NRTI backbone in HIV treatment: Will it remain relevant?

Drugs

Volumn 72, Issue 16, 2012, Pages 2051-2062

  Tressler, Randall ^a   Godfrey, Catherine ^b  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

^b NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

Author keywords

Abacavir; Antiretrovirals; Atazanavir; Didanosine; Drug resistance; Efavirenz; Emtricitabine; HIV infections; Lamivudine; Lopinavirritonavir; Nevirapine; Non nucleoside reverse transcriptase inhibitors; Nucleoside reverse transcriptase inhibitors; Stavudine; Tenofovir; Zidovudine.

Indexed keywords

ABACAVIR; BMS 986001; DIDANOSINE; EMTRICITABINE; LAMIVUDINE; OBP 601; RNA DIRECTED DNA POLYMERASE INHIBITOR; STAVUDINE; TENOFOVIR; TENOFOVIR 3 HEXADECYLOXYPROPYL ESTER; TENOFOVIR ALAFENAMIDE; TENOFOVIR DISOPROXIL; UNCLASSIFIED DRUG; ZALCITABINE; ZIDOVUDINE;

ACUTE KIDNEY FAILURE; ANTIVIRAL ACTIVITY; ANTIVIRAL RESISTANCE; ANTIVIRAL THERAPY; ASTHENIA; BONE DENSITY; BONE MARROW SUPPRESSION; COMBINATION CHEMOTHERAPY; DEPRESSION; DIARRHEA; DRUG COST; DRUG EFFICACY; DRUG ERUPTION; DRUG FEVER; DRUG HYPERSENSITIVITY; DRUG INDUCED DISEASE; DRUG INDUCED HEADACHE; DRUG SAFETY; FANCONI RENOTUBULAR SYNDROME; FATIGUE; FATTY LIVER; HEPATITIS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERTENSION; KIDNEY DYSFUNCTION; LACTIC ACIDOSIS; LIPOATROPHY; LIVER FUNCTION; MYOPATHY; NAUSEA; NEUROPATHY; PAIN; PANCREATITIS; PERIPHERAL NEUROPATHY; PORTAL HYPERTENSION; REVIEW; SIDE EFFECT; TOXIC HEPATITIS; VIRUS REPLICATION;

ADULT; ANTI-HIV AGENTS; CHILD; DRUG RESISTANCE, VIRAL; HIV; HIV INFECTIONS; HIV REVERSE TRANSCRIPTASE; HUMANS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; REVERSE TRANSCRIPTASE INHIBITORS; TREATMENT OUTCOME;

EID: 84867699403     PISSN: 00126667     EISSN: 11791950     Source Type: Journal    
DOI: 10.2165/11640830-000000000-00000     Document Type: Review

References (99)

1. Department of Health and Human Services. Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. Updated September 14, 2011 [online]. Available from URL: http://aidsinfo.nih.gov/ contentfiles/lvguidelines/perinatalgl.pdf [Accessed 2012 Sep 26]
2. British HIV Association. Guidelines for the treatment of HIV-1 positive adults with antiretroviral therapy 2012. Updated 30th April 2012 [online]. Available from URL: http://arvt.ru/sites/default/files/BHIVA-Guidelines-2012.pdf [Accessed 2012 Sep 26]
3. WHO. Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach, 2010 revision [online]. Available from URL: http://whqlibdoc.who.int/publications/2010/9789241599764-eng.pdf [Accessed 2012 Sep 26]
4. Welch S, Sharland M, Lyall EG, et al., PENTA Steering Committee. PENTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection. HIV Med 2009 Nov; 10 (10): 591-613
5. 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; 304 (3): 321-33
6. Gerschenson M, Kim C, Berzins G, et al. Mitochondrial function, morphology and metabolic parameters improve after switching from stavudine to a tenofovir-containing regimen. J Antimicrob Chemother 2009; 63 (6): 1244-50
7. Moyle GM. Clinical manifestations and management of antiretroviral nucleoside analog-related mitochondrial toxicity. Clin Ther 2000 Aug; 22 (8): 911-36
8. Koczor C, Lewis W. Nucleoside reverse transcriptase inhibitor toxicity and mitochondrial DNA. Expert Opin Drug Metab Toxicol 2010 Dec; 6 (12): 1493-504
9. Maagaard A, Kvale D. Long term adverse effects related to nucleoside reverse transcriptase inhibitors: clinical impact of mitochondrial toxicity. Scand J Infect Dis 2009; 41 (11-12): 808-17
10. Mallon PW, Unemori P, Sedwell R, et al., SAMA Investigators. In vivo, nucleoside reverse-transcriptase inhibitors alter expression of both mitochondrial and lipid metabolism genes in the absence of depletion of mitochondrial DNA. J Infect Dis 2005 May 15; 191 (10): 1686-96
11. Bolhaar MG, Karstaedt AS. A high incidence of lactic acidosis and symptomatic hyperlactatemia in women receiving highly active antiretroviral therapy in Soweto, South Africa. Clin Infect Dis 2007; 45 (2): 254-60
12. Currier JS. Sex differences in antiretroviral therapy toxicity: lactic acidosis, stavudine, and women [published erratum appears in Clin Infect Dis 2007 Dec 1; 45 (11): 1534]. Clin Infect Dis 2007 Jul 15; 45 (2): 261-2
13. Lake Bakaar G, Mazzoccoli V, Dickman K, et al. Differential effects of nucleoside analogs on oxidative phosphorylation in human pancreatic cells. Dig Dis Sci 2001; 46 (9): 1853-63
14. Dalakas MC, Illa I, Pezeshkpour GH, et al. Mitochondrial myopathy caused by long-term zidovudine therapy.NEngl J Med 1990 Apr 19; 322 (16): 1098-105
15. Frerichs FC, Dingemans KP, Brinkman K. Cardiomyopathy with mitochondrial damage associated with nucleoside reverse-transcriptase inhibitors. N Engl J Med 2002 Dec 5; 347 (23): 1895-6
16. McComsey GA, Libutti DE, O'Riordan M, et al. Mitochondrial RNA and DNA alterations in HIV lipoatrophy are linked to antiretroviral therapy and not to HIV infection. Antivir Ther 2008; 13 (5): 715-22
17. Haubrich RH, Riddler SA, Havlir DV, et al. Metabolic outcomes in a randomized trial of nucleoside, nonnucleoside and protease inhibitor-sparing regimens for initial HIV treatment. AIDS 2009 June 1; 23 (9): 1109-18
18. Curran A, Martinez E, Podzamczer D, et al. Changes in body composition and mitochondrial DNA in HIV-1-infected patients switching to fixed-dose abacavir/lamivudine or tenofovir/emtricitabine: a substudy of the BICOMBO trial. Antivir Ther 2012; 17: 711-8
19. Melikian GL, Rhee SY, Taylor J, et al. Standardized comparison of the relative impacts of HIV-1 reverse transcriptase (RT) mutations on nucleoside RT inhibitor susceptibility. Antimicrob Agents Chemother 2012 May; 56 (5): 2305-13
20. Bacheler L, Koontz D, Mellors JW. The K65R mutation in human immunodeficiency virus type 1 reverse transcriptase exhibits bidirectional phenotypic antagonism with thymidine analog mutations. J Virol 2006 May; 80 (10): 4971-7
21. Xu HT, Martinez-Cajas JL, Ntemgwa ML, et al. Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Retrovirology 2009 Feb 11; 6: 14
22. Marcelin AG, Charpentier C, Wirden M, et al. Resistance profiles of emtricitabine and lamivudine in tenofovircontaining regimens. J Antimicrob Chemother 2012 Jun; 67 (6): 1475-8
23. Coutsinos D, Invernizzi CF, Xu H, et al. Factors affecting template usage in the development of K65R resistance in subtype C variants of HIV type-1. Antivir Chem Chemother 2010 Jan 5; 20 (3): 117-31
24. Sunpath H, Wu B, Gordon M, et al. High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. AIDS 2012 Aug 24; 26 (913): 1679-84
25. Acosta-Hoyos AJ, Matsuura SE, Meyer PR, et al. A role of template cleavage in reduced excision of chain-terminating nucleotides by human immunodeficiency virus type 1 reverse transcriptase containing the M184V mutation. J Virol 2012 May; 86 (9): 5122-33
26. Gupta S, Fransen S, Paxinos EE, et al. Combinations of mutations in the connection domain of human immunodeficiency virus type 1 reverse transcriptase: assessing the impact on nucleoside and nonnucleoside reverse transcriptase inhibitor resistance. Antimicrob Agents Chemother 2010 May; 54 (5): 1973-80
27. Nikolenko GN, Palmer S, Maldarelli F, et al. Mechanism for nucleoside analog-mediated abrogation of HIV-1 replication: balance between RNase H activity and nucleotide excision. ProcNatl Acad SciUSA 2005 Feb 8; 102 (6): 2093-8
28. Feng JY, Myrick FT, Margot NA, et al. Virologic and enzymatic studies revealing the mechanism of K65R-and Q151M-associated HIV-1 drug resistance towards emtricitabine and lamivudine. Nucleosides Nucleotides Nucleic Acids 2006; 25 (1): 89-107
29. Sax PE, Islam R, Walensky RP, et al. Should resistance testing be performed for treatment-naive HIV-infected patients? A cost-effectiveness analysis. Clin Infect Dis 2005 Nov 1; 41 (9): 1316-23
30. Hosseinipour MC, van Oosterhout JJ, Weigel R, et al. The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. AIDS 2009 Jun 1; 23 (9): 1127-34
31. Hamers RL, Sigaloff KC, Wensing AM, et al. PharmAccess African Studies to Evaluate Resistance (PASER). Patterns of HIV-1 drug resistance after first-line antiretroviral therapy (ART) failure in 6 sub-Saharan African countries: implications for second-line ART strategies. Clin Infect Dis 2012 Jun; 54 (11): 1660-9
32. Vaz P, Augusto O, Bila D, et al. Surveillance of HIV drug resistance in children receiving antiretroviral therapy: a pilot study of the World Health Organization's generic protocol in Maputo, Mozambique. Clin Infect Dis 2012 May; 54 Suppl. 4: S369-74
33. Wadonda-Kabondo N, Bennett D, van Oosterhout JJ, et al. Prevalence of HIV drug resistance before and 1 year after treatment initiation in 4 sites in the Malawi antiretroviral treatment program. Clin Infect Dis 2012 May; 54 Suppl. 4: S362-8
34. Ugbena R, Aberle-Grasse J, Diallo K, et al. Yang Virological response and HIV drug resistance 12 months after antiretroviral therapy initiation at 2 clinics in Nigeria. Clin Infect Dis 2012 May; 54 Suppl. 4: S375-80
35. Wadonda-Kabondo N, Hedt BL, van Oosterhout JJ, et al. A retrospective survey of HIV drug resistance among patients 1 year after initiation of antiretroviral therapy at 4 clinics in Malawi. Clin Infect Dis 2012 May; 54 Suppl. 4: S355-61
36. Nielsen-Saines K, Watts DH, Veloso VG, et al. Three postpartum antiretroviral regimens to prevent intrapartum HIV infection. N Engl J Med 2012 Jun 21; 366 (25): 2368-79
37. Taha TE, Kumwenda NI, Gibbons A, et al. Short postexposure prophylaxis in newborn babies to reduce motherto-child transmission of HIV-1: NVAZ randomized clinical trial. Lancet 2003 Oct 11; 362 (9391): 1171-7
38. McIntyre JA, Hopley M, Moodley D, et al. Efficacy of short-course AZT plus 3TC to reduce nevirapine resistance in the prevention of mother-to-child HIV transmission: a randomized clinical trial. PLoS Med 2009 Oct; 6 (10): e1000172
39. Else LJ, Taylor S, Back DJ, et al. Pharmacokinetics of antiretroviral drugs in anatomical sanctuary sites: the fetal compartment (placenta and amniotic fluid). Antivir Ther 2011; 16 (8): 1139-47
40. Dumond JB, Reddy YS, Troiani L, et al. Differential extracellular and intracellular concentrations of zidovudine and lamivudine in semen and plasma of HIV-1-infected men. J Acquir Immune Defic Syndr 2008 Jun 1; 48 (2): 156-62
41. Hirt D, Urien S, Rey E, et al. Population pharmacokinetics of emtricitabine in human immunodeficiency virus type 1-infected pregnant women and their neonates. Antimicrob Agents Chemother 2009 Mar; 53 (3): 1067-73
42. Kwara A, Delong A, Rezk N, et al. Antiretroviral drug concentrations and HIV RNA in the genital tract of HIVinfected women receiving long-term highly active antiretroviral therapy. Clin Infect Dis 2008 Mar 1; 46 (5): 719-25
43. Cohen MS, Gay C, Kashuba AD, et al. Narrative review: antiretroviral therapy to prevent the sexual transmission of HIV-1. Ann Intern Med 2007 Apr 17; 146 (8): 591-601
44. 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): 1899-907
45. Giacomet V, Mora S, Martelli L, et al. A 12-month treatment with tenofovir does not impair bone mineral accrual in HIV-infected children. J Acquir Immune Defic Syndr 2005; 40: 448-50
46. Gallant JE, DeJesus E, Arribas JR, et al., for the Study 934 Group. Tenofovir DF, emtricitibine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. N Engl J Med 2006; 354: 251-60
47. Arribas JR, Pozniak AL, Gallant JE, et al. Tenofovir disoproxil fumarate, emtricitabine, and efavirenz compared with zidovudine/lamivudine and efavirenz in treatmentnaive patients: 144-week analysis. J Acquir Immune Defic Syndr 2008 Jan 1; 47 (1): 74-8
48. Sax PE, Tierney C, Collier AC, et al., for the AIDS Clinical Trials Group Study A5202 Team. Abacavir-lamivudine versus tenofovir-emtricitabine for initial HIV-1 therapy. N Engl J Med 2009; 361: 2230-40
49. Sax PE, Tierney C, Collier AC, et al., on behalf of the AIDS Clinical Trials Group Study A5202 Team. Abacavir/lamivudine versus tenofovir DF/emtricitabine as part of combination regimens for initial treatment of HIV: final results. J Infect Dis 2011; 204 (8): 1191-201
50. Martínez E, Arranz JA, Podzamczer D, et al., BICOMBO Study Team. A simplification trial switching from nucleoside reverse transcriptase inhibitors to once-daily fixeddose abacavir/lamivudine or tenofovir/emtricitabine in HIV-1-infected patients with virological suppression. J Acquir Immune Defic Syndr 2009; 51: 290-7
51. Hill A, Sawyer W. Effects of nucleoside reverse transcriptase inhibitor backbone on the efficacy of first-line boosted highly active antiretroviral therapy based on protease inhibitors: meta-regression analysis of 12 clinical trial in 5168 patients. HIV Med 2009; 10: 527-35
52. Kohler JJ, Hosseini H, Green E, et al. Tenofovir renal proximal tubular toxicity is regulate by OAT1 and MRP4 transporters. Lab Invest 2011; 91: 852-8
53. Cooper RD, Wiebe N, Smith N, et al. Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients.Clin InfectDis 2010; 51 (5): 496-505
54. Gallant JE, Parish MA, Keruly JC, et al. Changes in renal function associated with tenofovir disoproxil fumarate treatment, compared with nucleoside reverse transcriptase inhibitor treatment. Clin Infect Dis 2005; 40: 1194-8
55. Goicoechea M, Lui S, Best B, et al., and the California Collaborative Treatment Group 578 Team. Greater tenofovir-associated renal function decline with protease inhibitor-based versus nonnucleoside reverse-transcriptase inhibitor-based therapy. J Infect Dis 2008; 197 (1): 102-8
56. Gallant JE, Moore RD. Renal function with the use of tenofovir containing initial antiretroviral regimen. AIDS 2009; 23: 1971-5
57. Bierman WFW, Scheffer GL, Schoonderwoerd A, et al. Protease inhibitors atazanavir, lopinavir and ritonavir are potent blockers, but poor substrates, of ABC transporters in a broad panel of ABC transporter-overexpressing cell lines. J Antimivrob Chemother 2010; 65: 1672-80
58. Wever K, van Agtmael MA, Carr A. Incomplete reversibility of tenofovir-related renal toxicity in HIV-infected men. JAIDS 2010; 55: 78-81
59. Brown TT, McComsey GA, King MS, et al. Loss of bone mineral density after antiretroviral therapy initiation, independent of antiretroviral regimen. J Acquir Immune Defic Syndr 2009; 51 (5): 554-61
60. Gallant JE, Staszewski S, Pozniak AL, et al. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral naive patients: a 3-year randomized trial. JAMA 2004; 292: 191-201
61. McComsey GA, Kitch D, Daar ES, et al. Bone mineral density and fractures in antiretroviral-na?̈ve persons randomized to receive abacavir-lamivudine or tenofovir disoproxil fumarate-emtricitabine along with efavirenz or atazanavir-ritonavir: AIDS Clnical Trial Group A5224s, a substudy of A5202. J Infect Dis 2011; 203: 1791-801
62. Stellbrink HJ, Orkin C, Arribas JR, et al. Comparison of changes in bone density and turnover with abacavirlamivudine versus tenofovir-emtricitabine in HIV-infected adults: 48-week results from the ASSERT study. Clin Infect Dis 2010; 963-72
63. Gafni RI, Hazra R, Reynolds JC, et al. Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy: impact on bone mineral density in HIV-infected children. Pediatrics 2006; 118: e711-8
64. Viganò A, Zuccotti GV, Puzzovio M, et al. Tenofovir disoproxil fumarate and bone mineral density: a 60-month longitudinal study in a cohort of HIV-infected youths. Antivir Ther 2010; 15: 1053-8
65. Best BM, Letendre SL, Koopmans P, et al., CHARTER Study Group. Low cerebrospinal fluid concentrations of the nucleotide HIV reverse transcriptase inhibitor, tenofovir. J Acquir Immune Defic Syndr 2012; 59: 376-81
66. Smurzynski M, Wu K, Letendre S, et al. Effects of central nervous system antiretroviral penetration on cognitive functioning in the ALLRT cohort. AIDS 2011; 25: 357-65
67. Hirt D, Urien S, Ekouevi DK, et al. Population pharmacokinetics of tenofovir in HIV-1 infected pregnant women and their neonates (ANRS 12109). Clin Pharmacol Ther 2009; 85 (2): 182-9
68. US Department of Health and Human Services. US Food and Drug Administration. FDA approves first drug for reducing the risk of sexually acquired HIV infection: evidence-based approach enhances existing prevention strategies [media release]. 2012 Jul 16 [online]. Available from URL: http://www.fda.gov/NewsEvents/Newsroom/Press Announcements/ucm312210.htm
69. Grant RM, Lama JR, Anderson PL, et al., iPrEx Study Team. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010; 363 (27): 2587-99
70. Baeten JM, Donnell D, Ndase P, et al.; the Partners PrEP Study Team. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. Epub 2012 Jul 11
71. Centers for Disease Control and Prevention. Results of REM-PrEP clinical trial examining pre-exposure prophylaxis (PrEP) for HIV prevention among heterosexual women [media release]. 2011 Apr 18 [online]. Available from URL: http://www.cdc.gov/hiv/prep/femprep.htm [Accessed 2012 May 1]
72. Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med 2012 Jul 11
73. US Department of Health and Human Services. US Food and Drug Administration. Slides for the May 11, 2012 Antiviral Drugs Advisory Committee (AVDAC) meeting [online]. Available from URL: http://www.fda.gov/Advisory Committees/CommitteesMeetingMaterials/Drugs/Antiviral DrugsAdvisoryCommittee/ ucm305850.htm [Accessed 2012 May 20]
74. Sax PE, Tierney C, Collier AC, et al., AIDS Clinical Trials Group Study A5202 Team. Abacavir-lamivudine versus tenofovir-emtricitabine for initial HIV-1 therapy. N Engl J Med 2009 Dec 3; 361 (23): 2230-40
75. Mallal S, Phillips E, Carosi G, et al., PREDICT-1 Study Team. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med 2008 Feb 7; 358 (6): 568-79
76. Ostrov DA, Grant BJ, Pompeu YA, et al. Drug hypersensitivity caused by alteration of the MHC-presented selfpeptide repertoire. Proc Natl Acad Sci USA 2012 Jun 19; 109 (25): 9959-64
77. Strategies for Management of Anti-Retroviral Therapy/INSIGHT; DAD Study Groups. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients. AIDS 2008 Sep 12; 22 (14): F17-24
78. McComsey GA, Kitch D, Daar ES, et al. Inflammation markers after randomization to abacavir/lamivudine or tenofovir/emtricitabine with efavirenz or atazanavir/ritonavir. AIDS 2012 Jul 17; 26 (11): 1371-85
79. Ding X, Andraca-Carrera E, Cooper C, et al. No association of myocardial infarction with ABC use: an FDA metaanalysis [abstract no. 808 plus poster]. 18th Conference on Retroviruses and Opportunistic Infections; 2011 Feb 27-Mar 2; Boston (MA)
80. US Department of Health and Human Services. US Food and Drug Administration. Abacavir: ongoing safety review. Possible increased risk of heart attack including ziagen, trizivir, and epzicom [media release]. 2011 Mar 1 [online]. Available from URL: http://www.fda.gov/Safety/MedWatch/SafetyInforma tion/SafetyAlertsforHumanMedicalProducts/ucm245190.htm [Accessed 2012 Jun 25]
81. McColl DJ, Margot N, Chen SS, et al. Reduced emergence of the M184V/I resistance mutation when antiretroviralna? ̈ve subjects use emtricitabine versus lamivudine in regimens composed of two NRTIs plus the NNRTI efavirenz. HIV Clin Trials 2011 Mar-April; 12 (2): 61-70
82. WHO. Technical Update on Treatment Optimization. Pharmacological equivalence and clinical interchangeability of lamivudine and emtricitabine: a review of current literature. Geneva: WHO, 2012 Jun [online]. Available from URL: http://whqlibdoc.who.int/publications/2010/9789241599764-eng.pdf [Accessed 2012 Sep 26]
83. Sax PE, Tierney C, Collier AC, et al., AIDS Clinical Trials Group Study A5202 Team. Abacavir/lamivudine versus tenofovir DF/emtricitabine as part of combination regimens for initial treatment of HIV: final results. J Infect Dis 2011 Oct 15; 204 (8): 1191-2011
84. Marcelin AG, Charpentier C, Wirden M, et al. Resistance profile of emtricitabine and lamivudine in tenofovircontaining regimens. J Antimicrob Chemotherapy 2012; 67: 1475-8
85. Campbell TB, Smeaton LM, Kumarasamy N, et al., for the PEARLS study team of the ACTG. Efficacy and safety of three antiretroviral regimens for initial treatment of HIV-1: a randomized clinical trial in diverse multinational settings. PLoS Med 2012; 9 (8): e1001290
86. Wang F, Flint O. The HIV NRTI BMS-986001 does not degrade mitochondrial DNA in long term primary cultures of cells isolated from human kidney, muscle and subcutaneous fat [poster abstract no. TUPE042]. 19th International AIDS Conference; 2012 Jul 22-27; Washington
87. Guha M, Pilcher G, Moehlencamp J, et al. Absence of renal and bone toxicity in non-clinical studies of BMS-986001, a nucleoside transcriptase inhibitor (NRTI) of human immunodeficiency virus (HIV) [poster abstract no. TUPE041]. 19th International AIDS Conference; 2012 Jul 22-27; Washington
88. Hwang C, Zhu L, Chan H, et al. Antiviral activity, exposureresponse, and resistance analyses of monotherapy with the novel HIV NRTI BMS-986001 in ART-experienced subjects [abstract no. O06]. 13th International Workshop on Clinical Pharmacology of HIV Therapy; 2012 Apr 16-18; Barcelona
89. Li P, et al. The in vitro cross-resistance profile of the NRTI BMS-986001 against known NRTI resistance mutations [abstract no. 2]. 20th International Drug Resistance Workshop; 2012 Jun 5-9; Sitges. Antiviral Ther 2012: 17 Suppl. 1: A10
90. Eisenberg EJ, He GX, Lee WA. Metabolism of GS-7340, a novel phenyl monophosphoramidate intracellular prodrug of PMPA, in blood. Nucleosides Nucleotides Nucleic Acids 2001 Apr-Jul; 20 (4-7): 1091-8
91. Markowitz M, Zolopa A, Ruane P, et al. GS-7340 demonstrates greater declines in HIV-1 RNA than TDF during 14 days of monotherapy in HIV-1-infected subjects [abstract no. 152LB]. 18th Conference on Retroviruses and Opportunistic Infections; 2011 Feb 27-Mar 2; Boston (MA)
92. Chimerix, Inc. Chimerix signs worldwide license agreement with Merck for CMX157, a novel candidate for the treatment of HIV [media release]. 2012 Jul 24 [online]. Available from URL: http://www.prnewswire.com/news-releases/ chimerixsigns-worldwide-license-agreement-with-merck-for-cmx157-anovel- candidate-for-the-treatment-of-hiv-163523946.html
93. Long L, Fox M, Sanne I. Cost and cost-effectiveness of switching from stavudine to tenofovir in first-line antiretroviral regimens in South Africa. J Acquir Immune Defic Syndr 2008; 48: 334-44
94. Prabhu V, Broyles L, Raizes E, et al. Is substituting 3TC for FTC in combination with tenofovir and nevirapine really cost-effective in resource-limited settings? A simulated cost-efficacy analysis of 3TC vs. FTC in first-line regimens [abstract no. 666]. 19th Conference on Retroviruses and Opportunistic Infections; 2012 Mar 5-8; Seattle (WA)
95. Reynes J, Lawal A, Pulido F, et al. Examination of noninferiority, safety, and tolerability of lopinavir/ritonavir and raltegravir compared with lopinavir/ritonavir and tenofovir/emtricitabine in antiretroviral-näve subjects: the progress study, 48-week results. HIV Clin Trials 2011 Sep-Oct; 12 (5): 255-67
96. Duvivier C, Ghosn J, Assoumou L, et al., ANRS 121 study group. Initial therapy with nucleoside reverse transcriptase inhibitor-containing regimens is more effective than with regimens that spare them with no difference in short-term fat distribution: Hippocampe-ANRS 121 Trial. J Antimicrob Chemother 2008 Oct; 62 (4): 797-808
97. Patricia E, Domingo P, Gutierrez M, et al. Saquinavir/ritonavir monotherapy as a new nucleoside-sparing maintenance strategy in long-term virologically suppressed HIV-infected patients. Curr HIV Res 2010 Sep; 8 (6): 467-70
98. Mathis S, Khanlari B, Pulido F, et al. Effectiveness of protease inhibitor monotherapy versus combination antiretroviral maintenance therapy: a meta-analysis. PLoS One 2011; 6 (7): e22003
99. Kozal MJ, Lupo S, Dejesus E, et al., The Spartan Study Team. A nucleoside-and ritonavir-sparing regimen containing atazanavir plus raltegravir in antiretroviral treatment-naive HIV-infected patients: SPARTAN study results. HIV Clin Trials 2012 May-Jun; 13 (3): 119-30