Depletion of CD4+ T cells in semen during HIV infection and their restoration following antiretroviral therapy

Journal of Acquired Immune Deficiency Syndromes

Volumn 50, Issue 3, 2009, Pages 283-289

  Politch, Joseph A ^a,b   Mayer, Kenneth H ^c,d   Anderson, Deborah J ^a,b  

^a BOSTON MEDICAL CENTER   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

^c FENWAY INSTITUTE   (United States)

^d BROWN UNIVERSITY   (United States)

Author keywords

Antiretroviral therapy; CD4+ lymphocytes; HIV 1; Macrophages; Protease inhibitor; Semen; White blood cells

Indexed keywords

ANTIVIRUS AGENT; DIDANOSINE PLUS ZIDOVUDINE; INDINAVIR; INTERLEUKIN 2 RECEPTOR ALPHA; LAMIVUDINE PLUS NEVIRAPINE PLUS STAVUDINE; LAMIVUDINE PLUS ZIDOVUDINE; RNA DIRECTED DNA POLYMERASE INHIBITOR; UNCLASSIFIED DRUG; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT;

ANTIVIRAL THERAPY; ARTICLE; CD4 LYMPHOCYTE COUNT; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNITY; IMMUNOHISTOLOGY; LEUKOCYTE; MACROPHAGE; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; SPERM; T LYMPHOCYTE; VIRUS TRANSMISSION; CD4+ T LYMPHOCYTE; CYTOLOGY; IMMUNOLOGY; LYMPHOCYTE DEPLETION;

ANTI-HIV AGENTS; CD4-POSITIVE T-LYMPHOCYTES; HIV INFECTIONS; HUMANS; LYMPHOCYTE DEPLETION; MALE; SEMEN;

EID: 63149107039     PISSN: 15254135     EISSN: None     Source Type: Journal    
DOI: 10.1097/QAI.0b013e3181989870     Document Type: Article

References (100)

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2. Fowler MG, Melnick SL, Mathieson BJ. Women and HIV Epidemiology and global overview. Obstet Gynecol Clin North Am. 1997;24:705-729.
3. HIV/AIDS Surveillance Report. Centers for Disease Control and Prevention.
4. Beyrer C. HIV epidemiology update and transmission factors: risks and risk contexts-16th International AIDS Conference epidemiology plenary. Clin Infect Dis. 2007;44:981-987.
5. Cohen MS. HIV and sexually transmitted diseases: lethal synergy. Top HIV Med. 2004;12:104-107.
6. Shattock RJ, Moore JP Inhibiting sexual transmission of HIV-1 infection. Nat Rev Microbiol. 2003;1:25-34.
7. Anderson DJ, Pudney J. Human male genital tract immunity and experimental models. In: Mestecky J, Lamm ME, Strober W, et al, eds. Mucosal Immunol. Vol 2. 3rd ed. Boston, MA: Elsevier Academic Press; 2005:1647-1660.
8. Pudney J, Anderson D. Orchitis and human immunodeficiency virus type 1 infected cells in reproductive tissues from men with the acquired immune deficiency syndrome. Am J Pathol. 1991;139:149-160.
9. Quayle AJ, Xu C, Mayer KH, et al. T lymphocytes and macrophages, but not motile spermatozoa, are a significant source of human immunodeficiency virus in semen. J Infect Dis. 1997;176:960-968.
10. Collins KB, Patterson BK, Naus GJ, et al. Development of an in vitro organ culture model to study transmission of HIV-1 in the female genital tract. Nat Med. 2000;6:475-479.
11. Girard M, Mahoney J, Wei Q, et al. Genital infection of female chimpanzees with human immunodeficiency virus type 1. AIDS Res Hum Retroviruses. 1998;14:1357-1367.
12. Kaizu M, Weiler AM, Weisgrau KL, et al. Repeated intravaginal inoculation with cell-associated simian immunodeficiency virus results in persistent infection of nonhuman primates. J Infect Dis. 2006;194: 912-916.
13. Khanna KV, Whaley KJ, Zeitlin L, et al. Vaginal transmission of cell-associated HIV-1 in the mouse is blocked by a topical, membrane-modifying agent. J Clin Invest. 2002;109:205-211.
14. Picker LJ. Immunopathogenesis of acute AIDS virus infection. Curr Opin Immunol. 2006;18:399-405.
15. Brenchley JM, Schacker TW, Ruff LE, et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med. 2004;200:749-759.
16. Lim SG, Condez A, Lee CA, et al. Loss of mucosal CD4 lymphocytes is an early feature of HIV infection. Clin Exp Immunol. 1993;92:448-454.
17. Grossman Z, Meier-Schellersheim M, Paul WE, et al. Pathogenesis of HIV infection: what the virus spares is as important as what it destroys. Nat Med. 2006;12:289-295.
18. Arthos J, Cicala C, Martinelli E, et al. HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells. Nat Immunol. 2008;9:301-309.
19. Mattapallil JJ, Douek DC, Hill B, et al. Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature. 2005;434:1093-1097.
20. Quayle AJ, Kourtis AP, Cu-Uvin S, et al. T-lymphocyte profile and total and virus-specific immunoglobulin concentrations in the cervix of HIV-1-infected women. J Acquir Immune Defic Syndr. 2007;44: 292-298.
21. Veazey RS, Marx PA, Lackner AA. Vaginal CD4+ T cells express high levels of CCR5 and are rapidly depleted in simian immunodeficiency virus infection. J Infect Dis. 2003;187:769-776.
22. Denny TN, Skurnick JH, Garcia A, et al. Lymphocyte immunoregulatory cells present in semen from human immunodeficiency virus (HIV)-infected individuals: a report from the HIV Heterosexual Transmission Study. Cytometry. 1996;26:47-51.
23. Pudney J, Anderson DJ. Immunobiology of the human penile urethra. Am J Pathol. 1995;147:155-165.
24. Le Tortorec A, Le Grand R, Denis H, et al. Infection of semen-producing organs by SIV during the acute and chronic stages of the disease. PLoS ONE. 2008;3:e1792.
25. Guadalupe M, Sankaran S, George MD, et al. Viral suppression and immune restoration in the gastrointestinal mucosa of human immunodeficiency virus type 1-infected patients initiating therapy during primary or chronic infection. J Virol. 2006;80:8236-8247.
26. Torre D, Speranza F, Martegani R. Impact of highly active antiretroviral therapy on organ-specific manifestations of HIV-1 infection. HIV Med. 2005;6:66-78.
27. Mayer K, Appelbaum J, Rogers T, et al. The evolution of the Fenway Community Health model. Am J Public Health. 2001;91:892-894.
28. Mayer KH, Boswell S, Goldstein R, et al. Persistence of human immunodeficiency virus in semen after adding indinavir to combination antiretroviral therapy. Clin Infect Dis. 1999;28:1252-1259.
29. Politch JA, Wolff H, Hill JA, et al. Comparison of methods to enumerate white blood cells in semen. Fertil Steril. 1993;60:372-375.
30. Wolff H, Anderson DJ. Immunohistologic characterization and quantitation of leukocyte subpopulations in human semen. Fertil Steril. 1988;49: 497-504.
31. Siegel S, Castellan NJ. Nonparametric Statistics for the Behavioral Sciences. 2nd ed. New York, NY: McGraw-Hill; 1988.
32. Lewin SR, Sonza S, Irving LB, et al. Surface CD4 is critical to in vitro HIV infection of human alveolar macrophages. AIDS Res Hum Retroviruses. 1996;12:877-883.
33. Wood GS, Warner NL, Warnke RA. Anti-Leu-3/T4 antibodies react with cells of monocyte/macrophage and Langerhans lineage. J Immunol. 1983; 131:212-216.
34. Anderson DJ, O'Brien TR, Politch JA, et al. Effects of disease stage and zidovudine therapy on the detection of human immunodeficiency virus type 1 in semen. JAMA. 1992;267:2769-2774.
35. Mehandru S, Poles MA, Tenner-Racz K, et al. Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med. 2004;200:761-770.
36. Guadalupe M, Reay E, Sankaran S, et al. Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy. J Virol. 2003;77:11708-11717.
37. Talal AH, Monard S, Vesanen M, et al. Virologic and immunologic effect of antiretroviral therapy on HIV-1 in gut-associated lymphoid tissue. J Acquir Immune Defic Syndr. 2001;26:1-7.
38. Leruez-Ville M, Dulioust E, Costabliola D, et al. Decrease in HIV-1 seminal shedding in men receiving highly active antiretroviral therapy: an 18 month longitudinal study (ANRS EP012). AIDS. 2002;16:486-488.
39. Taylor S, Ferguson NM, Cane PA, et al. Dynamics of seminal plasma HIV-1 decline after antiretroviral treatment. AIDS. 2001;15:424-426.
40. Zhang H, Dornadula G, Beumont M, et al. Human immunodeficiency virus type 1 in the semen of men receiving highly active antiretroviral therapy. N Engl J Med. 1998;339:1803-1809.
41. Chan DJ, Ray JE. Quantification of antiretroviral drugs for HIV-1 in the male genital tract: current data, limitations and implications for laboratory analysis. J Pharm Pharmacol. 2007;59:1451-1462.
42. Solas C, Lafeuillade A, Halfon P, et al. Discrepancies between protease inhibitor concentrations and viral load in reservoirs and sanctuary sites in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother. 2003;47:238-243.
43. Taylor S, Reynolds H, Sabin CA, et al. Penetration of efavirenz into the male genital tract: drug concentrations and antiviral activity in semen and blood of HIV-1-infected men. AIDS. 2001;15:2051-2053.
44. Chao C, Jacobson LP, Tashkin D, et al. Recreational drug use and T lymphocyte subpopulations in HIV-uninfected and HIV-infected men. Drug Alcohol Depend. 2008;94:165-171.
45. Anderson DJ, Politch JA, Tucker LD, et al. Quantitation of mediators of inflammation and immunity in genital tract secretions and their relevance to HIV type 1 transmission. AIDS Res Hum Retroviruses. 1998;14 (Suppl 1):S43-S49.
46. Coombs RW, Speck CE, Hughes JP, et al. Association between culturable human immunodeficiency virus type 1 (HIV-1) in semen and HIV-1 RNA levels in semen and blood: evidence for compartmentalization of HIV-1 between semen and blood. J Infect Dis. 1998;177: 320-330.
47. Sadiq ST, Taylor S, Kaye S, et al. The effects of antiretroviral therapy on HIV-1 RNA loads in seminal plasma in HIV-positive patients with and without urethritis. AIDS. 2002;16:219-225.
48. Xu C, Politch JA, Tucker L, et al. Factors associated with increased levels of human immunodeficiency virus type 1 DNA in semen. J Infect Dis. 1997;176:941-947.
49. Cohen MS, Hoffman IF, Royce RA, et al. Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. AIDSCAP Malawi Research Group. Lancet. 1997;349:1868-1873.
50. Speck CE, Coombs RW, Koutsky LA, et al. Risk factors for HIV-1 shedding in semen. Am J Epidemiol. 1999;150:622-631.
51. AIDS Epidemic Update. Geneva, Switzerland: Joint United Nations Programme on HIV/AIDS and World Health Organization; 2006.
52. Fowler MG, Melnick SL, Mathieson BJ. Women and HIV Epidemiology and global overview. Obstet Gynecol Clin North Am. 1997;24:705-729.
53. HIV/AIDS Surveillance Report. Centers for Disease Control and Prevention.
54. Beyrer C. HIV epidemiology update and transmission factors: risks and risk contexts-16th International AIDS Conference epidemiology plenary. Clin Infect Dis. 2007;44:981-987.
55. Cohen MS. HIV and sexually transmitted diseases: lethal synergy. Top HIV Med. 2004;12:104-107.
56. Shattock RJ, Moore JP Inhibiting sexual transmission of HIV-1 infection. Nat Rev Microbiol. 2003;1:25-34.
57. Anderson DJ, Pudney J. Human male genital tract immunity and experimental models. In: Mestecky J, Lamm ME, Strober W, et al, eds. Mucosal Immunol. Vol 2. 3rd ed. Boston, MA: Elsevier Academic Press; 2005:1647-1660.
58. Pudney J, Anderson D. Orchitis and human immunodeficiency virus type 1 infected cells in reproductive tissues from men with the acquired immune deficiency syndrome. Am J Pathol. 1991;139:149-160.
59. Quayle AJ, Xu C, Mayer KH, et al. T lymphocytes and macrophages, but not motile spermatozoa, are a significant source of human immunodeficiency virus in semen. J Infect Dis. 1997;176:960-968.
60. Collins KB, Patterson BK, Naus GJ, et al. Development of an in vitro organ culture model to study transmission of HIV-1 in the female genital tract. Nat Med. 2000;6:475-479.
61. Girard M, Mahoney J, Wei Q, et al. Genital infection of female chimpanzees with human immunodeficiency virus type 1. AIDS Res Hum Retroviruses. 1998;14:1357-1367.
62. Kaizu M, Weiler AM, Weisgrau KL, et al. Repeated intravaginal inoculation with cell-associated simian immunodeficiency virus results in persistent infection of nonhuman primates. J Infect Dis. 2006;194: 912-916.
63. Khanna KV, Whaley KJ, Zeitlin L, et al. Vaginal transmission of cell-associated HIV-1 in the mouse is blocked by a topical, membrane-modifying agent. J Clin Invest. 2002;109:205-211.
64. Picker LJ. Immunopathogenesis of acute AIDS virus infection. Curr Opin Immunol. 2006;18:399-405.
65. Brenchley JM, Schacker TW, Ruff LE, et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med. 2004;200:749-759.
66. Lim SG, Condez A, Lee CA, et al. Loss of mucosal CD4 lymphocytes is an early feature of HIV infection. Clin Exp Immunol. 1993;92:448-454.
67. Grossman Z, Meier-Schellersheim M, Paul WE, et al. Pathogenesis of HIV infection: what the virus spares is as important as what it destroys. Nat Med. 2006;12:289-295.
68. Arthos J, Cicala C, Martinelli E, et al. HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells. Nat Immunol. 2008;9:301-309.
69. Mattapallil JJ, Douek DC, Hill B, et al. Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature. 2005;434:1093-1097.
70. Quayle AJ, Kourtis AP, Cu-Uvin S, et al. T-lymphocyte profile and total and virus-specific immunoglobulin concentrations in the cervix of HIV-1-infected women. J Acquir Immune Defic Syndr. 2007;44: 292-298.
71. Veazey RS, Marx PA, Lackner AA. Vaginal CD4+ T cells express high levels of CCR5 and are rapidly depleted in simian immunodeficiency virus infection. J Infect Dis. 2003;187:769-776.
72. Denny TN, Skurnick JH, Garcia A, et al. Lymphocyte immunoregulatory cells present in semen from human immunodeficiency virus (HIV)-infected individuals: a report from the HIV Heterosexual Transmission Study. Cytometry. 1996;26:47-51.
73. Pudney J, Anderson DJ. Immunobiology of the human penile urethra. Am J Pathol. 1995;147:155-165.
74. Le Tortorec A, Le Grand R, Denis H, et al. Infection of semen-producing organs by SIV during the acute and chronic stages of the disease. PLoS ONE. 2008;3:e1792.
75. Guadalupe M, Sankaran S, George MD, et al. Viral suppression and immune restoration in the gastrointestinal mucosa of human immunodeficiency virus type 1-infected patients initiating therapy during primary or chronic infection. J Virol. 2006;80:8236-8247.
76. Torre D, Speranza F, Martegani R. Impact of highly active antiretroviral therapy on organ-specific manifestations of HIV-1 infection. HIV Med. 2005;6:66-78.
77. Mayer K, Appelbaum J, Rogers T, et al. The evolution of the Fenway Community Health model. Am J Public Health. 2001;91:892-894.
78. Mayer KH, Boswell S, Goldstein R, et al. Persistence of human immunodeficiency virus in semen after adding indinavir to combination antiretroviral therapy. Clin Infect Dis. 1999;28:1252-1259.
79. Politch JA, Wolff H, Hill JA, et al. Comparison of methods to enumerate white blood cells in semen. Fertil Steril. 1993;60:372-375.
80. Wolff H, Anderson DJ. Immunohistologic characterization and quantitation of leukocyte subpopulations in human semen. Fertil Steril. 1988;49: 497-504.
81. Siegel S, Castellan NJ. Nonparametric Statistics for the Behavioral Sciences. 2nd ed. New York, NY: McGraw-Hill; 1988.
82. Lewin SR, Sonza S, Irving LB, et al. Surface CD4 is critical to in vitro HIV infection of human alveolar macrophages. AIDS Res Hum Retroviruses. 1996;12:877-883.
83. Wood GS, Warner NL, Warnke RA. Anti-Leu-3/T4 antibodies react with cells of monocyte/macrophage and Langerhans lineage. J Immunol. 1983; 131:212-216.
84. Anderson DJ, O'Brien TR, Politch JA, et al. Effects of disease stage and zidovudine therapy on the detection of human immunodeficiency virus type 1 in semen. JAMA. 1992;267:2769-2774.
85. Mehandru S, Poles MA, Tenner-Racz K, et al. Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med. 2004;200:761-770.
86. Guadalupe M, Reay E, Sankaran S, et al. Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy. J Virol. 2003;77:11708-11717.
87. Talal AH, Monard S, Vesanen M, et al. Virologic and immunologic effect of antiretroviral therapy on HIV-1 in gut-associated lymphoid tissue. J Acquir Immune Defic Syndr. 2001;26:1-7.
88. Leruez-Ville M, Dulioust E, Costabliola D, et al. Decrease in HIV-1 seminal shedding in men receiving highly active antiretroviral therapy: an 18 month longitudinal study (ANRS EP012). AIDS. 2002;16:486-488.
89. Taylor S, Ferguson NM, Cane PA, et al. Dynamics of seminal plasma HIV-1 decline after antiretroviral treatment. AIDS. 2001;15:424-426.
90. Zhang H, Dornadula G, Beumont M, et al. Human immunodeficiency virus type 1 in the semen of men receiving highly active antiretroviral therapy. N Engl J Med. 1998;339:1803-1809.
91. Chan DJ, Ray JE. Quantification of antiretroviral drugs for HIV-1 in the male genital tract: current data, limitations and implications for laboratory analysis. J Pharm Pharmacol. 2007;59:1451-1462.
92. Solas C, Lafeuillade A, Halfon P, et al. Discrepancies between protease inhibitor concentrations and viral load in reservoirs and sanctuary sites in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother. 2003;47:238-243.
93. Taylor S, Reynolds H, Sabin CA, et al. Penetration of efavirenz into the male genital tract: drug concentrations and antiviral activity in semen and blood of HIV-1-infected men. AIDS. 2001;15:2051-2053.
94. Chao C, Jacobson LP, Tashkin D, et al. Recreational drug use and T lymphocyte subpopulations in HIV-uninfected and HIV-infected men. Drug Alcohol Depend. 2008;94:165-171.
95. Anderson DJ, Politch JA, Tucker LD, et al. Quantitation of mediators of inflammation and immunity in genital tract secretions and their relevance to HIV type 1 transmission. AIDS Res Hum Retroviruses. 1998;14 (Suppl 1):S43-S49.
96. Coombs RW, Speck CE, Hughes JP, et al. Association between culturable human immunodeficiency virus type 1 (HIV-1) in semen and HIV-1 RNA levels in semen and blood: evidence for compartmentalization of HIV-1 between semen and blood. J Infect Dis. 1998;177: 320-330.
97. Sadiq ST, Taylor S, Kaye S, et al. The effects of antiretroviral therapy on HIV-1 RNA loads in seminal plasma in HIV-positive patients with and without urethritis. AIDS. 2002;16:219-225.
98. Xu C, Politch JA, Tucker L, et al. Factors associated with increased levels of human immunodeficiency virus type 1 DNA in semen. J Infect Dis. 1997;176:941-947.
99. Cohen MS, Hoffman IF, Royce RA, et al. Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. AIDSCAP Malawi Research Group. Lancet. 1997;349:1868-1873.
100. Speck CE, Coombs RW, Koutsky LA, et al. Risk factors for HIV-1 shedding in semen. Am J Epidemiol. 1999;150:622-631.