Chapter 30 : Immune Intervention in AIDS

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This chapter reviews concepts and strategies that are being considered for the development of effective immune interventions for the treatment of human immunodeficiency virus (HIV) disease. It is likely that the development of effective immune-based interventions for the treatment of HIV infection will be greatly facilitated by an improved understanding of the fundamental mechanisms of the immunopathogenesis of AIDS. An important challenge for future research efforts will be to discover ways of modulating the host immune response so its beneficial aspects are enhanced without simultaneously increasing its deleterious aspects. Similarly, any attempt to use immunosuppression as an approach to abrogation of the deleterious indirect consequences of HIV infection will need to be done in a way that does not also compromise the beneficial aspects of immunemediated control of HIV replication. The idea of therapeutic vaccination of HIVinfected individuals dates back to the early years of the AIDS epidemic, and clinical trials aimed at augmenting anti-HIV cellular immune responses in infected patients by immunization with the recombinant HIV envelope glycoproteins gp120 and gp160 were first performed in the early 1990s. Recent studies of prophylactic DNA vaccine in macaque models of simian immunodeficiency virus (SIV) infection have shown that DNA vaccines, in combination with cytokines (e.g., interleukin-2 [IL-2]) or followed by boosting with recombinant viral vectors (e.g., an attenuated strain of vaccinia virus known as modified vaccinia Ankara), can induce potent anti-HIV CD4 and CD8 T-cell responses and enable substantial control of SIV viremia following experimental challenge with virulent virus strains.

Citation: Silvestri G, Feinberg M. 2002. Immune Intervention in AIDS, p 453-477. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch30

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Human immunodeficiency virus 1
Humoral Immune Response
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Figure 1

Immunopathogenesis of HIV infection (A) in humans and SIV infection (B) in a natural host species (sooty mangabeys). Straight lines represent specific pathogenic mechanisms contributing to disease progression in chronically infected individuals. Dotted-bar lines represent physiologic (CTL) or therapeutic (HAART) events opposing the progression of the infection toward chronic immunodeficiency and AIDS. Dotted lines in panel B represent immunopathologic mechanisms of disease that are absent in the nonpathogenic chronic SIV infection of sooty mangabeys.

Citation: Silvestri G, Feinberg M. 2002. Immune Intervention in AIDS, p 453-477. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch30
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Image of Figure 2
Figure 2

Virology and immunology in three subjects who controlled viremia after the first treatment interruption. In all three, the plasma viral load rose but then dropped, remaining consistently below 5,000 copies of HIV-1 RNA per ml (top row). Gag-specific T-helper-cell responses were maintained in all three subjects (middle row). CTL responses increased significantly from baseline values and are shown as responses to individual CTL epitopes with HLA restriction (bottom row). CTL responses were confirmed by cloning and testing in cytolytic assays. The shaded area indicates antiviral therapy reinitiated for subject 3, despite not meeting protocol indication for retreatment. Reprinted from with permission of the publisher.

Citation: Silvestri G, Feinberg M. 2002. Immune Intervention in AIDS, p 453-477. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch30
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1. Amado, R. G.,, R. T. Mitsuyasu,, and J. A. Zack. 1999. Gene therapy for the treatment of AIDS: animal models and human clinical experience. Front. Biosci. 4:D468D475.
2. Amara, R. R.,, F. Villinger,, J. D. Altman,, S. L. Lydy,, S. P. O’Neil,, S. I. Staprans,, D. C. Montefiori,, Y. Xu,, J. G. Herndon,, L. S. Wyatt,, M. A. Candido,, N. L. Kozyr,, P. L. Earl,, J. M. Smith,, H.-L. Ma,, B. D. Grimm,, M. L. Hulsey,, J. Miller,, H. M. Mc- Clure,, J. M. McNicholl,, B. Moss,, and H. L. Robinson. 2001. Control of mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine. Science 292:6974.
3. Andrieu, J. M.,, W. Lu,, and R. Levy. 1995. Sustained increases in CD4 cell counts in asymptomatic human immunodeficiency virus type 1-seropositive patients treated with prednisolone for 1 year. J. Infect. Dis. 17:523530.
4. Appay, V.,, D. F. Nixon,, S. M. Donahoe,, G. M. Gillespie,, T. Dong,, A. King,, G. S. Ogg,, H. M. Spiegel,, C. Conlon,, C. A. Spina,, D. V. Havlir,, D. D. Richman,, A. Waters,, P. Easterbrook,, A. J. McMichael,, and S. L. Rowland-Jones. 2000. HIV-specific CD8(+) T cells produce antiviral cytokines but are impaired in cytolytic function. J. Exp. Med. 192:6375.
5. Ardizzoni, A.,, M. Bonavia,, M. Viale,, E. Baldini,, C. Mereu,, A. Verna,, S. Ferrini,, A. Cinquegrana,, S. Molinari,, and G. L. Mariani. 1994. Biologic and clinical effects of continuous infusion interleukin-2 in patients with non-small cell lung cancer. Cancer 73:13531360.
6. Arno, A.,, L. Ruiz,, M. Juan,, A. Jou,, C. Balague,, M. K. Zayat,, S. Marfil,, J. Martinez-Picado,, M. A. Martinez,, J. Romeu,, R. Pujol- Borrell,, C. Lane,, and B. Clotet. 1999. Efficacy of low-dose subcutaneous interleukin-2 to treat advanced human immunodeficiency virus type 1 in persons with ≤250/μl CD4 T cells and undetectable plasma virus load. J. Infect. Dis. 180:5660.
7. Badley, A. D.,, A. A. Pilon,, A. Landay,, and D. H. Lynch. 2000. Mechanisms of HIV-associated lymphocyte apoptosis. Blood 96: 29512964.
8. Barouch, D. H.,, S. Santra,, J. E. Schmitz,, M. J. Kuroda,, T. M. Fu,, W. Wagner,, M. Bilska,, A. Craiu,, X. X. Zheng,, G. R. Krivulka,, K. Beaudry,, M. A. Lifton,, C. E. Nickerson,, W. L. Trigona,, K. Punt,, D. C. Freed,, L. Guan,, S. Dubey,, D. Casimiro,, A. Simon,, M. E. Davies,, M. Chastain,, T. B. Strom,, R. S. Gelman,, D. C. Montefiori,, and M. G. Lewis. 2000. Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination. Science 290:486492.
9. Bartz, S. R.,, E. Hohenwalter,, M. K. Hu,, D. H. Rich,, and M. Malkovsky. 1995. Inhibition of human immunodeficiency virus replication by nonimmunosuppressive analogs of cyclosporin A. Proc. Natl. Acad. Sci. USA 92:53815385.
10. Belyakov, I. M.,, J. D. Ahlers,, B. Y. Brandwein,, P. Earl,, B. L. Kelsall,, B. Moss,, W. Strober,, and J. A. Berzofsky. 1998. The importance of local mucosal HIV-specific CD8(+) cytotoxic T lymphocytes for resistance to mucosal viral transmission in mice and enhancement of resistance by local administration of IL-12. J. Clin. Invest. 102:20722081.
11. Berger, E. A.,, P. M. Murphy,, and J. M. Farber. 1999. Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu. Rev. Immunol. 17:657700.
12. Billich, A.,, F. Hammerschmid,, P. Peichl,, R. Wenger,, G. Zenke,, V. Quesniaux,, and B. Rosenwirth. 1995. Mode of action of SDZ NIM 811, a nonimmunosuppressive cyclosporin A analog with activity against human immunodeficiency virus (HIV) type 1: interference with HIV protein-cyclophilin A interactions. J. Virol. 69:24512461.
13. Birx, D. L.,, L. D. Loomis-Price,, N. Aronson,, J. Brundage,, C. Davis,, L. Dayton,, R. P. Garner,, F. Gordin,, D. Henry,, W. Holloway,, T. Kerkering,, R. Luskin-Hawk,, J. McNeil,, N. Michael,, P. Foster Pierce,, D. Poretz,, S. Ratto-Kim,, P. Renzullo,, N. Ruiz,, K. V. Sitz,, G. Smith,, C. Tacket,, M. Thompson,, E. Tramont,, B. Yangco,, R. Yarrish,, and R. R. Redfield. 2000. Efficacy testing of recombinant HIV gp160 as a therapeutic vaccine in earlystage HIV-1 infected volunteers. rgp160 phase II vaccine investigators. J. Infect. Dis. 181:881889.
14. Blankson, J. N.,, D. Finzi,, T. C. Pierson,, B. P. Sabundayo,, K. Chadwick,, J. B. Margolick,, T. C. Quinn,, and R. F. Siliciano. 2000. Biphasic decay of latently infected CD4+ T cells in acute human immunodeficiency virus type 1 infection. J. Infect. Dis. 182:16361642.
15. Boyer, J. D.,, M. A. Chattergoon,, K. E. Ugen,, A. Shah,, M. Bennett,, A. Cohen,, S. Nyland,, K. E. Lacy,, M. L. Bagarazzi,, T. J. Higgins,, Y. Baine,, R. B. Ciccarelli,, R. S. Ginsberg,, R. R. MacGregor,, and D. B. Weiner. 1999. Enhancement of cellular immune response in HIV-1 seropositive individuals: a DNA-based trial. Clin. Immunol. 90:100107.
16. Brodie, S. J.,, D. A. Lewinsohn,, B. K. Patterson,, D. Jiyamapa,, J. Krieger,, L. Corey,, P. D. Greenberg,, and S. D. Riddell. 1999. In vivo migration and function of transferred HIV-1 specific cytotoxic T cells. Nat. Med. 5:3441.
17. Brodie, S. J.,, B. K. Patterson,, D. A. Lewinsohn,, K. Diem,, D. Spach,, P. D. Greenberg,, S. D. Riddell,, and L. Corey. 2000. HIV-specific cytotoxic T lymphocytes traffic to lymph nodes and localize at sites of HIV replication and cell death. J. Clin. Investig. 105:14071417.
18. Calarota, S.,, G. Bratt,, S. Nordlund,, J. Hinkula,, A. C. Leandersson,, E. Sandstrom,, and B. Wahren. 1998. Cellular cytotoxic response induced by DNA vaccination in HIV-1-infected patients. Lancet 351:13201325.
19. Calarota, S. A.,, A. C. Leandersson,, G. Bratt,, J. Hinkula,, D. M. Klinman,, K. J. Weinhold,, E. Sandstrom,, and B. Wahren. 1999. Immune responses in asymptomatic HIV-1-infected patients after HIV-DNA immunization followed by highly active antiretroviral treatment. J. Immunol. 163:23302338.
20. Cannavo, G.,, M. Paiardini,, D. Galati,, B. Cervasi,, M. Montroni,, D. Guetard,, G. DeVico,, R. Ientile,, I. Picerno,, M. Magnani,, G. Silvestri,, and G. Piedimonte. 2001. Abnormal intracellular kinetics of cell cycle dependent proteins during HIV-infection: a novel biological link between immune activation, accelerated T cell turnover and high level of apoptosis. Blood 97:6.
21. Cao, Y.,, L. Qin,, L. Zhang,, J. Safrit,, and D. D. Ho. 1995. Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. N. Engl. J. Med. 332:201208.
22. Carcelain, G.,, R. Tubiana,, A. Samri,, V. Calvez,, C. Delaugeree,, H. Agut,, C. Kathama,, and B. Autran. 2001. Transient mobilization of human immunodeficiency virus (HIV)-specific CD4 T-helper cells fails to control viral rebounds during intermittent antiretroviral therapy in chronic HIV type-1 infection. J. Virol. 75: 234241.
23. Carroll, R. G.,, J. L. Riley,, B. L. Levine,, Y. Feng,, S. Kaushal,, D. W. Ritchey,, W. Bernstein,, O. S. Weislow,, C. R. Brown,, E. A. Berger,, C. H. June,, and D. C. St. Louis. 1997. Differential regulation of HIV-1 fusion cofactor expression by CD28 costimulation of CD4+ T cells. Science 276:273276.
24. Chapuis, A. G.,, G. P. Rizzardi,, C. D’Agostino,, A. Attinger,, C. Knabenhans,, S. Fleury,, H. Acha-Orbea,, and G. Pantaleo. 2000. Effects of mycophenolic acid on human immunodeficiency virus infection in vitro and in vivo. Nat. Med. 6:762768.
25. Chia, W. K.,, E. Nisbet-Brown,, X. Li,, I. Salit,, S. Joshi,, and S. E. Read. 1994. Lack of correlation between phenotype activation markers of CD8 lymphocytes and cytotoxic T lymphocyte (CTL) function in HIV-1 infection: evidence for rescue with rIL- 2. Viral Immunol. 7:8195.
26. Chun, T. W.,, D. Engel,, S. B. Mizell,, C. W. Hallahan,, M. Fischette,, S. Park,, R. T. Davey Jr,, M. Dybul,, J. A. Kovacs,, J. Metcalf,, J. M. Mican,, M. M. Berrey,, L. Corey,, H. C. Lane,, and A. S. Fauci. 1999. Effect of IL-2 on the pool of latently infected, resting CD4+ T cells in HIV-1-infected patients receiving highly active anti-retroviral therapy. Nat. Med. 5:651655.
27. Churdboonchart, V.,, R. B. Moss,, W. Sirawaraporn,, B. Smutharaks,, R. Sutthent,, F. C. Jensen,, P. Vacharak,, J. Grimes,, G. Theofan,, and D. J. Carlo. 1998. Effect of HIV-specific immune-based therapy in subjects infected with HIV-1 subtype E in Thailand. AIDS 12:15211527.
28. Clark, S. J.,, M. S. Saag,, W. D. Decker,, S. Campbell-Hill,, J. L. Roberson,, P. J. Veldkamp,, J. C. Kappes,, B. H. Hahn,, and G. M. Shaw. 1991. High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection. N. Engl. J. Med. 324:954960.
29. Cohen, O. J.,, A. Kinter,, and A. S. Fauci. 1997. Host factors in the pathogenesis of HIV disease. Immunol. Rev. 159:3148.
30. Collaborative Group on AIDS Incubation and HIV Survival. 2000. Time from HIV-1 seroconversion to AIDS and death before widespread use of highly-active antiretroviral therapy: a collaborative reanalysis. Collaborative Group on AIDS Incubation and HIV Survival including the CASCADE EU Concerted Action. Concerted Action on SeroConversion to AIDS and Death in Europe. Lancet 355:11311137.
31. Connors, M.,, J. A. Kovacs,, S. Krevat,, J. C. Gea-Banacloche,, M. C. Sneller,, M. Flanigan,, J. A. Metcalf,, R. E. Walker,, J. Falloon,, M. Baseler,, I. Feuerstein,, H. Masur,, and H. C. Lane. 1997. HIV infection induces changes in CD4+ T-cell phenotype and depletions within the CD4+ T-cell repertoire that are not immediately restored by antiviral or immune-based therapies. Nat. Med. 3:533540.
32. Crabtree, G. R. 1999. Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NF-AT. Cell 96:611614.
33. Daar, E. S.,, T. Moudgil,, R. D. Meyer,, and D. D. Ho. 1991. Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection. N. Engl. J. Med. 324: 961964.
34. Dalgleish, A. G.,, P. C. Beverley,, P. R. Clapham,, D. H. Crawford,, M. F. Greaves,, and R. A. Weiss. 1984. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 312:763767.
35. Davey, R. T., Jr.,, D. G. Chaitt,, J. M. Albert,, S. C. Piscitelli,, J. A. Kovacs,, R. E. Walker,, J. Falloon,, M. A. Polis,, J. A. Metcalf,, H. Masur,, R. Dewar,, M. Baseler,, G. Fyfe,, M. A. Giedlin,, and H. C. Lane. 1999. A randomized trial of high- versus low-dose subcutaneous interleukin-2 outpatient therapy for early human immunodeficiency virus type 1 infection. J. Infect. Dis. 179:849858.
36. Davey, R. T., Jr.,, D. G. Chaitt,, S. C. Piscitelli,, M. Wells,, J. A. Kovacs,, R. E. Walker,, J. Falloon,, M. A. Polis,, J. A. Metcalf,, H. Masur,, G. Fyfe,, and H. C. Lane. 1997. Subcutaneous administration of interleukin-2 in human immunodeficiency virus type 1-infected persons. J. Infect. Dis. 175:781789.
37. Davey, R. T., Jr.,, R. L. Murphy,, F. M. Graziano,, S. L. Boswell,, A. T. Pavia,, M. Cancio,, J. P. Nadler,, D. G. Chaitt,, R. L. Dewar,, D. K. Sahner,, A. M. Duliege,, W. B. Capra,, W. P. Leong,, M. A. Giedlin,, H. C. Lane,, and J. O. Kahn. 2000. Immunologic and virologic effects of subcutaneous interleukin 2 in combination with antiretroviral therapy: a randomized controlled trial. JAMA 284:183189.
38. De Paoli, P.,, S. Zanussi,, C. Simonelli,, M. T. Bortolin,, M. D’Andrea,, C. Crepaldi,, R. Talamini,, M. Comar,, M. Giacca,, and U. Tirelli. 1997. Effects of subcutaneous interleukin-2 therapy on CD4 subsets and in vitro cytokine production in HIV+ subjects. J. Clin. Immunol. 100:27372743.
39. Douek, D. C.,, R. D. McFarland,, P. H. Keiser,, E. A. Gage,, J. M. Massey,, B. F. Haynes,, M. A. Polis,, A. T. Haase,, M. B. Feinberg,, J. L. Sullivan,, B. D. Jamieson,, J. A. Zack,, L. J. Picker,, and R. A. Koup. 1998. Changes in thymic function with age and during the treatment of HIV infection. Nature 396:690695.
40. Durack, D. T. 1981. Opportunistic infections and Kaposi’s sarcoma in homosexual men. N. Engl. J. Med. 305:14651467.
41. Dybul, M.,, G. Mercier,, M. Belson,, C. W. Hallahan,, S. Liu,, C. Perry,, B. Herpin,, L. Ehler,, R. T. Davey,, J. A. Metcalf,, J. M. Mican,, R. A. Seder,, and A. S. Fauci. 2000. CD40 ligand trimer and IL-12 enhance peripheral blood mononuclear cells and CD4+ T cell proliferation and production of IFN-gamma in response to p24 antigen in HIV-infected individuals: potential contribution of anergy to HIV-specific unresponsiveness. J. Immunol. 165:16851691.
42. Emery, S.,, W. B. Capra,, D. A. Cooper,, R. T. Mitsuyasu,, J. A. Kovacs,, P. Vig,, M. Smolskis,, L. D. Saravolatz,, H. C. Lane,, G. A. Fyfe,, and P. T. Curtin. 2000. Pooled analysis of 3 randomized, controlled trials of interleukin-2 therapy in adult human immunodeficiency virus type 1 disease. J. Infect. Dis. 182:428434.
43. Fauci, A. S. 1988. The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science 239:617622.
44. Finzi, D.,, J. Blankson,, J. D. Siliciano,, J. B. Margolick,, K. Chadwick,, T. Pierson,, K. Smith,, J. Lisziewicz,, F. Lori,, C. Flexner,, T. C. Quinn,, R. E. Chaisson,, E. Rosenberg,, B. Walker,, S. Gange,, J. Gallant,, and R. F. Siliciano. 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. 5:512517.
45. Fogelman, I.,, V. Davey,, H. D. Ochs,, M. Elashoff,, M. B. Feinberg,, J. Mican,, J. P. Siegel,, M. Sneller,, and H. C. Lane III. 2000. Evaluation of CD4+ T cell function in vivo in HIV-infected patients as measured by bacteriophage phiX174 immunization. J. Infect. Dis. 182:435441.
46. Fomsgaard, A. 1999. HIV-1 DNA vaccines. Immunol. Lett. 65: 127131.
47. Franke, E. K.,, and J. Luban. 1996. Inhibition of HIV-1 replication by cyclosporine A or related compounds correlates with the ability to disrupt the Gag-cyclophilin A interaction. Virology 222: 279282.
48. Frankel, A. D.,, and J. A. Young. 1998. HIV-1: fifteen proteins and an RNA. Annu. Rev. Biochem. 67:125.
49. Gao, F.,, E. Bailes,, D. L. Robertson,, Y. Chen,, C. M. Rodenburg,, S. F. Michael,, L. B. Cummins,, L. O. Arthur,, M. Peters,, G. M. Shaw,, P. M. Sharp,, and B. H. Hahn. 1999. Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes. Nature 397:436441.
50. Gea-Banacloche, J. C.,, S. A. Migueles,, L. Martino,, W. L. Shupert,, A. C. McNeil,, M. S. Sabbaghian,, L. Ehler,, C. Prussin,, R. Stevens,, L. Lambert,, J. Altman,, C. W. Hallahan,, J. C. de Quiros,, and M. Connors. 2000. Maintenance of large numbers of virus-specific CD8+ T cells in HIV-infected progressors and long-term nonprogressors. J. Immunol. 165:10821092.
51. Giorgi J. V.,, L. E. Hultin,, J. A. McKeating,, T. D. Johnson,, B. Owens,, L. P. Jacobson,, R. Shih,, J. Lewis,, D. J. Wiley,, J. P. Phair,, S. M. Wolinsky,, and R. Detels. 1999. Shorter survival in advanced HIV-1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine co-receptor usage. J. Infect. Dis. 179:859870.
52. Goebel, F. D.,, J. W. Manhalter,, R. B. Belshe,, M. M. Eibl,, P. J. Grob,, V. de Gruttola,, P. D. Griffiths,, V. Erfle,, M. Kunschack,, and W. Engl. 1999. Recombinant gp160 as a therapeutic vaccine for HIV-infection: results of a large randomized, controlled trial. European Multinational IMMUNO AIDS vaccine study group. AIDS 13:14611468.
53. Golding, H.,, R. Blumenthal,, J. Manischewitz,, D. R. Littman,, and D. S. Dimitrov. 1993. Cell fusion mediated by interaction of a hybrid CD4. CD8 molecule with the human immunodeficiency virus type 1 envelope glycoprotein does occur after a long lag time. J. Virol. 67:64696475.
54. Gougeon, M. L.,, H. Lecoeur,, A. Dulioust,, M. G. Enouf,, M. Crouvoiser,, C. Goujard,, T. Debord,, and L. Montagnier. 1996. Programmed cell death in peripheral lymphocytes from HIV-infected persons: increased susceptibility to apoptosis of CD4 and CD8 T cells correlates with lymphocyte activation and with disease progression. J. Immunol. 156:35093520.
55. Greenberg, P. D.,, and S. D. Riddell. 1999. Deficient cellular immunity-finding and fixing the defects. Science 285:546561.
56. Grossman, Z.,, M. Polis,, M. B. Feinberg,, Z. Grossman,, I. Levi,, S. Jankelevich,, R. Yarchoan,, J. Boon,, F. de Wolf,, J. M. Lange,, J. Goudsmit,, D. S. Dimitrov,, and W. E. Paul. 1999. Ongoing HIV dissemination during HAART. Nat. Med. 5:10991104.
57. Haase, A. T. 1999. Population biology of HIV-1 infection: viral and CD4+ T cell demographics and dynamics in lymphatic tissues. Annu. Rev. Immunol. 17:625656.
58. Hahn, B. H.,, G. M. Shaw,, K. M. De Cock,, and P. M. Sharp. 2000. AIDS as a zoonosis: scientific and public health implications. Science 287:607614.
59. Harrer, T.,, E. Harrer,, S. A. Kalams,, T. Elbeik,, S. I. Staprans,, M. B. Feinberg,, Y. Cao,, D. D. Ho,, T. Yilma,, A. M. Caliendo,, R. P. Johnson,, S. P. Buchbinder,, and B. D. Walker. 1996. Strong cytotoxic T cell and weak neutralizing antibody responses in a subset of persons with stable nonprogressing HIV type 1 infection. AIDS Res. Hum. Retroviruses 12:585592.
60. Harrison, T. S.,, and S. M. Levitz. 1996. Role of IL-12 in peripheral blood mononuclear cell responses to fungi in persons with and without HIV infection. J. Immunol. 156:44924497.
61. Harty, J. T.,, A. R. Tvinnereim,, and D. W. White. 2000. CD8+ T cell effector mechanisms in resistance to infection. Annu. Rev. Immunol. 18:275308.
62. Hazenberg, M. D.,, S. A. Otto,, J. W. Cohen Stuart,, M. C. Verschuren,, J. C. Borleffs,, C. A. Boucher,, R. A. Coutinho,, J. M. Lange,, T. F. Rinke de Wit,, A. Tsegaye,, J. J. van Dongen,, D. Hamann,, R. J. de Boer,, and F. Miedema. 2000. Increased cell division but not thymic dysfunction rapidly affects the T-cell receptor excision circle content of the naive T cell population in HIV-1 infection. Nat. Med. 6:10361042.
63. Hel, Z.,, D. Venzon,, M. Poudyal,, W. P. Tsai,, L. Giuliani,, R. Woodward,, C. Chougnet,, G. Shearer,, J. D. Altman,, D. Watkins,, N. Bischofberger,, A. Abimiku,, P. Markham,, J. Tartaglia,, and G. Franchini. 2000. Viremia control following antiretroviral treatment and therapeutic immunization during primary SIV251 infection of macaques. Nat. Med. 6:11401146.
64. Hellerstein, M.,, M. B. Hanley,, D. Cesar,, S. Siler,, C. Papageorgopoulos,, E. Wieder,, D. Schmidt,, R. Hoh,, R. Neese,, D. Macallan,, S. Deeks,, and J. M. McCune. 1999. Directly measured kinetics of circulating T lymphocytes in normal and HIV-1- infected humans. Nat. Med. 5:8389.
65. Hengel, R. L.,, B. M. Jones,, M. S. Kennedy,, M. R. Hubbard,, and J. S. McDougal. 1999. Lymphocyte kinetics and precursor frequency- dependent recovery of CD4(+)CD45RA(+)CD62L(+) naive T cells following triple-drug therapy for HIV type 1 infection. AIDS Res. Hum. Retroviruses 15:435443.
66. Ho, D. D.,, A. U. Neumann,, A. S. Perelson,, W. Chen,, J. M. Leonard,, and M. Markowitz. 1995. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373:123126.
67. Jin, X.,, D. E. Bauer,, S. E. Tuttleton,, S. Lewin,, A. Gettie,, J. Blanchard,, C. E. Irwin,, J. T. Safrit,, J. Mittler,, L. Weinberger,, L. G. Kostrikis,, L. Zhang,, A. S. Perelson,, and D. D. Ho. 1999. Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected macaques. J. Exp. Med. 189:991998.
68. Kahn, J. O.,, D. W. Cherng,, K. Mayer,, H. Murray,, and S. Lagakos, for the 806 Investigator Team. 2000. Evaluation of HIV-1 immunogen, and immunologic modifier, administered to patients infected with HIV having 300 to 549 × 106 /L CD4 cell counts. JAMA 284:21932202.
69. Kalams, S. A.,, and B. D. Walker. 1998. The critical need for CD4 help in maintaining effective cytotoxic T lymphocyte responses. J. Exp. Med. 188:21992204.
70. Kamp, W.,, B. M. Berk,, C. J. Visser,, and H. S. Nottet. 2000. Mechanisms of HIV-1 to escape from the host immune surveillance. Eur. J. Clin. Investig. 30:740746.
71. Kaplan, G.,, W. J. Britton,, G. E. Hancock,, W. J. Theuvenet,, K. A. Smith,, C. K. Job,, P. W. Roche,, A. Molloy,, R. Burkhardt,, and J. Barker. 1991. The systemic influence of recombinant interleukin 2 on the manifestations of lepromatous leprosy. J. Exp. Med. 173:9931006.
72. Kinoshita, S.,, B. K. Chen,, H. Kaneshima,, and G. P. Nolan. 1998. Host control of HIV-1 parasitism in T cells by the nuclear factor of activated T cells. Cell 95:595604.
73. Koenig, S.,, A. J. Conley,, Y. A. Brewah,, G. M. Jones,, S. Leath,, L. J. Boots,, V. Davey,, G. Pantaleo,, J. F. Demarest,, C. Carter, et al. 1995. Transfer of HIV-1-specific cytotoxic T lymphocytes to an AIDS patient leads to selection for mutant HIV variants and subsequent disease progression. Nat. Med. 1:330336.
74. Komanduri, K. V.,, M. N. Viswanathan,, E. D. Wieder,, D. K. Schmidt,, B. M. Bredt,, M. A. Jacobson,, and J. M. Mc- Cune. 1998. Restoration of cytomegalovirus-specific CD4+ T-lymphocyte responses after ganciclovir and highly active antiretroviral therapy in individuals infected with HIV-1. Nat. Med. 4:953956.
75. Kovacs, J. A.,, M. Baseler,, R. J. Dewar,, S. Vogel,, R. T. Davey, Jr.,, J. Falloon,, M. A. Polis,, R. E. Walker,, R. Stevens,, N. P. Salzman, et al. 1995. Increases in CD4 T lymphocytes with intermittent courses of interleukin-2 in patients with human immunodeficiency virus infection. A preliminary study. N. Engl. J. Med. 332: 567575.
76. Kovacs, J. A.,, H. Imamichi,, S. Vogel,, J. A. Metcalf,, R. L. Dewar,, M. Baseler,, R. Stevens,, J. Adelsberger,, L. Lambert,, R. T. Davey, Jr.,, R. E. Walker,, J. Falloon,, M. A. Polis,, H. Masur,, and H. C. Lane. 2000. Effects of intermittent interleukin-2 therapy on plasma and tissue human immunodeficiency virus levels and quasispecies expression. J. Infect. Dis. 182:10631069.
77. Kovacs, J. A.,, S. Vogel,, J. M. Albert,, J. Falloon,, R. T. Davey, Jr.,, R. E. Walker,, M. A. Polis,, K. Spooner,, J. A. Metcalf,, M. Baseler,, G. Fyfe,, and H. C. Lane. 1996. Controlled trial of interleukin- 2 infusions in patients infected with the human immunodeficiency virus. N. Engl. J. Med. 335:13501356.
78. Lambert, J. S.,, J. McNamara,, S. L. Katz,, T. Fenton,, M. Kang,, T. C. VanCott,, R. Livingston,, E. Hawkins,, J. Moye,, W. Borkowsky,, D. Johnson,, R. Yogev,, A. M. Duliege,, D. Francis,, A. Gershon,, D. Wara,, N. Martin,, M. Levin,, G. McSherry,, and G. Smith. 1998. Safety and immunogenicity of HIV-recombinant envelope vaccines in HIV-infected infants and children. NIH-sponsored pediatric AIDS clinical trials group (ACTG-218). AIDS Res. Hum. Retroviruses 19:451461.
79. Lanzavecchia, A.,, G. Lezzi,, and A. Viola. 1999. From TCR engagement to T cell activation: a kinetic view of T cell behavior. Cell 96:14.
80. Levy, R.,, J. P. Jais,, J. M. Tourani,, P. Even,, and J. M. Andrieu. 1995. Long-term follow-up of HIV positive asymptomatic patients having received cyclosporin A. Adv. Exp. Med. Biol. 374: 229234.
81. Lieberman, J.,, P. R. Skolink,, G. R. Parkerson,, J. A. Fabry,, B. Landry,, J. Bethel,, and J. Kagan. 1997. Safety of autologous, ex vivo expanded HIV-1 specific cytotoxic T-lymphocyte infusion in HIV-1 infected patients. Blood 90:21962206.
82. Lori, F.,, M. G. Lewis,, J. Xu,, G. Varga,, D. E. Zinn,, C. Crabbs,, W. Wagner,, J. Greenhouse,, P. Silvera,, J. Valley-Ogunro,, C. Tinelli,, and J. Lisziewicz. 2000. Control of SIV rebound through structured treatment interruptions during early infection. Science 290:15911593.
83. Losso, M. H.,, W. H. Belloso,, S. Emery,, J. A. Benetucci,, P. E. Cahn,, M. C. Lasala,, G. Lopardo,, H. Salomon,, M. Saracco,, E. Nelson,, M. G. Law,, R. T. Davey,, M. C. Allende,, and H. C. Lane. 2000. A randomized, controlled, phase II trial comparing escalating doses of subcutaneous interleukin-2 plus antiretrovirals versus antiretrovirals alone in human immunodeficiency virus-infected patients with CD4+ cell counts nu ≥350/mm3. J. Infect. Dis. 181:16141621.
84. MacGregor, R. R.,, J. D. Boyer,, K. E. Ugen,, K. E. Lacy,, S. J. Gluckman,, M. L. Bagarazzi,, M. A. Chattergoon,, Y. Baine,, T. J. Higgins,, R. B. Ciccarelli,, L. R. Coney,, R. S. Ginsberg,, and D. B. Weiner. 1998. First human trial of a DNA-based vaccine for treatment of human immunodeficiency virus type 1 infection: safety and host response. J. Infect. Dis. 178:92100.
85. Malhotra, U.,, M. M. Berrey,, Y. Huang,, J. Markee,, D. J. Brown,, S. Ap,, L. Musey,, T. Schacker,, L. Corey,, and M. J. McElrath. 2000. Effect of combination antiretroviral therapy on T-cell immunity in acute human immunodeficiency virus type 1 infection. J. Infect. Dis. 181:121131.
86. Margolis, D.,, A. Heredia,, J. Gaywee,, D. Oldach,, G. Drusano,, and R. Redfield. 1999. Abacavir and mycophenolic acid, an inhibitor of inosine monophosphate dehydrogenase, have profound and synergistic anti-HIV activity. J. Acquired Immune Defic. Syndr. 21:362370.
87. Mastroianni, C. M.,, G. d’Ettorre,, G. Forcina,, M. Lichtner,, F. Mengoni,, C. D’Agostino,, A. Corpolongo,, A. P. Massetti,, and V. Vullo. 2000. Interleukin-15 enhances neutrophil functional activity in patients with human immunodeficiency virus infection. Blood 96:19791984.
88. McCune, J. M.,, M. B. Hanley,, D. Cesar,, R. Halvorsen,, R. Hoh,, D. Schmidt,, E. Wieder,, S. Deeks,, S. Siler,, R. Neese,, and M. Hellerstein. 2000. Factors influencing T-cell turnover in HIV-1- seropositive patients. J. Clin. Investig. 105:R1R8.
89. McFarland, E. J.,, P. A. Harding,, S. McWhinney,, R. T. Schooley,, and D. R. Kuritzkes. 1998. In vitro effects of IL-12 on HIV-specific CTL lines from HIV-infected children. J. Immunol. 161: 513519.
90. McKinney, D. M.,, D. A. Lewinsohn,, S. R. Riddell,, P. D. Greenberg,, and D. E. Moisier. 1999. The antiviral activity of HIV-specific CD8+ CTL clones is limited by elimination due to encounter with HIV-infected targets. J. Immunol. 163:861867.
91. Mellors, J. W.,, A. Munoz,, J. V. Giorgi,, J. B. Margolick,, C. J. Tassoni,, P. Gupta,, L. A. Kingsley,, J. A. Todd,, A. J. Saah,, R. Detels,, J. P. Phair,, and C. R. Rinaldo, Jr. 1997. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann. Intern. Med. 126:946954.
92. Metzner, K. J.,, X. Jin,, F. V. Lee,, A. Gettie,, D. E. Bauer,, M. Di Mascio,, A. S. Perelson,, P. A. Marx,, D. D. Ho,, L. G. Kostrikis,, and R. I. Connor. 2000. Effects of in vivo CD8(+) T cell depletion on virus replication in rhesus macaques immunized with a live, attenuated simian immunodeficiency virus vaccine. J. Exp. Med. 191:19211931.
93. Mitsuyasu, R. T.,, P. A. Anton,, S. G. Deeks,, D. T. Scadden,, E. Connick,, M. T. Downs,, A. Bakker,, M. R. Roberts,, C. H. June,, S. Jalali,, A. A. Lin,, R. Pennathur-Das,, and K. M. Hege. 2000. Prolonged survival and tissue trafficking following adoptive transfer of CD4zeta gene-modified autologous CD4(+) and CD8(+) T cells in human immunodeficiency virus-infected subjects. Blood 96:785793.
94. Mollet, L.,, T. S. Li,, A. Samri,, C. Tournay,, R. Tubiana,, V. Calvez,, P. Debre,, C. Katlama,, and B. Autran. 2000. Dynamics of HIV-specific CD8+ T lymphocytes with changes in viral load. The RESTIM and COMET Study Groups. J. Immunol. 165:16921704.
95. Moore, J. P.,, A. Trkola,, and T. Dragic. 1997. Co-receptors for HIV-1 entry. Curr. Opin. Immunol. 9:551562.
96. Moses, A.,, J. Nelson,, and G. C. Bagby. 1998. The influence of human immunodeficiency virus-1 on hematopoiesis. Blood 91: 14791495.
97. Moss, R. B.,, W. K. Giermakowska,, J. R. Savary,, G. Theofan,, A. E. Daigle,, S. P. Richieri,, F. C. Jensen,, and D. J. Carlo. 1998. A primer on HIV type 1-specific immune function and REMUNE. AIDS Res. Hum. Retroviruses 14:S167S175.
98. Muro-Cacho, C. A.,, G. Pantaleo,, and A. S. Fauci. 1995. Analysis of apoptosis in lymph nodes of HIV-infected persons. Intensity of apoptosis correlates with the general state of activation of the lymphoid tissue and not with stage of disease or viral burden. J. Immunol. 154:55555566.
99. Nagy-Agren, S. E.,, and E. L. Cooney. 1999. Interleukin-12 enhancement of antigen-specific lymphocyte proliferation correlates with stage of human immunodeficiency virus infection. J. Infect. Dis. 179:493496.
100. Nelson, B. H.,, and D. M. Willerford. 1998. Biology of the interleukin- 2 receptor. Adv. Immunol. 70:181.
101. Ogg, G. S.,, X. Jin,, S. Bonhoeffer,, P. R. Dunbar,, M. A. Nowak,, S. Monard,, J. P. Segal,, Y. Cao,, S. L. Rowland-Jones,, V. Cerundolo,, A. Hurley,, M. Markowitz,, D. D. Ho,, D. F. Nixon,, and A. J. McMichael. 1998. Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. Science 279: 21032106.
102. Ogg, G. S.,, X. Jin,, S. Bonhoeffer,, P. Moss,, M. A. Nowak,, S. Monard,, J. P. Segal,, Y. Cao,, S. L. Rowland-Jones,, A. Hurley,, M. Markowitz,, D. D. Ho,, A. J. McMichael,, and D. F. Nixon. 1999a. Decay kinetics of human immunodeficiency virus-specific effector cytotoxic T lymphocytes after combination antiretroviral therapy. J. Virol. 73:797800.
103. Ogg, G. S.,, S. Kostense,, M. R. Klein,, S. Jurriaans,, D. Hamann,, A. J. McMichael,, and F. Miedema. 1999b. Longitudinal phenotypic analysis of human immunodeficiency virus type 1- specific cytotoxic T lymphocytes: correlation with disease progression. J. Virol. 73:91539160.
104. Oxenius, A.,, D. A. Price,, P. J. Easterbrook,, C. A. O’Callaghan,, A. D. Kelleher,, J. A. Whelan,, G. Sontag,, A. K. Sewell,, and R. E. Phillips. 2000. Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD8+ and CD4+ T lymphocytes. Proc. Natl. Acad. Sci. USA 97:33823387.
105. Paiardini, M.,, D. Galati,, B. Cervasi,, G. Cannavo,, L. Galluzzi,, M. Montroni,, D. Guetard,, M. Magnani,, G. Piedimonte,, and G. Silvestri. Exogenous interleukin-2 administration corrects the cell cycle perturbation of lymphocytes from human immunodeficiency virus-infected individuals. J. Virol., in press.
106. Pantaleo, G.,, and A. S. Fauci. 1995. New concepts in the immunopathogenesis of HIV infection. Annu. Rev. Immunol. 13:487512.
107. Pantaleo, G.,, S. Menzo,, M. Vaccarezza,, C. Graziosi,, O. J. Cohen,, J. F. Demarest,, D. Montefiori,, J. M. Orenstein,, C. Fox,, L. K. Schrager,, and A. S. Fauci. 1995. Studies in subjects with long-term nonprogressive human immunodeficiency virus infection. N. Engl. J. Med. 332:209216.
108. Perelson, A. S.,, A. U. Neumann,, M. Markowitz,, J. M. Leonard,, and D. D. Ho. 1996. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science 271:15821586.
109. Peters, B. S. 2000. HIV immunotherapeutic vaccines. Antiviral Chem. Chemother. 11:311320.
110. Piedimonte, G.,, D. Corsi,, M. Paiardini,, G. Cannavo,, R. Ientile,, I. Picerno,, M. Montroni,, G. Silvestri,, and M. Magnani. 1999. Unscheduled cyclin B expression and p34 cdc2 activation in T lymphocytes from HIV-infected patients. AIDS 13:11591165.
111. Pierson T.,, J. McArthur,, and R. F. Siliciano. 1998. Reservoirs for HIV-1: mechanisms for viral persistence in the presence of antiviral immune responses and antiretroviral therapy. Annu. Rev. Immunol. 18:665708.
112. Pitcher, C. J.,, C. Quittner,, D. M. Peterson,, M. Connors,, R. A. Koup,, V. C. Maino,, and L. J. Picker. 1999. HIV-1-specific CD4+ T cells are detectable in most individuals with active HIV-1 infection, but decline with prolonged viral suppression. Nat. Med. 5:518525.
113. Pomerantz, R. J.,, and D. Trono. 1995. Genetic therapies for HIV infections: promise for the future. AIDS 9:985993.
114. Pontesilli, O.,, M. R. Klein,, S. R. Kerkhof-Garde,, N. G. Pakker,, F. de Wolf,, H. Schuitemaker,, and F. Miedema. 1997. Kinetics of immune functions and virus replication during HIV-1 infection. Immunol. Lett. 57:125130.
115. Powderly, W. G.,, A. Landay,, and M. M. Lederman. 1998. Recovery of the immune system with antiretroviral therapy: the end of opportunism? JAMA 280:7277.
116. Ranga, U.,, C. Woffendin,, S. Verma,, L. Xu,, C. H. June,, D. K. Bishop,, and G. J. Nabel. 1998. Enhanced T cell engraftment after retroviral delivery of an antiviral gene in HIV-infected individuals. Proc. Natl. Acad. Sci. USA 95:12011206.
117. Ravot, E.,, J. Lisziewicz,, and F. Lori. 1999. New uses for old drugs in HIV infection: the role of hydroxyurea, cyclosporin and thalidomide. Drugs 58:953963.
118. Redfield, R. R.,, D. L. Birx,, N. Ketter,, E. Tramont,, V. Polonis,, C. Davis,, J. F. Brundage,, G. Smith,, S. Johnson,, and A. Fowler. 1991. A phase 1 evaluation of the safety and immunogenicity of vaccination with recombinant gp160 in patients with early HIV-infection. N. Engl. J. Med. 324:16771684.
119. Rey-Cuille, M. A.,, J. L. Berthier,, M. C. Bomsel-Demontoy,, Y. Chaduc,, L. Montagnier,, A. G. Hovanessian,, and L. A. Chakrabarti. 1998. Simian immunodeficiency virus replicates to high levels in sooty mangabeys without inducing disease. J. Virol. 72: 38723886.
120. Riddell, S. R.,, M. Elliott,, D. A. Lewinsohn,, M. J. Gilbert,, L. Wilson,, S. A. Manley,, S. D. Lupton,, R. W. Overell,, T. C. Reynolds,, L. Corey,, and P. D. Greenberg. 1996. T-cell mediated rejection of gene-modified HIV-specific cytotoxic T lymphocytes in HIV-infected patients. Nat. Med. 2:216223.
121. Riley, J. L.,, K. Schlienger,, P. J. Blair,, B. Carreno,, N. Craighead,, D. Kim,, R. G. Carroll,, and C. H. June. 2000. Modulation of susceptibility to HIV-1 infection by the cytotoxic T lymphocyte antigen 4 costimulatory molecule. J. Exp. Med. 191:19871997.
122. Rosenberg, E. S.,, M. Altfeld,, S. H. Poon,, M. N. Phillips,, B. M. Wilkes,, R. L. Elridge,, G. K. Robbins,, R. T. D’Aquila,, P. J. R. Goulder,, and B. D. Walker. 2000. Immune control of HIV-1 after early treatment of acute infection. Nature 407:523526.
123. Rosenberg, E. S.,, J. M. Billingsley,, A. M. Caliendo,, S. L. Boswell,, P. E. Sax,, S. A. Kalams,, and B. D. Walker. 1997. Vigorous HIV- 1 specific CD4+ T cell responses associated with control of viremia. Science 278:14471450.
124. Ruiz, L.,, J. Martinez-Picado,, J. Romeu,, R. Paredes,, M. K. Zayat,, S. Marfil,, E. Negredo,, G. Sirera,, C. Tural,, and B. Clotet. 2000. Structured treatment interruption in chronically HIV-1 infected patients after long-term viral suppression. AIDS 14:397403.
125. Saag, M. S.,, M. Holodniy,, D. R. Kuritzkes,, W. A. O’Brien,, R. Coombs,, M. E. Poscher,, D. M. Jacobsen,, G. M. Shaw,, D. D. Richman,, and P. A. Volberding. 1996. HIV viral load markers in clinical practice. Nat. Med. 2:625629.
126. Samson, M.,, F. Libert,, B. J. Doranz,, J. Rucker,, C. Liesnard,, C. M. Farber,, S. Saragosti,, C. Lapoumeroulis,, J. Cognaux,, C. Forceille,, G. Muyldermans,, C. Verhofstede,, G. Burtonboy,, M. Georges,, T. Imai,, S. Rana,, Y. Yi,, R. J. Smyth,, R. G. Collman,, R. W. Doms,, G. Vassart,, and M. Parmentier. 1996. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382:722725.
127. Sandstrom, E.,, and B. Wahren. 1999. Therapeutic immunisation with rgp160 in HIV-1 infection: a randomised double-blind placebo-controlled trial. Nordic VAC-40 study group. Lancet 353:17351742.
128. Schmitz, J. E.,, M. J. Kuroda,, S. Santra,, V. G. Sasseville,, M. A. Simon,, M. A. Lifton,, P. Racz,, K. Tenner-Racz,, M. Dalesandro,, B. J. Scallon,, J. Ghrayeb,, M. A. Forman,, D. C. Montefiori,, E. P. Rieber,, N. L. Letvin,, and K. A. Reimann. 1999. Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 283:857860.
129. Silvestri, G.,, C. Munoz-Calleja,, P. Bagnarelli,, G. Piedimonte,, M. Clementi,, and M. Montroni. 1998. Early increase of CD4+ CD45RA+ and CD4+ CD95- cells with conserved repertoire induced by anti-retroviral therapy in HIV-infected patients. Clin. Exp. Immunol. 111:311.
130. Skowron, G.,, D. Stein,, G. Drusano,, K. Melbourne,, J. Bilello,, D. Mikolich,, K. Rana,, J. M. Agosti,, A. Mongillo,, J. Whitmore,, and M. J. Gilbert. 1999. The safety and efficacy of granulocyte-macrophage colony-stimulating factor (Sargramostim) added to indinavir- or ritonavir-based antiretroviral therapy: a randomized double-blind, placebo-controlled trial. J. Infect. Dis. 180: 10641071.
131. Stevenson, M.,, B. Brichacek,, N. Heinzinger,, S. Swindells,, S. Pirruccello,, E. Janoff,, and M. Emerman. 1995. Molecular basis of cell cycle dependent HIV-1 replication. Implications for control of virus burden. Adv. Exp. Med. Biol. 374:3345.
132. Tan, R.,, X. Xu,, G. S. Ogg,, P. Hansasuta,, T. Dong,, T. Rostron,, G. Luzzi,, C. P. Conlon,, G. R. Screaton,, A. J. McMichael,, and S. Rowland-Jones. 1999. Rapid death of adoptively transferred T cells in acquired immunodeficiency syndrome. Blood 93: 15061510.
133. Thali, M.,, A. Bukovsky,, E. Kondo,, B. Rosenwirth,, C. T. Walsh,, J. Sodroski,, and H. G. Gottlinger. 1994. Functional association of cyclophilin A with HIV-1 virions. Nature 372:363365.
134. Tsoukas C. M.,, J. Raboud,, N. F. Bernard,, J. S. Montaner, M. J. Gill, A. Rachlis, I. W. Fong, W. Schlech, O. Djurdjev, J. Freedman, R. Thomas, R. Iafreniere, M. A. Weinberg, S. Cassol, M. O’Shaughnessy, J. Todd, F. Volvovitz, and G. E. Smith. 1998. Active immunization of patients with HIV infection: a study of the effect of VaxSyn, a recombinant HIV envelope subunit vaccine, on progression of immunodeficiency. AIDS Res. Hum. Retroviruses 14:483490.
135. UNAIDS/WHO Joint United Nations Programme on HIV/AIDS. 2000. AIDS Epidemic Update: December 2000. United Nations, Geneva, Switzerland.
136. Walker, B. D.,, E. S. Rosenberg,, C. M. Hay,, N. Basgoz,, and O. O. Yang. 1998. Immune control of HIV-1 replication. Adv. Exp. Med. Biol. 452:159167.
137. Walker, R. E.,, C. M. Bechtel,, V. Natarajan,, M. Baseler,, K. M. Hege,, J. A. Metcalf,, R. Stevens,, A. Hazen,, R. M. Blaese,, C. C. Chen,, S. F. Leitman,, J. Palensky,, J. Wittes,, R. T. Davey, Jr.,, J. Falloon,, M. A. Polis,, J. A. Kovacs,, D. F. Broad,, B. L. Levine,, M. R. Roberts,, H. Masur,, and H. C. Lane. 2000. Long-term in vivo survival of receptor-modified syngeneic T cells in patients with human immunodeficiency virus infection. Blood 96:467474.
138. Watanabe, N.,, J. P. Sypek,, S. Mittler,, K. A. Reimann,, P. Flores- Villanueva,, G. Voss,, C. I. Lord,, and N. L. Letvin. 1998. Administration of recombinant human interleukin 12 to chronically SIVmac-infected rhesus monkeys. AIDS Res. Hum. Retroviruses 14:393399.
139. Wei, X.,, S. K. Ghosh,, M. E. Taylor,, V. A. Johnson,, E. A. Emini,, P. Deutsch,, J. D. Lifson,, S. Bonhoeffer,, M. A. Nowak,, B. H. Hahn,, and G. M. Shaw. 1995. Viral dynamics in human immunodeficiency virus type 1 infection. Nature 373:117122.
140. Weissman, D.,, M. Dybul,, M. B. Daucher,, R. T. Davey, Jr.,, R. E. Walker,, and J. A. Kovacs. 2000. Interleukin-2 up-regulates expression of the human immunodeficiency virus fusion coreceptor CCR5 by CD4+ lymphocytes in vivo. J. Infect. Dis. 181: 933938.
141. Whitmire, J. K.,, and R. Ahmed. 2000. Costimulation in antiviral immunity: differential requirements for CD4(+) and CD8(+) T cell responses. Curr. Opin. Immunol. 12:448455.
142. Wright, P. F.,, J. S. Lambert,, G. J. Gorse,, R. H. Hsieh,, M. J. McElrath K. Weinhold, D. W. Wara, E. L. Anderson, M. C. Keefer, S. Jackson, L. J. Wagner, D. P. Francis, P. E. Fast, and J. McNamara. 1999. Immunization with envelope MN rgp120 vaccine in HIV-infected pregnant women. J. Infect. Dis. 180: 10801088.
143. Wyatt, R.,, and J. Sodroski. 1998. The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science 280:18841888.
144. Yamaguchi, S.,, M. Onji,, H. Kondoh,, H. Miyaoka,, and Y. Ohta. 1988. Immunologic effects on peripheral lymphoid cells from patients with chronic hepatitis type B during administration of recombinant interleukin 2. Clin. Exp. Immunol. 74:16.
145. Zajac, A. J.,, J. N. Blattman,, K. Murali-Krishna,, D. J. Sourdive,, M. Suresh,, J. D. Altman,, and R. Ahmed. 1998. Viral immune evasion due to persistence of activated T cells without effector function. J. Exp. Med. 188:22052213.
146. Zinkernagel, R. M.,, and H. Hengartner. 1994. T-cell-mediated immunopathology versus direct cytolysis by virus: implications for HIV and AIDS. Immunol. Today 15:262268.
147. Zou, W.,, A. Foussat,, C. Capitant,, I. Durand-Gasselin,, L. Bouchet,, P. Galanaud,, Y. Levy,, and D. Emilie. 1999. Acute activation of CD8+ T lymphocytes in interleukin-2-treated HIV-infected patients. ANRS-048 IL-2 Study Group. Agence Nationale de Recherches sur le SIDA. J. Acquired Immune Defic. Syndr. 22:3138.


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Table 1

Mechanisms of immune evasion by HIV

Citation: Silvestri G, Feinberg M. 2002. Immune Intervention in AIDS, p 453-477. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch30
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Table 2

Immune interventions in HIV-infected individuals

Citation: Silvestri G, Feinberg M. 2002. Immune Intervention in AIDS, p 453-477. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch30

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