LopinavirRitonavir: A review of its use in the management of HIV-1 infection

Drugs

Volumn 70, Issue 14, 2010, Pages 1885-1915

  Croxtall, Jamie D ^a   Perry, Caroline M ^a  

^a ADIS INTERNATIONAL LIMITED   (New Zealand)

Author keywords

Adis Drug Evaluations; HIV infections; Lopinavirritonavir, general

Indexed keywords

ABACAVIR PLUS LAMIVUDINE; AMPRENAVIR; ATAZANAVIR; ATAZANAVIR PLUS RITONAVIR; DARUNAVIR; DARUNAVIR PLUS RITONAVIR; EFAVIRENZ; EMTRICITABINE; EMTRICITABINE PLUS TENOFOVIR DISOPROXIL; FOSAMPRENAVIR PLUS RITONAVIR; INDINAVIR; LOPINAVIR; LOPINAVIR PLUS RITONAVIR; NELFINAVIR; NEVIRAPINE; RITONAVIR; RITONAVIR PLUS SAQUINAVIR; RNA DIRECTED DNA POLYMERASE INHIBITOR; SAQUINAVIR; TENOFOVIR DISOPROXIL; TIPRANAVIR; VIRUS RNA; HUMAN IMMUNODEFICIENCY VIRUS PROTEINASE INHIBITOR; PYRIMIDINONE DERIVATIVE;

ANTIVIRAL ACTIVITY; CARDIOVASCULAR RISK; CD4 LYMPHOCYTE COUNT; CLINICAL TRIAL; CONSTIPATION; COST CONTROL; COST EFFECTIVENESS ANALYSIS; DIARRHEA; DOSAGE SCHEDULE COMPARISON; DRUG ABSORPTION; DRUG ANTAGONISM; DRUG BIOAVAILABILITY; DRUG DISTRIBUTION; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG ELIMINATION; DRUG METABOLISM; DRUG POTENTIATION; DRUG TOLERABILITY; DRUG WITHDRAWAL; GASTROINTESTINAL SYMPTOM; GENE MUTATION; GENOTYPE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HYPERCHOLESTEROLEMIA; HYPERTRIGLYCERIDEMIA; IN VITRO STUDY; ISCHEMIC HEART DISEASE; LIPID BLOOD LEVEL; MAXIMUM PLASMA CONCENTRATION; NAUSEA AND VOMITING; NONHUMAN; OUTCOME ASSESSMENT; PHENOTYPE; REVIEW; SIDE EFFECT; TRIACYLGLYCEROL BLOOD LEVEL; VIRION; VIRUS ISOLATION; VIRUS RESISTANCE; VIRUS STRAIN; DRUG ADMINISTRATION; DRUG COMBINATION; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION;

HUMAN IMMUNODEFICIENCY VIRUS 1;

ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; DRUG ADMINISTRATION SCHEDULE; DRUG COMBINATIONS; HIV INFECTIONS; HIV PROTEASE INHIBITORS; HIV-1; HUMANS; PYRIMIDINONES; RITONAVIR;

EID: 77956607815     PISSN: 00126667     EISSN: 11791950     Source Type: Journal    
DOI: 10.2165/11204950-000000000-00000     Document Type: Review

References (91)

1. Dybul M, Fauci AS, Bartlett JG, et al. Guidelines for using antiretroviral agents among HIV-infected adults and adolescents: recommendations of the Panel on Clinical Practices for Treatment of HIV. MMWR Recomm Rep 2002 May 17; 51 (RR-7): 1-55
2. DHHS panel on antiretroviral guidelines for adults and adolescents: a working group of the Office of AIDS Research Advisory Council (OARAC). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents [online]. Available from URL http://www.aidsinfo. nih.gov/contentfiles/AdultandAdolescentGL.pdf [Accessed 2010 Apr 15]
3. DHHS panel on antiretroviral guidelines for adults and adolescents: a working group of the Office of AIDS Research Advisory Council (OARAC). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents [online]. Available from URL http://www.aidsinfo. nih.gov/contentfiles/AdultandAdolescentGL.pdf [Accessed 2010 Apr 15]
4. WHO, UNAIDS, UNICEF. Towards universal access: scaling up priority HIV/AIDS interventions in the health sector: progress report 2008 [online]. Available from URL: http://www.who.int/hiv/pub/towards-universal-access-re port-2008.pdf [Accessed 2010 Apr 15]
5. Shet A, Berry L, Mohri H, et al. Tracking the prevalence of transmitted antiretroviral drug-resistant HIV-1: a decade of experience. J Acquir Immune Defic Syndr 2006 Apr 1; 41 (4): 439-446
6. Gazzard BG, Anderson J, Babiker A, et al. British HIV Association Guidelines for the treatment of HIV-1-infected adults with antiretroviral therapy 2008. HIV Med 2008 Oct; 9 (8): 563-608
7. Thompson MA, Aberg JA, Cahn P, et al. Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society-USA Panel. JAMA 2010 Jul 21; 304 (3): 321-333
8. European AIDS Clinical Society (EACS). Guidelines for the clinical management and treatment of HIV infected adults in Europe [online]. Available from URL http://www.europeanaidsclinicalsociety.org/guidelinespdf/1-Treatment- of-HIV- Infected-Adults.pdf [Accessed 2010 Apr 15]
9. National Guideline Clearinghouse. Antiretroviral therapy [online]. Available from URL: http://www.guideline.gov/summary/summary.aspx?ss=15&doc- id=12939&string= [Accessed 2010 Jun 22]
10. Abbott Laboratories. Kaletra® (lopinavir/ritonavir) tablets and oral solution. Prescribing information [online]. Available from URL: http://www.kaletra.com [Accessed 2010 Jun 22]
11. European Medicines Agency. Kaletra® (lopinavir/ritonavir) soft capsules. Summary of product characteristics [online]. Available from URL: http://emc.medicines.org [Accessed 2010 Jun 22]
12. Scott JD. Simplifying the treatment of HIV infection with ritonavir-boosted protease inhibitors in antiretroviral-experienced patients. Am J Health Syst Pharm 2005 Apr; 62: 809-815
13. Cvetkovic RS, Goa KL. Lopinavir/ritonavir: a review of its use in the management of HIV infection. Drugs 2003; 63 (8): 769-802
14. Oldfield V, Plosker GL. Lopinavir/ritonavir: a review of its use in the management of HIV infection. Drugs 2006; 66 (9): 1275-1299
15. Sham HL, Kempf DJ, Molla A, et al. ABT-378, a highly potent inhibitor of the human immunodeficiency virus protease. Antimicrob Agents Chemother 1998; 42 (12): 3218-3224
16. Murphy RL, da Silva BA, Hicks CB, et al. Seven-year effi-cacy of a lopinavir/ritonavir-based regimen in antiretro-viral-naive HIV-1-infected patients. HIV Clin Trials 2008; 9 (1): 1-10
17. Gathe J, da Silva BA, Cohen DE, et al. A once-daily lopi-navir/ritonavir- based regimen is noninferior to twice-daily dosing and results in similar safety and tolerability in antiretroviral-naive subjects through 48 weeks. J Acquir Immune Defic Syndr 2009 Apr 15; 50 (5): 474-481
18. Johnson MA, Gathe Jr JC, Podzamczer D, et al. A once-daily lopinavir/ritonavir-based regimen provides non-inferior antiviral activity compared with a twice-daily regimen. J Acquir Immune Defic Syndr 2006 Oct 1; 43 (2): 153-160
19. Molina JM, Podsadecki TJ, Johnson MA, et al. A lopina-vir/ritonavir-based once-daily regimen results in better compliance and is non-inferior to a twice-daily regimen through 96 weeks. AIDS Res Hum Retroviruses 2007 Dec; 23 (12): 1505-1514
20. Kempf DJ, King MS, Bernstein B, et al. Incidence of resis-tance in a double-blind study comparing lopinavir/ritonavir plus stavudine and lamivudine to nelfinavir plus stavudine and lamivudine. J Infect Dis 2004 Jan 1; 189 (1): 51-60
21. Molina JM, Andrade-Villanueva J, Echevarria J, et al. Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and em-tricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study. Lancet 2008 Aug 23; 372 (9639): 646-655
22. Ortiz R, Dejesus E, Khanlou H, et al. Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1-infected patients at week 48. AIDS 2008 Jul 31; 22 (12): 1389-1397
23. Mills AM, Nelson M, Jayaweera D, et al. Once-daily dar-unavir/ritonavir vs. lopinavir/ritonavir in treatment-naive, HIV-1-infected patients: 96-week analysis. AIDS 2009 Aug 24; 23 (13): 1679-1688
24. Eron Jr J, Yeni P, Gathe Jr J. The KLEAN study of fosamprenavir-ritonavir versus lopinavir-ritonavir, each in combination with abacavir-lamivudine, for initial treatment of HIV infection over 48 weeks: a randomised non-inferiority trial. Lancet 2006; 368 (9534): 476-482
25. Pulido F, Estrada V, Baril JG, et al. Long-term efficacy and safety of fosamprenavir plus ritonavir versus lopinavir/ritonavir in combination with abacavir/lamivudine over 144 weeks. HIV Clin Trials 2009; 10 (2): 76-87
26. Riddler SA, Haubrich R, DiRienzo AG, et al. Class-sparing regimens for initial treatment of HIV-1 infection. N Engl J Med 2008 May 15; 358 (20): 2095-2106
27. Saez-Llorens X, Violari A, Deetz CO, et al. Forty-eight-week evaluation of lopinavir/ritonavir, a new protease inhibitor, in human immunodeficiency virus-infected children. Pediatr Infect Dis J 2003 Mar; 22: 216-223
28. Kempf DJ, Isaacson JD, King MS, et al. Identification of genotypic changes in human immunodeficiency virus protease that correlate with reduced susceptibility to the protease inhibitor lopinavir among viral isolates from protease inhibitor-experienced patients. J Virol 2001 Aug; 75 (16): 7462-7469
29. Mo H, King MS, King K, et al. Selection of resistance in protease inhibitor-experienced, human immunodeficiency virus type 1-infected subjects failing lopinavir-and ritonavir-based therapy: mutation patterns and baseline correlates. J Virol 2005 Mar; 79 (6): 3329-3338
30. Garriga C, Perez-Elias MJ, Delgado R, et al. Mutational patterns and correlated amino acid substitutions in the HIV-1 protease after virological failure to nelfinavir-and lopinavir/ritonavir-based treatments. J Med Virol 2007 Nov; 79 (11): 1617-1628
31. Kempf DJ, Isaacson JD, King MS, et al. Analysis of the virologic response with respect to baseline viral phenotype and genotype in protease inhibitor-experienced HIV-1-infected patients receiving lopinavir/ritonavir. Antiviral Ther 2002 Sep; 7 (3): 165-174
32. King M, Rode R, Cohen-Codar I, et al. Predictive genotypic algorithm for virologic response to lopinavir-ritonavir in protease inhibitor-experienced patients. Antimicrob Agents Chemother 2007; 51 (9): 3067-3074
33. Loutfy MR, Raboud JM, Walmsley SL, et al. Predictive value of HIV-1 protease genotype and virtual phenotype on the virological response to lopinavir/ritonavir-contain-ing salvage regimens. Antivir Ther 2004 Aug; 9 (4): 595-602
34. Grant P, Wong E, Rode R, et al. Virologic response to lopinavir-ritonavir-based antiretroviral regimens in a multi-center international clinical cohort: Comparison of geno-typic interpretation scores. Antimicrob Agents Chemother 2008; 52 (11): 4050-4056
35. Di Giambenedetto S, Barcarelli A, Pinnetti C, et al. Geno-typic resistance to lopinavir and fosamprenavir with or without ritonavir of clinical isolates from patients failing protease inhibitors-containing HAART regimens: prevalence and predictors. Scand J Infect Dis 2007 Oct; 39 (No.9): 813-818
36. Jimenez JL, Resino S, Martinez-Colom A, et al. Mutations at codons 54 and 82 of HIV protease predict virological response of HIV-infected children on salvage lopina-vir/ritonavir therapy. J Antimicrob Chemother 2005 Dec; 56 (No.6): 1081-1086
37. Johnson M, Grinsztejn B, Rodriguez C, et al. Atazanavir plus ritonavir or saquinavir, and lopinavir/ritonavir in patients experiencing multiple virological failures. AIDS 2005 Apr 29; 19 (7): 685-694
38. Johnson M, Grinsztejn B, Rodriguez C, et al. 96-Week comparison of once-daily atazanavir/ritonavir and twice-daily lopinavir/ritonavir in patients with multiple virologic failures. AIDS 2006; 20 (5): 711-718
39. Madruga JV, Berger D, McMurchie M, et al. Efficacy and safety of darunavir-ritonavir compared with that of lopinavir-ritonavir at 48 weeks in treatment-experienced, HIV-infected patients in TITAN: a randomised controlled phase III trial. Lancet 2007; 370 (9581): 49-58
40. De Meyer S, Hill A, Picchio G, et al. Influence of baseline protease inhibitor resistance on the efficacy of dar-unavir/ritonavir or lopinavir/ritonavir in the TITAN trial [letter]. J Acquir Immune Defic Syndr 2008 Dec 15; 49 (5): 563-564
41. Fischl MA, Collier AC, Mukherjee AL, et al. Randomized open-label trial of two simplified, class-sparing regimens following a first suppressive three or four-drug regimen. AIDS 2007 Jan 30; 21 (3): 325-333
42. Parkin NT, Chappey C, Petropoulos CJ. Improving lopi-navir genotype algorithm through phenotype correlations: novel mutation patterns and amprenavir cross-resistance. AIDS 2003; 17: 955-961
43. Eron J, Feinberg J, Kessler HA, et al. Once-daily versus twice-daily lopinavir/ritonavir in antiretroviral-naive HIV-positive patients: a 48-week randomized clinical trial. J Infect Dis 2004 Jan 15; 189 (2): 265-272
44. Crommentuyn KML, Mulder JW, Mairuhu ATA, et al. The plasma and intracellular steady-state pharmacokinetics of lopinavir/ritonavir in HIV-1-infected patients. Antiviral Ther 2004 Oct; 9 (5): 779-785
45. Klein CE, Chiu YL, Awni W, et al. The tablet formulation of lopinavir/ritonavir provides similar bioavailability to the soft-gelatin capsule formulation with less pharmacokinetic variability and diminished food effect. J Acquir Immune Defic Syndr 2007 Apr 1; 44 (4): 401-410
46. Hull MW, Harris M, Lima V, et al. Lopinavir/ritonavir pharmacokinetics in a substitution of high-dose soft-gelatin capsule to tablet formulation. J Clin Pharmacol 2009 Feb; 49 (2): 155-161
47. Murphy RL, Brun S, Hicks C, et al. ABT-378/ritonavir plus stavudine and lamivudine for the treatment of antiretro-viral-naive adults with HIV-1 infection: 48-week results. AIDS 2001 Jan 5; 15 (1): F1-9
48. Stek AM, Mirochnick M, Capparelli E, et al. Reduced lopinavir exposure during pregnancy. AIDS 2006 Oct 3; 20 (15): 1931-1939
49. Peng JZ, Pulido F, Kemmis Causemaker SJ, et al. Pharm-acokinetics of lopinavir/ritonavir in HIV/Hepatitis C virus-coinfected subjects with hepatic impairment. J Clin Pharmacol 2006 Mar; 46 (No.3): 265-274
50. Kumar GN, Rodrigues AD, Buko AM, et al. Cytochrome P450-mediated metabolism of the HIV-1 protease inhibitor ritonavir (ABT-538) in human liver microsomes. J Pharmacol Exp Ther 1996; 277: 423-431
51. Kumar GN, Dykstra J, Roberts EM, et al. Potent inhibition of the cytochrome P-450 3A-mediated human liver micro-somal metabolism of a novel HIV protease inhibitor by ritonavir: a positive drug-drug interaction. Drug Metab Dispos 1999; 27 (8): 902-908
52. Sankatsing SU, Droste J, Burger D, et al. Limited penetra-tion of lopinavir into seminal plasma of HIV-1-infected men [letter]. AIDS 2002 Aug 16; 16 (12): 1698-1700
53. Vergara TRC, Estrela RCE, Suarez-Kurtz G, et al. Limited penetration of lopinavir and ritonavir in the genital tract of men infected with HIV-1 in Brazil. Ther Drug Monit 2006 Apr; 28 (No.2): 175-179
54. Dumond JB, Yeh RF, Patterson KB, et al. Antiretroviral drug exposure in the female genital tract: implications for oral pre-and post-exposure prophylaxis. AIDS 2007 Sep 12; 21 (14): 1899-1907
55. Corbett A, Martinson F, Rezk N, et al. Lopinavir/ritonavir concentrations in breast milk and breast-feeding infants [abstract no. 947]. 16th Conference on Retroviruses and Opportunistic Infections; 2009 Feb 8-11; Montreal
56. Capparelli EV, Holland D, Okamoto C, et al. Lopinavir concentrations in cerebrospinal fluid exceed the 50% inhibitory concentration for HIV. AIDS 2005 Jun 10; 19 (9): 949-952
57. Kumar GN, Jayanti V, Lee RD, et al. In vitro metabolism of the HIV-1 protease inhibitor ABT-378: species comparison and metabolite identification. Drug Metab Dispos 1999; 27 (1): 86-91
58. Kumar GN, Jayanti VK, Johnson MK, et al. Metabolism and disposition of the HIV-1 protease inhibitor lopinavir (ABT-378) given in combination with ritonavir in rats, dogs, and humans. Pharm Res 2004 Sep; 21 (9): 1622-1630
59. Walmsley S, Avihingsanon A, Slim J, et al. Gemini: a non-inferiority study of saquinavir/ritonavir versus lopina-vir/ritonavir as initial HIV-1 therapy in adults. J Acquir Immune Defic Syndr 2009 Apr 1; 50 (4): 367-374
60. Hicks C, King MS, Gulick RA, et al. Long-term safety and durable antiretroviral activity of lopinavir/ritonavir in treatment-naive patients: 4 year follow-up study. AIDS 2004 Mar 26; 18 (5): 775-779
61. Molina JM, Andrade-Villanueva J, Echevarria J, et al. Once-daily atazanavir/ritonavir compared with twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 96-week efficacy and safety results of the CASTLE study. J Acquir Immune Defic Syndr 2010 Mar 1; 53 (3): 323-332
62. Pollard RB, Thompson M, Hicks M, et al. Phase 3 com-parison of lopinavir/ritonavir vs investigator-selected protease inhibitors in single PI-experienced, NNRTI-naive patients: 48-week results of study M98-888 [abstract no. PI.3.2 plus poster]. 7th International Congress on Drug Therapy in HIV Infection; 2004 Nov 14-18; Glasgow
63. Cohen C, Nieto-Cisneros L, Zala C, et al. Comparison of atazanavir with lopinavir/ritonavir in patients with prior protease inhibitor failure: a randomized multinational trial. Curr Med Res Opin 2005 Oct; 21 (10): 1683-1692
64. Eron JJ, Young B, Cooper DA, et al. Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials. Lancet 2010 Jan 30; 375 (9712): 396-407
65. Dragsted UB, Gerstoft J, Youle M, et al. A randomized trial to evaluate lopinavir/ritonavir versus saquinavir/ritonavir in HIV-1-infected patients: the MaxCmin2 trial. Antiviral Ther 2005; 10 (6): 735-743
66. Zajdenverg R, Podsadecki T, Badal-Faesen S, et al. Similar safety and efficacy of once-and twice-daily lopinavir/ritonavir tablets in treatment-experienced HIV-1-infected subjects at 48 weeks. J Aquir Immune Defic Syndr 2010; 54 (2): 143-151
67. Walmsley S, Bernstein B, King M, et al. Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection. N Engl J Med 2002 Jun 27; 346 (26): 2039-2046
68. Ghosn J, Flandre P, Cohen-Codar I, et al. Long-term (96-week) follow-up of antiretroviral-naive HIV-infected patients treated with first-line lopinavir/ritonavir mono-therapy in the MONARK trial. HIV Med 2010; 11 (2): 137-142
69. Cameron DW, Da Silva BA, Arribas JR, et al. A 96-week comparison of lopinavir-ritonavir combination therapy followed by lopinavir-ritonavir monotherapy versus efavi-renz combination therapy. J Infect Dis 2008; 198 (2): 234-240
70. Banhegi D, Katlama C, Da Cunha C, et al. Phase III TITAN week 96 final analysis: efficacy/safety of darunavir/r (DRV/r) vs. lopinavir/r (LPV/r) in LPV-naive treatment-experienced patients [abstract no. 22]. 9th International Congress on Drug Therapy in HIV Infection; 2008 Nov 9-13; Glasgow
71. Podzamczer D, King MS, Klein CE, et al. High-dose lopi-navir/ritonavir in highly treatment-experienced HIV-1 patients: efficacy, safety, and predictors of response. HIV Clin Trials 2007; 8 (4): 193-204
72. Pulido F, Arribas JR, Delgado R, et al. Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and two nucleo-sides for maintenance therapy of HIV. AIDS 2008 Jan 11; 22 (2): F1-9
73. Arribas J, Delgado R, Arranz A, et al. Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and 2 nucleosides for maintenance therapy of HIV: 96-Week analysis. J Ac-quir Immune Defic Syndr 2009; 51 (2): 147-152
74. Bongiovanni M, Bini T, Capetti A, et al. Long-term anti-retroviral efficacy and safety of lopinavir/ritonavir in HAART-experienced subjects: 4 year follow-up study. AIDS 2005; 19 (16): 1934-1936
75. Kosalaraksa P, Bunupuradah T, Engchanil C, et al. Double boosted protease inhibitors, saquinavir, and lopina-vir/ritonavir, in nucleoside pretreated children at 48 weeks. Pediatr Infect Dis J 2008 Jul; 27 (7): 623-628
76. Bunupuradah T, van Der Lugt J, Kosalaraksa P, et al. Safety and efficacy of a double-boosted protease inhibitor combination, saquinavir and lopinavir/ritonavir, in pretreated children at 96 weeks. Antivir Ther 2009; 14 (2): 241-248
77. Kline MW, Rugina S, Ilie M, et al. Long-term follow-up of 414 HIV-infected Romanian children and adolescents receiving lopinavir/ritonavir- containing highly active antire-troviral therapy. Pediatrics 2007 May; 119 (5): e1116-20
78. WHO. Antiretroviral therapy of HIV infection in infants and children in resource-limited settings, towards iniversal access: recommendations for a public health approach [online]. Available from URL http://www.who.int/hiv/pub/ guidelines/WHOpaediatric.pdf [Accessed 2010 Mar 23]
79. Ministry of Public Health, Thailand. National guidelines for the clinical management of HIV infection in children and adults. Bangkok: Ministry of Public Health, 2004
80. De La Fuente JS, Granja V, Escobar I, et al. Study of the gastrointestinal tolerance of a new tablet formulation of the lopinavir/ritonavir antiretroviral in HIV-infected patients. J Acquir Immune Defic Syndr 2009 Mar 1; 50 (3): 294-298
81. Simpson KN, Jones WJ, Rajagopalan R, et al. Cost effec-tiveness of lopinavir/ritonavir compared with atazanavir plus ritonavir in antiretroviral-experienced patients in the US. Clin Drug Investig 2007; 27 (7): 443-452
82. Simpson KN, Rajagopalan R, Dietz B. Cost-effectiveness analysis of lopinavir/ritonavir and atazanavir+ritonavir regimens in the CASTLE study. Adv Ther 2009 Feb; 26 (2): 185-193
83. Simpson KN, Jones WJ, Rajagopalan R, et al. Cost effec-tiveness of lopinavir/ritonavir tablets compared with ata-zanavir plus ritonavir in antiretroviral-experienced patients in the UK, France, Italy and Spain. Clin Drug Investig 2007; 27 (12): 807-817
84. Fletcher CV. Translating efficacy into effectiveness in anti-retroviral therapy: beyond the pill count. Drugs 2007; 67 (14): 1969-1979
85. WHO. Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach [online]. Available from URL http://www.who.int/hiv/pub/guidelines/artadultguidelines.pdf [Accessed 2010 Apr 30]
86. Cooper CL, van Heeswijk RP, Gallicano K, et al. A review of low-dose ritonavir in protease inhibitor combination therapy. Clin Infect Dis 2003 Jun 15; 36 (12): 1585-1592
87. Swainston Harrison T, Scott LJ. Atazanavir: a review of its use in the management of HIV infection. Drugs 2005; 65 (16): 2309-2336
88. Croom KF, Dhillon S, Keam SJ. Atazanavir: a review of its use in the management of HIV-1 infection. Drugs 2009; 69 (8): 1107-1140
89. Friis-Moller N, Weber R, Reiss P, et al. Cardiovascular disease risk factors in HIV patients-association with antiretroviral therapy. Results from the DAD study. AIDS 2003 May 23; 17 (8): 1179-1193
90. Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the use of antiretroviral agents in pediatric HIV infection [online]. Available from URL http://aidsinfo.nih.gov/con tentfiles/PediatricGuidelines.pdf [Accessed 2010 Apr 29]
91. Martinez B, Riordan F. Novel strategies in the use of lopinavir/ritonavir for the treatment of HIV infection in children. HIV/AIDS Res Pall Care 2010; 2: 59-67