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Antiretroviral Drug Guidelines for the Treatment of HIV Infection

Should Protease Inhibitors Always be Included in the Initial Regimen or Not?

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Abstract

Combination antiretroviral therapy, usually consisting of 2 nucleoside analogue reverse transcriptase inhibitors and a protease inhibitor (PI), has revolutionised the management of patients with HIV infection. Pi-containing combinations are significantly superior to combinations of 2 nucleoside analogues, and the latter combination is now indicated only in very exceptional circumstances. However, long term adherence to complex regimens of antiretroviral drugs, and the emerging longer term toxicity associated with PIs and to a lesser extent, problems with long term adherence to complex regimens of antiretroviral drugs, make the use of ’protease-sparing’ regimens attractive. Although in some cases such regimens may be associated with a lower chance of sustained suppression of viral load, leading to the development of drug resistance and virological rebound, they allow the preservation of a whole class of antiretrovirals for later use, avoid the risk of PI toxicity, and their use can also help to avoid important drug interactions associated with PIs.

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References

  1. Torres RA, Barr M. Impact of combination therapy for HIV infection on inpatient census. N Engl J Med 1997; 336: 1531–2

    Article  PubMed  CAS  Google Scholar 

  2. Hogg RS, O’Shaughnessy MV, Gataric N, et al. Decline in deaths from AIDS due to new antiretrovirals [letter]. Lancet 1997; 349: 1294

    Article  PubMed  CAS  Google Scholar 

  3. Mouton Y, Alfandari S, Valette M, et al. Impact of protease inhibitors on AIDS-defining events and hospitalizations in 10 French AIDS reference centres. AIDS 1997; 11: F101–5

    Article  PubMed  CAS  Google Scholar 

  4. Anonymous. AIDS deaths fell by 44%, but over 2500 HIV infections were reported in 1997. CDR Weekly 1998; 8: 29

  5. Carr A, Marriott D, Field A, et al. Treatment of HIV-1-associated microsporidiosis and cryptosporidiosis with combination antiretroviral therapy. Lancet 1998; 351: 256–61

    Article  PubMed  CAS  Google Scholar 

  6. Conant M, Opp KM, Poretz D, et al. Reduction of Kaposi’s sarcoma lesions following treatment of AIDS with ritonavir. AIDS 1997; 11: 1300–1

    PubMed  CAS  Google Scholar 

  7. Sepkowitz K. Effect of HAART on natural history of AIDS-related opportunistic disorders. Lancet 1998; 351: 228–30

    Article  PubMed  CAS  Google Scholar 

  8. Mellors JW, Munoz A, Giorgi JV, et al. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med 1997; 126: 946–54

    PubMed  CAS  Google Scholar 

  9. Katzenstein DA, Hammer SM, Hughes MD, et al. The relation of virologie and immunologic markers to clinical outcomes after nucleoside therapy in HIV-infected adults with 200 to 500 CD4 cells per cubic millimeter. New Engl J Med 1996; 335: 1091–8

    Article  PubMed  CAS  Google Scholar 

  10. Brun-Vezinet F, Boucher C, Loveday C, et al. HIV-1 viral load, phenotype, and resistance in a subset of drug-naive participants from the Delta trial. Lancet 1997; 350: 983–90

    Article  PubMed  CAS  Google Scholar 

  11. Carpenter CJ, Fischl MA, Hammer SM, et al. Antiretroviral therapy for HIV infection in 1997. Updated recommendations of the International AIDS Society-USA panel. JAMA 1997; 277: 1962–9

    Article  PubMed  CAS  Google Scholar 

  12. BHIVA Guidelines Co-ordinating Committee. British HIV Association guidelines for antiretroviral treatment of HIV seropositive individuals. Lancet 1997; 349: 1086–92

    Article  Google Scholar 

  13. Montaner JSG, Reiss P, Cooper D, et al. Arandomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients. The INCAS Trial. JAMA 1998; 279: 930–7

    Article  PubMed  CAS  Google Scholar 

  14. Vella S, Floridia M, Tomino C, et al. A triple combination of reverse transcriptase inhibitors (2 NRTI + NNRTI) induces pronounced and sustained effects on RNA and CD4 in anti-retroviral-naive patients with very advanced disease (Trial ISS 047). 37th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1997 Toronto: Abstract LB-7

  15. Gazzard B, Moyle G, on behalf of the BHlVA Guidelines Writing Committee. 1998 revision to the British HIV Association guidelines for antiretroviral treatment of HIV seropositive individuals. Lancet 1998; 352: 314–6

    Article  PubMed  CAS  Google Scholar 

  16. Myers MW, Montaner JG. Arandomized, double-blinded comparative trial of the effects of zidovudine, didanosine, and nevirapine combinations in antiviral naive, AIDS-free, HIV-infected patients with CD4 counts 200-600 per cubic millimetre. XI International Conference on AIDS. Vancouver, 1996 Jul 7-12: Abstract Mo.B.294

  17. Vella S, Floridia M, Tomino C, et al. A triple combination of reverse transcriptase inhibitors (2 NRTI + 1 NNRTI) induces pronounced and sustained effects on RNA and CD4 in anti-retroviral-naive patients with very advanced disease (Trial ISS 047). 37th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1997 Sep 28-Oct 1: Toronto. Abstract LB-7

  18. Green S, Para MF, Daly PW, et al. Interim analysis of plasma viral burden reductions and CD4 increases in HIV-1 infected patients with Rescriptor (DLV) + Retrovir (ZDV) + Epivir (3TC). 12th World AIDS Conference; 1998 Jun 28-Jul 3: Geneva. Abstract 129/12219

  19. Haas D, Hicks C, Seekins D, et al. A Phase II, double-blind, placebo-controlled, dose-ranging study to assess the antiretroviral activity and safety of DMP 266 (efavirenz, Sustiva) in combination with open-label zidovudine (ZDV) with lamivudine (3TC) [DMP 266-005]. 5th Conference on Retro-viruses and Opportunistic Infections; 1998 Feb 1–5: Chicago (IL). Abstract 698

  20. Staszewski S, Morales-Ramirez J, Tashima K, et al. A phase III, multicenter, randomized, open-label study to compare the antiretroviral activity and tolerability of efavirenz (EFV)+ indinavir (IDV, versus EFV +zidovudine (ZDV) + lamivudine (3TC), versus IDV + ZDV + 3TC at 24 weeks (DMP-266-006). 12th World AIDS Conference; 1998 Jun 28-Jul 3: Geneva. Abstract 22336

  21. Montaner JSG, Reiss P, Cooper D, et al. Arandomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients. The INCAS Trial. JAMA 1998; 279: 930–7

    Article  PubMed  CAS  Google Scholar 

  22. Montaner J, Reiss P, Cooper D, et al. Long-term follow-up of patients treated with nevirapine based combination therapy within the INCAS trial. 5th Conference on Retroviruses and Opportunistic Infections; 1998 Feb 1–5: Chicago (IL). Abstract 695

  23. Wong JK, Hezareh M, Gunthard HF, et al. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science 1997; 278: 1291–5

    Article  PubMed  CAS  Google Scholar 

  24. Finzi D, Hermankova M, Pierson T, et al. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 1997; 278: 1295–300

    Article  PubMed  CAS  Google Scholar 

  25. Dever LL, Oruwari PA, O’Donovan CA, et al. Hyperglycemia associated with protease inhibitors in HIV-infected patients. 37th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1997 Sep 28-Oct 1: Toronto. Abstract LB-8

  26. Dube MP, Johnson DL, Currier JS. Protease inhibitor-associated hyperglycaemia [letter]. Lancet 1997; 350: 713

    Article  PubMed  CAS  Google Scholar 

  27. Ruane PJ. Atypical accumulations of fatty tissue. 37th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1997 Sep28-Oct 1: Toronto. Abstract I-185

  28. Hengel RL, Watts NB, Lennox JL. Benign symmetric lipomatosis associated with protease inhibitors [letter]. Lancet 1997; 350: 1596

    Article  PubMed  CAS  Google Scholar 

  29. Herry I, Bernard L, de Truchis P, et al. Hypertrophy of the breasts in a patient treated with indinavir. Clin Infect Dis 1997; 25: 937–8

    Article  PubMed  CAS  Google Scholar 

  30. Carr A, Samaras K, Burton S, et al. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS 1998; 12: F51–8

    Article  PubMed  CAS  Google Scholar 

  31. Viraben R, Aquilina C. Indinavir-associated lipodystrophy. AIDS 1998; 12: F37–9

    Article  PubMed  CAS  Google Scholar 

  32. Sullivan AK, Nelson MR. Marked hyperlipidaemia on ritonavir therapy. AIDS 1997; 11: 938–9

    Article  PubMed  CAS  Google Scholar 

  33. Ginsburg C, Salmon-Ceron D, Vassilief D, et al. Unusual occurrence of spontaneous haematomas in three asymptomatic HIV-infected haemophilia patients a few days after the onset of ritonavir treatment. AIDS 1997; 11: 388–9

    PubMed  CAS  Google Scholar 

  34. Bonfanti P, Capetti A, Riva P, et al. Hypersensitivity reactions during antiretroviral regimens with protease inhibitors. AIDS 1997; 11: 1301–2

    PubMed  CAS  Google Scholar 

  35. Rijnders B, Kooman J. Severe allergic reaction after repeated exposure to indinavir. Clin Infect Dis 1998; 26: 523–4

    Article  PubMed  CAS  Google Scholar 

  36. Daudon M, Estepa L, Viard JP, et al. Urinary stones in HIV-1-positive patients treated with indinavir. Lancet 1997; 349: 1294–5

    Article  PubMed  CAS  Google Scholar 

  37. Tashima KT, Horowitz JD, Rosen S. Indinavir nephropathy. N Engl J Med 1997; 336: 138–40

    Article  PubMed  CAS  Google Scholar 

  38. Kopp JB, Miller KD, Mican AM, et al. Crystalluria and urinary tract abnormalities associated with indinavir. Ann Intern Med 1997; 127: 119–25

    PubMed  CAS  Google Scholar 

  39. Gulick RM, Mellors JW, Havlir D, et al. Simultaneous vs. sequential initiation of therapy with indinavar, zidovudine and lamivudine for HIV-1 infection. JAMA 1998; 280: 35–41

    Article  PubMed  CAS  Google Scholar 

  40. Cameron DW, Japour A, Mellors J, et al. Antiretroviral safety and durability of ritonavir (RIT)-saquinavir (SQV) in protease inhibitor-naive patients in year two follow-up. 5th Conference on Retroviruses and Opportunistic Infections; 1998 Chicago: Abstract 388

  41. Reijers MHE, Weverling GJ, Jurriaans S, et al. Maintenance therapy after quadruple induction therapy in HIV-1 infected individuals: the Amsterdam Duration of Antiretroviral Medication (ADAM) study. Lancet 1998; 352: 195–90

    Article  Google Scholar 

  42. Harris M, Durakovic C, Rae S, et al. A pilot study of nevirapine, indinavir, and lamivudine among patients with advanced human immunodeficiency virus disease who have had failure of combination nucleoside therapy. J Infect Dis 1998; 177: 1514–20

    Article  PubMed  CAS  Google Scholar 

  43. Albrecht M, Katzenstein D, Bosch RJ, et al. ACTG 364: Virologic efficacy of nelfinavir (NFV) and/or efavirenz (EFV) in combination with new nucleoside analogs in nucleoside experienced subjects. 12th World AIDS Conference; 1998 Jun 28-Jul 3: Geneva. Abstract 125/12203

  44. Farthing C, Mess T, Ried C, et al. Ritonavir, saquinavir, and nevirapine as a salvage regimen for indinavir or ritonavir resistance. 12th World AIDS Conference; 1998 Jun 28-Jul 3: Geneva. Abstract 22356

  45. Ruane PJ, Tarn JT, Libraty DH, et al. Salvage therapy using ritonavir/saquinavir with a non-nucleoside reverse trans-criptase inhibitor after prolonged failure with indinavir or ritonavir. 12th World AIDS Conference; 1998 Jun 28-Jul 3: Geneva. Abstract 32308

  46. Warren KJ, Boxwell DE, Kim NY, et al. Nevirapine-associated Stevens-Johnson syndrome [letter]. Lancet 1998; 351: 567

    Article  PubMed  CAS  Google Scholar 

  47. HIV/AIDS Treatment Information Service (ATIS). Available from: URL: http://www.hivatis.org/upguidaa.html [website updated 1998 Dec 1]

  48. Leibowitch J. The triple combination of stavudine, didanosine and lamivudine as first or second line treatment in patients with AIDS. Stavudine in the management of HIV disease. 1997 Mar 22 Cannes, France

  49. Leibowitch J. The triple combination of stavudine, didanosine and lamivudine as first- or second-line treatment in patients with AIDs. Antiviral Therapy 1997; 2 Suppl. 3: 125–8

    Google Scholar 

  50. CAESAR Coordinating Committee. Randomised trial of addition of lamivudine or lamivudine plus loviride to zidovudine-containing regimens for patients with HIV-1 infection: the CAESAR trial. Lancet 1997; 349: 1413–21

    Article  Google Scholar 

  51. Staszewski S, Katlama C, HarrerT, et al. Preliminary long-term open-label data from patients using abacavir (1592) containing antiretroviral treatment regimens. 5th Conference on Retroviruses and Opportunistic Infections; 1998 Feb 1-5: Chicago (IL). Abstract 658

  52. Fischl M, Greenberg S, Clumeck N, et al. Safety and activity of abacavir (1592, ABC) with 3TC/ZDV in antiretroviral naive subjects. 12th World AIDS Conference; 1998 Jun 28-Jul 3: Geneva. Abstract 127/12230

  53. Lori F, Malykh A, Cara A, et al. Hydroxyurea as an inhibitor of Human Immunodeficiency Virus Type-1 replication. Science 1994; 266: 801–5

    Article  PubMed  CAS  Google Scholar 

  54. Galpin J, Lori F, Globe DR, et al. Safety, sheltering and synergy of hydroxyurea with ddI or ddI plus d4Tin HIV-infected patients. 5th Conference on Retroviruses and Opportunistic Infections; 1998 Feb 1–5: Chicago (IL). Abstract 654

  55. Galpin J, 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. 5th Conference on Retroviruses and Opportunistic Infections; 1998 Feb 1–5: Chicago (IL). Abstract 657

  56. Rossero R, McKinsey D, Green S, et al. Open label combination therapy with stavudine, didanosine and hydroxyurea in nucleoside experienced HIV-1 infected patients. 5th Conference on Retroviruses and Opportunistic Infections; 1998 Feb 1–5: Chicago (IL). Abstract 653

  57. O’Shaughnessy MV, Hogg RS, Rhone SA, et al. Do dual nucleoside regimens have a role in an era of plasma viral load driven antiretroviral therapy? 5th Conference on Retroviruses and Opportunistic Infections; 1998 Feb 1–5: Chicago (IL). Abstract 668

  58. Brun-Vezinet F, Boucher C, Loveday C, et al. HIV-1 viral load, phenotype, and resistance in a subset of drug-naive participants from the Delta trial. Lancet 1997; 350: 983–90

    Article  PubMed  CAS  Google Scholar 

  59. Hammer SM, Squires KM, Hughes MD, et al. Acontrolled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter orless.NEnglJMed 1997; 337: 725–33

    Article  CAS  Google Scholar 

  60. Delta Coordinating Committee. Delta: a randomised double-blind controlled trial comparing combinations of zidovudine plus didanosine or zalcitabine with zidovudine alone in HIV infected individuals. Lancet 1996; 348: 283–91

    Article  Google Scholar 

  61. Hammer SM, Katzenstein DA, Hughes MD, et al. A trial comparing nucleoside monotherapy with combination therapy in HIV-infected adults with CD4 cell counts from 200 to 500 per cubic millimeter. N Engl J Med 1996; 335: 1081–90

    Article  PubMed  CAS  Google Scholar 

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  1. Clinical Trials Centre, Winston Churchill Wing, St. Mary’s Hospital, Praed St., London, W2 1NY, England

    Duncan Churchill & Jonathan Weber

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  1. Duncan Churchill
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  2. Jonathan Weber
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Correspondence to Duncan Churchill.

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Churchill, D., Weber, J. Antiretroviral Drug Guidelines for the Treatment of HIV Infection. BioDrugs 11, 147–153 (1999). https://doi.org/10.2165/00063030-199911030-00001

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