TR, Winkler C, Dean M, Nelson JA, Carrington M, Michael NL, White GC 2nd (1997) HIV-1 infection in a man homozygous for CCR5 delta 32. Lancet 349:1219PubMedGoogle Scholar
  83. Overbaugh J, Donahue PR, Quackenbush SL, Hoover EA, Mullins JI (1988) Molecular cloning of a feline leukemia virus that induces fatal immunodeficiency disease in cats. Science 239:906–910PubMedGoogle Scholar
  84. Oxenius A, Hirschel B (2003) Structured treatment interruptions in HIV infection: benefit or disappointment? Expert Rev Anti Infect Ther 1:129–139CrossRefPubMedGoogle Scholar
  85. Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD (1998) Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 338:853–860CrossRefPubMedGoogle Scholar
  86. Perelson AS, Neumann AU, Markowitz M, Leonard JM, Ho DD (1996) HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science 271:1582–1586PubMedGoogle Scholar
  87. Quinones-Mateu ME, Arts EJ (2002) HIV-1 fitness: implications for drug resistance, disease progression, and global epidemic evolution. In: Kuiken C, Foley B, Hahn B, Marx P, McCutchan F, Mellors J, Wolinsky S, Korber B (eds) HIV Sequence Compendium 2001. Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM, pp 134–170Google Scholar
  88. Quinones-Mateu ME, Ball SC, Marozsan AJ, Torre VS, Albright JL, Vanham G, van Der Groen G, Colebunders RL, Arts EJ (2000) A dual infection/competition assay shows a correlation between ex vivo human immunodeficiency virus type 1 fitness and disease progression. J Virol 74:9222–9233CrossRefPubMedGoogle Scholar
  89. Resch W, Hoffman N, Swanstrom R (2001) Improved success of phenotype prediction of the human immunodeficiency virus type 1 from envelope variable loop 3 sequence using neural networks. Virology 288:51–62CrossRefPubMedGoogle Scholar
  90. Rhodes T, Wargo H, Hu WS (2003) High rates of human immunodeficiency virus type 1 recombination: near-random segregation of markers one kilobase apart in one round of viral replication. J Virol 77:11193–11200CrossRefPubMedGoogle Scholar
  91. Rodrigo AG (1997) Dynamics of syncytium-inducing and non-syncytium-inducing type 1 human immunodeficiency viruses during primary infection. AIDS Res Human Retrovir 13:1447–1451Google Scholar
  92. Rosenberg ES, Altfeld M, Poon SH, Phillips MN, Wilkes BM, Eldridge RL, Robbins GK, D’Aquila RT, Goulder PJ, Walker BD (2000) Immune control of HIV-1 after early treatment of acute infection. Nature 407:523–526PubMedGoogle Scholar
  93. Ruiz L, Martinez-Picado J, Romeu J, Paredes R, Zayat MK, Marfil S, Negredo E, Sirera G, Tural C, Clotet B (2000) Structured treatment interruption in chronically HIV-1 infected patients after long-term viral suppression. Aids 14:397–403PubMedGoogle Scholar
  94. Sagar M, Lavreys L, Baeten JM, Richardson BA, Mandaliya K, Chohan BH, Kreiss JK, Overbaugh J (2003) Infection with multiple human immunodeficiency virus type 1 variants is associated with faster disease progression. J Virol 77:12921–12926CrossRefPubMedGoogle Scholar
  95. Schacker TW, Hughes JP, Shea T, Coombs RW, Corey L (1998) Biological and virologic characteristics of primary HIV infection. Ann Intern Med 128:613–620PubMedGoogle Scholar
  96. Schrager LK, D’Souza MP (1998) Cellular and anatomical reservoirs of HIV-1 in patients receiving potent antiretroviral combination therapy. JAMA 280:67–71CrossRefPubMedGoogle Scholar
  97. Shankarappa R, Margolick JB, Gange SJ, Rodrigo AG, Upchurch D, Farzadegan H, Gupta P, Rinaldo CR, Learn GH, He X, Huang XL, Mullins JI (1999) Consistent viral evolutionary changes associated with the progression of human immunodeficiency virus type 1 infection. J Virol 73:10489–10502PubMedGoogle Scholar
  98. Shpaer EG, Delwart EL, Kuiken CL, Goudsmit J, Bachmann MH, Mullins JI (1994) Conserved V3 loop sequences and transmission of human immunodeficiency virus type 1. AIDS Res Hum Retroviruses 10:1679–1684PubMedGoogle Scholar
  99. Shriner D, Rodrigo AG, Nickle DC, Mullins JI (2004a) Pervasive genomic recombination of HIV-1 in vivo. Genetics 167:1573–1583CrossRefPubMedGoogle Scholar
  100. Shriner D, Shankarappa R, Jensen MA, Nickle DC, Mittler JE, Margolick JB, Mullins JI (2004b) Influence of random genetic drift on HIV-1 env evolution during chronic infection. Genetics 166:1155–1164CrossRefPubMedGoogle Scholar
  101. Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, Margolick JB, Kovacs C, Gange SJ, Siliciano RF (2003) Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4(+) T cells. Nat Med 9:727–728CrossRefPubMedGoogle Scholar
  102. Stoddart CA, Geleziunas R, Ferrell S, Linquist-Stepps V, Moreno ME, Bare C, Xu W, Yonemoto W, Bresnahan PA, McCune JM, Greene WC (2003) Human immunodeficiency virus type 1 nef-mediated downregulation of CD4 correlates with nef enhancement of viral pathogenesis. J Virol 77:2124–2133CrossRefPubMedGoogle Scholar
  103. Tanaka M, Ueno T, Nakahara T, Sasaki K, Ishimoto A, Sakai H (2003) Downregulation of CD4 is required for maintenance of viral infectivity of HIV-1. Virology 311:316–325CrossRefPubMedGoogle Scholar
  104. Tang J, Tang S, Lobashevsky E, Zulu I, Aldrovandi G, Allen S, Kaslow RA (2004) HLA allele sharing and HIV type 1 viremia in seroconverting Zambians with known transmitting partners. AIDS Res Hum Retroviruses 20:19–25CrossRefPubMedGoogle Scholar
  105. Tersmette M, de Goede REY, Al BJM, Winkel IN, Gruters RA, Cuypers HT, Huisman HG, Miedema F (1988) Differential syncytium-inducing capacity of HIV isolates: frequent detection of syncytium-inducing isolates in patients with AIDS and AIDS-related complex. J Virol 62:2026–2032PubMedGoogle Scholar
  106. Tersmette M, Gruters RA, de Wolf F, de Goede RE, Lange JM, Schellekens PT, Goudsmit J, Huisman HG, Miedema F (1989) Evidence for a role of virulent human immunodeficiency virus (HIV) variants in the pathogenesis of acquired immunodeficiency syndrome: studies on sequential HIV isolates. J Virol 63:2118–2125PubMedGoogle Scholar
  107. Theodorou I, Meyer L, Magierowska M, Katlama C, Rouzioux C (1997) HIV-1 infection in an individual homozygous for CCR5 delta 32. Seroco Study Group. Lancet 349:1219–1220CrossRefPubMedGoogle Scholar
  108. Trachtenberg E, Korber B, Sollars C, Kepler TB, Hraber PT, Hayes E, Funkhouser R, Fugate M, Theiler J, Hsu YS, Kunstman K, Wu S, Phair J, Erlich H, Wolinsky S (2003) Advantage of rare HLA supertype in HIV disease progression. Nat Med 9:928–935CrossRefPubMedGoogle Scholar
  109. Tremblay CL, Hicks JL, Sutton L, Giguel F, Flynn T, Johnston M, Sax PE, Walker BD, Hirsch MS, Rosenberg ES, D’Aquila RT (2003) Antiretroviral resistance associated with supervised treatment interruptions in treated acute HIV infection. Aids 17:1086–1089CrossRefPubMedGoogle Scholar
  110. Van’ t Wout AB, Kootstra NA, Mulder-Kampinga GA, Albrecht-van Lent N, Scherpbier HJ, Veenstra J, Boer K, Coutinho RA, Miedema F, Schuitemaker H (1994) Macrophage-tropic variants initiate HIV-1 infection after sexual, parenteral, and vertical transmission. J Clin Invest 94:2060–2067Google Scholar
  111. Van Rij RP, Blaak H, Visser JA, Brouwer M, Rientsma R, Broersen S, de Roda Husman AM, Schuitemaker H (2000) Differential coreceptor expression allows for independent evolution of non-syncytium-inducing and syncytium-inducing HIV-1. J Clin Invest 106:1039–1052PubMedGoogle Scholar
  112. Wei X, Ghosh SK, Taylor ME, Johnson VA, Emini EA, Deutsch P, Lifson JD, Bonhoeffer S, Nowak MA, Hahn BH, Saag MS, Shaw GM (1995) Viral dynamics in human immunodeficiency virus type 1 infection. Nature 373:117–122CrossRefPubMedGoogle Scholar
  113. Wein LM, D’Amato RM, Perelson AS (1997) Mathematical analysis of antiviral therapy aimed at HIV-1 eradication or maintenance of low viral loads. J Theor Biol 192:81–98Google Scholar
  114. Yang OO, Daar ES, Jamieson BD, Balamurugan A, Smith DM, Pitt JA, Petropoulos CJ, Richman DD, Little SJ, Brown AJ (2005) Human immunodeficiency virus type 1 clade B superinfection: evidence for differential immune containment of distinct clade B strains. J Virol 79:860–868PubMedGoogle Scholar
  115. Yusim K, Kesmir C, Gaschen B, Addo MM, Altfeld M, Brunak S, Chigaev A, Detours V, Korber BT (2002) Clustering patterns of cytotoxic T-lymphocyte epitopes in human immunodeficiency virus type 1 (HIV-1) proteins reveal imprints of immune evasion on HIV-1 global variation. J Virol 76:8757–8768CrossRefPubMedGoogle Scholar
  116. Zhang LQ, MacKenzie P, Cleland A, Holmes EC, Leigh Brown AJ, Simmonds P (1993) Selection for specific sequences in the external envelope protein of HIV-1 upon primary infection. J Virol 67:3345–3356PubMedGoogle Scholar
  117. Zhu T, Mo H, Wang N, Nam DS, Cao Y, Koup RA, Ho DD (1993) Genotypic and phenotypic characterization of HIV-1 in patients with primary infection. Science 261:1179–1181PubMedGoogle Scholar
  118. Zhu T, Corey L, Akridge R, Change Y, Feng F, Kim J, Alef C, McElroy A, Mullins J, McElrath J (1999) Evidence for HIV-1 latent infection in exposed seronegative individuals. 6th Conference on Retroviruses and Opportunistic Infections, ChicagoGoogle Scholar
  119. Zhu T, Brodie S, Mullins JI, Corey L (2000) Reservoirs of viral persistence after HAART therapy of primary HIV. International meeting of the Institute of Human Virology, BaltimoreGoogle Scholar
  120. Zhu T, Muthui D, Holte S, Nickle D, Feng F, Brodie S, Hwangbo Y, Mullins JI, Corey L (2002) Evidence for human immunodeficiency virus type 1 replication in vivo in CD14(+) monocytes and its potential role as a source of virus in patients on highly active antiretroviral therapy. J Virol 76:707–716PubMedGoogle Scholar
  121. Zhu T, Corey L, Hwangbo Y, Lee JM, Learn GH, Mullins JI, McElrath MJ (2003) Persistence of extraordinarily low levels of genetic homogeneous human immunodeficiency virus type 1 in exposed seronegative individuals. J Virol 77:6108–6116PubMedGoogle Scholar
  122. Zhu T, Hu S-L, Feng F, Polacino P, Liu H, Hwangbo Y, Learn GH, Mullins JI, Corey L (2004) Persistence of low levels of simian immunodeficiency virus in macaques that were transiently viremic by conventional testing. Virology 323:208–219CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • J. I. Mullins
    • 1
  • M. A. Jensen
    • 1
  1. 1.Departments of MicrobiologyUniversity of Washington School of MedicineSeattleUSA

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