Immunologic response to protease inhibitor-based highly active antiretroviral therapy: A review

AIDS Patient Care and STDs

Volumn 21, Issue 9, 2007, Pages 609-620

  Wainberg, Mark A ^a   Clotet, Bonaventura ^b  

^a MCGILL UNIVERSITY   (Canada)

^b HOSPITAL UNIVERSITARI GERMANS TRIAS I PUJOL   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ABACAVIR; AMPRENAVIR; AMPRENAVIR PHOSPHATE; AMPRENAVIR PLUS RITONAVIR; ATAZANAVIR; CD4 ANTIGEN; DARUNAVIR; DARUNAVIR PLUS RITONAVIR; DIDANOSINE; EFAVIRENZ; EMTRICITABINE; ENFUVIRTIDE; INDINAVIR; LAMIVUDINE; LOPINAVIR; NELFINAVIR; NEVIRAPINE; PROTEINASE INHIBITOR; RITONAVIR; RITONAVIR PLUS SAQUINAVIR; SAQUINAVIR; STAVUDINE; TENOFOVIR; UNCLASSIFIED DRUG; VIRUS RNA; ZIDOVUDINE;

APOPTOSIS; CD4 LYMPHOCYTE COUNT; CELLULAR DISTRIBUTION; CLINICAL TRIAL; DISEASE MARKER; DRUG EFFECT; DRUG EFFICACY; DRUG PENETRATION; DRUG RESPONSE; FOLLOW UP; HEMATOPOIESIS; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LYMPHOID TISSUE; OUTCOME ASSESSMENT; REVIEW; ADULT; BLOOD; HUMAN IMMUNODEFICIENCY VIRUS; IMMUNOLOGY; RANDOMIZED CONTROLLED TRIAL;

ADULT; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; CD4 LYMPHOCYTE COUNT; HIV; HUMANS; RANDOMIZED CONTROLLED TRIALS; RNA, VIRAL;

EID: 34948848004     PISSN: 10872914     EISSN: None     Source Type: Journal    
DOI: 10.1089/apc.2006.0176     Document Type: Review

References (73)

1. De Milito A, Titanji K, Zazzi M. Surrogate markers as a guide to evaluate response to antiretroviral therapy. Curr Med Chem 2003;10:349-365.
2. Vlahov D, Graham N, Hoover D, et al. Prognostic indicators for AIDS and infectious disease death in HIV-infected injection drug users: plasma viral load and CD4+ cell count. JAMA 1998;279:35-40.
3. Hogg RS, Yip B, Chan KJ, et al. Rates of disease progression by baseline CD4 cell count and viral load after initiating triple-drug therapy. JAMA 2001;286:2568-2577.
4. 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;126:946-954.
5. Phillips A. Short-term risk of AIDS according to current CD4 cell count and viral load in antiretroviral drug-naive individuals and those treated in the monotherapy era. AIDS 2004;18:51-58.
6. Ledergerber B, Lundgren JD, Walker AS, et al. Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes. Lancet 2004;364:51-62.
7. Staszewski S, Miller V, Sabin C, et al. Determinants of sustainable CD4 lymphocyte count increases in response to antiretroviral therapy. AIDS 1999;13:951-956.
8. Egger M, May M, Chene G, et al. Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: A collaborative analysis of prospective studies. Lancet 2002;360:119-129.
9. Chene G, Sterne JA, May M, et al. Prognostic importance of initial response in HIV-1 infected patients starting potent antiretroviral therapy: Analysis of prospective studies. Lancet 2003;362:679-686.
10. Loutfy MR, Walmsley SL, Mullin CM, et al. CD4(+) cell count increase predicts clinical benefits in patients with advanced HIV disease and persistent viremia after 1 year of combination antiretroviral therapy. J Infect Dis 2005;192:1407-1411.
11. Singer J, Ayers D, Cameron D, et al. Predictors of clinical response to salvage therapy in a late salvage population with multi-drug resistant HIV in the OPTIMA trial [Abstract 526]. 13th Conference on Retroviruses and Opportunistic Infections. Denver, CO: February 5-8, 2006.
12. Sanne I, Piliero P, Squires K, et al. Results of a phase 2 clinical trial at 48 weeks (AI424-007): A dose-ranging, safety, and efficacy comparative trial of atazanavir at three doses in combination with didanosine and stavudine in antiretroviral-naive subjects. J Acquir Immune Defic Syndr 2003;32:18-29.
13. Murphy RL, Sanne I, Cahn P, et al. Dose-ranging, randomized, clinical trial of atazanavir with lamivudine and stavudine in antiretroviral-naive subjects: 48-week results. AIDS 2003;17:2603-2614.
14. Squires K, Lazzarin A, Gatell JM, et al. Comparison of once-daily atazanavir with efavirenz, each in combination with fixed-dose zidovudine and lamivudine, as initial therapy for patients infected with HIV. J Acquir Immune Defic Syndr 2004;36:1011-1019.
15. van Leeuwen R, Katlama C, Murphy RL, et al. A randomized trial to study first-line combination therapy with or without a protease inhibitor in HIV-1-infected patients. AIDS 2003;17:987-999.
16. Cohen Stuart JW, Schuurman R, Burger DM, et al. Randomized trial comparing saquinavir soft gelatin capsules versus indinavir as part of triple therapy (CHEESE study). AIDS 1999;13:F53-F58.
17. Podzamczer D, Ferrer E, Consiglio E, et al. A randomized clinical trial comparing nelfinavir or nevirapine associated to zidovudine/lamivudine in HIV-infected naive patients (the Combine Study). Antivir Ther 2002;7:81-90.
18. Staszewski S, Morales-Ramirez J, Tashima KT, et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team. N Engl J Med 1999;341:1865-1873.
19. Rodriguez-French A, Boghossian J, Gray GE, et al. The NEAT study: A 48-week open-label study to compare the antiviral efficacy and safety of GW433908 versus nelfinavir in antiretroviral therapy-naive HIV-1-infected patients. J Acquir Immune Defic Syndr 2004;35:22-32.
20. Squires KE, Gulick R, Tebas P, et al. A comparison of stavudine plus lamivudine versus zidovudine plus lamivudine in combination with indinavir in antiretroviral naive individuals with HIV infection: Selection of thymidine analog regimen therapy (START I). AIDS 2000;14:1591-1600.
21. Eron JJ Jr, Murphy RL, Peterson D, et al. A comparison of stavudine, didanosine and indinavir with zidovudine, lamivudine and indinavir for the initial treatment of HIV-1 infected individuals: Selection of thymidine analog regimen therapy (START II). AIDS 2000;14:1601-1610.
22. Squires K, Currier J, Clark R, et al. Final 48-week results of a phase II, randomized study of the safety, efficacy, and pharmacokinetics of BID vs TID nelfinavir and saquinavir in combination with lamivudine and stavudine in HIV-positive women (women first trial) [Abstract 330]. 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL: February 4-8, 2001.
23. Bartlett JA, Johnson J, Herrera J, et al. Initial therapy with abacavir and lamivudine (ABC+3TC) combined with efavirenz (NNRTI), amprenavir/ritonavir (PI), or stavudine (NRTI): ESS40001 (CLASS) [Abstract TuPeB4544]. Int Conf AIDS 2004;15.
24. Walmsley S, Bernstein B, King M, et al. Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection. N Engl J Med 2002;346:2039-2046.
25. Gathe JC Jr, Ive P, Wood R, et al. SOLO: 48-week efficacy and safety comparison of once-daily fosamprenavir/ritonavir versus twice-daily nelfinavir in naive HIV-1-infected patients. AIDS 2004;18:1529-1537.
26. Gathe J, Podzamczer D, Johnson M, et al. Once-daily versus twice-daily lopinavir/ritonavir in antiretroviral naïve patients: 48 week results [Abstract 570]. 11th Conference on Retroviruses and Opportunistic Infections. San Francisco, CA: February 5-8, 2004.
27. Riddler SA, Haubrich R, DiRienzo G, et al. A prospective randomized phase III trial of NRTI-, PI-, and NNRTI-sparing regimens for initial treatment of HIV-1 infection - ACT 5142 [Abst. THLB0204]. 16th International AIDS Conference, Toronto, 2006.
28. Zeldin RK, Petruschke RA. Pharmacological and therapeutic properties of ritonavir-boosted protease inhibitor therapy in HIV-infected patients. J Antimicrob Chemother 2004;53:4-9.
29. Rathbun RC, Rossi DR. Low-dose ritonavir for protease inhibitor pharmacokinetic enhancement. Ann Pharmacother 2002;36:702-706.
30. Flexner C. Dual protease inhibitor therapy in HIV-infected patients: pharmacologic rationale and clinical benefits. Annu Rev Pharmacol Toxicol 2000;40:649-674.
31. Albrecht MA, Bosch RJ, Hammer SM, et al. Nelfinavir, efavirenz, or both after the failure of nucleoside treatment of HIV infection. N Engl J Med 2001;345:398-407.
32. Staszewski S, Keiser P, Montaner J, et al. Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral-naive HIV-infected adults: A randomized equivalence trial. JAMA 2001;285:1155-1163.
33. Benson CA, Deeks SG, Brun SC, et al. Safety and antiviral activity at 48 weeks of lopinavir/ritonavir plus nevirapine and 2 nucleoside reverse-transcriptase inhibitors in human immunodeficiency virus type 1-infected protease inhibitor-experienced patients. J Infect Dis 2002;185:599-607.
34. Hammer SM, Vaida F, Bennett KK, et al. Dual vs single protease inhibitor therapy following antiretroviral treatment failure: A randomized trial. JAMA 2002;288:169-180.
35. Haas DW, Zala C, Schrader S, et al. Therapy with atazanavir plus saquinavir in patients failing highly active antiretroviral therapy: A randomized comparative pilot trial. AIDS 2003;17:1339-1349.
36. Nieto-Cisneros L, Zala C, Fessel WJ, et al. Antiviral efficacy, metabolic changes and safety of atazanavir (ATV) versus lopinavir/ritonavir (LPV/r) in combination with 2 NRTIs in patients who have experienced virologic failure with prior PI-containing regimen(s): 24-week results from BMS A1424-043 [Abstract 117]. Antivir Ther 2003;8:S212.
37. De Jesus E, LaMarca A, Sension M, et al. The CONTEXT study: efficacy and safety of GW433908/r in PI-experienced subjects with virological failure (24 week results) [Abstract 178. 10th Conference on Retroviruses and Opportunistic Infections. Boston, MA: February 10-13, 2003..
38. Johnson M, Grinsztejn B, Rodriguez C, et al. Atazanavir plus ritonavir or saquinavir, and lopinavir/ritonavir in patients experiencing multiple virological failures. AIDS 2005;19:685-694.
39. Hicks CB. RESIST-1: A phase 3, randomized, controlled, open-label, multicenter trial comparing tipranavir/ritonavir (TPV/r) to an optimized comparator protease inhibitor/r (CPI/r) regimen in antiretroviral (ARV)-experienced patients: 24-week data [Abstract LBH-1137]. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, D.C.: October 29-November 2, 2004.
40. Cahn P. 24-week data from RESIST 2: Phase 3 study of the efficacy and safety of either tipranavir/ritonavir (TPV/r) or an optimized ritonavir (RTV)-boosted standard-of-care (SOC) comparator PI (CPI) in a large randomized multicenter trial in treatment-experienced HIV+ patients. 7th International Congress of Drug Therapy in HIV Infection [Abstract PL14.3]. Glasgow, Scotland: November 14-18, 2004.
41. Hicks CB, Cahn P, Cooper DA, et al. Durable efficacy of tipranavir-ritonavir in combination with an optimised background regimen of antiretroviral drugs for treatment-experienced HIV-1-infected patients at 48 weeks in the Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST) studies: An analysis of combined data from two randomised open-label trials. Lancet 2006;368:466-475.
42. Katlama C, Carvalho MTM, Cooper D, et al. TMC114/r outperforms investigator-selected PI(s) in 3-class-experienced patients: Week 24 primary analysis of POWER 1 (TMC114-C213) [Abstract WeOaLB0102]. 3rd IAS Conference on HIV Pathogenesis and Treatment. Rio de Janeiro, Brazil: July 24-27, 2005.
43. Wilkin T, Haubrich R, Steinhart CR, et al. POWER 2 (TMC114-C202 study) Week 24 efficacy analysis. 45th Interscience Conference on Antimicrobial Agents and Chemotherapy [Abstract 2860]. Washington, D.C.: December 16-19, 2005.
44. Yazdanpanah Y, Sissoko D, Egger M, et al. Clinical efficacy of antiretroviral combination therapy based on protease inhibitors or non-nucleoside analogue reverse transcriptase inhibitors: Indirect comparison of controlled trials. BMJ 2004;328:249.
45. US Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents - May 4, 2006. http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. 2006. (Last accessed July 13, 2006).
46. Bucy RP, Hockett RD, Derdeyn CA, et al. Initial increase in blood CD4(+) lymphocytes after HIV antiretroviral therapy reflects redistribution from lymphoid tissues. J Clin Invest 1999;103:1391-1398.
47. Douek DC, McFarland RD, Keiser PH, et al. Changes in thymic function with age and during the treatment of HIV infection. Nature 1998;396:690-695.
48. Ensoli F, Fiorelli V, Alario C, et al. Decreased T cell apoptosis and T cell recovery during highly active antiretroviral therapy (HAART). Clin Immunol 2000;97:9-20.
49. Estaquier J, Lelievre JD, Petit F, et al. Effects of antiretroviral drugs on human immunodeficiency virus type 1-induced CD4(+) T-cell death. J Virol 2002;76:5966-5973.
50. Steinberg HN, Crumpacker CS, Chatis PA. In vitro suppression of normal human bone marrow progenitor cells by human immunodeficiency virus. J Virol 1991;65:1765-1769.
51. Isgro A, Mezzaroma I, Aiuti A, et al. Recovery of hematopoietic activity in bone marrow from human immunodeficiency virus type 1-infected patients during highly active antiretroviral therapy. AIDS Res Hum Retroviruses 2000;16:1471-1479.
52. Moore DM, Hogg RS, Chan K, et al. Disease progression in patients with virological suppression in response to HAART is associated with the degree of immunological response. AIDS 2006;20:371-377.
53. Hoffmann C, Mulcahy F. ART 2005/2006: The horizon and beyond. In: Hoffmann C, Rockstroh J, Kamps BS, eds. HIV Medicine, 2nd ed. Flying Publisher; 2005:146-155.
54. Kovacs JA, Vogel S, Albert JM, et al. Controlled trial of interleukin-2 infusions in patients infected with the human immunodeficiency virus. N Engl J Med 1996;335:1350-1356.
55. Wood R, Montoya JG, Kundu SK, et al. Safety and efficacy of polyethylene glycol-modified interleukin-2 and zidovudine in human immunodeficiency virus type 1 infection: a phase I/II study. J Infect Dis. 1993;167:519-525.
56. Katlama C, Carcelain G, Duvivier C, et al. Interleukin-2 accelerates CD4 cell reconstitution in HIV-infected patients with severe immunosuppression despite highly active antiretroviral therapy: The ILSTIM study - ANRS 082. AIDS 2002;16:2027-2034.
57. Abrams DI, Bebchuk JD, Denning ET, et al. Randomized, open-label study of the impact of two doses of subcutaneous recombinant interleukin-2 on viral burden in patients with HIV-1 infection and CD4+ cell counts of > or = 300/mm3: CPCRA 059. J Acquir Immune Defic Syndr 2002;29:221-231.
58. Rizzardi GP, Harari A, Capiluppi B, et al. Treatment of primary HIV-1 infection with cyclosporin A coupled with highly active antiretroviral therapy. J Clin Invest 2002;109:681-688.
59. Lederman MM, Smeaton L, Smith KY, et al. Cyclosporin A provides no sustained immunologic benefit to persons with chronic HIV-1 infection starting suppressive antiretroviral therapy: Results of a randomized, controlled trial of the AIDS Clinical Trials Group A5138. J Infect Dis 2006;194:1677-1685.
60. Grabar S, Le Moing V, Goujard C, et al. Clinical outcome of patients with HIV-1 infection according to immunologic and virologic response after 6 months of highly active antiretroviral therapy. Ann Intern Med 2000;133:401-410.
61. Piketty C, Castiel P, Belec L, et al. Discrepant responses to triple combination antiretroviral therapy in advanced HIV disease. AIDS 1998;12:745-750.
62. Piketty C, Weiss L, Thomas F, et al. Long-term clinical outcome of human immunodeficiency virus-infected patients with discordant immunologic and virologic responses to a protease inhibitor-containing regimen. J Infect Dis 2001;183:1328-1335.
63. Negredo E, Molto J, Burger D, et al. Unexpected CD4 cell count decline in patients receiving didanosine and tenofovir-based regimens despite undetectable viral load. AIDS 2004;18:459-463.
64. Negredo E, Bonjoch A, Paredes R, et al. Compromised immunologic recovery in treatment-experienced patients with HIV infection receiving both tenofovir disoproxil fumarate and didanosine in the TORO studies. Clin Infect Dis 2005;41:901-905.
65. Pruvost A, Negredo E, Benech H, et al. Measurement of intracellular didanosine and tenofovir phosphorylated metabolites and possible interaction of the two drugs in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 2005;49:1907-1914.
66. Benveniste O, Flahault A, Rollot F, et al. Mechanisms involved in the low-level regeneration of CD4+ cells in HIV-1-infected patients receiving highly active antiretroviral therapy who have prolonged undetectable plasma viral loads. J Infect Dis 2005;191:1670-1679.
67. Marziali M, De Santis W, et al. T-cell homeostasis alteration in HIV-1 infected subjects with low CD4 T-cell count despite undetectable virus load during HAART. AIDS 2006;20:2033-2041.
68. Paterson DL, Swindells S, Mohr J, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med 2000;133:21-30.
69. Maggiolo F, Ravasio L, Ripamonti D, et al. Similar adherence rates favor different virologic outcomes for patients treated with nonnucleoside analogues or protease inhibitors. Clin Infect Dis 2005;40:158-163.
70. Bangsberg DR. Less than 95% adherence to nonnucleoside reverse-transcriptase inhibitor therapy can lead to viral suppression. Clin Infect Dis 2006;43:939-941.
71. Staszewski S, Morales-Ramirez J, Tashima KT, et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team. N Engl J Med 1999;341:1865-1873.
72. Robbins GK, De Gruttola V, Shafer RW, et al. Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med 2003;349:2293-2303.
73. Gulick RM. Adherence to antiretroviral therapy: How much is enough? Clin Infect Dis 2006;43:942-944.