Rapid suppression of plasma HIV RNA and sustained increase in CD4 cell count following highly active antiretroviral therapy (HAART) regimens can be prognostic indicators of long-term virologic treatment success. Routine measurement of plasma HIV RNA levels (viral load or VL) at four and eight or 12 weeks is recommended after initiating treatment because favorable changes are predictive of durable success at six months and longer. Early favorable response of VL, as soon as six days after HAART initiation, can signify that the patient is initially adherent to treatment, which is necessary in the long term for a successful regimen. Early favorable response is also an indicator of adequate pharmacokinetic profile and potent antiviral activity of the drug regimen. It also can indicate that the predominant HIV strain infecting the patient is sensitive to the treatment regimen. These factors of adherence, drug levels, potency, and susceptibility favor a long-term durable response. Evaluation of early treatment responses may create the opportunity to promptly change the HAART regimen in the event of an anticipated long-term failure, delaying or preventing the evolution of drug resistance, and improving the effectiveness of treatment overall.
Palella FJ Jr, Delaney KM, Moorman AC, et al.Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med1998;338(13):853-860.
2.
Panel on Clinical Practices for Treatment of HIV Infection convened by the Department of Health and Human Services (DHHS) and the Henry J. Kaiser Family Foundation. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. Accessed February 12, 2003 at: http://www.aidsinfo.nih.gov/guidelines/default_db2.asp?id=50
3.
Demeter LM, Hughes MD, Coombs RW, et al.Predictors of virologic and clinical outcomes in HIV-1-infected patients receiving concurrent treatment with indinavir, zidovudine, and lamivudine. AIDS Clinical Trials Group Protocol 320. Ann Intern Med2001;135(11):954-964.
4.
Polis MA, Sidorov IA, Yoder C, et al.Correlation between reduction in plasma HIV-1 RNA concentration 1 week after start of antiretroviral treatment and longer-term efficacy. Lancet2001;358(9295):1760-1765.
5.
Mittler J, Essunger P, Yuen GJ, et al.Short-term measures of relative efficacy predict longer-term reductions in human immunodeficiency virus type 1 RNA levels following nelfinavir monotherapy. Antimicrob Agents Chemother2001;45(5):1438-1443.
6.
Mueller BU, Zeichner SL, Kuznetsov VA, et al.Individual prognoses of long-term responses to antiretroviral treatment based on virological, immunological and pharmacological parameters measured during the first week under therapy. AIDS1998;12(15):F191-F196.
7.
Cozzi-Lepri A, Miller V, Phillips AN, et al.The virological response to highly active antiretroviral therapy over the first 24 weeks of therapy according to the pre-therapy viral load and the weeks 4-8 viral load. AIDS2001;15(1):47-54.
8.
Carpenter CC, Cooper DA, Fischl MA, et al.Antiretroviral therapy in adults. Updated recommendations of the International AIDS Society—USA Panel. JAMA2000;283(3):381-390.
9.
Clumeck N, De Wit S. Update on highly active antiretroviral therapy: Progress and strategies. Biomed Pharmacother2000;54(1):7-12.
10.
Ho D, Ramratnam B, Louie M, Markowitz M. Latent reservoir and residual HIV-1 replication on antiretroviral therapy. 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, Feb 4-8, 2001. (Abstract S17). Accessed April 26, 2001 at: http://retroconference.org/2001/abstracts/abstracts/abstracts/S17.htm
11.
Kempf DJ, Rode RA, Xu Y, et al.The duration of viral suppression during protease inhibitor therapy for HIV-1 infection is predicted by plasma HIV-1 RNA at the nadir. AIDS1998;12(5):F9-F14.
12.
Marschner IC, Collier AC, Coombs RW, et al.Use of changes in plasma levels of human immunodeficiency virus type 1 RNA to assess the clinical benefit of antiretroviral therapy. J Infect Dis1998;177(1):40-47.
13.
Raboud JM, Montaner JS, Conway B, et al.Suppression of plasma viral load below 20 copies/ml is required to achieve a long-term response to therapy. AIDS1998;12(13):1619-1624.
14.
Katzenstein DA, Hammer SM, Hughes MD, et al.The relation of virologic and immunologic markers to clinical outcomes after nucleoside therapy in HIV-infected adults with 200 to 500 CD4 cells per cubic millimeter. N Engl J Med1996;335(15):1091-1098.
15.
Mellors JW, Muñoz A, Giorgi JV, et al.Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med1997;126(12):946-954.
16.
Komanduri KV, Viswanathan MN, Wieder ED, et al.Restoration of cytomegalovirus-specific CD4+ T-lymphocyte responses after ganciclovir and highly active antiretroviral therapy in individuals infected with HIV-1. Nat Med1998;4(8):953-956.
17.
Havlir DV, Bassett R, Levitan D, et al.Prevalence and predictive value of intermittent viremia with combination HIV therapy. JAMA2001;286(2):171-179.
18.
Greub G, Cozzi Lepri A, Ledergerber B, et al.Low-level HIV viral rebound and blips in patients receiving potent antiretroviral therapy. 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, February 4-8, 2001. (Abstract 522). Accessed April 24, 2001 at: http://retroconference.org/2001/abstracts/abstracts/abstracts/522.htm
19.
Ramratnam B, Mittler JE, Zhang L, et al.The decay of the latent reservoir of replication-competent HIV-1 is inversely correlated with the extent of residual viral replication during prolonged anti-retroviral therapy. Nat Med2000;6(1):82-85.
20.
Acosta EP, Henry K, Baken L, Page LM, Fletcher CV. Indinavir concentrations and antiviral effect. Pharmacotherapy1999;19(6): 708-712.
21.
Durant J, Clevenbergh P, Garraffo R, et al.Importance of protease inhibitor plasma levels in HIV-infected patients treated with genotypic-guided therapy: pharmacological data from the Viradapt Study. AIDS2000;14(10):1333-1339.
22.
Hoetelmans RM, van Heeswijk RP, Profijt M, et al.Comparison of the plasma pharmacokinetics and renal clearance of didanosine during once and twice daily dosing in HIV-1 infected individuals. AIDS1998;12(17):F211-F216.
23.
Huisman MT, Smit JW, Wiltshire HR, et al.P-glycoprotein limits oral availability, brain, and fetal penetration of saquinavir even with high doses of ritonavir. Mol Pharmacol2001;59(4):806-813.
24.
Kim RB, Fromm MF, Wandel C, et al.The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest1998;101(2):289-294.
25.
Kim RB. Drugs as P-glycoprotein substrates, inhibitors, and inducers. Drug Metab Rev2002;34(1-2):47-54.
26.
Huang L, Wring SA, Woolley JL, et al.Induction of P-glycoprotein and cytochrome P450 3A by HIV protease inhibitors. Drug Metab Dispos2001;29(5):754-760.
27.
Dresser GK, Spence JD, Bailey DG. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet2000;38:41-57.
28.
Wacher VJ, Silverman JA, Zhang Y, Benet LZ. Role of P-glycoprotein and cytochrome P450 3A in limiting oral absorption of peptides and peptidomimetics. J Pharm Sci1998;87(11):1322-1330.
29.
Gibson GG, Plant NJ, Swales KE, Ayrton A, El-Sankary W. Receptor-dependent transcriptional activation of cytochrome P4503A genes: Induction mechanisms, species differences and interindividual variation in man. Xenobiotica London2002;32(3):165-206.
30.
Kilby JM, Sfakianos G, Gizzi N, et al.Safety and pharmacokinetics of once-daily regimens of soft-gel capsule saquinavir plus minidose ritonavir in human immunodeficiency virus-negative adults. Antimicrob Agents Chemother2000;44(10):2672-2678.
31.
Cozzi Lepri A, Sabin CA, Staszewski S, et al.Resistance profiles in patients with viral rebound on potent antiretroviral therapy. J Infect Dis2000;181(3):1143-1147.
32.
Havlir DV, Hellmann NS, Petropoulos CJ, et al.Drug susceptibility in HIV infection after viral rebound in patients receiving indinavir-containing regimens. JAMA2000;283(2):229-234.
33.
Deeks SG. Failure of HIV-1 protease inhibitors to fully suppress viral replication. Implications for salvage therapy. Adv Exp Med Biol1999;458:175-182.
34.
Race E, Gilbert SM, Sheldon JG, et al.Correlation of response to treatment and HIV genotypic changes during phase III trials with saquinavir and reverse transcriptase inhibitor combination therapy. AIDS1998;12(12):1465-1474.
35.
Brown AJ, Precious HM, Whitcomb JM, et al.Reduced susceptibility of human immunodeficiency virus type 1 (HIV-1) from patients with primary HIV infection to nonnucleoside reverse transcriptase inhibitors is associated with variation at novel amino acid sites. J Virol2000;74(22):10269-10273.
36.
Little SJ. Transmission and prevalence of HIV resistance among treatment-naive subjects. Antivir Ther2000;5(1):33-40.
37.
Wegner SA, Brodine SK, Mascola JR, et al.Prevalence of genotypic and phenotypic resistance to anti-retroviral drugs in a cohort of therapy-naive HIV-1 infected US military personnel. AIDS2000;14(8):1009-1015.
38.
Little SJ, Holte S, Routy JP, et al.Antiretroviral-drug resistance among patients recently infected with HIV. N Engl J Med2002; 347(6):385-394.
39.
Winters MA, Baxter JD, Mayers DL, et al.Frequency of antiretroviral drug resistance mutations in HIV-1 strains from patients failing triple drug regimens. The Terry Beirn Community Programs for Clinical Research on AIDS. Antivir Ther2000;5(1):57-63.
40.
Lambotte O, Demoustier A, de Goer MG, et al.Persistence of infectious HIV in both memory and naive CD4 T-cell subsets in patients on prolonged and effective HAART. 9th Conference on Retroviruses and Opportunistic Infections. Seattle, WA, February 24-28, 2002. (Poster 505-M). Accessed May 17, 2002 at: http://63.126.3.84/2002/Abstract/13554.htm
41.
Blankson JN, Persaud D, Siliciano RF. The challenge of viral reservoirs in HIV-1 infection. Annu Rev Med2002;53:557-593.
42.
Strain MC, Havlir D, Gunthard H, et al.Intrinsic decay rate of lymphocyte reservoirs of HIV-1. 9th Conference on Retroviruses and Opportunistic Infections. Seattle, WA; February 24-28, 2002. (Poster 492-M). Accessed May 17, 2002 at: http://63.126.3.84/2002/Abstract/13616.htm
43.
Siliciano R.Viral reservoirs and ongoing virus replication in patients on HAART: implications for clinical management. 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, February 4-8, 2001. (Abstract L5). Accessed April 25, 2001 at: www.retroconference.org/2001/abstracts/abstracts/abstracts/L5.htm
44.
Finzi D, Hermankova M, Pierson T, et al.Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science1997;278(5341):1295-1300.
45.
De Pasquale MP, Allega J, Sutton L, et al.Drug-selected HIV-1 mutations can differ in cervico-vaginal and blood plasma RNA. 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, February 4-8, 2001. (Abstract 446). Accessed April 25, 2001 at: http://retroconference.org/2001/abstracts/abstracts/abstracts/446.htm
46.
Ellis R.Dynamics of HIV replication and persistence in the CNS after antiretroviral therapy. 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, February 4-8, 2001. (Abstract S19). Accessed April 25, 2001 at: http://retroconference.org/2001/abstracts/abstracts/abstracts/S19.htm
47.
Vigouroux C, Gharakhanian S, Salhi Y, et al.Adverse metabolic disorders during highly active antiretroviral treatments (HAART) of HIV disease. Diabetes Metab1999;25(5):383-392.
48.
Henry K, Zackin R, Dube M, et al.ACTG 5056: Metabolic status and cardiovascular disease risk for a cohort of HIV-1-infected persons durably suppressed on an indinavir-containing regimen (ACTG 372A). 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, February 4-8, 2001. (Abstract 656). Accessed February 12, 2003 at: http://retroconference.org/2001/abstracts/abstracts/abstracts/656.htm
49.
Hruz PW, Murata H, Mueckler M. Adverse metabolic consequences of HIV protease inhibitor therapy: the search for a central mechanism. Am J Physiol Endocrinol Metab2001;280(4):E549-E553.
50.
Petit JM, Duong M, Duvillard L, et al.HIV-1 protease inhibitors induce an increase of triglyceride level in HIV-infected men without modification of insulin sensitivity: a longitudinal study. Horm Metab Res2000;32(9):367-372.
51.
Moyle G.The etiology of metabolic and morphological changes during antiretroviral therapy: many small pieces in a large jigsaw. Accessed November 8, 2001 at: http://www.aidsreviews.com/2001/rev02/art_03.html
52.
Tsiodras S, Mantzoros C, Hammer S, Samore M. Effects of protease inhibitors on hyperglycemia, hyperlipidemia, and lipodystrophy: a 5-year cohort study. Arch Intern Med2000;160(13):2050-2056.
53.
Kingsley L, Smit E, Riddler S, et al.Prevalence of lipodystrophy and metabolic abnormalities in the Multicenter AIDS Cohort Study (MACS). 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, February 4-8, 2001. (Abstract 538). Accessed April 26, 2001 at: http://retroconference.org/2001/abstracts/abstracts/abstracts/538.htm
54.
Kakuda TN. Pharmacology of nucleoside and nucleotide reverse transcriptase inhibitor-induced mitochondrial toxicity. Clin Ther2000;22(6):685-708.
55.
Dubé MP, Shankar S, Vanderluitgaren JM, et al.Effect of indinavir (IDV) monotherapy on endothelial function in men without HIV infection. 9th Conference on Retroviruses and Opportunistic Infections. Seattle, WA, February 24-28, 2002. (Abstract LB10). Accessed June 4, 2002 at: http://63.126.3.84/2002/Abstract/14099.htm
56.
Holmberg S, Moorman A, Tong T, et al.Protease inhibitor use and adverse cardiovascular outcomes in ambulatory HIV patients. 9th Conference on Retroviruses and Opportunistic Infection. Seattle, WA, February 24-28, 2002. (Poster 698-T). Accessed February 12, 2003 at: http://63.126.3.84/2002/Abstract/12803.htm
57.
Leport C, Saves M, Ducimetiere P, et al.Coronary heart disease risk (CHD) in French HIV-infected men started on a protease inhibitor (PI)-containing regimen compared to the general population. 9th Conference on Retroviruses and Opportunistic Infections. Seattle, WA, February 24-28, 2002. (Poster 697-T). Accessed May 17, 2002 at: http://63.126.3.84/2002/Abstract/12682.htm
58.
Henry K, Zackin R, Dube M, et al.ACTG 5056: C-reactive protein (CRP) levels and cardiovascular risk status for a cohort of HIV-1 infected persons durably suppressed on an indinavir (IDV)-containing regimen. 9th Conference on Retroviruses and Opportunistic Infections. Seattle, WA, February 24-28, 2002. (Poster 694-T). Accessed May 17, 2002 at: http://63.126.3.84/2002/Abstract/12819.htm
59.
Gifford AL, Bormann JE, Shively MJ, et al.Predictors of self-reported adherence and plasma HIV concentrations in patients on multidrug antiretroviral regimens. Journal of Acquired Immune Deficiency Syndrome. 2000;23:386-395.
60.
Kastrissios H, Suárez JR, Hammer S, Katzenstein D, Blaschke TF. The extent of non-adherence in a large AIDS clinical trial using plasma dideoxynucleoside concentrations as a marker. AIDS1998; 12(17):2305-2311.
61.
Paterson DL, Swindells S, Mohr J, et al.Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med2000;133(1):21-30.
62.
Haubrich RH, Little SJ, Currier JS, et al.The value of patient-reported adherence to antiretroviral therapy in predicting virologic and immunologic response. AIDS1999;13(9):1099-1107.
63.
Montaner JS, Reiss P, Cooper D, et al.A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. JAMA1998;279(12):930-937.
64.
Bartlett JA. Addressing the challenges of adherence. J Acquir Immune Defic Syndr2002;29(Suppl 1):S2-S10.
65.
Lee K, Gulick RM. New drugs for the treatment of HIV infection. Curr Infect Dis Rep2001;3(2):193-200.
66.
Miller MD, Margot NA, Schooley R, McGowan I. Baseline and week 48 final phenotype analysis of HIV-1 from patients adding tenofovir disoproxil fumarate (TDF) therapy to background ART. 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, February 4-8, 2001. (Abstract 441). Accessed April 26, 2001 at: www.retroconference.org/2001/abstracts/abstracts/abstracts/441.htm
67.
Schooley R, Myers R, Ruane P, et al.A double-blind, placebo-controlled study of tenofovir disoproxil fumarate (TDF) for the treatment of HIV infection. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco, CA, September 26-29, 1999. (Abstract 1650).
68.
Schooley R, Myers R, Ruane P, et al.Tenofovir disoproxil fumarate (TDF) for the treatment of antiretroviral experienced patients. A double-blind, placebo-controlled study. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy. Toronto, Canada, September 17-20, 2000. (Abstract 34690).
69.
Squires K, Pierone G, Berger Det al.Tenofovir DF: A 48-week final analysis from a phase III randomized, double blind placebo controlled study in antiretroviral experienced patients. 9th Conference on Retroviruses and Opportunistic Infections. Seattle, WA, February 24-28, 2002. (Poster 413-W). Accessed May 17, 2002 at: http://www.retroconference.org/2002/Abstract/12601.htm
70.
Nelson M, Boyle B. Tenofovir in the treatment of individuals co-infected with HIV and hepatitis B. XIV International AIDS Conference. Barcelona, Spain, July 7-12, 2002. (Abstract B7302). Accessed October 9, 2002 at: http://www.hivandhepatitis.com/hep_b/news/080202a.html
71.
Kilby JM, Hopkins S, Venetta TM, et al.Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nat Med1998;4(11):1302-1307.
72.
Fusion inhibitor T-20 continues to show promise in heavily pretreated patients. XIV International AIDS Conference. Barcelona, Spain, July 7-12, 2002. Accessed October 9, 2002 at: http://www.hivandhepatitis.com/2002conf/14th_aids/8.html
73.
Darque A, Valette G, Rousseau F, et al.Quantitation of intracellular triphosphate of emtricitabine in peripheral blood mononuclear cells from human immunodeficiency virus-infected patients. Antimicrob Agents Chemother1999;43(9):2245-2250.
74.
Delehanty J, Wakeford C, Hulett L, et al.A phase I/II randomized, controlled study of FTC versus 3TC in HIV-infected patients. 6th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, January 31-February 4, 1999. (Abstract 16). Accessed April 26, 2001 at: http://www.retroconference.org/99/abstracts/16.htm
75.
Van Der Horst C, Sanne I, Wakeford C, Quinn J, Rousseau F. Two randomized, controlled, equivalence trials of emtricitibine (FTC) to lamivudine (3TC). 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, Feb 4-8, 2001. (Abstract 18). Accessed April 26, 2001 at: www.retroconference.org/2001/abstracts/abstracts/abstracts/18.htm
76.
Molina JM, Ferchal F, Rancinan C, et al.Once-daily combination therapy with emtricitabine, didanosine, and efavirenz in human immunodeficiency virus-infected patients. J Infect Dis2000;182(2): 599-602.
77.
Molina JM, Perusat S, Ferchal F, et al.Once-daily combination therapy with emtricitabine, didanosine and efavirenz in treatment-naive HIV-infected adults: 64-week follow-up of the ANRS 091 Trial. 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, February 6, 2001. (Abstract 321). Accessed April 27, 2001 at: www.retroconference.org/2001/abstracts/abstracts/abstracts/321.htm
78.
Turner SR, Strohbach JW, Tommasi RA, et al.Tipranavir (PNU-140690): a potent, orally bioavailable nonpeptidic HIV protease inhibitor of the 5,6-dihydro-4-hydroxy-2-pyrone sulfonamide class. J Med Chem1998;41(18):3467-3476.
79.
Back NK, van Wijk A, Remmerswaal D, et al.In-vitro tipranavir susceptibility of HIV-1 isolates with reduced susceptibility to other protease inhibitors (letter). AIDS2000;14(1):101-102.
Rusconi S, La Seta Catamancio S, Citterio P, et al.Susceptibility to PNU-140690 (tipranavir) of human immunodeficiency virus type 1 isolates derived from patients with multidrug resistance to other protease inhibitors. Antimicrob Agents Chemother2000; 44(5):1328-1332.
82.
Wang Y, Daenzer C, Wood R, et al.The safety, efficacy and viral dynamics analysis of tipranavir, a new-generation protease inhibitor, in a phase II study in antiretroviral-naive HIV-1-infected patients. 7th Conference on Retroviruses and Opportunistic Infections. San Francisco, CA, January 30-February 4, 2000. (Abstract 673). Accessed April 26, 2001 at: www.retroconference.org/2000/abstracts/673.htm
83.
Slater L, Farthing C, Jayaweera J, et al.Safety and efficacy of tipranavir (TPV), a novel non-peptidic protease inhibitor, plus ritonavir (RTV), in PI-failure patients. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL, December 18, 2001. (LB-15).
84.
Curry R, Markowitz M, Slater L, et al.Safety and efficacy of tipranavir, a non-peptidic protease inhibitor, in multiple PI-failure patients (BI 1182.2). International AIDS Society Conference on HIV Pathogenesis and Treatment. Buenos Aires, Argentina, July 8-11, 2001. (Abstract 3). Accessed November 8, 2001 at: http://www.ias.se/abstract/show.asp?abstract_id=3
85.
Phillips L, Borin MT, Hopkins NK, Daenzer CL, Wang Y. The pharmacokinetics of nucleoside reverse transcriptase inhibitors when coadministered with the HIV protease inhibitor tipranavir in HIV-1 infected patients. 7th Conference on Retroviruses and Opportunistic Infections. San Francisco, CA, January 30-February 2, 2000. (Abstract 81). Accessed April 26, 2001 at: http://www.retroconference.org/2000/abstracts/81.htm
86.
Rabasseda X, Silvestre J, Castañer J. BMS-232632. Drugs of the Future1999;24:375-380.
87.
Robinson B, Riccardi K, Deminie C, et al.Two-drug combination studies on the protease inhibitor BMS-232632 on HIV-1 replication. 38th International Conference on Antimicrobial Agents and Chemotherapy. San Diego, CA, September 24-27, 1998. (Abstract I-20).
88.
Zhang KE, Wu E, Patick AK, et al.Circulating metabolites of the human immunodeficiency virus protease inhibitor nelfinavir in humans: structural identification, levels in plasma, and antiviral activities. Antimicrob Agents Chemother2001;45(4):1086-1093.
89.
Piliero P.The utility of inhibitory quotients in determining the relative potency of protease inhibitors. AIDS2002;16(5):799-800.
90.
Duval X, Lamotte C, Race E, et al.Amprenavir inhibitory quotient and virological response in human immunodeficiency virus-infected patients on an amprenavir-containing salvage regimen without or with ritonavir. Antimicrob Agents Chemother. 2002;46:570-574.
91.
Shulman N, Zolopa A, Havlir D, et al.Virtual inhibitory quotient predicts response to ritonavir boosting of indinavir-based therapy in human immunodeficiency virus-infected patients with ongoing viremia. Antimicrob Agents Chemother2002;46(12):3907-3916.
92.
Haas DW, Zala C, Schrader S, et al.Atazanavir plus saquinavir once daily favorably affects total cholesterol (TC), fasting triglyceride (TG), and fasting LDL cholesterol (LDL) profiles in patients failing prior therapy (Trial AI424-009, week 48). 9th Conference for Retroviruses and Opportunistic Infections. Seattle, WA, February 26, 2002. (Abstract 42). Accessed February 12, 2003 at: http://63.126.3.84/2002/Abstract/13797.htm
93.
Sanne I, Piliero P, Wood R, et al.Safety and antiviral efficacy of a once-daily HIV-1 protease inhibitor BMS-232632: 24 week results from a phase II clinical trial40th Interscience Conference on Antimicrobial Agents and Chemotherapy. Toronto, Canada, September 17-20, 2000. (Abstract 691).
94.
Squires K, Gatell J, Piliero P, et al.AI424-007: 48-week safety and efficacy results from a phase II study of a once-daily HIV-1 protease inhibitor (PI), BMS-232632. 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, February 4-8, 2001. (Abstract 15). Accessed March 14, 2001 at: http://www.retroconference.org/2001/abstracts/abstracts/abstracts/15.htm
95.
Piliero P, Cahn P, Pantaleo G, et al.Atazanavir: a once-daily protease inhibitor with a superior lipid profile—results of clinical trials beyond week 48. 9th Conference on Retroviruses and Opportunistic Infections. Seattle, WA, February 24-28, 2002. (Abstract 706-T). Accessed February 12, 2003 at: http://www.retroconference.org/2002/Abstract/13827.htm
96.
Carr A, Samaras K, Burton S, et al.A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS1998;12(7):F51-F58.
97.
Hadigan C, Meigs JB, Corcoran C, et al.Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy. Clin Infect Dis2001;32(1):130-139.
98.
Christeff N, Melchior JC, de Truchis P, et al.Lipodystrophy defined by a clinical score in HIV-infected men on highly active antiretroviral therapy: correlation between dyslipidaemia and steroid hormone alterations. AIDS1999;13(16):2251-2260.
99.
Ammassari A, Murri R, Pezzotti P, et al.Self-reported symptoms and medication side effects influence adherence to highly active antiretroviral therapy in persons with HIV infection. J Acquir Immune Defic Syndr2001;28(5):445-449.
100.
Duran S, Savès M, Spire B, et al.Failure to maintain long-term adherence to highly active antiretroviral therapy: the role of lipodystrophy. AIDS2001;15(18):2441-2444.
101.
Crommentuyn KM, Rosing H, Nan-Offeringa LG, et al.Rapid quantification of HIV protease inhibitors in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. J Mass Spectrom2003; 38(2):157-166.
102.
Wongvipat N.Adherence matters. Therapeutic drug monitoring (TDM) may detect drug failure. Posit Living1999;8(8):16, 18-19.
103.
Clevenbergh P, Garraffo R, Durant J, Dellamonica P. PharmAdapt: A randomized prospective study to evaluate the benefit of therapeutic monitoring of protease inhibitors: 12 week results. AIDS2002;16(17):2311-2315.
104.
Back D, Khoo S, Gibbons S. The role of therapeutic drug monitoring (TDM) in clinical practice. 9th Conference on Retroviruses and Opportunistic Infections. Seattle, WA, February 24-28, 2002. (S20). Accessed May 17, 2002 at: http://63.126.3.84/2002/Abstract/S20.htm
105.
Clevenbergh P, Garraffo R, Durant J, et al.Long term efficacy of protease inhibitor plasma drug levels monitoring (PI TDM): PharmAdapt W 32 results. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL, December 16-19, 2001. (Abstract I-1730).
106.
Burger DM, Hugen PW, Droste J, et al.Therapeutic drug monitoring of indinavir in treatment-naive patients improves therapeutic outcome after 1 year: results from Athena. 2nd International Workshop on Clinical Pharmacology of HIV Therapy. Noordwijk, The Netherlands, April 2-4, 2001. (Abstract 6.2a).
107.
Burger DM, Hugen PW, Droste J, et al.Therapeutic drug monitoring of nelfinavir 1250 mg bid in treatment-naive patients improves therapeutic outcome after 1 year: results from Athena. 2nd International Workshop on Clinical Pharmacology of HIV Therapy; Noordwijk, The Netherlands, April 2-4, 2001. (Abstract 6.2b).
108.
Flexner C.Dual protease inhibitor therapy in HIV-infected patients: pharmacologic rationale and clinical benefits. Annu Rev Pharmacol Toxicol2000;40:649-674.
109.
Brundage RC, Kline MW, Lindsey J, Fenton T, Fletcher CV. Pharmacokinetics of saquinavir (SQV) with nelfinavir (NFV) or ritonavir (RTV) in HIV-infected children. 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, Feb 4-8, 2001. (Abstract 728). Accessed June 19, 2001 at: http://www.retroconference.org/2001/abstracts/abstracts/abstracts/728.htm
110.
Hsu A, Zolopa A, Shulman NS, et al.Final analysis of ritonavir (RTV) intensification in indinavir (IDV) recipients with detectable HIV RNA levels. 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, February 4-9, 2001. (Abstract 337). Accessed April 26, 2001 at: http://retroconference.org/2001/abstracts/abstracts/abstracts/337.htm
111.
Lamotte C, Peytavin G, Perre P, et al.Increasing adverse events (AE) with indinavir (IDV) dosages and plasma concentration in four different ritonavir (RTV)-IDV-containing regimens in HIV-infected patients. 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, Feb 4-8, 2001. (Abstract 738). Accessed April 26, 2001 at: http://www.retroconference.org/2001/abstracts/abstracts/abstracts/738.htm
112.
Mallolas J, Blanco JL, Sarasa M, et al.Dose-finding study of once-daily indinavir/ritonavir plus zidovudine and lamivudine in HIV-infected patients. Journal of Acquired Immune Deficiency Syndr2000;25(3):229-235.
113.
Degen O, Kurowski M, van Lunzen J, Schewe CK, Stellbrink HJ. Amprenavir (APV) and ritonavir (RTV): intraindividual comparison of different doses and influence of concomitant NNRTI on steady-state pharmacokinetics in HIV-infected patients. 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, February 4-8, 2001. (Abstract 739). Accessed April 26, 2001 at: http://www.retroconference.org/2001/abstracts/abstracts/abstracts/739.htm
114.
Markowitz M, Hurley A, Ramratnam B, et al.The safety and efficacy of a ritonavir-boosted amprenavir-based regimen after switch from amprenavir-based HAART. 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, February 4-8, 2001. (Abstract 405). Accessed April 26, 2001 at: www.retroconference.org/2001/abstracts/abstracts/abstracts/405.htm
115.
Wood R, Trepo C, Livrozet JM, et al.Amprenavir (APV) 600 mg/ritonavir (RTV) 100 mg BID or APV 1200 mg/RTV 200 mg QD given in combination with abacavir (ABC) and lamivudine (3TC) maintains efficacy in ART naive HIV-1 infected adults over 12 weeks (APV20001). 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, February 4-8, 2001. (Abstract 332). Accessed August 22, 2001 at: http://www.retroconference.org/2001/abstracts/abstracts/abstracts/332.htm
116.
Bardsley-Elliot A, Plosker GL. Nelfinavir: An update on its use in HIV infection. Drugs2000;59(3):581-620.
117.
Mallolas J, Blanco J, Sarasa M, et al.A dose-finding study of once-daily indinavir/ritonavir plus Combivir in HIV-infected patients. 7th Conference on Retroviruses and Opportunistic Infections. San Francisco, CA, January 30-February 2, 2000. (Abstract 512). Accessed September 27, 2000 at: http://retroconference.org/2000/abstracts/512.htm
118.
Boyd M, Duncombe C, Ruxrungthram K, et al.Indinavir TID vs indinavir/ritonavir BID in combination with AZT/3TC for HIV infection in nucleoside pretreated patients: HIV-NAT 005 76-week follow up. 9th Conference on Retroviruses and Opportunistic Infections. Seattle, WA, February 24-28, 2002. (Poster 422-W). Accessed May 17, 2002 at: http://63.126.3.84/2002/Abstract/13001.htm
119.
Kumar GN, Dykstra J, Roberts EM, et al.Potent inhibition of the cytochrome P-450 3A-mediated human liver microsomal metabolism of a novel HIV protease inhibitor by ritonavir: A positive drug-drug interaction. Drug Metab Dispos1999;27(8): 902-908.
Bernstein B, Moseley J, Kempf D, et al.Absence of resistance to Kaletra (ABT-378/r) observed through 48 weeks of therapy in antiretroviral-naive subjects. 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, Feb 4-8, 2001. (Abstract 453). Accessed October 16, 2001 at: http://retroconference.org/2001/abstracts/abstracts/abstracts/453.htm
122.
Clumeck N, Brun S, Sylte J, et al.Kaletra (ABT-378/r) and efavirenz: one-year safety/efficacy evaluation and phenotypic breakpoints in multiple-PI-experienced patients. 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, February 4-8, 2001. (Abstract 525). Accessed September 27, 2001 at: http://retroconference.org/2001/abstracts/abstracts/abstracts/525.htm
