Evolutionary mechanisms of retroviral persistence

AIDS Reviews

Volumn 13, Issue 4, 2011, Pages 234-239

  Whitney, James B ^a   Lim, So Yon ^a   Wainberg, Mark A ^b,c  

^a HARVARD MEDICAL SCHOOL   (United States)

^b MCGILL UNIVERSITY   (Canada)

^c MCGILL UNIVERSITY   (Canada)

Author keywords

Antiretroviral therapy; HIV eradication; Persistence; Virus evolution

Indexed keywords

RNA DIRECTED DNA POLYMERASE;

ALLELE; CD4+ T LYMPHOCYTE; EVOLUTION; GENETIC VARIABILITY; HEREDITY; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LENTIVIRINAE; LENTIVIRUS INFECTION; MAJOR HISTOCOMPATIBILITY COMPLEX; NONHUMAN; RETROVIRUS; REVIEW; SIMIAN IMMUNODEFICIENCY VIRUS; SINGLE NUCLEOTIDE POLYMORPHISM; VIRAL GENETICS; VIRUS DNA CELL DNA INTERACTION; VIRUS LATENCY; VIRUS RECOMBINATION; VIRUS REPLICATION; VIRUS TRANSCRIPTION;

ANTI-HIV AGENTS; BIOLOGICAL EVOLUTION; DISEASE RESERVOIRS; DRUG RESISTANCE, VIRAL; HIV INFECTIONS; HIV-1; HUMANS; VIREMIA; VIRUS LATENCY; VIRUS REPLICATION;

EID: 80655148150     PISSN: 11396121     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (128)

1. Coffin J. HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science. 1995;267:483-9.
2. Nowak M. HIV mutation rate. Nature. 1990;347:522. (Pubitemid 20341540)
3. Nowak M, Anderson R, McLean A, et al. Antigenic diversity thresholds and the development of AIDS. Science. 1991;254:963-9. (Pubitemid 21917418)
4. Kimata J, Kuller L, Anderson D, Dailey P, Overbaugh J. Emerging cytopathic and antigenic simian immunodeficiency virus variants influence AIDS progression. Nat Med. 1999;5:535-41. (Pubitemid 29220212)
5. Nowak M, Anderson R, Boerlijst M, et al. HIV-1 evolution and disease progression. Science. 1996;274:1008-11.
6. Malim M, Emerman M. HIV-1 sequence variation: drift, shift, and attenuation. Cell. 2001;104:469-72. (Pubitemid 32201943)
7. Hazuda D, Young S, Guare J, et al. Integrase inhibitors and cellular immunity suppress retroviral replication in rhesus macaques. Science. 2004;305:528-32. (Pubitemid 38971345)
8. Maldarelli F, Palmer S, King M, et al. ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathog. 2007:3:e46.
9. Biebricher C, Eigen M. What is a quasispecies? Curr Top Microbiol Immunol. 2006;299:1-31. (Pubitemid 43086559)
10. Ho D, Neumann A, Perelson A, et al. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995;373:123-6.
11. Markowitz M, Louie M, Hurley A, et al. A novel antiviral intervention results in more accurate assessment of human immunodeficiency virus type 1 replication dynamics and T-cell decay in vivo. J Virol. 2003;77:5037-8. (Pubitemid 36402857)
12. Wei X, Ghosh S, Taylor M, et al. Viral dynamics in human immunodeficiency virus type 1 infection. Nature. 1995;373:117-22.
13. Korber B, Muldoon M, Theiler J, et al. Timing the ancestor of the HIV-1 pandemic strains. Science. 2000;288:1789-96. (Pubitemid 30399011)
14. Rong L, Gilchrist M, Feng Z, Perelson A. Modeling within-host HIV-1 dynamics and the evolution of drug resistance: trade-offs between viral enzyme function and drug susceptibility. J Theor Biol. 2007;247:804-18. (Pubitemid 47081052)
15. Gratton S, Cheynier R, Dumaurier M, Oksenhendler E, Wain-Hobson S. Highly restricted spread of HIV-1 and multiply infected cells within splenic germinal centers. Proc Natl Acad Sci USA. 2000;97:14566-71. (Pubitemid 32016616)
16. Quan Y, Brenner B, Dascal A, Wainberg M. Highly diversified multiply drug-resistant HIV-1 quasispecies in PBMCs: a case report. Retrovirology. 2008;5:43.
17. Quan Y, Liang C, Brenner B, Wainberg M. Multidrug-resistant variants of HIV type 1 (HIV-1) can exist in cells as defective quasispecies and be rescued by superinfection with other defective HIV-1 variants. J Infect Dis. 2009;200:1479-83.
18. Bebenek K, Abbotts J, Wilson S, Kunkel T. Error-prone polymerization by HIV-1 reverse transcriptase. Contribution of template-primer misalignment, miscoding, and termination probability to mutational hot spots. J Biol Chem. 1993;268:10324-34. (Pubitemid 23150215)
19. Boyer J, Bebenek K, Kunkel T. Unequal human immunodeficiency virus type 1 reverse transcriptase error rates with RNA and DNA templates. Proc Natl Acad Sci USA. 1992;89:6919-23.
20. Preston B, Poiesz B, Loeb L. Fidelity of HIV-1 reverse transcriptase. Science. 1988;242:1168-71. (Pubitemid 19007042)
21. Mansky L. In vivo analysis of human T-cell leukemia virus type 1 reverse transcription accuracy. J Virol. 2000;74:9525-31.
22. Wainberg M, Drosopoulos W, Salomon H, et al. Enhanced fidelity of 3TC-selected mutant HIV-1 reverse transcriptase. Science. 1996;271:1282-5. (Pubitemid 26082649)
23. Patel P, Preston B. Marked infidelity of human immunodeficiency virus type 1 reverse transcriptase at RNA and DNA template ends. Proc Natl Acad Sci USA. 1994;91:549-53. (Pubitemid 24041439)
24. Kohlstaedt L, Wang J, Friedman J, Rice P, Steitz T. Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science. 1992;256:1783-90.
25. Ding J, Das K, Hsiou Y, et al. Structure and functional implications of the polymerase active site region in a complex of HIV-1 RT with a double-stranded DNA template-primer and an antibody Fab fragment at 2.8 A resolution. J Mol Biol. 1998;284:1095-111. (Pubitemid 28558559)
26. Vartanian J, Meyerhans A, Sala M, Wain-Hobson S. G - >A hypermutation of the human immunodeficiency virus type 1 genome: evidence for dCTP pool imbalance during reverse transcription. Proc Natl Acad Sci USA. 1994;91:3092-6.
27. Arts E, Quinones-Mateu M. Sorting out the complexities of HIV-1 fitness. AIDS. 2003;17:780-1. (Pubitemid 36521094)
28. Henry K, Weber J, Quinones-Mateu M, Arts E. The impact of viral and host elements on HIV fitness and disease progression. Curr HIV/AIDS Rep. 2007;4:36-41. (Pubitemid 46555250)
29. Quinones-Mateu M, Arts E. Virus fitness: concept, quantification, and application to HIV population dynamics. Curr Top Microbiol Immunol. 2006;299:83-140. (Pubitemid 43086562)
30. Brown R, Peters P, Caron C, et al. Inter-compartment recombination of HIV-1 contributes to env intra-host diversity and modulates viral tropism and senstivity to entry inhibitors. J Virol. 2011;85:6024-37.
31. Hu W, Temin H. Retroviral recombination and reverse transcription. Science. 1990;250:1227-33. (Pubitemid 120031830)
32. Temin H. Sex and recombination in retroviruses. Trends Genet. 1991;7:71-4.
33. Zhang J, Temin H. Rate and mechanism of nonhomologous recombination during a single cycle of retroviral replication. Science. 1993;259:234-8. (Pubitemid 23041801)
34. Anastassopoulou C, Marozsan A, Matet A, et al. Escape of HIV-1 from a small molecule CCR5 inhibitor is not associated with a fitness loss. PLoS Pathog. 2007;3:e79.
35. Muller H. The relation of recombination to mutational advance. Mutat Res. 1964;106:2-9.
36. Negroni M, Buc H. Copy-choice recombination by reverse transcriptases: reshuffling of genetic markers mediated by RNA chaperones. Proc Natl Acad Sci USA. 2000;97:6385-90. (Pubitemid 30412723)
37. Negroni M, Buc H. Retroviral recombination: what drives the switch? Nat Rev Mol Cell Biol. 2001;2:151-5. (Pubitemid 33674044)
38. Zhuang J, Jetzt A, Sun G, et al. Human immunodeficiency virus type 1 recombination: rate, fidelity, and putative hot spots. J Virol. 2002;76:11273-82. (Pubitemid 35231282)
39. Jetzt A, Yu H, Klarmann G, et al. High rate of recombination throughout the human immunodeficiency virus type 1 genome. J Virol. 2000;74:1234-40. (Pubitemid 30044072)
40. Whitney J, Wainberg M. Impaired RNA incorporation and dimerization in live attenuated leader-variants of SIVmac239. Retrovirology. 2006;3:96.
41. Whitney J, Wainberg M. Recovery of fitness of a live attenuated simian immunodeficiency virus through compensation in both the coding and non-coding regions of the viral genome. Retrovirology. 2007;4:44.
42. Archer J, Pinney J, Fan J, et al. Identifying the important HIV-1 recombination breakpoints. PLoS Comput Biol. 2008;4:e1000178.
43. Baird H, Gao Y, Galetto R, et al. Influence of sequence identity and unique breakpoints on the frequency of intersubtype HIV-1 recombination. Retrovirology. 2006;3:91.
44. Shao W, Kearney M, Maldarelli F, Mellors JW, Stephens RM, et al. (2009) RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. Retrovirology 2009;6:101.
45. Shi B, Kitchen C, Weiser B, et al. Evolution and recombination of genes encoding HIV-1 drug resistance and tropism during antiretroviral therapy. Virology. 2010;404:5-20.
46. Tebit D, Nankya I, Arts E, Gao Y. HIV diversity, recombination and disease progression: how does fitness "fit" into the puzzle? AIDS Rev. 2007;9:75-87. (Pubitemid 47162247)
47. Bukrinsky M, Stanwick T, Dempsey M, Stevenson M. Quiescent T lymphocytes as an inducible virus reservoir in HIV-1 infection. Science. 1991;254:423-7. (Pubitemid 21917358)
48. Swingler S, Brichacek B, Jacque J, et al. HIV-1 Nef intersects the macrophage CD40L signalling pathway to promote resting-cell infection. Nature. 2003;424:213-19. (Pubitemid 36858691)
49. Arts E, Quinones-Mateu M, Albright J, et al. 3'-Azido-3'-deoxythymidine (AZT) mediates cross-resistance to nucleoside analogs in the case of AZT-resistant human immunodeficiency virus type 1 variants. J Virol. 1998;72:4858-65. (Pubitemid 28215663)
50. Arts E, Wainberg M. Human immunodeficiency virus type 1 reverse transcriptase and early events in reverse transcription. Adv Virus Res. 1996;46:97-163. (Pubitemid 3027544)
51. Geleziunas R, Arts E, Boulerice F, Goldman H, Wainberg M. Effect of 3′-azido-3′-deoxythymidine on human immunodeficiency virus type 1 replication in human fetal brain macrophages. Antimicrob Agents Chemother. 1993;37:1305-12. (Pubitemid 23166731)
52. Chun T, Davey R, Ostrowski M, et al. Relationship between pre-existing viral reservoirs and the re-emergence of plasma viremia after discontinuation of highly active anti-retroviral therapy. Nat Med. 2000;6:757-61. (Pubitemid 30469423)
53. Ho D, Zhang L. HIV-1 rebound after antiretroviral therapy. Nat Med. 2000;6:736-7.
54. Sharkey M, Babic D, Greenough T, et al. Episomal viral cDNAs identify a reservoir that fuels viral rebound after treatment interruption and that contributes to treatment failure. PLoS Pathog. 2011;7:e1001303.
55. Westermann J, Persin S, Matyas J, van der Meide P, Pabst R. Migration of so-called naive and memory T lymphocytes from blood to lymph in the rat. The influence of IFN-gamma on the circulation pattern. J Immunol. 1994;152:1744-50. (Pubitemid 24075705)
56. Westermann J, Pabst R. Distribution of lymphocyte subsets and natural killer cells in the human body. Clin Investig. 1992;70:539-44.
57. Westermann J, Blaschke V, Zimmermann G, Hirschfeld U, Pabst R. Random entry of circulating lymphocyte subsets into peripheral lymph nodes and Peyer's patches: no evidence in vivo of a tissue-specific migration of B and T lymphocytes at the level of high endothelial venules. Eur J Immunol. 1992;22:2219-23.
58. Sopper S, Nierwetberg D, Halbach A, et al. Impact of simian immunodeficiency virus (SIV) infection on lymphocyte numbers and T-cell turnover in different organs of rhesus monkeys. Blood. 2003;101:1213-19. (Pubitemid 36182488)
59. Chun T, Carruth L, Finzi D, et al. Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature. 1997;387:183-8. (Pubitemid 27209433)
60. McNamara L, Collins K. Hematopoietic stem/precursor cells as HIV reservoirs. Curr Opin HIV AIDS. 2011;6:43-8.
61. Schrager L, D'Souza M. Cellular and anatomical reservoirs of HIV-1 in patients receiving potent antiretroviral combination therapy. JAMA. 1998;280:67-71. (Pubitemid 28414999)
62. Vernazza P, Gilliam B, Flepp M, et al. Effect of antiviral treatment on the shedding of HIV-1 in semen. AIDS. 1997;11:1249-54. (Pubitemid 27298091)
63. Pilcher C, Shugars D, Fiscus S, et al. HIV in body fluids during primary HIV infection: implications for pathogenesis, treatment and public health. AIDS. 2001;15:837-45. (Pubitemid 32424387)
64. Pilcher C, Eron J, Vemazza P, et al. Sexual transmission during the incubation period of primary HIV infection. JAMA. 2001;286:1713-14. (Pubitemid 33010256)
65. Eron J, Vernazza P, Johnston D, et al. Resistance of HIV-1 to antiretroviral agents in blood and seminal plasma: implications for transmission. AIDS. 1998;12:F181-9. (Pubitemid 28479268)
66. Zhang L, Rowe L, He T, et al. Compartmentalization of surface envelope glycoprotein of human immunodeficiency virus type 1 during acute and chronic infection. J Virol. 2002;76:9465-73. (Pubitemid 34919903)
67. Nunnari G, Otero M, Dornadula G, et al. Residual HIV-1 disease in seminal cells of HIV-1-infected men on suppressive HAART: latency without ongoing cellular infections. AIDS. 2002;16:39-45. (Pubitemid 34062180)
68. Kemal K, Foley B, Burger H, et al. HIV-1 in genital tract and plasma of women: compartmentalization of viral sequences, coreceptor usage, and glycosylation. Proc Natl Acad Sci USA. 2003;100:12972-7. (Pubitemid 37340010)
69. Zhu T, Wang N, Carr A, et al. Genetic characterization of human immunodeficiency virus type 1 in blood and genital secretions: evidence for viral compartmentalization and selection during sexual transmission. J Virol. 1996;70:3098-107. (Pubitemid 26121927)
70. Whitney J, Hraber P, Luedemann C, et al. Genital tract sequestration of SIV following acute infection. PLoS Pathog. 2011;7:e1001293.
71. Lerner P, Guadalupe M, Donovan R, et al. Gut mucosal viral reservoir in HIV infected patients is not the major source of rebound plasma viremia following HAART interruption. J Virol. 2011;85:4772-82.
72. Carter C, McNamara L, Onafuwa-Nuga A, et al. HIV-1 utilizes the CXCR4 chemokine receptor to infect multipotent hematopoietic stem and progenitor cells. Cell Host Microbe. 2011;9:223-34.
73. Brenner B, Routy J, Quan Y, et al. Persistence of multidrug-resistant HIV-1 in primary infection leading to superinfection. AIDS. 2004;18:1653-60. (Pubitemid 39095782)
74. Carter C, Onafuwa-Nuga A, McNamara L, et al. HIV-1 infects multipotent progenitor cells causing cell death and establishing latent cellular reservoirs. Nat Med. 2010;16:446-51.
75. Hakre S, Chavez L, Shirakawa K, Verdin E. Epigenetic regulation of HIV latency. Curr Opin HIV AIDS. 2011;6:19-24.
76. Kingman J. Origins of the coalescent. 1974-1982. Genetics. 2000;156:1461-3.
77. Leslie A, Pfafferott K, Chetty P, et al. HIV evolution: CTL escape mutation and reversion after transmission. Nat Med. 2004;10:282-9. (Pubitemid 38667619)
78. Allen T, Jing P, Calore B, et al. Effects of cytotoxic T lymphocytes (CTL) directed against a single simian immunodeficiency virus (SIV) Gag CTL epitope on the course of SIVmac239 infection. J Virol. 2002;76:10507-11.
79. Loffredo J, Friedrich T, Leon E, et al. CD8+ T cells from SIV elite controller macaques recognize Mamu-B*08-bound epitopes and select for widespread viral variation. PLoS ONE. 2007;2:e1152.
80. Watkins D, Chen Z, Hughes A, et al. Evolution of the MHC class I genes of a New World primate from ancestral homologues of human non-classical genes. Nature. 1990;346:60-3.
81. Kaslow R, Carrington M, Apple R, et al. Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat Med. 1996;2:405-11. (Pubitemid 26193012)
82. Fellay J, Shianna K, Ge D, et al. A whole-genome association study of major determinants for host control of HIV-1. Science. 2007;317:944-7. (Pubitemid 47301321)
83. Thomas R, Apps R, Qi Y, et al. HLA-C cell surface expression and control of HIV/AIDS correlate with a variant upstream of HLA-C. Nat Genet. 2009;41:1290-4.
84. Martin M, Gao X, Lee J, et al. Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Nat Genet. 2002;31:429-34. (Pubitemid 35154456)
85. Dean M, Carrington M, Winkler C, et al. 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. Science. 1996;273:1856-62.
86. Huang Y, Paxton WA, Wolinsky SM, et al. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med. 1996;2:1240-3. (Pubitemid 26375409)
87. Smith MW, Dean M, Carrington M, et al. Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study. Science. 1997;277:959-65.
88. Carrington M, Nelson GW, Martin MP, et al. HLA and HIV-1: Heterozygote Advantage and B*35-Cw*04 Disadvantage. Science. 1999;283(5408):1748- 52.
89. Gao X, Nelson GW, Karacki P, et al. Effect of a Single Amino Acid Change in MHC Class I Molecules on the Rate of Progression to AIDS. N Engl J Med. 2001;344(22):1668-75. (Pubitemid 32479964)
90. An P, Nelson G, Wang L, et al. Modulating influence on HIV/AIDS by interacting RANTES gene variants. Proc Natl Acad Sci USA. 2002;99(15):10002-7. (Pubitemid 34831162)
91. Saha K, Bentsman G, Chess L, Volsky DJ. Endogenous production of beta-chemokines by CD4+, but not CD8+, T-cell clones correlates with the clinical state of human immunodeficiency virus type 1 (HIV-1)-infected individuals and may be responsible for blocking infection with non-syncytium-inducing HIV-1 in vitro. J Virol. 1998;72(1):876-81.
92. González E, Dhanda R, Bamshad M, et al. Global survey of genetic variation in CCR5, RANTES, and MIP-1alpha: impact on the epidemiology of the HIV-1 pandemic. Proc Natl Acad Sci USA. 2001;98(9):5199-204. (Pubitemid 32397106)
93. González E, Kulkarni H, Bolivar H, et al. (2005) The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science. 2005;307(5714):1434-40. (Pubitemid 40321934)
94. van Rij RP, Broersen S, Goudsmit J, Coutinho RA, Schuitemaker H. The role of a stromal cell-derived factor-1 chemokine gene variant in the clinical course of HIV-1 infection. AIDS. 1998;12(9):F85-F90. (Pubitemid 28276962)
95. Winkler C, Modi W, Smith MW, et al. Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC). Science. 1998;279(5349):389-93.
96. Julg B, Reddy S, van der Stok M, et al. Lack of Duffy antigen receptor for chemokines: no influence on HIV disease progression in an African treatment-naive population. Cell Host Microbe. 2009;5:413-15.
97. Hunt P, Carrington M. Host genetic determinants of HIV pathogenesis: an immunologic perspective. Curr Opin HIV AIDS. 2008;3:342-8. (Pubitemid 351521019)
98. Stremlau M, Owens CM, Perron MJ, et al. The cytoplasmic body component TRIM5alpha restricts HIV-1 infection in Old World monkeys. Nature. 2004;427:848-53. (Pubitemid 38297747)
99. Lim SY, Rogers T, Chan T, et al. TRIM5α modulates immunodeficiency virus control in rhesus monkeys. PLoS Pathogens. 2010;6(1):e1000738.
100. Sheehy AM, Gaddis N, Choi JD, Malim MH. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature. 2002;418(6898):646-50.
101. An P, Bleiber G, Duggal P, et al. APOBEC3G genetic variants and their influence on the progression to AIDS. J Virol. 2004;78(20):11070-6. (Pubitemid 39299647)
102. Javanbakht H, An P, Gold B, et al. Effects of human TRIM5α polymorphisms on antiretroviral function and susceptibility to human immunodeficiency virus infection. Virology 2006;353:234-46.
103. Sawyer SL, Wu LI, Akey JM, Emerman M, Malik HS. High-frequency persistence of an impaired allele of the retroviral defense gene TRIM5α in humans. Curr Biol. 2006;16:95-100. (Pubitemid 43049892)
104. Speelmon EC, Livingston-Rosanoff D, Li SS, et al. Genetic association of the antiviral restriction factor TRIM5α with human immunodeficiency virus type 1 infection. J Virol. 2006;80:2463-71. (Pubitemid 43271552)
105. van Manen D, Rits MA, Beugeling C, et al. The effect of Trim5 polymorphisms on the clinical course of HIV-1 infection. PLoS Pathog. 2008;4:e18.
106. Goldschmidt V, Bleiber G, May M, et al. Role of common human TRIM5α variants in HIV-1 disease progression. Retrovirology. 2006;22:54-61.
107. Do H, Vasilescu A, Diop G, et al. Exhaustive genotyping of the CEM15 (APOBEC3G) gene and absence of association with AIDS progression in a French cohort. J Infect Dis. 2004;191(2):159-63.
108. Perelson A, Neumann A, Markowitz M, Leonard JM, Ho DD. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science. 1996;271:1582-6. (Pubitemid 26097216)
109. Chun T, Chadwick K, Margolick J, Siliciano R. Differential susceptibility of naive and memory CD4+ T cells to the cytopathic effects of infection with human immunodeficiency virus type 1 strain LAI. J Virol. 1997;71:4436-44. (Pubitemid 27204133)
110. Finzi D, Blankson J, Siliciano J, et al. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med. 1999;5:512-17. (Pubitemid 29220209)
111. Zhang L, Ramratnam B, Tenner-Racz K, et al. Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. N Engl J Med. 1999;340:1605-13. (Pubitemid 29249429)
112. Pomerantz R, Zhang H. Residual HIV-1 persistence during suppressive HAART. Curr Clin Top Infect Dis. 2001;21:1-30. (Pubitemid 33712806)
113. Dornadula G, Zhang H, VanUitert B, et al. Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy. JAMA. 1999;282:1627-32. (Pubitemid 29513968)
114. Chun T, Davey R, Engel D, Lane H, Fauci A. Re-emergence of HIV after stopping therapy. Nature. 1999;401:874-5. (Pubitemid 129516777)
115. Persaud D, Zhou Y, Siliciano J, Siliciano R. Latency in human immunodeficiency virus type 1 infection: no easy answers. J Virol. 2003;77:1659-65. (Pubitemid 36109978)
116. Gunthard H, Havlir D, Fiscus S, et al. Residual human immunodeficiency virus (HIV) Type 1 RNA and DNA in lymph nodes and HIV RNA in genital secretions and in cerebrospinal fluid after suppression of viremia for 2 years. J Infect Dis. 2001;183:1318-27. (Pubitemid 32337113)
117. Smith D, Wong J, Shao H, et al. Long-term persistence of transmitted HIV drug resistance in male genital tract secretions: implications for secondary transmission. J Infect Dis. 2007;196:356-60. (Pubitemid 47093885)
118. Dinoso J, Kim S, Wiegand A, et al. Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy. Proc Natl Acad Sci USA. 2009;106:9403-8.
119. Rong L, Perelson A. Modeling latently infected cell activation: viral and latent reservoir persistence, and viral blips in HIV-infected patients on potent therapy. PLoS Comput Biol. 2009;5:e1000533.
120. Bailey J, Sedaghat A, Kieffer T, et al. Residual human immunodeficiency virus type 1 viremia in some patients on antiretroviral therapy is dominated by a small number of invariant clones rarely found in circulating CD4+ T cells. J Virol. 2006;80:6441-57. (Pubitemid 43927447)
121. Brennan T, Woods J, Sedaghat A, et al. Analysis of human immunodeficiency virus type 1 viremia and provirus in resting CD4+ T cells reveals a novel source of residual viremia in patients on antiretroviral therapy. J Virol. 2009;83:8470-81.
122. Brennan T, Woods J, Sedaghat A, et al. Analysis of HIV-1 viremia and provirus in resting CD4+ T cells reveals a novel source of residual viremia in patients on antiretroviral therapy. J Virol. 2009;83:8470-81.
123. Dinoso J, Rabi S, Blankson J, et al. A SIV-infected macaque model to study viral reservoirs that persist during highly active antiretroviral therapy. J Virol. 2009;83:9247-57.
124. Masek-Hammerman K, Li H, Liu J, et al. Mucosal trafficking of vector-specific CD4+ T lymphocytes following adenovirus serotype 5 vaccination of rhesus monkeys. J Virol. 2010;84:9810-16.
125. Rong L, Perelson A. Modeling HIV persistence, the latent reservoir, and viral blips. J Theor Biol. 2009;260:308-31.
126. Buzon M, Massanella M, Llibre J, et al. HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. Nat Med. 2010;16:460-5.
127. Maldarelli F. Targeting viral reservoirs: ability of antiretroviral therapy to stop viral replication. Curr Opin HIV AIDS. 2011;6:49-56.
128. Chun T, Justement J, Murray D, et al. Rebound of plasma viremia following cessation of antiretroviral therapy despite profoundly low levels of HIV reservoir: implications for eradication. AIDS. 2010;24:2803-8.