Drug Safety

, Volume 26, Issue 9, pp 605–624 | Cite as

Hydroxyurea in the Treatment of HIV Infection

Clinical Efficacy and Safety Concerns
  • Julianna Lisziewicz
  • Andrea Foli
  • Mark Wainberg
  • Franco Lori
Review Article


Data from basic science and clinical studies suggest that hydroxyurea (hydroxycarbamide)-based regimens are effective treatment options for patients with HIV at various stages of disease. In vitro studies of HIV-infected lymphocytes have shown that hydroxyurea: (i) inhibits viral DNA synthesis; (ii) synergistically interacts with nucleoside reverse transcriptase inhibitors (NRTI); and (iii) increases the antiviral activity of didanosine. Clinical studies have confirmed that hydroxyurea in combination with didanosine produces potent and sustained viral suppression in patients with HIV infection. However, some concerns have been recently raised on the use of hydroxyurea in association with NRTI.

Hydroxyurea can cause myelosuppression, skin toxicities, mild gastrointestinal toxicity, and abnormalities of renal and liver functions. In addition, hydroxyurea may accentuate the toxic effects of nucleoside analogues. In fact, some clinical data seem to indicate an increased risk of pancreatitis and neuropathy when hydroxyurea is combined with didanosine and stavudine. Since hydroxyurea-related toxicity is dose dependent, a systematic study of hydroxyurea optimal dosage and schedule was initiated to monitor patients for possible nucleoside toxicity. In the Research Institute for Genetic and Human Therapy (RIGHT) 702 study it was shown that a low, well-tolerated hydroxyurea dose (600mg daily) achieved better antiretroviral activity than higher doses, together with better CD4+ cell count increase and fewer adverse effects.

In this paper the effects of hydroxyurea as salvage therapy for heavily pretreated patients with advanced HIV disease are presented. These studies have shown that some patients with extensive pretreatment experience and advanced disease can respond substantially to the addition of hydroxyurea. The addition of hydroxyurea to didanosine does not prevent the emergence of resistance to didanosine; nonetheless, the efficacy of this therapeutic regimen may not be attenuated by the presence of didanosine-resistant HIV mutants.

Since CD4 T lymphocyte activation is essential for virus replication and CD8 T lymphocyte activation may contribute to pathogenesis, the combination of hydroxyurea with other drugs may lead to the inhibition of HIV, by blocking the ‘cell activation-virus production-pathogenesis’ cycle. Clinical data indicate that hydroxyurea may play a role in attenuation of viral rebound and immune reconstitution by decreasing CD4 T cell proliferation, as well as preventing the exhaustion of CD8 T cell populations that may result from excessive activation during HIV infection.

While the combination of hydroxyurea with didanosine has provided hope, future studies including those that evaluate optimal dosing and long-term toxicity are needed to define the role for this agent in the treatment of HIV infection.


Viral Load Indinavir Hydroxyurea Nucleoside Analogue Didanosine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We are very grateful to Ian Frank, Bernard Hirschel, Olivier Rutschmann, Sergio Lupo, Jorge Palazzi, Diane Havlir, and Douglas Richman for their discussion and for reviewing parts of the manuscript. We also thank Sylva Petrocchi and Laurene Kelly for editorial assistance.

The work was supported in part by Istituto Superiore di Sanita Grants: 30D.46 and 40D.49. The authors have no potential conflicts of interest directly relevant to the contents of this manuscript.


  1. 1.
    Zhang L, Ramratnam B, Tenner-Racz K, et al. Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. N Engl J Med 1999; 340(21): 1605–13PubMedCrossRefGoogle Scholar
  2. 2.
    Finzi D, Blankson J, Siliciano JD, et al. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med 1999; 5(5): 512–7PubMedCrossRefGoogle Scholar
  3. 3.
    Carr A, Samaras K, Thorisdottir A, et al. Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet 1999; 353(9170): 2093–9PubMedCrossRefGoogle Scholar
  4. 4.
    Donehower RC. An overview of the clinical experience with hydroxyurea. Semin Oncol 1992; 19(3 Suppl. 9): 11–9PubMedGoogle Scholar
  5. 5.
    Charache S, Terrin ML, Moore RD, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med 1995; 332(20): 1317–22PubMedCrossRefGoogle Scholar
  6. 6.
    Gao WY, Cara A, Gallo RC, et al. Low levels of deoxynucleotides in peripheral blood lymphocytes: a strategy to inhibit human immunodeficiency virus type 1 replication. Proc Natl Acad Sci U S A 1993; 90(19): 8925–8PubMedCrossRefGoogle Scholar
  7. 7.
    Lori F, Malykh A, Cara A, et al. Hydroxyurea as an inhibitor of human immunodeficiency virus-type 1 replication. Science 1994; 266(5186): 801–5PubMedCrossRefGoogle Scholar
  8. 8.
    Lori F, Gallo RC. Hydroxyurea and AIDS: an old drug finds a new application? AIDS Res Hum Retroviruses 1995; 11(10): 1149–51PubMedCrossRefGoogle Scholar
  9. 9.
    Lori F. Hydroxyurea and HIV: 5 years later: from antiviral to immune-modulating effects. AIDS 1999; 13(12): 1433–42PubMedCrossRefGoogle Scholar
  10. 10.
    Gao WY, Johns DG, Mitsuya H. Anti-human immunodeficiency virus type 1 activity of hydroxyurea in combination with 2′,3′-dideoxynucleosides. Mol Pharmacol 1994; 46(4): 767–72PubMedGoogle Scholar
  11. 11.
    Johns DG, Gao WY. Selective depletion of DNA precursors: an evolving strategy for potentiation of dideoxynucleoside activity against human immunodeficiency virus. Biochem Pharmacol 1998; 55(10): 1551–6PubMedCrossRefGoogle Scholar
  12. 12.
    Malley SD, Grange JM, Hamedi-Sangsari F, et al. Synergistic anti-human immunodeficiency virus type 1 effect of hydroxamate compounds with 2′,3′-dideoxyinosine in infected resting human lymphocytes. Proc Natl Acad Sci U S A 1994; 91(23): 11017–21PubMedCrossRefGoogle Scholar
  13. 13.
    Palmer S, Shafer RW, Merigan TC. Hydroxyurea enhances the activities of didanosine, 9-[2- (phosphonylmethoxy) ethyl] adenine, and 9-[2- (phosphonylmethoxy)propyl] adenine against drug-susceptible and drug-resistant human immunodeficiency virus isolates. Antimicrob Agents Chemother 1999; 43(8): 2046–50PubMedGoogle Scholar
  14. 14.
    Lori F, Lisziewicz J. Hydroxyurea: mechaninsms of HIV-1 inhibition. Antivir Ther 1998; 3Suppl. 4: 25–33PubMedGoogle Scholar
  15. 15.
    Gao WY, Johns DG, Chokekuchai S, et al. Disparate actions of hydroxyurea in potentiation of purine and pyrimidine 2′,3′-dideoxynucleoside activities against replication of human immunodeficiency virus. Proc Natl Acad Sci U S A 1995; 92(18): 8333–7PubMedCrossRefGoogle Scholar
  16. 16.
    Moore RD, Keruly JC, Chaisson RE. Incidence of pancreatitis in HIV-infected patients receiving nucleoside reverse transcriptase inhibitor drugs. AIDS 2001; 15(5): 617–20PubMedCrossRefGoogle Scholar
  17. 17.
    Moore RD, Wong WM, Keruly JC, et al. Incidence of neuropathy in HIV-infected patients on monotherapy versus those on combination therapy with didanosine, stavudine and hydroxyurea. AIDS 2000; 14(3): 273–8PubMedCrossRefGoogle Scholar
  18. 18.
    Wainberg MA, Miller MD, Quan Y, et al. In vitro selection and characterization of HIV-1 with reduced susceptibility to PMPA. Antivir Ther 1999; 4(2): 87–94PubMedGoogle Scholar
  19. 19.
    Piccinini G, Foli A, Comolli G, et al. Complementary antiviral efficacy of hydroxyurea and protease inhibitors in human immunodeficiency virus-infected dendritic cells and lymphocytes. J Virol 2002; 76(5): 2274–8PubMedCrossRefGoogle Scholar
  20. 20.
    Perno CF, Newcomb FM, Davis DA, et al. Relative potency of protease inhibitors in monocytes/macrophages acutely and chronically infected with human immunodeficiency virus. J Infect Dis 1998; 178(2): 413–22PubMedCrossRefGoogle Scholar
  21. 21.
    Zagury D, Bernard J, Leonard R, et al. Long-term cultures of HTLV-III-infected T cells: a model of cytopathology of T-cell depletion in AIDS. Science 1986; 231(4740): 850–3PubMedCrossRefGoogle Scholar
  22. 22.
    Zack JA, Arrigo SJ, Weitsman SR, et al. HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure. Cell 1990; 61(2): 213–22PubMedCrossRefGoogle Scholar
  23. 23.
    Stevenson M, Stanwick TL, Dempsey MP, et al. HIV-1 replication is controlled at the level of T cell activation and proviral integration. EMBO J 1990; 9(5): 1551–60PubMedGoogle Scholar
  24. 24.
    Lori F, Malykh AG, Foli A, et al. Combination of a drug targeting the cell with a drug targeting the virus controls human immunodeficiency virus type 1 resistance. AIDS Res Hum Retroviruses 1997; 13(16): 1403–9PubMedCrossRefGoogle Scholar
  25. 25.
    Frank I. Clinical use of hydroxyurea in HIV-1 infected patients. J Biol Regul Homeost Agents 1999; 13(3): 186–91PubMedGoogle Scholar
  26. 26.
    Rutschmann OT, Opravil M, Iten A, et al. A placebo-controlled trial of didanosine plus stavudine, with and without hydroxyurea, for HIV infection. The Swiss HIV Cohort Study. AIDS 1998; 12(8): F71–7PubMedCrossRefGoogle Scholar
  27. 27.
    Federici ME, Lupo S, Cahn P, et al. Hydroxyurea in combination regimens for the treatment of antiretroviral naive, HIV-infected adults[abstract no. 287/12235]. Proceedings of the 12th World AIDS Conference 1998 Jun 28-Jul 3; Geneva; 12: 58–9Google Scholar
  28. 28.
    Havlir DV, Gilbert PB, Bennett K, et al. Effects of treatment intensification with hydroxyurea in HIV-infected patients with virologic suppression. AIDS 2001; 15(11): 1379–88PubMedCrossRefGoogle Scholar
  29. 29.
    Biron F, Lucht F, Peyramond D, et al. Anti-HIV activity of the combination of didanosine and hydroxyurea in HIV-1-infected individuals. J Acquir Immune Defic Syndr Hum Retrovirol 1995; 10(1): 36–40PubMedCrossRefGoogle Scholar
  30. 30.
    Clotet B, Ruiz L, Cabrera C, et al. Short-term anti-HIV activity of the combination of didanosine and hydroxyurea. Antivir Ther. 1996 Aug; 1(3): 189–93PubMedGoogle Scholar
  31. 31.
    Simonelli C, Nasti G, Vaccher E, et al. Hydroxyurea treatment in HIV-infected patients. J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Dec 15; 13(5): 462–4PubMedCrossRefGoogle Scholar
  32. 32.
    Montaner JS, Zala C, Conway B, et al. A pilot study of hydroxyurea among patients with advanced human immunodeficiency virus (HIV) disease receiving chronic didanosine therapy: Canadian HIV trials network protocol 080. J Infect Dis 1997; 175(4): 801–6PubMedCrossRefGoogle Scholar
  33. 33.
    Foli A, Lori F, Maserati R, et al. Hydroxyurea and didanosine as a more potent combination than hydroxyurea and zidovudine. Antivir Ther 1997; 2(1): 33–40Google Scholar
  34. 34.
    Simonelli C, Comar M, Zanussi S, et al. No therapeutic advantage from didanosine (ddI) and hydroxyurea versus ddI alone in patients with HIV infection. AIDS. 1997 Aug; 11(10): 1299–300PubMedGoogle Scholar
  35. 35.
    Foli A, Maserati R, Minoli L, et al. Therapeutic advantage of hydroxyurea and didanosine combination therapy in patients previously treated with zidovudine. AIDS. 1998 Jun 18; 12(9): 1113–4PubMedGoogle Scholar
  36. 36.
    Murphy R, Katlama C, Autran B, et al. The effects of hydroxyurea or placebo combined with efavirenz, didanosine, and stavudine in treatment naive and experienced patients: preliminary 24 week results from the 3rd study [abstract no.We-OrB603]. The XIII International AIDS Conference; 2000 Jul 9-14; Durban, South AfricaGoogle Scholar
  37. 37.
    Thurman WG, Bloedow C, Howe CD, et al. A phase I study of hydroxyurea. Cancer Chemother Rep 1963; 29: 103–7PubMedGoogle Scholar
  38. 38.
    Griffith K. Hydroxyurea (NSC 32065): results of a phase I study. Cancer Chemother Rep 1964; 40: 33–8PubMedGoogle Scholar
  39. 39.
    Rossero R, McKinsey D, Green S, et al. Open label combination therapy with stavudine, didanosine, and hydroxyurea in nucleoside experienced HIV-1 infected patients [abstract 653]. The 5th International Conference on Retroviruses and Opportunistic Infections; 1998 Feb 1-5; Chicago (IL)Google Scholar
  40. 40.
    Goodrich J, Khardori N. Hydroxyurea toxicity in human immunodeficiency virus-positive patients. Clin Infect Dis 1999; 29(3): 692–3PubMedCrossRefGoogle Scholar
  41. 41.
    Lori F, Lisziewicz J. Targeting HIV reservoirs and reconstituting the immune system. The 2nd Annual Meeting of the Research Institute for Genetic and Human Therapy; 1999; Washington, DC. AIDS Res Hum Retroviruses 1999 Dec 10; 15(18): 1597–617PubMedCrossRefGoogle Scholar
  42. 42.
    Wilson JG, Scott WJ, Ritter EJ, et al. Comparative distribution and embryotoxicity of hydroxyurea in pregnant rats and rhesus monkeys. Teratology 1975; 11 (2): 169–78CrossRefGoogle Scholar
  43. 43.
    Brinkman K, ter Hofstede HJ, Burger DM, et al. Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as common pathway. AIDS 1998; 12(14): 1735–44PubMedCrossRefGoogle Scholar
  44. 44.
    Weissman SB, Sinclair GI, Green CL, et al. Hydroxyurea-induced hepatitis in human immunodeficiency virus-positive patients. Clin Infect Dis 1999; 29 (1): 223–4CrossRefGoogle Scholar
  45. 45.
    Harris M, Tesiorowski A, Montaner JS. Screening for nucleoside-associated lactic acidosis [abstract TuPpB1233]. The XIII International AIDS Conference; 2000 Jul 9-14; Durban, South AfricaGoogle Scholar
  46. 46.
    Cote HC, Brumme ZL, Craib KJ, et al. Changes in mitochondrial DNA as a marker of nucleoside toxicity in HIV- infected patients. N Engl J Med 2002; 346(11): 811–20PubMedCrossRefGoogle Scholar
  47. 47.
    Alpha International Coordinating Committee. The Alpha trial: European/Australian randomized double-blind trial of two doses of didanosine in zidovudine-intolerant patients with symptomatic HIV disease. AIDS 1996; 10 (8): 867–80Google Scholar
  48. 48.
    Maxson CJ, Greenfield SM, Turner JL. Acute pancreatitis as a common complication of 2′,3′-dideoxyinosine therapy in the acquired immunodeficiency syndrome. Am J Gastroenterol 1992; 87(6): 708–13PubMedGoogle Scholar
  49. 49.
    Jablonowski H, Arasteh K, Staszewski S, et al. A dose comparison study of didanosine in patients with very advanced HIV infection who are intolerant to or clinically deteriorate on zidovudine. German ddI Trial Group. AIDS 1995; 9(5): 463–9Google Scholar
  50. 50.
    Nguyen BY, Yarchoan R, Wyvill KM, et al. Five-year follow-up of a phase I study of didanosine in patients with advanced human immunodeficiency virus infection. J Infect Dis 1995; 171(5): 1180–9PubMedCrossRefGoogle Scholar
  51. 51.
    Foli A, Benvenuto F, Piccinini G, et al. Direct analysis of mitochondrial toxicity of antiretroviral drugs. AIDS 2001; 15(13): 1687–94PubMedCrossRefGoogle Scholar
  52. 52.
    Lori F, Pollard R, Shalit P, et al. A low hydroxyurea dose (600mg daily) is found optimal in a randomized, controlled trial (RIGHT 702) [abstract TuPeB4465]. The XIV International AIDS Conference; 2002 Jul 7-12; Barcelona, SpainGoogle Scholar
  53. 53.
    Montaner J, Jahnke N, Yip B, et al. Multi-drug rescue therapy (MDRT) for HIV-infected individuals with prior virologic failure to multiple regimes. Preliminary results [abstract 22495]. Proceedings of the 12th World AIDS Conference 1998 Jun 28-Jul 3; Geneva, SwitzerlandGoogle Scholar
  54. 54.
    Youle M, Mocroft A, Johnson M, et al. Surrogate marker responses to multidrug combinations comprising hydroxyurea, efavirenz, double protease inhibitors and nucleoside analogues in protease inhibitor failure [abstract 400s]. The 6th Conference on Retroviruses and Opportunistic Infections; 1999 Jun 28-Jul 3; Chicago (IL)Google Scholar
  55. 55.
    Miles S, Winters RE, Ruane P. Salvage of multi-drug resistant HIV infection with D4T/3TC/hydroxyurea [abstract #288/12205]. The 12th World AIDS Conference; 1998, Geneva, SwitzerlandGoogle Scholar
  56. 56.
    Cadden JJ, Dube MP. Hydroxyurea (HU) plus ddI as salvage therapy in HIV [abstract I-202]. The 38th International Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 24-27; San Diego (CA)Google Scholar
  57. 57.
    Grunke M, Dechant C, Low P, et al. Hydroxyurea as part of a salvage regimen for heavily pretreated patients with advanced HIV infection. J Acquir Immune Defic Syndr 1999; 21(5): 424–6PubMedGoogle Scholar
  58. 58.
    Solas C, Lafeuillads A, Halfon P, et al. Discrepancies between protease inhibitor concentrations and viral load in reservoirs and santuary sites in human immunodeficiency virus-infected patients. Antimicrob Agent Chemother 2003; 47(1): 238–43CrossRefGoogle Scholar
  59. 59.
    De Antoni A, Foli A, Lisziewicz J, et al. Mutations in the pol gene of human immunodeficiency virus type 1 in infected patients receiving didanosine and hydroxyurea combination therapy. J Infect Dis 1997; 176(4): 899–903PubMedCrossRefGoogle Scholar
  60. 60.
    Rosenberg ES, Billingsley JM, Caliendo AM, et al. Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science 1997; 278(5342): 1447–50PubMedCrossRefGoogle Scholar
  61. 61.
    Ogg GS, Kostense S, Klein MR, et al. Longitudinal phenotypic analysis of human immunodeficiency virus type 1- specific cytotoxic T lymphocytes: correlation with disease progression. J Virol 1999; 73(11): 9153–60PubMedGoogle Scholar
  62. 62.
    Schwartz D, Sharma U, Busch M, et al. Absence of recoverable infectious virus and unique immune responses in an asymptomatic HIV+ long-term survivor. AIDS Res Hum Retroviruses 1994; 10(12): 1703–11PubMedCrossRefGoogle Scholar
  63. 63.
    Pontesilli O, Carotenuto P, Kerkhof-Garde SR, et al. Lympho-proliferative response to HIV type 1 p24 in long-term survivors of HIV type 1 infection is predictive of persistent AIDS-free infection. AIDS Res Hum Retroviruses 1999; 15(11): 973–81PubMedCrossRefGoogle Scholar
  64. 64.
    Goulder PJ, Bunce M, Krausa P, et al. Novel, cross-restricted, conserved, and immunodominant cytotoxic T lymphocyte epitopes in slow progressors in HIV type 1 infection. AIDS Res Hum Retroviruses 1996; 12(18): 1691–8PubMedCrossRefGoogle Scholar
  65. 65.
    Harrer E, Harrer T, Barbosa P, et al. Recognition of the highly conserved YMDD region in the human immunodeficiency virus type 1 reverse transcriptase by HLA-A2-restricted cytotoxic T lymphocytes from an asymptomatic long-term nonprogressor. J Infect Dis 1996; 173(2): 476–9PubMedCrossRefGoogle Scholar
  66. 66.
    Galpin JE, Lori F, Globe DR, et al. Improvement in CD4 cell diversity during 7-month trial of hydroxyurea in combination with ddI or ddI and d4T [abstract 657]. The 5th International Conference on Retroviruses and Opportunistic Infections; 1998 Feb 5, Chicago (IL)Google Scholar
  67. 67.
    Lori F, Jessen H, Lieberman J, et al. Immune restoration by combination of a cytostatic drug (hydroxyurea) and anti-HIV drugs (didanosine and indinavir). AIDS Res Hum Retroviruses 1999; 15(7): 619–24PubMedCrossRefGoogle Scholar
  68. 68.
    Lori F, Jessen H, Lieberman J, et al. Treatment of human immunodeficiency virus infection with hydroxyurea, didanosine, and a protease inhibitor before seroconversion is associated with normalized immune parameters and limited viral reservoir. J Infect Dis 1999; 180(6): 1827–32PubMedCrossRefGoogle Scholar
  69. 69.
    Autran B, Carcelain G, Li TS, et al. Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science 1997; 277(5322): 112–6PubMedCrossRefGoogle Scholar
  70. 70.
    Plana M, Garcia F, Gallart T, et al. Lack of T-cell proliferative response to HIV-1 antigens after 1 year of highly active antiretroviral treatment in early HIV-1 disease. Immunology Study Group of Spanish EARTH-1 Study. Lancet 1998; 352(9135): 1194–5Google Scholar
  71. 71.
    Pitcher CJ, Quittner C, Peterson DM, et al. HIV-1-specific CD4+ T cells are detectable in most individuals with active HIV-1 infection, but decline with prolonged viral suppression. Nat Med 1999; 5(5): 518–25PubMedCrossRefGoogle Scholar
  72. 72.
    Pantaleo G, Menzo S, Vaccarezza M, et al. Studies in subjects with long-term nonprogressive human immunodeficiency virus infection. N Engl J Med 1995; 332(4): 209–16PubMedCrossRefGoogle Scholar
  73. 73.
    Cao Y, Qin L, Zhang L, et al. Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. N Engl J Med 1995; 332(4): 201–8PubMedCrossRefGoogle Scholar
  74. 74.
    Clerici M, Stocks NI, Zajac RA, et al. Detection of three distinct patterns of T helper cell dysfunction in asymptomatic, human immunodeficiency virus-seropositive patients: independence of CD4+ cell numbers and clinical staging. J Clin Invest 1989; 84(6): 1892–9PubMedCrossRefGoogle Scholar
  75. 75.
    Giorgi JV, Liu Z, Hultin LE, et al. Elevated levels of CD38+ CD8+ T cells in HIV infection add to the prognostic value of low CD4+ T cell levels: results of 6 years of follow-up. The Los Angeles Center, Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr 1993; 6 (8): 904–12Google Scholar
  76. 76.
    Plana M, Martinez C, Garcia F, et al. Immunologic reconstitution after 1 year of highly active antiretroviral therapy, with or without protease inhibitors. J Acquir Immune Defic Syndr 2002; 29(5): 429–34PubMedGoogle Scholar
  77. 77.
    Lange CG, Lederman MM, Madero JS, et al. Impact of suppression of viral replication by highly active antiretroviral therapy on immune function and phenotype in chronic HIV-1 infection. J Acquir Immune Defic Syndr 2002; 30(1): 33–40PubMedGoogle Scholar
  78. 78.
    Ogorman M, Alatrakchi N, Belsey E, et al. Hydroxyurea therapy spares the naive T cell compartment in patients treate with antiretroviral drugs: the 3D Study. The 1st IAS Conference on HIV Pathogenesis and Treatment; 2001 Jul 8-11; Buenos Aires, ArgentinaGoogle Scholar
  79. 79.
    Ravot E, Tambussi G, Jessen H, et al. Effects of hydroxyurea on T cell count changes during primary HIV infection. AIDS 2000; 14(5): 619–22PubMedCrossRefGoogle Scholar
  80. 80.
    Zinkernagel RM, Hengartner H. T-cell-mediated immunopathology versus direct cytolysis by virus: implications for HIV and AIDS. Immunol Today 1994; 15(6): 262–8PubMedCrossRefGoogle Scholar
  81. 81.
    Zinkernagel RM, Hengartner H. Correlates of protective viruses damaging to HIV infection. Science 1996; 272(5266): 1362PubMedCrossRefGoogle Scholar
  82. 82.
    Lori F, Rosenberg E, Lieberman J, et al. Hydroxyurea and didanosine long-term treatment prevents HIV breakthrough and normalizes immune parameters. AIDS Res Hum Retroviruses 1999; 15(15): 1333–8PubMedCrossRefGoogle Scholar
  83. 83.
    Weverling GJ, Lange JM, Jurriaans S, et al. Alternative multidrug regimen provides improved suppression of HIV-1 replication over triple therapy. AIDS 1998; 12(11): F117–22PubMedCrossRefGoogle Scholar
  84. 84.
    Vila J, Biron F, Nugier F, et al. 1-year follow-up of the use of hydroxycarbamide and didanosine in HIV infection. Lancet 1996; 348(9021): 203–4PubMedCrossRefGoogle Scholar
  85. 85.
    Vila J, Nugier F, Bargues G, et al. Absence of viral rebound after treatment of HIV-infected patients with didanosine and hydroxycarbamide. Lancet 1997; 350(9078): 635–6PubMedCrossRefGoogle Scholar
  86. 86.
    Plana M, Lopalco L, Garcia F, et al. Effect of associating a cytostatic drug + HAART and holding the cytostatic drug after STI and definitive interruption of HAART on HIV-1 specific immune response [abstract 535-Ms]. The 9th Conference on Retroviruses and Opportunistic Infections; 2002 Feb 24-28; Seattle (WA)Google Scholar

Copyright information

© Adis Data Information BV 2003

Authors and Affiliations

  • Julianna Lisziewicz
    • 1
  • Andrea Foli
    • 1
  • Mark Wainberg
    • 2
  • Franco Lori
    • 1
  1. 1.Research Institute for Genetic and Human Therapy (RIGHT) at IRCCS PoliclinicoWashington DCUSA
  2. 2.McGill — Hôpital General JuifQuebecCanada

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