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In vivo Models of HIV Disease and Control pp 121–147Cite as

SIV Infection of Macaques as a Model for AIDS Drug Studies

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Part of the book series: Infectious Diseases and Pathogenesis ((IAPA))

Abstract

An increasing arsenal of anti-HIV drugs is currently being used, and many new candidates are continuously being developed. Based on their viral targets during the viral replication cycle, the main antiviral drugs that have been approved or are being developed belong to several groups: inhibitors of attachment, fusion, reverse transcriptase (RT), integrase or protease (Figure 1). During recent years, combination therapy of these compounds, so-called highly active antiretroviral therapy (HAART), has led to major improvement in the clinical management of HIV-infected people in the developed countries. Despite this considerable success, there is still much room for improvement, as not everyone can experience the desired longterm benefits. Once established, HIV infection can probably never be cured, so long-term administration of these drugs is usually required for the majority of individuals, and problems of toxicity, compliance, drug resistance, and costs become very relevant. In addition, due to the current costs of antiviral drugs and the need for expertise monitoring of viral and immunological parameters and toxicity, current drug regimens are beyond the reach of the majority of HIV-infected people who live in developing countries.

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References

  1. De Clercq, E., New anti-HIV agents and targets, Medicinal Res. Rev 22: 531–565 (2002).

    Article  Google Scholar 

  2. Centers for Disease Control and Prevention, Update: Trends in AIDS incidence-United States, 1996, MMRW 46: 862–867 (1997).

    Google Scholar 

  3. Finzi, D., J. Blankson, J. D. Siciliano, 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. Siciliano, Latent infection of CD4+ T-cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy, Nature Med. 5: 512–517 (1999).

    Article  PubMed  CAS  Google Scholar 

  4. Letvin, N. L., and N. W. King, Immunologic and pathologic manifestations of the infection of rhesus monkeys with simian immunodeficiency virus of macaques, J. Acquir. Immune Defic. Syndr. 3: 1023–1040 (1990).

    PubMed  CAS  Google Scholar 

  5. Desrosiers, R. C., The simian immunodeficiency viruses, Ann. Rev. Immunol. 8: 557–578 (1990).

    Article  CAS  Google Scholar 

  6. Bohm, R. P., L. N. Martin, B. Davison-Fairburn, G. B. Baskin, and M. Murphey-Corb, Neonatal disease induced by SIV infection of the rhesus monkey (Macaca mulatta), AIDS Res. Hum. Retroviruses 9: 1131–1137 (1993).

    PubMed  Google Scholar 

  7. Marthas, M. L., K. K. A. Van Rompay, M. Otsyula, C. J. Miller, D. Canfield, N. C. Pedersen, and M. B. McChesney, Viral factors determine progression to AIDS in simian immunodeficiency virus-infected newborn rhesus macaques, J. Virol. 69: 4198–4205 (1995).

    PubMed  CAS  Google Scholar 

  8. Black, P. L., M. B. Downs, M. G. Lewis, M. A. Ussery, G. B. Dreyer, S. R. J. Petteway, and D. M. Lambert, Antiretroviral activities of protease inhibitors against murine leukemia virus and simian immunodeficiency virus in culture, Antimicrob. Agents Chemother. 37: 71–77 (1993).

    PubMed  CAS  Google Scholar 

  9. Sager, P. R., J. C. Cradock, C. L. Litterst, L. N. Martin, K. F. Soike, M. Murphey-Corb, P. A. Marx, C. C. Tsai, A. Fridland, A. Bodner, L. Resnick, and R. F. Schinazi, In vitro testing of therapeutics against SIV and HIV, Ann. N.Y. Acad. Sci. 616: 599–605 (1990).

    Article  Google Scholar 

  10. De Clercq, E., HIV inhibitors targeted at the reverse transcriptase, AIDS Res. Hum. Retroviruses 8: 119–134 (1992).

    PubMed  Google Scholar 

  11. Überla, K., C. Stahl-Hennig, D. Böttiger, K. Mätz-Rensing, F. J. Kaup, J. Li, W. A. Haseltine, B. Fleckenstein, G. Hunsmann, B. Öberg, and J. Sodroski, Animal model for the therapy of acquired immunodefiency syndrome with reverse transcriptase inhibitors, Proc. Natl. Acad. Sci. USA 92: 8210–8214 (1995).

    Article  PubMed  Google Scholar 

  12. Balzarini, J., E. De Clercq, and K. Überla, SIV/HIV-1 hybrid virus expressing the reverse transcriptase gene of HIV-1 remains sensitive to HIV-1-specific reverse transcriptase inhibitors after passage in rhesus macaques, J. Acquir. Immune Defic. Syndr. Human Retrovirol. 15: 1–4 (1997).

    CAS  Google Scholar 

  13. Mori, K., Y. Yasumoti, S. Sawada, F. Villinger, K. Sugama, B. Rosenwirth, J. L. Heeney, K. Überla, S. Yamazaki, A. A. Ansari, and H. Rübsammen-Waigmann, Suppression of acute viremia by short-term postexposure prophylaxis of simian/human immunodeficiency virus SHIV-RT-infected monkeys with a novel reverse transcriptase inhibitor (GW420867) allows for development of potent antiviral immune responses resulting in efficient containment of infection, J. Virol. 74: 5747–5753 (2000).

    Article  PubMed  CAS  Google Scholar 

  14. Zuber, B., D. Böttiger, R. Benthin, P. Ten Haaft, J. Heeney, B. Wahren, and B. Öberg, An in vivo model for HIV resistance development, AIDS Res. Hum. Retroviruses 17: 631–635 (2001).

    Article  PubMed  CAS  Google Scholar 

  15. Ha, J. C., C. Nosbisch, S. H. Conrad, G. C. Ruppenthal, G. P. Sackett, J. Abkowitz, and J. D. Unadkat, Fetal toxicity of zidovudine (azidothymidine) in macaca nemestrina: preliminary observations, J. Acquired Immune Defic. Syndr. 7: 154–157 (1994).

    CAS  Google Scholar 

  16. Lopez-Anaya, A., J. D. Unadkat, L. A. Schumann, and A. L. Smith, Pharmacokinetics of zidovudine (azidothymidine). II. Development of metabolic and renal clearance pathways in the neonate, J. Acquir. Immune Defic. Syndr. 3: 1052–1058 (1990).

    PubMed  CAS  Google Scholar 

  17. Lopez-Anaya, A., J. D. Unadkat, L. A. Schumann, and A. L. Smith, Pharmacokinetics of zidovudine (azidothymidine). I. Transplacental transfer, J. Acquir. Immune Defic. Syndr. 3: 959–964 (1990).

    PubMed  CAS  Google Scholar 

  18. Lopez-Anaya, A., J. D. Unadkat, L. A. Schumann, and A. L. Smith, Pharmacokinetics of zidovudine (Azidothymidine). III. Effect of pregnancy, J. Acquir. Immune Defic. Syndr. 4: 64–68 (1991).

    PubMed  CAS  Google Scholar 

  19. Odineces, A., C. Pereira, C. Nosbisch, and J. D. Unadkat, Prenatal and postpartum pharmacokinetics of stavudine (2′,3′-didehydro-3′-deoxythymidine) and didanosine (dideoxyinosine) in pigtailed macaques (Macaca nemestrina), Antimicrob. Agents Chemother. 40: 2423–2425 (1996).

    Google Scholar 

  20. Odinecs, A., C. Nosbisch, and J. D. Unadkat, Zidovudine does not affect transplacental transfer of systemic clearance of stavudine (2′,3′-didehydro-deoxythymidine) in the pigtailed macaque (Macaca nemestrina), Antimicrob. Agents Chemother. 40: 1569–1571 (1996).

    PubMed  CAS  Google Scholar 

  21. Odinecs, A., C. Nosbisch, R. D. Keller, W. L. Baughman, and J. D. Unadkat, In vivo maternal-fetal pharmacokinetics of stavudine (2′,3′-didehydro-3′-deoxythymidine) in pigtailed macaques (Macaca nemestrina), Antimicrob. Agents Chemother. 40: 196–202 (1996).

    PubMed  CAS  Google Scholar 

  22. Pereira, C. M., C. Nosbisch, H. R. Winter, W. L. Baughman, and J. D. Unadkat, Transplacental pharmacokinetics of dideoxyinosine in pigtailed macaques, Antimicrob. Agents Chemother. 38: 781–786 (1994).

    PubMed  CAS  Google Scholar 

  23. Pereira, C. M., C. Nosbisch, and J. D. Unadkat, Pharmacokinetics of dideoxyinosine in neonatal pigtailed macaques, Antimicrob. Agents Chemother. 38: 787–789 (1994).

    PubMed  CAS  Google Scholar 

  24. Pereira, C. M., C. Nosbisch, W. L. Baughman, and J. D. Unadkat, Effect of zidovudine on transplacental pharmacokinetics of ddI in the pigtailed macaque (Macaca nemestrina), Antimicrob. Agents Chemother. 39: 343–345 (1995).

    PubMed  CAS  Google Scholar 

  25. Qian, M., T. Bui, R. J. Y. Ho, and J. D. Unadkat, Metabolism of 3′-azido-3′-deoxythymidine (AZT) in human placental trophoblasts and Hofbauer cells, Biochem. Pharmacol. 48: 383–389 (1994).

    Article  PubMed  CAS  Google Scholar 

  26. Qian, M., G. Chandrasena, R. J. H. Ho, and J. D. Unadkat, Comparison of rates of intracellular metabolism of zidovudine in human and primate peripheral blood mononuclear cells, Antimicrob. Agents Chemother. 38: 2398–2403 (1994).

    PubMed  CAS  Google Scholar 

  27. Ravasco, R. J., J. D. Unadkat, C.-C. Tsai, and C. Nosbisch, Pharmacokinetics of dideoxyinosine in pigtailed macaques (Macaca nemestrina) after intravenous and subcutaneous administration., J. Acquired Immune Defic. Syndr. 5: 1016–1018 (1992).

    CAS  Google Scholar 

  28. Tuntland, T., C. Nosbisch, W. Baughman, J. Massarella, and J. Unadkat, Mechanism and rate of placental transfer of zalcitabine (2′,3′-dideoxycytidine) in Macaca nemestrina, Am. J. Obstet. Gynecol. 174: 856–863 (1996).

    Article  PubMed  CAS  Google Scholar 

  29. Tarantal, A. F., R. J. Spanggord, and A. G. Hendrickx, Pre-and postnatal treatment of the rhesus macaque (Macaca mulatta) with azidothymidine: I. Fetal studies, Pediatr. AIDS HIV Infect. 5: 10–19 (1994).

    Google Scholar 

  30. Van Rompay, K. K. A., M. G. Otsyula, M. L. Marthas, C. J. Miller, M. B. McChesney, and N. C. Pedersen, Immediate zidovudine treatment protects simian immunodeficiency virus-infected newborn macaques against rapid onset of AIDS, Antimicrob. Agents Chemother. 39: 125–131 (1995).

    PubMed  Google Scholar 

  31. Böttiger, D., L. Ståhle, S.-L. Li, and B. Öberg, Long-term tolerance and efficacy of 3′-azido-thymidine and 3′-fluorothymidine treatment of asymptomatic monkeys infected with simian immunodeficiency virus, Antimicrob. Agents Chemother. 36: 1770–1772 (1992).

    PubMed  Google Scholar 

  32. Wingfield, C., J. Booth, P. Sheridan, J. Detmer, and J. Turczyn, SIV 4.0, performance characteristics of an exceptionally sensitive, quantitative assay for SIV RNA using branched DNA technology, in: 20th Annual Symposium on Nonhuman Primate Models for AIDS, Monterey, CA (2002).

    Google Scholar 

  33. Lifson, J. D., M. A. Nowak, S. Goldstein, J. L. Rossio, A. Kinter, G. Vasquez, T. Wiltrout, C. Brown, D. Schneider, L. Wahl, A. L. Lloyd, J. Williams, W. R. Elkins, A. S. Fauci, and V. M. Hirsch, The extent of early viral replication is a critical determinant of the natural history of simian immunodeficiency virus infection, J. Virol. 71: 9508–9514 (1997).

    PubMed  CAS  Google Scholar 

  34. Leutenegger, C. M., J. Higgins, T. B. Matthews, A. F. Tarantal, P. A. Luciw, N. C. Pedersen, and T. W. North, Real-time Taqman PCR as a specific and more sensitive alternative to the branched-chain DNA assay for quantitation of simian immunodeficiency virus RNA, AIDS Res. Hum. Retroviruses 17: 243–251 (2001).

    Article  PubMed  CAS  Google Scholar 

  35. Van Rompay, K. K. A., M. Otsyula, M. L. Marthas, and N. C. Pedersen, Simian immunodeficiency virus infection of newborn and infant rhesus macaques: an animal model for testing antiretroviral drugs, Inter. Antiviral News 2: 5–6 (1994).

    Google Scholar 

  36. Van Rompay, K. K. A., and M. L. Marthas, Non-human primate models for testing anti-HIV drugs, in: Antivirals against AIDS, edited by J. Kreuter, R. Unger, and Rüebsamen-Waigmann (Marcel Dekker, New York, 2000), pp. 295–320.

    Google Scholar 

  37. Van Rompay, K. K. A., J. M. Cherrington, M. L. Marthas, C. J. Berardi, A. S. Mulato, A. Spinner, R. P. Tarara, D. R. Canfield, S. Telm, N. Bischofberger, and N. C. Pedersen, 9-[2-(Phosphonomethoxy)propyl] adenine therapy of established simian immunodeficiency virus infection in infant rhesus macaques, Antimicrob. Agents Chemother. 40: 2586–2591 (1996).

    PubMed  Google Scholar 

  38. Grob, P. M., Y. Cao, E. Muchmore, D. D. Ho, S. Norris, J. W. Pav, C.-K. Shih, and J. Adams, Prophylaxis against HIV-1 infection in chimpanzees by nevirapine, a nonnucleoside inhibitor of reverse transcriptase, Nature Med. 3: 665–670 (1997).

    Article  PubMed  CAS  Google Scholar 

  39. Van Rompay, K. K. A., M. B. McChesney, N. L. Aguirre, K. A. Schmidt, N. Bischofberger, and M. L. Marthas, Two low doses of tenofovir protect newborn macaques against oral simian immunodeficiency virus infection, J. Infect. Dis. 184: 429–438 (2001).

    Article  PubMed  Google Scholar 

  40. Wyand, M. S., The use of SIV-infected rhesus monkeys for the preclinical evaluation of AIDS drugs and vaccines, AIDS Res. Hum. Retrovir. 8: 349–356 (1992).

    PubMed  CAS  Google Scholar 

  41. Fazely, F., W. A. Haseltine, R. F. Rodger, and R. M. Ruprecht, Postexposure chemoprophylaxis with ZDV or ZDV combined with interferon-a: failure after inoculating rhesus monkeys with a high dose of SIV, J. Acquir. Immune Defic. Syndr. 4: 1093–1097 (1991).

    PubMed  CAS  Google Scholar 

  42. Lundgren, B., D. Bottiger, E. Ljungdahl-Ståhle, E. Norrby, L. Ståhle, B. Wahren, and B. Öberg, Antiviral effects of 3′-fluorothymidine and 3′-azidothymidine in cynomolgus monkeys infected with simian immunodeficiency virus, J. Acquir. Immune Defic. Syndr. 4: 489–498 (1991).

    PubMed  CAS  Google Scholar 

  43. McClure, H. M., D. C. Anderson, A. A. Ansari, P. N. Fultz, S. A. Klumpp, and R. F. Schinazi, Nonhuman primate models for evaluation of AIDS therapy, Ann. N.Y. Acad. Sci. 616: 287–298 (1990).

    Article  PubMed  CAS  Google Scholar 

  44. Van Rompay, K. K. A., M. L. Marthas, J. D. Lifson, C. J. Berardi, G. M. Vasquez, E. Agatep, Z. A. Dehqanzada, K. C. Cundy, N. Bischofberger, and N. C. Pedersen, Administration of 9-[2-(phosphonomethoxy)propyl] adenine (PMPA) for prevention of perinatal simian immunodeficiency virus infection in rhesus macaques, AIDS Res. Hum. Retrovir. 14: 761–773 (1998).

    PubMed  Google Scholar 

  45. Van Rompay, K. K. A., C. J. Berardi, N. L. Aguirre, N. Bischofberger, P. S. Lietman, N. C. Pedersen, and M. L. Marthas, Two doses of PMPA protect newborn macaques against oral simian immunodeficiency virus infection, AIDS 12: F79–F83 (1998).

    PubMed  Google Scholar 

  46. Böttiger, D., P. Putkonen, and B. Öberg, Prevention of HIV-2 and SIV infections in cynomolgus macaques by prophylactic treatment with 3′-fluorothymidine, AIDS Res. Hum. Retrovir. 8: 1235–1238 (1992).

    PubMed  Google Scholar 

  47. Böttiger, D., L. Vrang, and B. Öberg, Influence of the infectious dose of simian immunodeficiency virus on the acute infection in cynomolgus monkeys and on the effect of treatment with 3′-fluorothymidine, Antivir. Chem. Chemother. 3: 267–271 (1992).

    Google Scholar 

  48. Tsai, C.-C., K. E. Follis, A. Sabo, R. F. Grant, C. Bartz, R. E. Nolte, R. E. Benveniste, and N. Bischofberger, Preexposure prophylaxis with 9-(-2-phosphonylmethoxyethyl) adenine against simian immunodeficiency virus infection in macaques, J. Infect. Dis. 169: 260–266 (1994).

    PubMed  CAS  Google Scholar 

  49. Tsai, C.-C., K. E. Follis, T. W. Beck, A. Sabo, R. F. Grant, N. Bischofberger, and R. E. Benveniste, Prevention of simian immunodeficiency virus infection in macaques by 9-(2-phosphonylmethoxypropyl) adenine (PMPA), Science 270: 1197–1199 (1995).

    Article  PubMed  CAS  Google Scholar 

  50. Böttiger, D., N. G. Johansson, B. Samuelsson, H. Zhang, P. Putkonen, L. Vrang, and B. Öberg, Prevention of simian immunodeficiency virus, SIVsm, or HIV-2 infection in cynomolgus monkeys by pre-and postexposure administration of BEA-005, AIDS 11: 157–162 (1997).

    Article  PubMed  Google Scholar 

  51. Otten, R. A., D. K. Smith, D. R. Adams, J. K. Pullium, E. Jackson, C. N. Kim, H. Jaffe, R. Janssen, S. Butera, and T. M. Folks, Efficacy of postexposure prophylaxis after intravaginal exposure of pig-tailed macaques to a human-derived retrovirus (human immunodeficiency virus type 2). J. Virol. 74: 9771–9775 (2000).

    Article  PubMed  CAS  Google Scholar 

  52. Van Rompay, K. K. A., M. D. Miller, M. L. Marthas, N. A. Margot, P. J. Dailey, R. P. Tarara, D. R. Canfield, J. M. Cherrington, N. L. Aguirre, N. Bischofberger, and N. C. Pedersen, Prophylactic and therapeutic benefits of short-term 9-[2-(phosphonomethoxy)propyl] adenine (PMPA) administration to newborn macaques following oral inoculation with simian immunodeficiency virus with reduced susceptibility to PMPA, J. Virol. 74: 1767–1774 (2000).

    Article  PubMed  Google Scholar 

  53. Van Rompay, K. K. A., K. A. Schmidt, J. R. Lawson, R. Singh, N. Bischofberger, and M. L. Marthas, Topical administration of low-dose tenofovir disoproxyl fumarate to protect infant macaques against multiple oral exposures of low doses of simian immunodeficiency virus, J. Infect. Dis. 186: 1508–1513 (2002).

    Article  PubMed  Google Scholar 

  54. Miller, C., Z. Rosenberg, and N. Bischofberger, Use of topical PMPA to prevent vaginal transmission of SIV, in: Ninth International Conference on Antiviral Research, Fukushima, May 19–24 (1996).

    Google Scholar 

  55. Manson, K. H., M. S. Wyand, C. Miller, and A. R. Neurath, Effect of a cellulose acetate phtalate topical cream on vaginal transmission of simian immunodeficiency virus in rhesus monkeys, Antimicrob. Agents Chemother. 44: 3199–3202 (2000).

    Article  PubMed  CAS  Google Scholar 

  56. Wyand, M. S., K. H. Manson, C. J. Miller, and A. R. Neurath, Effect of 3-hydroxyphthaloylb-lactoglobulin on vaginal transmission of simian immunodeficiency virus in rhesus monkeys, Antimicrob. Agents Chemother. 43: 978–980 (1999).

    PubMed  CAS  Google Scholar 

  57. Weber, J., A. Nunn, T. O’Connor, D. Jeffries, V. Kitchen, S. McCormack, J. Stott, N. Almond, A. Stone, and J. Darbyshire, “Chemical condoms” for the prevention of HIV infection: evaluation of novel agents against SHIV98.6PD in vitro and in vivo, AIDS 15: 1563–1568 (2001).

    Article  PubMed  CAS  Google Scholar 

  58. Centers for Disease Control and Prevention, Update: provisional Public Health Service recommendations for chemoprophylaxis after occupational exposure to HIV, MMRW 45: 468–472 (1996).

    Google Scholar 

  59. Centers for Disease Control and Prevention, Management of possible sexual, injecting-drug-use, or other nonoccupational exposure to HIV, including considerations related to antiretroviral therapy. Public Health Service Statement, MMRW 47: 1–14 (1998).

    Google Scholar 

  60. Mofenson, L. M., and M. G. Fowler, Interruption of materno-fetal transmission, AIDS 13: S205–S14 (1999).

    Article  PubMed  CAS  Google Scholar 

  61. Connor, E. M., R. S. Sperling, R. Gelber, P. Kiselev, G. Scott, M. J. O’Sullivan, R. VanDyke, M. Bey, W. Shearer, R. L. Jacobson, E. Jiminez, E. O’Neill, B. Bazin, J.-F. Delfraissy, M. Culnane, R. Coombs, M. Elkins, J. Moye, P. Stratton, J. Balsley, for the Pediatric AIDS Clinical Trials Group Protocol 076 Study Group, Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment, N. Engl. J. Med. 331: 1173–1180 (1994).

    Article  PubMed  CAS  Google Scholar 

  62. Centers for Disease Control and Prevention, Administration of zidovudine during late pregnancy and delivery to prevent perinatal HIV transmission-Thailand, 1996–1998, MMWR 47: 151–154 (1998).

    Google Scholar 

  63. Wade, N. A., G. S. Birkhead, B. L. Warren, T. T. Charbonneau, P. T. French, L. Wang, J. B. Baum, J. M. Tesoriero, and R. Savicki, Abbreviated regimens of zidovudine prophylaxis and perinatal transmission of the human immunodeficiency virus, N. Engl. J. Med. 339: 1409–1414 (1998).

    Article  PubMed  CAS  Google Scholar 

  64. The Petra Study Team, Efficacy of three short-course regimens of zidovudine and lamivudine in preventing early and late transmission of HIV-1 from mother to child in Tanzania, South Africa and Uganda (Petra Study): a randomized, double-blind, placebo-controlled trial, Lancet 359: 1178–1186 (2002).

    Article  Google Scholar 

  65. Moodley, D., J. Moodley, H. Coovadia, G. Gray, J. McIntyre, J. Hofmyer, C. Nikodem, D. Hall, F. Gigliotti, P. Robinson, L. Boshoff, J. L. Sullivan, for the South African Intrapartum Nevirapine Trial (SAINT) Investigators, A multicenter randomized controlled trial of nevirapine versus a combination of zidovudine and lamivudine to reduce intrapartum and early postpartum mother-to-child transmission of human immunodeficiency virus type 1, J. Infect. Dis. 187: 725–735 (2003).

    Article  PubMed  CAS  Google Scholar 

  66. Guay, L. A., P. Musoke, T. Fleming, D. Bagenda, M. Allen, C. Nakabiito, J. Sherman, P. Bakaki, C. Ducar, M. Deseyve, L. Emel, M. Mirochnick, M. G. Fowler, L. Mofenson, P. Miotti, K. Dransfield, D. Bray, F. Mmiro, and J. B. Jackson, Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomized trial, Lancet 354:795–802 (1999).

    PubMed  CAS  Google Scholar 

  67. Eshleman, S. H., M. Mracna, L. A. Guay, M. Deseyve, S. Cunningham, M. Mirochnick, P. Musoke, T. Fleming, M. G. Fowler, L. M. Mofenson, F. Mmiro, and J. B. Jackson, Selection and fading of resistance mutations in women and infants receiving nevirapine to prevent HIV-1 vertical transmission (HIVNET012), AIDS 15: 1951–1957 (2001).

    Article  PubMed  CAS  Google Scholar 

  68. Martin, L. N., M. Murphey-Corb, K. F. Soike, B. Davison-Fairburn, and G. B. Baskin, Effects of initiation of 3′-azido-3′-deoxythymidine treatment at different times after infection of rhesus monkeys with simian immunodeficiency virus, J. Infect. Dis. 168: 825–835 (1993).

    PubMed  CAS  Google Scholar 

  69. Tsai, C.-C., K. E. Follis, R. F. Grant, R. E. Nolte, C. R. Bartz, R. E. Benveniste, and P. R. Sager, Effect of dosing frequency on ZDV prophylaxis in macaques infected with simian immunodeficiency virus, J. Acquired Immune Defic. Syndr. 6: 1086–1092 (1993).

    CAS  Google Scholar 

  70. Joag, S. V., Z. Li, L. Foresman, D. M. Pinson, E. B. Stephens, R. Raghavan, J.-F. Navé, P. Casara, and O. Narayan, Early treatment with 9-(2-phosphonylmethoxyethyl) adenine reduces virus burdens for a prolonged period in SIV-infected rhesus macaques, AIDS Res. Hum. Retrovir. 13: 241–246 (1997).

    PubMed  CAS  Google Scholar 

  71. Le Grand, R., P. Clayette, O. Noack, B. Vaslin, F. Theodoro, G. Michel, P. Roques, and D. Dormont, An animal model for antilentiviral therapy: effect of zidovudine on viral load during acute infection after exposure of macaques to simian immunodeficiency virus, AIDS Res. Hum. Retrovir. 10: 1279–1287 (1994).

    PubMed  CAS  Google Scholar 

  72. Le Grand, R., B. Vaslin, J. Larghero, O. Neidez, H. Thiebot, P. Sellier, P. Clayette, N. Dereuddre-Bosquet, and D. Dormont, Post-exposure prophylaxis with highly active antiretroviral therapy could not protect macaques from infection with SIV/HIV chimera, AIDS 14: 1864–1866 (2000).

    Article  PubMed  Google Scholar 

  73. Van Rompay, K. K. A., P. J. Dailey, R. P. Tarara, D. R. Canfield, N. L. Aguirre, J. M. Cherrington, P. D. Lamy, N. Bischofberger, N. C. Pedersen, and M. L. Marthas, Early short-term 9-[2-(phosphonomethoxy)propyl] adenine (PMPA) treatment favorably alters subsequent disease course in simian immunodeficiency virus-infected newborn rhesus macaques, J. Virol. 73: 2947–2955 (1999).

    PubMed  Google Scholar 

  74. Watson, A., J. McClure, J. Ranchalis, M. Scheibel, A. Schmidt, B. Kennedy, W. R. Morton, N. L. Haigwood, and S.-L. Hu, Early postinfection antiviral treatment reduces viral load and prevents CD4+ cell decline in HIV type 2-infected macaques, AIDS Res. Hum. Retrovir. 13: 1375–1381 (1997).

    PubMed  CAS  Google Scholar 

  75. Rausch, D. M., M. P. Heyes, E. A. Murray, and L. E. Eiden, Zidovudine treatment prolongs survival and decreases virus load in the central nervous system of rhesus macaques infected perinatally with simian immunodeficiency virus, J. Infect. Dis. 172: 59–69 (1995).

    PubMed  CAS  Google Scholar 

  76. Rosenwirth, B., P. ten Haaft, W. M. J. M. Bogers, I. G. Nieuwenhuis, H. Niphuis, E.-M. Kuhn, N. Bischofberger, J. L. Heeney, and K. Überla, Antiretroviral therapy during primary immunodeficiency virus infection can induce persistent suppression of virus load and protection from heterologous challenge in rhesus macaques, J. Virol. 74:1704–1711 (2000).

    Article  PubMed  CAS  Google Scholar 

  77. Smith, M. S., L. Foresman, G. J. Lopez, J. Tsay, D. Wodarz, J. D. Lifson, A. Page, C. Wang, Z. Li, I. Adany, S. Buch, N. Bischofberger, and O. Narayan, Lasting effects of transient postinoculation tenofovir [9-R-(2-phosphonomethoxypropyl) adenine] treatment of SHIVKU2 infection of rhesus macaques, Virology 277: 306–315 (2000).

    Article  PubMed  CAS  Google Scholar 

  78. Hodge, S., J. De Rosayro, A. Glenn, I. C. Ojukwu, S. Dewhurst, H. M. McClure, N. Bischofberger, D. C. Anderson, S. A. Klumpp, and F. J. Novembre, Postinoculation PMPA treatment, but not preinoculation immunomodulatory therapy, protects against development of acute disease induced by the unique simian immunodeficiency virus SIVsmmPBj, J. Virol. 73: 8630–8639 (1999).

    PubMed  CAS  Google Scholar 

  79. Lifson, J. D., J. L. Rossio, R. Arnaout, L. Li, T. L. Parks, D. K. Schneider, R. F. Kiser, V. J. Coalter, G. Walsh, R. J. Imming, B. Fisher, B. M. Flynn, N. Bischofberger, M. J. Piatak, V. M. Hirsch, M. A. Nowak, and D. Wodarz, Containment of simian immunodeficiency virus infection: cellular immune responses and protection from rechallenge following transient postinoculation antiretroviral treatment, J. Virol. 74: 2584–2593 (2000).

    Article  PubMed  CAS  Google Scholar 

  80. Berrey, M. M., T. Schacker, A. C. Collier, T. Shea, S. J. Brodie, D. Mayers, R. Coombs, J. Krieger, T.-W. Chun, A. Fauci, S. G. Self, and L. Corey, Treatment of primary human immunodeficiency virus type 1 infection with potent antiretroviral therapy reduces frequency of rapid progression to AIDS, J. Infect. Dis. 183: 1466–1475 (2001).

    Article  PubMed  CAS  Google Scholar 

  81. Kinloch-de Loës, S., B. J. Hirschel, B. Hoen, D. A. Cooper, B. Tindall, A. Carr, J.-H. Saurat, N. Clumeck, A. Lazzarin, L. Mathiesen, F. Raffi, F. Antunes, J. Von Overbeck, R. Lüthy, M. Glauser, D. Hawkins, C. Baumberger, S. Yerly, T. V. Perneger, and L. Perrin, A controlled trial of zidovudine in primary human immunodeficiency virus infection, N. Engl. J. Med. 333: 408–413 (1995).

    Article  PubMed  Google Scholar 

  82. Lafeuillade, A., C. Poggi, C. Tamalet, N. Profizi, C. Tourres, and O. Costes, Effects of a combination of zidovudine, didanosine, and lamivudine on primary human immunodeficiency virus type 1 infection, J. Infect. Dis. 175: 1051–1055 (1997).

    PubMed  CAS  Google Scholar 

  83. Rosenberg, E. S., M. Altfeld, S. H. Poon, M. N. Phillips, B. M. Wilkes, R. L. Eldridge, G. K. Robbins, R. T. D’Aquila, P. J. R. Goulder, and B. D. Walker, Immune control of HIV-1 after early treatment of acute infection, Nature 407: 523–526 (2000).

    Article  PubMed  CAS  Google Scholar 

  84. Igarashi, T., C. R. Brown, Y. Endo, A. Buckler-White, R. Plishka, N. Bischofberger, V. M. Hirsch, and M. A. Martin, Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+ T-cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): implications for HIV-1 infections of humans, Proc. Natl. Acad. Sci. USA 98: 658–663 (2001).

    Article  PubMed  CAS  Google Scholar 

  85. Lifson, J. D., and M. A. Martin, One step forwards, one step back, Nature 415: 272–273 (2002).

    Article  PubMed  CAS  Google Scholar 

  86. Feinberg, M. B., and J. P. Moore, AIDS vaccine models: challenging challenge viruses, Nature Med. 8: 207–210 (2002).

    Article  PubMed  CAS  Google Scholar 

  87. Van Rompay, K. K. A., M. L. Marthas, R. A. Ramos, C. P. Mandell, E. K. McGowan, S. M. Joye, and N. C. Pedersen, Simian immunodeficiency virus (SIV) infection of infant rhesus macaques as a model to test antiretroviral drug prophylaxis and therapy: oral 3′-azido-3′-deoxythymidine prevents SIV infection, Antimicrob. Agents Chemother. 36: 2381–2386 (1992).

    PubMed  Google Scholar 

  88. Van Rompay, K. K. A., T. B. Matthews, J. Higgins, D. R. Canfield, R. P. Tarara, M. A. Wainberg, R. F. Schinazi, N. C. Pedersen, and T. W. North, Virulence and reduced fitness of simian immunodeficiency virus with the M184V mutation in reverse transcriptase, J. Virol. 76: 6083–6092 (2002).

    Article  PubMed  CAS  Google Scholar 

  89. Tsai, C.-C., K. E. Follis, T. W. Beck, A. Sabo, N. Bischofberger, and P. J. Dailey, Effects of (R)-9-(2-phosphonylmethoxypropyl) adenine monotherapy on chronic SIV infection, AIDS Res. Hum. Retrovir. 13: 707–712 (1997).

    PubMed  CAS  Google Scholar 

  90. Tsai, C.-C., K. E. Follis, A. Sabo, R. Grant, and N. Bischofberger, Efficacy of 9-(2-phosphonylmethoxyethyl) adenine treatment against chronic simian immunodeficiency virus infection in macaques, J. Infect. Dis. 171: 1338–1343 (1995).

    PubMed  CAS  Google Scholar 

  91. Nowak, M. A., A. L. Lloyd, G. M. Vasquez, T. A. Wiltrout, L. M. Wahl, N. Bischofberger, J. Williams, A. Kinter, A. S. Fauci, V. M. Hirsch, and J. D. Lifson, Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection, J. Virol. 71: 7518–7525 (1997).

    PubMed  CAS  Google Scholar 

  92. Silvera, P., P. Racz, K. Racz, N. Bischofberger, C. Crabbs, J. Yalley-Ogunro, J. Greenhouse, J. Bo Jiang, and M. G. Lewis, Effect of PMPA and PMEA on the kinetics of viral load in simian immunodeficiency virus-infected macaques, AIDS Res. Hum. Retrovir. 16: 791–800 (2000).

    Article  PubMed  CAS  Google Scholar 

  93. Van Rompay, K. K. A., R. Singh, L. Brignolo, J. R. Lawson, K. A. Schmidt, B. Pahar, C. Wingfield, D. R. Canfield, R. P. Tarara, N. Bischofberger, and M. Marthas, The clinical benefits of tenofovir for simian immunodeficiency virus-infected macaques are larger than predicted by its effects on standard viral and immunological parameters, J. Acquir. Immune Defic. Syndr. 36: 900–914 (2004).

    Article  PubMed  Google Scholar 

  94. Van Rompay, K. K. A., R. P. Singh, B. Pahar, D. L. Sodora, C. Wingfield, J. R. Lawson, K. A. Reimann, M. L. Marthas, and N. Bischofberger, CD8+ cell-mediated suppression of virulent simian immunodeficiency virus during tenofovir treatment, J. Virol. 78: 5324–5337 (2004).

    Article  PubMed  CAS  Google Scholar 

  95. Shen, Y., L. Shen, P. Sehgal, D. Zhou, M. Simon, M. Miller, E. A. Emini, B. Henckler, L. Chalifoux, N. Sehgal, M. Gastron, N. L. Letvin, and Z. W. Chen, Antiretroviral agents restore mycobacterium-specific T-cell immune responses and facilitate controlling a fatal tuberculosis-like disease in macaques coinfected with simian immunodeficiency virus and Mycobacterium bovis BCG, J. Virol. 75: 8690–8696 (2001).

    Article  PubMed  CAS  Google Scholar 

  96. Shen, A., M. C. Zink, J. L. Mankowski, K. Chadwick, J. B. Margolick, L. M. Carruth, M. Li, J. E. Clements, and R. F. Siciliano, Resting CD4+ T lymphocytes but not thymocytes provide a latent viral reservoir in a simian immunodeficiency virus-Macaca nemestrina model of human immunodeficiency virus type 1 infected patients on highly active antiretroviral therapy, J. Virol. 77: 4938–4949 (2003).

    Article  PubMed  CAS  Google Scholar 

  97. Lori, F., M. G. Lewis, J. Xu, G. Varga, D. E. J. Zinn, C. Crabbs, W. Wagner, J. Greenhouse, P. Silvera, J. Yalley-Ogunro, C. Tinelli, and J. Lisziewicz, Control of SIV rebound through structured treatment interruptions during early infection, Science 290: 1591–1593 (2000).

    Article  PubMed  CAS  Google Scholar 

  98. Hel, Z., J. Nacsa, B. Kelsall, W.-P. Tsai, N. Letvin, R. Washington Parks, E. Tryniszewska, L. Picker, M. G. Lewis, Y. Edghill-Smith, M. Moniuszko, R. Pal, L. Stevceva, J. D. Altman, T. M. Allen, D. Watkins, J. V. Torres, J. A. Berzofsky, I. M. Belyakov, W. Strober, and G. Franchini, Impairment of gag-specific CD8+ T-cell function in mucosal and systemic compartments of simian immunodeficiency virus mac251-and simian-human immunodeficiency virus KU2-infected macaques, J. Virol. 75: 11483–11495 (2001).

    Article  PubMed  CAS  Google Scholar 

  99. Tryniszewska, E., J. Nacsa, M. G. Lewis, P. Silvera, D. Montefiori, D. Venzon, Z. Hel, R. W. Parks, M. Moniuszko, J. Tartaglia, K. A. Smith, and G. Franchini, Vaccination of macaques with long-standing SIVmac251 infection lowers the viral set point after cessation of antiretroviral therapy, J. Immunol. 169: 5347–5357 (2002).

    PubMed  Google Scholar 

  100. Hel, Z., J. Nacsa, W.-P. Tsai, A. Thornton, L. Giuliani, J. Tartaglia, and G. Franchini, Equivalent immunogenicity of the highly attenuated poxvirus-based ALVAC-SIV and NYVAC-SIV vaccine candidates in SIVmac251-infected macaques, Virology 304: 125–134 (2002).

    Article  PubMed  CAS  Google Scholar 

  101. Nacsa, J., J. Stanton, K. J. Kunstman, W.-P. Tsai, D. I. Watkins, S. M. Wolinsky, and G. Franchini, Emergence of cytotoxic T lymphocyte escape mutants following antiretroviral treatment suspension in rhesus macaques infected with SIVmac251, Virology 305: 210–218 (2003).

    Article  PubMed  CAS  Google Scholar 

  102. Villinger, F., G. T. Brice, A. E. Mayne, P. Bostik, K. Mori, C. H. June, and A. A. Ansari, Adoptive transfer of simian immunodeficiency virus (SIV) naive autologous CD4+ T-cells to macaques chronically infected with SIV is sufficient to induce long-term nonprogressor status, Blood 99: 590–599 (2002).

    Article  PubMed  CAS  Google Scholar 

  103. Darby, G., and B. A. Larder, The clinical significance of antiviral drug resistance, Res. Virol. 143: 116–120 (1992).

    PubMed  CAS  Google Scholar 

  104. Richman, D. D., The clinical significance of drug-resistant mutants of human immunodeficiency virus, Res. Virol. 143: 130–131 (1992).

    PubMed  CAS  Google Scholar 

  105. Richman, D. D., Resistance, drug failure, and disease progression, AIDS Res. Hum. Retrovir. 10: 901–905 (1994).

    PubMed  CAS  Google Scholar 

  106. Deeks, S. G., T. Wrin, T. Liegler, R. Hoh, M. Hayden, J. D. Barbour, N. S. Hellmann, C. J. Petropoulos, J. M. McCune, M. K. Hellerstein, and R. M. Grant, Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia, N. Engl. J. Med. 344: 472–480 (2001).

    Article  PubMed  CAS  Google Scholar 

  107. Deeks, S. G., R. Hoh, R. M. Grant, T. Wrin, J. D. Barbour, A. Narvaez, D. Cesar, K. Abe, M. B. Hanley, N. S. Hellmann, C. J. Petropoulos, J. M. McCune, and M. K. Hellerstein, CD4+ T-cell kinetics and activation in human immunodeficiency virus-infected patients who remain viremic despite long-term treatment with protease inhibitor-based therapy, J. Infect. Dis. 185: 315–323 (2002).

    Article  PubMed  CAS  Google Scholar 

  108. Deeks, S. G., J. D. Barbour, J. N. Martin, M. S. Swanson, and R. M. Grant, Sustained CD4+ T-cell response after virologic failure of protease inhibitor-based regimens in patients with human immunodeficiency virus infection, J. Infect. Dis. 181: 946–953 (2000).

    Article  PubMed  CAS  Google Scholar 

  109. Barbour, J. D., T. Wrin, R. M. Grant, J. N. Martin, M. R. Segal, C. J. Petropoulos, and S. G. Deeks, Evolution of phenotypic drug susceptibility and viral replication capacity during long-term virologic failure of protease inhibitor therapy in human immunodefi-ciency virus-infected adults, J. Virol. 76: 11104–11112 (2002).

    Article  PubMed  CAS  Google Scholar 

  110. Kestler, H. W., III, D. J. Ringler, K. Mori, D. L. Panicalli, P. K. Sehgal, M. D. Daniel, and R. C. Desrosiers, Importance of the nef gene for maintenance of high virus loads and for development of AIDS, Cell 65: 651–662 (1991).

    Article  PubMed  CAS  Google Scholar 

  111. Lohman, B. L., M. B. McChesney, C. J. Miller, E. McGowan, S. M. Joye, K. K. A. Van Rompay, E. Reay, L. Antipa, N. C. Pedersen, and M. L. Marthas, A partially attenuated simian immunodeficiency virus induces host immunity that correlates with resistance to pathogenic virus challenge, J. Virol. 68: 7021–7029 (1994).

    PubMed  CAS  Google Scholar 

  112. Cherry, E., M. Slater, H. Salomon, E. Rud, and M. A. Wainberg, Mutations at codon 184 in simian immunodeficiency virus reverse transcriptase confer resistance to the (-) enantiomer of 2′,3′-dideoxy-thiacytidine, Antimicrob. Agents Chemother. 41: 2763–2765 (1997).

    PubMed  CAS  Google Scholar 

  113. Murry, J. P., J. Higgins, T. B. Matthews, V. Y. Huang, K. K. A. Van Rompay, N. C. Pedersen, and T. W. North, Reversion of the M184V mutation in simian immunodefi-ciency virus reverse transcriptase is selected by tenofovir, even in the presence of lamivudine, J. Virol. 77: 1120–1130 (2003).

    Article  PubMed  CAS  Google Scholar 

  114. Newstein, M. C., and R. C. Desrosiers, Effects of reverse-transcriptase mutations M184V and E89G on simian immunodeficiency virus in rhesus monkeys, J. Infect. Dis. 184: 1262–1267 (2001).

    Article  PubMed  CAS  Google Scholar 

  115. Böttiger, D., S. D. Kemp, B. A. Larder, H. Zhang, L. Vrang, and B. Öberg, AZT resistant SIVmac is refractile to AZT therapy in monkeys, in: 14th Annual Symposium on Nonhuman Primate Models for AIDS, October 23–26, Portland (OR) (1996).

    Google Scholar 

  116. Van Rompay, K. K. A., J. L. Greenier, M. L. Marthas, M. G. Otsyula, R. P. Tarara, C. J. Miller, and N. C. Pedersen, A zidovudine-resistant simian immunodeficiency virus mutant with a Q151M mutation in reverse transcriptase causes AIDS in newborn macaques., Antimicrob. Agents Chemother. 41: 278–283 (1997).

    PubMed  Google Scholar 

  117. Schmit, J.-C., J. Cogniaux, P. Hermans, C. Van Vaeck, S. Sprecher, B. Van Remoortel, M. Witvrouw, J. Balzarini, J. Desmyter, E. De Clercq, and A.-M. Vandamme, Multiple drug resistance to nucleoside analogues and non-nucleoside reverse transcriptase inhibitors in an efficienty replicating HIV-1 patient strain, J. Infect. Dis. 174: 962–968 (1996).

    PubMed  CAS  Google Scholar 

  118. Shafer, R. W., M. A. Winters, A. K. N. Iversen, and T. C. Merigan, Genotypic and phenotypic changes during culture of a multinucleoside-resistant human immunodeficiency virus type 1 strain in the presence and absence of additional reverse transcriptase inhibitors, Antimicrob. Agents Chemother. 40: 2887–2890 (1996).

    PubMed  CAS  Google Scholar 

  119. Schmit, J. C., B. Clotet, L. Ruiz, P. Hermans, S. Sprecher, V. Arendt, M. Leal, E. Lissen, T. Harrer, E. De Clercq, M. Witvrouw, and A.-M. Vandamme, Multiple dideoxynucleoside analogue-resistant HIV-1 in Europe, in: International Workshop on HIV Drug Resistance, Treatment Strategies and Eradication, St. Petersburg (Florida), 25–28 June (1997).

    Google Scholar 

  120. Colson, P., M. Henry, N. Tivoli, H. Gallais, J. A. Gastaut, J. Moreau, and C. Tamalet, Polymorphism and drug-selected mutations in the reverse transcriptase gene of HIV-2 from patients living in southern France, Antiviral Ther. 8: S161 (2003).

    Google Scholar 

  121. Descamps, D., F. Damond, S. Matheron, G. Collin, P. Campa, P. Foiny, S. Delarue, S. Pueyo, G. Chêne, F. Brun-Vézinet, and the French ANRS HIV-2 Cohort Study Group, High frequency of selection of the Q151M mutation in HIV-2-infected patients receiving nucleoside reverse transcriptase inhibitor-containing regimen, Antiviral Ther. 8: S162 (2003).

    Google Scholar 

  122. Wainberg, M. A., M. D. Miller, Y. Quan, H. Salomon, A. S. Mulato, P. D. Lamy, N. A. Margot, K. E. Anton, and J. M. Cherrington, In vitro selection and characterization of HIV-1 with reduced susceptibility to PMPA, Antiviral Ther. 4: 87–94 (1999).

    CAS  Google Scholar 

  123. Margot, N. A., E. Isaacson, I. McGowan, A. K. Cheng, R. T. Schooley, and M. D. Miller, Genotypic and phenotypic analyses of HIV-1 in antiretroviral-experienced patients treated with tenofovir DF, AIDS 16: 1227–1235 (2002).

    Article  PubMed  CAS  Google Scholar 

  124. Margot, N. A., E. Isaacson, I. McGowan, A. Cheng, and M. D. Miller, Extended treatment with tenofovir disoproxil fumarate in treatment-experienced HIV-1-infected patients: genotypic, phenotypic, and rebound analyses, J. Acquired Immune Defic. Syndr. 33: 15–21 (2003).

    CAS  Google Scholar 

  125. Van Rompay, K. K. A., J. M. Cherrington, M. L. Marthas, P. D. Lamy, P. J. Dailey, D. R. Canfield, R. P. Tarara, N. Bischofberger, and N. C. Pedersen, 9-[2-(Phosphonomethoxy) propyl] adenine (PMPA) therapy prolongs survival of infant macaques inoculated with simian immunodeficiency virus with reduced susceptibility to PMPA, Antimicrob. Agents Chemother. 43: 802–812 (1999).

    PubMed  Google Scholar 

  126. Balzarini, J., L. Naesens, J. Slachmuylders, H. Niphuis, I. Rosenberg, A. Holy, H. Schellekens, and E. De Clercq, 9-(2-phosphonylmethoxyethyl) adenine (PMEA) effectively inhibits retrovirus replication in vitro and simian immunodeficiency virus infection in rhesus monkeys, AIDS 5: 21–28 (1991).

    Article  PubMed  CAS  Google Scholar 

  127. Lori, F., R. C. Gallo, A. Malykh, A. Cara, J. Romano, P. Markham, and G. Franchini, Didanosine but not high doses of hydroxyurea rescue pigtail macaque from a lethal dose of SIVsmmpbj14, AIDS Res. Hum. Retrovir. 13: 1083–1088 (1997).

    Article  PubMed  CAS  Google Scholar 

  128. Spring, M., C. Stahl-Hennig, N. Stolte, N. Bischofberger, J. Heeney, P. ten Haaft, K. Tenner-Ràcz, P. Ràcz, D. Lorenzen, G. Hunsmann, and U. Dittmer, Enhanced cellular immune responses and reduced CD8+ lymphocytes apoptosis in acutely SIV-infected rhesus macaques after short-term antiretroviral treatment, Virology 279: 221–231 (2001).

    Article  PubMed  CAS  Google Scholar 

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  1. California National Primate Research Center, University of California, Davis, CA, 95616

    Koen K. A. van Rompay, Raman P. Singh & Marta L. Marthas

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  2. Department of Experimental Pathology and Retrovirus Center, University of Pisa, Via S. Zeno, 37, Pisa, I-56127, Italy

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van Rompay, K.K.A., Singh, R.P., Marthas, M.L. (2006). SIV Infection of Macaques as a Model for AIDS Drug Studies. In: Friedman, H., Specter, S., Bendinelli, M. (eds) In vivo Models of HIV Disease and Control. Infectious Diseases and Pathogenesis. Springer, Boston, MA. https://doi.org/10.1007/0-387-25741-1_6

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