PROGRESS AND PROSPECTS IN THERAPEUTICS AGAINST HIV INFECTION
Abstract
Tremendous advances have occurred in recent decades in the development of safe and effective medications for the treatment of viral diseases. Currently there are more than 20 HIV drugs approved for use in humans. Combined chemotherapy has been found useful for a number of viral infections comprising drugs with different mechanism of action. HIV treatment guidelines recommend the use of two nucleoside reverse transcriptase inhibitors (NsRTIs) plus a third antiretroviral drug for treatment-naive patients with AIDS that include non-nucleoside reverse transcriptase inhibitors (NNRTIs; eg, efavirenz), ritonavir-boosted protease inhibitors (eg, darunavir, atazanavir), and integrase inhibitors (eg, raltegravir, dolutegravir). However emergence of drug resistant HIV variants and their dissemination impede proper treatment of AIDS. Preferred regimens as first-line treatment in patients with suboptimum adherence comprise drugs with improved potency, safety and infrequent selection for resistance-associated mutations. The present review stands for an update on facts and phenomena of present, past, and future use of antiretrovirals based upon the available documents in SCI and non-SCI journals.
Keywords:
Antiretrovirals, reverse transcriptase inhibitors, viral protease inhibitors, viral coreceptor antagonist, fusion inhibitor, integrase inhibitorsDOI
https://doi.org/10.25004/IJPSDR.2015.076501References
1. UNAIDS. UNAIDS report on the global AIDS epidemic 2012. UNAIDS, Geneva, Switzerland. 2012.
2. Jaykare SC, Motghare VM, Padwal SL, Pise HN, Deshpande RP. Antiretroviral therapy- newer drugs on the anvil. Indian J Med Specialities 2013; 4:47-54.
3. Nabel GJ. Mapping the future of HIV vaccines. Nature Rev Microbiol 2007; 5: 482-84.
4. Menendez-Arias L. Molecular basis of human immunodeficiency virus type 1 drug resistance: Overview and recent developments. Antiviral Res 2013; 98:93-120.
5. Tremblay CL, Baril J, Fletcher D, Kilby D, MacPherson P, Shafran SD, et al. Challenges in initiating antiretroviral therapy in 2010 Can J Infect Dis Med Microbiol 2010; 21:1-15.
6. Cooper CL, Breau C, Laroche A, Lee C, Garber G. Clinical outcomes of first antiretroviral regimen in HIV/hepatitis C virus co-infection. HIV Med 2006; 7:32-37.
7. Mitsuya H, Weinhold K, Furman P, St Clair M, Li L, Lehrman S, et al. 3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc Natl Acad Sci USA 1985; 82:7096-100.
8. Sun R, Eriksson S, Wang L. Identification and characterization of mitochondrial factors modulating thymidine kinase 2 activity. Nucleosides, Nucleotides and Nucleic Acids. 2010; 29:382-5.
9. Scruggs ER, Dirks Naylor AJ. Mechanisms of zidovudine-induced mitochondrial toxicity and myopathy. Pharmacol 2008; 82:83-8.
10. Hivid (zalcitabine) tablets. Product information. (September 2002). Available from http://www.rocheusa.com/products/hivid/pi.pdf
11. Horwitz JP, Chua J, DaRooge MA, Noel M, Klundt IL. Nucleosides. IX. The formation of 2', 2'-unsaturated pyrimidine nucleosides via a novel beta-elimination reaction. J Org Chem1966; 31:205-11.
12. Wangsomboonsiri W, Mahasirimongkol S, Chantarangsu S, Kiertiburanakul S, Charoenyingwattana A, Komindr S, et al. Association between HLA-B*4001 and lipodystrophy among HIV-infected patients from Thailand who received a stavudine-containing antiretroviral regimen. Clin Infect Dis 2010; 50:597-604.
13. Hetherington S, Hughes AR, Mosteller M, Shortino D, Baker KL, Spreen W, et al. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet 2002; 359:1121-2.
14. Rauch A, Nolan D, Martin A, McKinnon E, Almeida C, Mallal S. Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV cohort study. Clin Infect Dis 2006; 43:99-102.
15. Fox Z, Dragsted UB, Gerstoft J, Phillips AN, Kjaer J, Mathiesen L, et al. A randomized trial to evaluate continuation versus discontinuation of lamivudine in individuals failing a lamivudine-containing regimen: The COLATE trial. Antivir Ther 2006; 11:761-70.
16. VIDEX (didanosine): chewable/dispersible buffered tablets; buffered powder for oral solution; pediatric powder for oral solution. Product information (July 2000). Available from http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm
17. Kimberlin DW. Antiviral therapies in children: Has their time arrived? Pediatr Clin N Am 2005; 52:837-67.
18. Oxenius A, Price DA, Günthard HF, Dawson SJ, Fagard C, Perrin L, et al. Stimulation of HIV-specific cellular immunity by structured treatment interruption fails to enhance viral control in chronic HIV infection. Proc Natl Acad Sci USA 2002; 99:13747-52.
19. Cahn P, Wainberg MA. Resistance profile of the new nucleoside reverse transcriptase inhibitor apricitabine. J Antimicrob Chemother 2010; 65:213-7.
20. Cahn P, Cassetti I, Wood R, Phanuphak P, Shiveley L, Bethel RC, et al. Efficacy and tolerability of 10-day monotherapy with apricitabine in antiretroviral-naive, HIV-infected patients. AIDS 2006; 20:1261-8.
21. Wainberg MA, Cahn P, Bethell RC, Sawyer J, Cox S. Apricitabine: a novel deoxycytidine analogue nucleoside reverse transcriptase inhibitor for the treatment of nucleoside-resistant HIV infection. Antivir Chem Chemother 2007; 18:61-70.
22. Ravichandran S, Veerasamy R, Raman S, Krishnan N, Agrawal RK. An overview on HIV-1 reverse transcriptase inhibitors. Digest J Nanomaterials Biostructures 2008; 3:171-87.
23. Albrecht MA, Wilkin TJ, Coakley EP, Hammer SM. Advances in antiretroviral therapy. Top HIV Med 2003; 11:97-127.
24. Herzmann C, Arasteh K, Murphy RL, Schulbin H, Kreckel P, Drauz D, et al. Safety, pharmacokinetics, and efficacy of (+/-)-β-2’,3’- dideoxy-5-fluoro-3’-thiacytidine with efavirenzand stavudine in antiretroviral-naive human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 2005; 49:2828-33.
25. Mehellou Y, de Clercq E. Twenty-six years of anti-HIV drug discovery: where do we stand and where do we go? J Med Chem 2010; 53:521-38.
26. Cihlar T, Ray AS. Nucleoside and nucleotide HIV reverse-transcriptase inhibitors: 25 years after zidovudine. Antiviral Res 2010; 85:39-58.
27. Barnhart M, Shelton J. A better state of ART improving anti-retroviral regimens to increase global access to HIV treatment. J AIDS HIV Res 2011; 3:71-8.
28. Otto MJ. New nucleoside reverse transcriptase inhibitors for the treatment of HIV infections. Curr Opin Pharmacol 2004; 4:431-6.
29. De Clercq E. Antiviral drugs in current clinical use. J Clin Virol 2004; 30:115-33.
30. Hodge RAV. Meeting report: 26th International conference on antiviral research. Antiviral Res 2013; 100:276-85.
31. Margot N, Isaacson E, McGowan I, Cheng AK, Schooley RT, Miller MD. Genotypic and phenotypic analyses of HIV-1 in antiretroviral experienced patients treated with tenofovir DF. AIDS 2002; 16:1227-35.
32. Huang H, Chopra R, Verdine GL, Harrison SC. Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance. Science 1998; 282:1669-75.
33. Das K, Bandwar RP, White KL, Feng JY, Sarafianos SG, Tuske S, et al. Structural basis for the role of the K65R mutation in HIV-1reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. J Biol Chem 2009; 284:35092-100.
34. Barrioluengo V, Álvarez M, Barbieri D, Menéndez-Arias L. Thermostable HIV-1 group O reverse transcriptase variants with the same fidelity as murine leukaemia virus reverse transcriptase. Biochem J 2011; 436:599-607.
35. Gao HQ, Boyer PL, Sarafianos SG, Arnold E, Hughes SH. The role of steric hindrance in 3TC resistance of human immunodeficiency virus type-1 reverse transcriptase. J Mol Biol 2000; 300:403-18.
36. Deval J, Selmi B, Boretto J, Egloff MP, Guerreiro C, Sarfati S, et al. The molecular mechanism of multidrug resistance by the Q151M human immunodeficiency virus type 1 reverse transcriptase and its suppression using boranophosphate nucleotide analogues. J Biol Chem 2002; 277:42097-104.
37. Frangeul A, Busetta C, Deval J, Barral K, Alvarez K, Canard B. Gln151 of HIV-1 reverse transcriptase acts as a steric gate towards clinically relevant acyclic phosphonate nucleotide analogues. Antivir Ther.2008; 13:115-24.
38. Gu Z, Allard B, de Muys JM, Lippens J, Rando RF, Nguyen-Ba N, et al. In vitro antiretroviral activity and in vitro toxicity profile of SPD754, a new deoxycytidine nucleoside reverse transcriptase inhibitor for treatment of human immunodeficiency virus infection. Antimicrob Agents Chemother 2006; 50:625-31.
39. Cahn P, Wainberg MA. Resistance profile of the new nucleoside reverse transcriptase inhibitor apricitabine. J Antimicrob Chemother 2010; 65:213-17.
40. Schinazi RF, Massud I, Rapp KL, Cristiano M, Detorio MA, Stanton RA, et al. Selection and characterization of HIV-1 with a novel S68 deletion in reverse transcriptase. Antimicrob Agents Chemother 2011; 55:2054-60.
41. Michailidis E, Marchand B, Kodama EN, Singh K, Matsuoka M, Kirby KA, et al. Mechanism of inhibition of HIV-1 reverse transcriptase by 40-ethynyl-2-fluoro-20-deoxyadenosine triphosphate, a translocation defective reverse transcriptase inhibitor. J Biol Chem 2009; 284:35681-91.
42. Kawamoto A, Kodama E, Sarafianos SG, Sakagami Y, Kohgo S, Kitano K, et al. 20-deoxy-40-C-ethynyl-2-halo-adenosines active against drug resistant human immunodeficiency virus type 1 variants. Int J Biochem Cell Biol 2008; 40:2410-20.
43. Yang G, Paintsil E, Dutschman GE, Grill SP, Wang CJ, Wang J, et al. Impact of novel human immunodeficiency virus type 1 reverse transcriptase mutations P119S andT165A on 40-ethynylthymidine analog resistance profile. Antimicrob Agents Chemother 2009; 53:4640-46.
44. Cihlar T, Ray AS, Boojamra CG, Zhang L, Hui H, Laflamme G, et al. Design and profiling of GS-9148, a novel nucleotide analog active against nucleoside-resistant variants of human immunodeficiency virus type 1, and its orally bioavailable phosphonoamidate prodrug, GS-9131. Antimicrob Agents Chemother 2008; 52:655-65.
45. Kohlstaedt LA, Wang J, Friedman JM, Rice PA, Steitz TA. Crystal structure at 3.5 Å resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 1992; 256:1783-90.
46. Sustiva (efavirenz) capsules and tablets. Product information (April 2005). Available from http://www.bms.com/cgi-bin/anybin.pl
47. Lowenhaupt EA, Matson K, Qureishi B, Saitoh A, Pugatch D. Psychosis in a 12-year-old HIV-positive girl with an increased serum concentration of efavirenz. Clin Infectious Dis 2007; 45:e128-30.
48. Ford N, Mofenson L, Kranzer K, Medu L, Frigati L, Mills EJ, Calmy A. Safety of efavirenz in first-trimester of pregnancy: A systematic review and meta-analysis of outcomes from observational cohorts. AIDS 2010; 24:1461-70.
49. Montaner JS, Reiss P, Cooper D. A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. Italy, The Netherlands, Canada and Australia Study. JAMA 1998; 279:930-7.
50. Podzamczer D, Ferrer E, Consiglio E, Gatell JM, Perez P, Perez JL, et al. A randomized clinical trial comparing nelfinavir or nevirapine associated to zidovudine/lamivudine in HIV-infected naive patients (the Combine Study). Antiviral Ther 2002; 7:81-90.
51. Wit FW, Kesselring AM, Gras L. Discontinuation of nevirapine because of hypersensitivity reactions in patients with prior treatment experience, compared with treatment-naive patients: the ATHENA cohort study. Clin Infect Dis 2008; 46: 933-40.
52. DHHS panel. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (May 4, 2006). (Available for download from AIDS Info).
53. Rescriptor brand of delavirdine mesylate tablets. Product information. Available from http://www.pfizer.com/pfizer/download/uspi_rescriptor.pdf
54. de Bethune MP. Non-nucleoside reverse transcriptase inhibitors (NNRTIs), their discovery development, and use in the treatment of HIV-1 infection: a review of the last 20 years (1989-2009). Antiviral Res 2010; 85:75-90.
55. Rathbun RC, Liedtke MD. The next generation: Etravirine in the treatment of HIV-1 infection in adults refractory to other antiretrovirals. Virus Adaptation and Treatment. 2010; 2:91-102.
56. Ford N, Lee J, Andrieux-Meyer I, Calmy A. Safety, efficacy, and pharmacokinetics of rilpivirine: systemic review with an emphasis on resource limited settings. HIV/AIDS 2011; 3:35-44.
57. James C, Preininger L, Sweet M. Rilpivirine: a second generation non-nucleoside reverse transcriptase inhibitor. Am J Health Syst Pharm 2012; 69:857-61.
58. De Clercq E. Where rilpivirine meets with tenofovir, the start of a new anti-HIV drug combination era. Biochem Pharmacol 2012; 84:241-8.
59. Panel on antiretroviral guidelines for adults and adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. December, 2009:1-161.
60. Paris KA, Haq O, Felts AK, Das K, Arnold E, Levy RM. Conformational landscape of the human immunodeficiency virus type 1 reverse transcriptase non-nucleoside inhibitor binding pocket: lessons for inhibitor design from a cluster analysis of many crystal structures. J Med Chem 2009; 52:6413-20.
61. Das K, Clark Jr AD, Lewi PJ, Heeres J, De Jonge MR, Koymans LM, et al. Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants. J Med Chem 2004; 47:2550-60.
62. Lansdon EB, Brendza KM, Hung M, Wang R, Mukund S, Jin D, et al. Crystal structures of HIV-1 reverse transcriptase with etravirine (TMC125) and rilpivirine (TMC278): implications for drug design. J Med Chem 2010; 53:4295-9.
63. Tambuyzer L, Azijn H, Rimsky LT, Vingerhoets J, Lecocq P, Kraus G. Compilation and prevalence of mutations associated with resistance to non-nucleoside reverse transcriptase inhibitors. Antivir Ther 2009; 14:103-9.
64. Javanbakht H, Ptak RG, Chow E, Yan JM, Russell JD, Mankowski MK, et al.In vitro resistance development for RO-0335, a novel diphenyl ether nonnucleoside reverse transcriptase inhibitor. Antiviral Res 2010; 86:212-9.
65. Cohen CJ, Andrade-Villanueva J, Clotet B, Fourie J, Johnson MA, RuxrungthamK, et al. On behalf of the THRIVE Study Group, Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial. Lancet 2011; 378:229-37.
66. Azijn H, Tirry I, Vingerhoets J, de Béthune MP, Kraus G, Boven K, et al. TMC278, a next generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1. Antimicrob Agents Chemother 2010; 54:718-27.
67. Asahchop EL, Wainberg MA, Oliveira M, Xu H, Brenner BG, Moisi D, et al. Distinct resistance patterns to etravirine and rilpivirine in viruses containing NNRTI mutations at baseline. AIDS 2012; http://dx.doi.org/10.1097/QAD.0b013e32835d9f6d.
68. Corbau R, Mori J, Phillips C, Fishburn L, Martin A, Mowbray C, et al. Lersivirine, a nonnucleoside reverse transcriptase inhibitor with activity against drug-resistant human immunodeficiency virus type 1. Antimicrob Agents Chemother 2010; 54:4451-63.
69. Vernazza P, Wang C, Pozniak A, Weil E, Pulik P, Cooper DA, et al. Efficacy and safety of lersivirine (UK-453,061) versus efavirenz in antiretroviral treatment-naïve HIV-1-infected patients: week 48 primary analysis results from an ongoing, multicenter, randomized, double-blind, phase IIb trial. J Acquir Immune Defic Syndr 2013; 62:171-9.
70. Boyer J, Arnoult E, Médebielle M, Guillemont J, Unge J, Jochmans D. Difluoromethylbenzoxazole pyrimidine thioether derivatives: a novel class of potent non-nucleoside HIV-1 reverse transcriptase inhibitors. J Med Chem 2011; 54:7974-85.
71. Pohlmann S, Reeves JD. Cellular entry of HIV: Evaluation of therapeutic targets. Curr Pharm Des 2006; 12:1963-73.
72. Greenberg ML, Cammack N. Resistance to enfuvirtide, the first HIV fusion inhibitor. J Antimicrob Chemother 2004; 54:333-40.
73. Greenberg ML, Sista P, Miralles G. Melby T, Davison D, Jin L, et al. Enfuvirtide (T-20) and T-1249 resistance: observations from Phase II clinical trials of enfuvirtide in combination with oral antiretrovirals (ARVs) and a Phase I/II dose-ranging monotherapy trial of T-1249. Antivir Ther 2002; 7:S106.
74. Mink M, Greenberg ML, Mosier S, Janumpalli S. Impact of HIV-1 gp41 amino acid substitutions (positions 36-45) on susceptibility to T-20 (enfuvirtide) in vitro: Analysis of primary virus isolates recovered from patients during chronic enfuvirtide treatment and site directed mutants in NL4-3. Antivir Ther 2002; 7:S24.
75. Lederman MM, Penn-Nicholson A, Cho M, Mosier D. Biology of CCR5 and its role in HIV infection and treatment. JAMA 2006; 296:815-26.
76. Kwong P. Human immunodeficiency virus: refolding the envelope. Nature 2005; 433:815-6.
77. Wood A, Armour D. The discovery of the CCR5 receptor antagonist, UK-427, 857, a new agent for the treatment of HIV infection and AIDS. Prog Med Chem 2005; 43:239-71.
78. Gorry PR, Ellett A, Lewin SR. Maraviroc. In Kucers’ The Use of Antibiotics. In: Grayson L, Crowe S, McCarthy J, Mills J, Mouton J, Norrby SR, Paterson D, Pfaller M, editors. 6th Ed. London: Hodder & Stoughton Ltd. 2010, pp. 2869-76.
79. Roche M, Salimi H, Duncan R, Wilkinson BL, Chikere K, Moore MS, et al. A common mechanism of clinical HIV-1 resistance to the CCR5 antagonist maraviroc despite divergent resistance levels and lack of common gp120 resistance mutations. Retrovirol 2013; 10:43-62.
80. Hazuda DJ, Felock P, Witmer M, Wolfe A, Stillmock K, Grobler JA, et al. Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. Science 2000; 287:646-50.
81. Eron JJ, Cooper DA, Steigbigel RT, Clotet B, Gatell JM, Kumar PN, et al. Efficacy and safety of raltegravir for treatment of HIV for 5 years in the BENCHMRK studies: final results of two randomised, placebo-controlled trials. Lancet Infect Dis 2013; 13:587-96.
82. Delelis O, Thierry S, Subra F, Simon F, Malet I, Alloui C, et al. Impact of Y143 HIV-1 integrase mutations on resistance to raltegravir in vitro and in vivo. Antimicrob Agents Chemother 2010; 54:491-501.
83. Dunn BM. Structure and mechanism of the pepsin-like family of aspartic peptidases. Chem Rev 2002; 102:4431-58.
84. De Clercq E. Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. Int J Antimicrob Agents 2009; 33:307-20.
85. Alfonso Y, Monzote L. HIV Protease Inhibitors: Effect on the opportunistic protozoan parasites. Open Med Chem J 2011; 5:40-50.
86. Vella S, Floridia M. Saquinavir. Clinical pharmacology and efficacy. Clin Pharmacokinet 1998; 34:189-201.
87. Hsu A, Granneman GR, Bertz RJ. Ritonavir. Clinical pharmacokinetics and interactions with other anti-HIV agents. Clin Pharmacokinet 1998; 35:275-91.
88. Dieleman JP, Salahuddin S, Hsu YS, Burger DM, Gyssens IC, Sturkenboom MC, et al. Indinavir crystallization around the loop of henle: Experimental evidence. J Acquir Immune Defic Syndr 2001; 28:9-13.
89. Wensing AM, van Maarseveen NM, Nijhuis M. Fifteen years of HIV protease inhibitors: Raising the barrier to resistance. Antiviral Res 2010; 85:59-74.
90. Fernández Montero JV, Barreiro P, Soriano V. HIV protease inhibitors: recent clinical trials and recommendations on use. Expert Opin Pharmacother 2009; 10:1615-29.
91. Eron JJ, Haubrich R, Lang W, Pagano G, Millard J, Wolfram J, et al. A phase II trial of dual protease inhibitor therapy: Amprenavir in combination with indinavir, nelfinavir, or saquinavir. J Acquir Immune Defic Syndr 2001; 26:458-61.
92. Rivas P, Morello J, Garrido C, Rodríguez-Nóvoa S, Soriano V. Role of atazanavir in the treatment of HIV infection. Ther Clin Risk Manag 2009; 5:1-18.
93. Möbius U, Lubach-Ruitman M, Castro-Frenzel B, Stoll M, Esser S, Voigt E, et al.Switching to atazanavir improves metabolic disorders in antiretroviral-experienced patients with severe hyperlipidemia. J Acquir Immune Defic Syndr 2005; 39:174-80.
94. Piacenti FJ. An update and review of antiretroviral therapy. Pharmacother 2006; 26:1111-33.
95. Shen CH, Wang YF, Kovalevsky AY, Harrison RW, Weber IT. Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. FEBS J 2010; 277:3699-714.
96. McKeage K, Perry CM, Keam SJ. Darunavir: A review of its use in the management of HIV infection in adults. Drugs 2009; 69:477-503.
97. Johnson VA, Calvez V, Günthard HF, Paredes R, Pillay D, Shafer R, et al. 2011 update of the drug resistance mutations in HIV-1. Top Antivir Med. 2011; 19:156–164.
98. Sugiura W, Matsuda Z, Yokomaku Y, Hertogs K, Larder B, Oishi T, et al. Interference between D30N and L90M in selection and development of protease inhibitor-resistant human immunodeficiency virus type 1. Antimicrob Agents Chemother 2002; 46:708-15.
99. Fun A, Wensing AMJ, Verheyen J, Nijhuis M. Human immunodeficiency virus gag and protease: partners in resistance. Retrovirol 2012; 9:63.
100. Rhee SY, Taylor J, Fessle WJ, Kaufman D, Towner W, Troia P, et al. HIV-1 protease mutations and protease inhibitor cross-resistance. Antimicrob Agents Chemother 2010; 54:4253-61.
101. Ide K, Aoki M, Amano M, Koh Y, Yedidi RS, Das D, et al. Novel HIV-1 protease inhibitors (PIs) containing a bicyclic P2 functional moiety, tetrahydropyrano-tetrahydrofuran, that are potent against multi-PI-resistant HIV-1 variants. Antimicrob Agents Chemother 2011; 55:1717-27.
102. Dierynck I, van Marck H, van Ginderen M, Jonckers THM, Nalam MNL, Schiffer CA, et al. TMC310911, a novel human immunodeficiency virus type 1 protease inhibitor, shows in vitro an improved resistance profile and higher genetic barrier to resistance compared with current protease inhibitors. Antimicrob Agents Chemother 2011; 55:5723-31.
103. Vidal JE, Wan Songa AT, Matosa ML, Bartmanna D, dos Anjosa G, de Mirandaa EJP, et al. High rate of virologic suppression with darunavir/ritonavir plus optimized background therapy among highly antiretroviral-experienced HIV-infected patients: results of a prospective cohort study in São Paulo, Brazil. Braz J Infect Dis 2013; 17:41-7.
104. Feng JY, Ly JK, Myrick F, Goodman D, White KL, Svarovskaia ES, et al. The triple combination of tenofovir, emtricitabine and efavirenz shows synergistic anti-HIV-1 activity in vitro: a mechanism of action study. Retrovirol 2009; 6:44.
105. Schader SM, Colby-Germinario SP, Schachter JR, Xu H, Wainberg MA. Synergy against drug-resistant HIV-1 with the microbicide antiretrovirals, dapivirine and tenofovir, in combination. AIDS 2011; 25:1585-94.
106. Kulkarni R, Feng JY, Miller MD, White KL. Dead-end complexes contribute to the synergistic inhibition of HIV-1 RT by the combination of rilpivirine, emtricitabine, and tenofovir. Antiviral Res 2014; 101:131-5.
107. Llibre JM, Clotet B. Once-daily single-tablet regimens: a long and winding road to excellence in antiretroviral treatment. AIDS Rev 2012; 14:168-78.
108. Thompson MA, Aberg JA, Hoy JF, Telenti A, Benson C, Cahn P, et al. Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA Panel. JAMA 2012; 308:387-402.
109. A Phase I, open label dose escalation study to evaluate safety of iHIVARNA-01 in chronically HIV-infected patients under stable combined antiretroviral therapy. Available from https://clinicaltrials.gov/ct2/show/NCT02413645.
110. Immunotherapy of HIV-infected patients an open, dose-escalating assessment of Vacc-C5 with either GM-CSF or Alhydrogel as adjuvant in HIV-1-infected subjects on antiretroviral therapy (ART). Available from https://clinicaltrials.gov/ct2/show/NCT01627678.
111. A Phase I randomized, double-blind, placebo-controlled study of a multi-antigen DNA vaccine prime delivered by in vivo electroporation, rVSV booster vaccine in HIV-infected patients who began antiretroviral therapy during acute/early infection. Available from https://clinicaltrials.gov/ct2/show/NCT01859325.
112. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R, et al.Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 2009; 361:2209-20.
113. Williams WB, Liao HX, Moody MA, Kepler TB, Alam SM, Gao F, et al. Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies. Science 2015; 349(6249):aab1253. doi: 10.1126/science.aab1253.
114. Walker LM, Phogat SK, Chan-Hui PY, Wagner D, Phung P, Goss JL, et al. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 2009; 326:285-9.
115. Wu X, Yang ZY, Li Y, Hogerkorp CM, Schief WR, Seaman MS, et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 2010; 329:856-61.
116. Zhou T, Georgiev I, Wu X, Yang ZY, Dai K, Finzi A, et al.Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science 2010; 329:811-7.
117. Arthos J, Cicala C, Martinelli E, Macleod K, Van Ryk D, Wei D, et al. HIV-1 envelope protein binds to and signals through integrin α4β7, the gut mucosal homing receptor for peripheral T cells. Nat Immunol 2008; 9:301-9.
118. Honnen WJ, Krachmarov C, Kayman SC, Gorny MK, Zolla-Pazner S, Pinter A. Type-specific epitopes targeted by monoclonal antibodies with exceptionally potent neutralizing activities for selected strains of human immunodeficiency virus type 1 map to a common region of the V2 domain of gp120 and differ only at single positions from the clade B consensus sequence. J Virol 2007; 81:1424-32.
119. Kwong PD, Mascola JR, Nabel GJ. Rational design of vaccines to elicit broadly neutralizing antibodies to HIV-1. Cold Spring Harbor Perspectives Med 2011; doi: 10.1101/cshperspect.a007278.
120. Ackerman M, Alter G. Mapping the Journey to an HIV Vaccine. N Engl J Med 2013; 369(4):389-391.
121. Mikell I, Sather DN, Kalams SA, Altfeld M, Alter G, Stamatatos L. Characteristics of the earliest cross-neutralizing antibody response to HIV-1. PLoS Pathog 2011; 7(1):e1001251.
122. Jardine J, Julien JP, Menis S, Ota T, Kalyuzhniy O, McGuire A, et al. Rational HIV immunogen design to target specific germline B cell receptors. Science 2013; 340, 711-6.
123. AS Fauci and HD Marston. Ending the HIV-AIDS pandemic-Follow the science. N Engl J Med 2015; 373(23):2197-9.
124. Implementation of HIV pre exposure prophylaxis with antiretroviral medications among people at high risk for HIV infection: A demonstration project. Available from https://clinicaltrials.gov/ct2/show/NCT02206555.
125. A pilot trial evaluating maintenance therapy with lamivudine and dolutegravir in HIV-1 infected patients virologically suppressed with triple HAART - ANRS 167 lamidol. Available from https://clinicaltrials.gov/ct2/show/NCT02527096.
126. Outcomes of HIV infected individuals after ten years on antiretroviral treatment. Available from https://clinicaltrials.gov/ct2/show/NCT02514707.
127. An interventional, one-arm, open label pilot study to assess the feasibility of dolutegravir monotherapy in virologically suppressed patients on conventional triple antiretroviral therapy of dolutegravir plus two nucleoside reverse transcriptase inhibitors. Available from https://clinicaltrials.gov/ct2/show/NCT02572947.
128. Safety and efficacy of the histone deacetylase inhibitor chidamide in combination with antiretroviral therapy for eradication of the latent HIV-1 reservoir (CHARTER). Available from https://clinicaltrials.gov/ct2/show/NCT02513901.
129. A phase 3b, randomized, double-blind, switch study to evaluate F/TAF in HIV-1 infected subjects who are virologically suppressed on regimens containing ABC/3TC. Available from https://clinicaltrials.gov/ct2/show/NCT02469246.
130. Clotet B, Feinberg J, van Lunzen J, Khuong-Josses MA, Antinori A, Dumitru I, et al.Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomized open-label phase 3b study. Lancet 2014; 383:2222-31.
2. Jaykare SC, Motghare VM, Padwal SL, Pise HN, Deshpande RP. Antiretroviral therapy- newer drugs on the anvil. Indian J Med Specialities 2013; 4:47-54.
3. Nabel GJ. Mapping the future of HIV vaccines. Nature Rev Microbiol 2007; 5: 482-84.
4. Menendez-Arias L. Molecular basis of human immunodeficiency virus type 1 drug resistance: Overview and recent developments. Antiviral Res 2013; 98:93-120.
5. Tremblay CL, Baril J, Fletcher D, Kilby D, MacPherson P, Shafran SD, et al. Challenges in initiating antiretroviral therapy in 2010 Can J Infect Dis Med Microbiol 2010; 21:1-15.
6. Cooper CL, Breau C, Laroche A, Lee C, Garber G. Clinical outcomes of first antiretroviral regimen in HIV/hepatitis C virus co-infection. HIV Med 2006; 7:32-37.
7. Mitsuya H, Weinhold K, Furman P, St Clair M, Li L, Lehrman S, et al. 3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc Natl Acad Sci USA 1985; 82:7096-100.
8. Sun R, Eriksson S, Wang L. Identification and characterization of mitochondrial factors modulating thymidine kinase 2 activity. Nucleosides, Nucleotides and Nucleic Acids. 2010; 29:382-5.
9. Scruggs ER, Dirks Naylor AJ. Mechanisms of zidovudine-induced mitochondrial toxicity and myopathy. Pharmacol 2008; 82:83-8.
10. Hivid (zalcitabine) tablets. Product information. (September 2002). Available from http://www.rocheusa.com/products/hivid/pi.pdf
11. Horwitz JP, Chua J, DaRooge MA, Noel M, Klundt IL. Nucleosides. IX. The formation of 2', 2'-unsaturated pyrimidine nucleosides via a novel beta-elimination reaction. J Org Chem1966; 31:205-11.
12. Wangsomboonsiri W, Mahasirimongkol S, Chantarangsu S, Kiertiburanakul S, Charoenyingwattana A, Komindr S, et al. Association between HLA-B*4001 and lipodystrophy among HIV-infected patients from Thailand who received a stavudine-containing antiretroviral regimen. Clin Infect Dis 2010; 50:597-604.
13. Hetherington S, Hughes AR, Mosteller M, Shortino D, Baker KL, Spreen W, et al. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet 2002; 359:1121-2.
14. Rauch A, Nolan D, Martin A, McKinnon E, Almeida C, Mallal S. Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV cohort study. Clin Infect Dis 2006; 43:99-102.
15. Fox Z, Dragsted UB, Gerstoft J, Phillips AN, Kjaer J, Mathiesen L, et al. A randomized trial to evaluate continuation versus discontinuation of lamivudine in individuals failing a lamivudine-containing regimen: The COLATE trial. Antivir Ther 2006; 11:761-70.
16. VIDEX (didanosine): chewable/dispersible buffered tablets; buffered powder for oral solution; pediatric powder for oral solution. Product information (July 2000). Available from http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm
17. Kimberlin DW. Antiviral therapies in children: Has their time arrived? Pediatr Clin N Am 2005; 52:837-67.
18. Oxenius A, Price DA, Günthard HF, Dawson SJ, Fagard C, Perrin L, et al. Stimulation of HIV-specific cellular immunity by structured treatment interruption fails to enhance viral control in chronic HIV infection. Proc Natl Acad Sci USA 2002; 99:13747-52.
19. Cahn P, Wainberg MA. Resistance profile of the new nucleoside reverse transcriptase inhibitor apricitabine. J Antimicrob Chemother 2010; 65:213-7.
20. Cahn P, Cassetti I, Wood R, Phanuphak P, Shiveley L, Bethel RC, et al. Efficacy and tolerability of 10-day monotherapy with apricitabine in antiretroviral-naive, HIV-infected patients. AIDS 2006; 20:1261-8.
21. Wainberg MA, Cahn P, Bethell RC, Sawyer J, Cox S. Apricitabine: a novel deoxycytidine analogue nucleoside reverse transcriptase inhibitor for the treatment of nucleoside-resistant HIV infection. Antivir Chem Chemother 2007; 18:61-70.
22. Ravichandran S, Veerasamy R, Raman S, Krishnan N, Agrawal RK. An overview on HIV-1 reverse transcriptase inhibitors. Digest J Nanomaterials Biostructures 2008; 3:171-87.
23. Albrecht MA, Wilkin TJ, Coakley EP, Hammer SM. Advances in antiretroviral therapy. Top HIV Med 2003; 11:97-127.
24. Herzmann C, Arasteh K, Murphy RL, Schulbin H, Kreckel P, Drauz D, et al. Safety, pharmacokinetics, and efficacy of (+/-)-β-2’,3’- dideoxy-5-fluoro-3’-thiacytidine with efavirenzand stavudine in antiretroviral-naive human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 2005; 49:2828-33.
25. Mehellou Y, de Clercq E. Twenty-six years of anti-HIV drug discovery: where do we stand and where do we go? J Med Chem 2010; 53:521-38.
26. Cihlar T, Ray AS. Nucleoside and nucleotide HIV reverse-transcriptase inhibitors: 25 years after zidovudine. Antiviral Res 2010; 85:39-58.
27. Barnhart M, Shelton J. A better state of ART improving anti-retroviral regimens to increase global access to HIV treatment. J AIDS HIV Res 2011; 3:71-8.
28. Otto MJ. New nucleoside reverse transcriptase inhibitors for the treatment of HIV infections. Curr Opin Pharmacol 2004; 4:431-6.
29. De Clercq E. Antiviral drugs in current clinical use. J Clin Virol 2004; 30:115-33.
30. Hodge RAV. Meeting report: 26th International conference on antiviral research. Antiviral Res 2013; 100:276-85.
31. Margot N, Isaacson E, McGowan I, Cheng AK, Schooley RT, Miller MD. Genotypic and phenotypic analyses of HIV-1 in antiretroviral experienced patients treated with tenofovir DF. AIDS 2002; 16:1227-35.
32. Huang H, Chopra R, Verdine GL, Harrison SC. Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance. Science 1998; 282:1669-75.
33. Das K, Bandwar RP, White KL, Feng JY, Sarafianos SG, Tuske S, et al. Structural basis for the role of the K65R mutation in HIV-1reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. J Biol Chem 2009; 284:35092-100.
34. Barrioluengo V, Álvarez M, Barbieri D, Menéndez-Arias L. Thermostable HIV-1 group O reverse transcriptase variants with the same fidelity as murine leukaemia virus reverse transcriptase. Biochem J 2011; 436:599-607.
35. Gao HQ, Boyer PL, Sarafianos SG, Arnold E, Hughes SH. The role of steric hindrance in 3TC resistance of human immunodeficiency virus type-1 reverse transcriptase. J Mol Biol 2000; 300:403-18.
36. Deval J, Selmi B, Boretto J, Egloff MP, Guerreiro C, Sarfati S, et al. The molecular mechanism of multidrug resistance by the Q151M human immunodeficiency virus type 1 reverse transcriptase and its suppression using boranophosphate nucleotide analogues. J Biol Chem 2002; 277:42097-104.
37. Frangeul A, Busetta C, Deval J, Barral K, Alvarez K, Canard B. Gln151 of HIV-1 reverse transcriptase acts as a steric gate towards clinically relevant acyclic phosphonate nucleotide analogues. Antivir Ther.2008; 13:115-24.
38. Gu Z, Allard B, de Muys JM, Lippens J, Rando RF, Nguyen-Ba N, et al. In vitro antiretroviral activity and in vitro toxicity profile of SPD754, a new deoxycytidine nucleoside reverse transcriptase inhibitor for treatment of human immunodeficiency virus infection. Antimicrob Agents Chemother 2006; 50:625-31.
39. Cahn P, Wainberg MA. Resistance profile of the new nucleoside reverse transcriptase inhibitor apricitabine. J Antimicrob Chemother 2010; 65:213-17.
40. Schinazi RF, Massud I, Rapp KL, Cristiano M, Detorio MA, Stanton RA, et al. Selection and characterization of HIV-1 with a novel S68 deletion in reverse transcriptase. Antimicrob Agents Chemother 2011; 55:2054-60.
41. Michailidis E, Marchand B, Kodama EN, Singh K, Matsuoka M, Kirby KA, et al. Mechanism of inhibition of HIV-1 reverse transcriptase by 40-ethynyl-2-fluoro-20-deoxyadenosine triphosphate, a translocation defective reverse transcriptase inhibitor. J Biol Chem 2009; 284:35681-91.
42. Kawamoto A, Kodama E, Sarafianos SG, Sakagami Y, Kohgo S, Kitano K, et al. 20-deoxy-40-C-ethynyl-2-halo-adenosines active against drug resistant human immunodeficiency virus type 1 variants. Int J Biochem Cell Biol 2008; 40:2410-20.
43. Yang G, Paintsil E, Dutschman GE, Grill SP, Wang CJ, Wang J, et al. Impact of novel human immunodeficiency virus type 1 reverse transcriptase mutations P119S andT165A on 40-ethynylthymidine analog resistance profile. Antimicrob Agents Chemother 2009; 53:4640-46.
44. Cihlar T, Ray AS, Boojamra CG, Zhang L, Hui H, Laflamme G, et al. Design and profiling of GS-9148, a novel nucleotide analog active against nucleoside-resistant variants of human immunodeficiency virus type 1, and its orally bioavailable phosphonoamidate prodrug, GS-9131. Antimicrob Agents Chemother 2008; 52:655-65.
45. Kohlstaedt LA, Wang J, Friedman JM, Rice PA, Steitz TA. Crystal structure at 3.5 Å resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 1992; 256:1783-90.
46. Sustiva (efavirenz) capsules and tablets. Product information (April 2005). Available from http://www.bms.com/cgi-bin/anybin.pl
47. Lowenhaupt EA, Matson K, Qureishi B, Saitoh A, Pugatch D. Psychosis in a 12-year-old HIV-positive girl with an increased serum concentration of efavirenz. Clin Infectious Dis 2007; 45:e128-30.
48. Ford N, Mofenson L, Kranzer K, Medu L, Frigati L, Mills EJ, Calmy A. Safety of efavirenz in first-trimester of pregnancy: A systematic review and meta-analysis of outcomes from observational cohorts. AIDS 2010; 24:1461-70.
49. Montaner JS, Reiss P, Cooper D. A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. Italy, The Netherlands, Canada and Australia Study. JAMA 1998; 279:930-7.
50. Podzamczer D, Ferrer E, Consiglio E, Gatell JM, Perez P, Perez JL, et al. A randomized clinical trial comparing nelfinavir or nevirapine associated to zidovudine/lamivudine in HIV-infected naive patients (the Combine Study). Antiviral Ther 2002; 7:81-90.
51. Wit FW, Kesselring AM, Gras L. Discontinuation of nevirapine because of hypersensitivity reactions in patients with prior treatment experience, compared with treatment-naive patients: the ATHENA cohort study. Clin Infect Dis 2008; 46: 933-40.
52. DHHS panel. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (May 4, 2006). (Available for download from AIDS Info).
53. Rescriptor brand of delavirdine mesylate tablets. Product information. Available from http://www.pfizer.com/pfizer/download/uspi_rescriptor.pdf
54. de Bethune MP. Non-nucleoside reverse transcriptase inhibitors (NNRTIs), their discovery development, and use in the treatment of HIV-1 infection: a review of the last 20 years (1989-2009). Antiviral Res 2010; 85:75-90.
55. Rathbun RC, Liedtke MD. The next generation: Etravirine in the treatment of HIV-1 infection in adults refractory to other antiretrovirals. Virus Adaptation and Treatment. 2010; 2:91-102.
56. Ford N, Lee J, Andrieux-Meyer I, Calmy A. Safety, efficacy, and pharmacokinetics of rilpivirine: systemic review with an emphasis on resource limited settings. HIV/AIDS 2011; 3:35-44.
57. James C, Preininger L, Sweet M. Rilpivirine: a second generation non-nucleoside reverse transcriptase inhibitor. Am J Health Syst Pharm 2012; 69:857-61.
58. De Clercq E. Where rilpivirine meets with tenofovir, the start of a new anti-HIV drug combination era. Biochem Pharmacol 2012; 84:241-8.
59. Panel on antiretroviral guidelines for adults and adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. December, 2009:1-161.
60. Paris KA, Haq O, Felts AK, Das K, Arnold E, Levy RM. Conformational landscape of the human immunodeficiency virus type 1 reverse transcriptase non-nucleoside inhibitor binding pocket: lessons for inhibitor design from a cluster analysis of many crystal structures. J Med Chem 2009; 52:6413-20.
61. Das K, Clark Jr AD, Lewi PJ, Heeres J, De Jonge MR, Koymans LM, et al. Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants. J Med Chem 2004; 47:2550-60.
62. Lansdon EB, Brendza KM, Hung M, Wang R, Mukund S, Jin D, et al. Crystal structures of HIV-1 reverse transcriptase with etravirine (TMC125) and rilpivirine (TMC278): implications for drug design. J Med Chem 2010; 53:4295-9.
63. Tambuyzer L, Azijn H, Rimsky LT, Vingerhoets J, Lecocq P, Kraus G. Compilation and prevalence of mutations associated with resistance to non-nucleoside reverse transcriptase inhibitors. Antivir Ther 2009; 14:103-9.
64. Javanbakht H, Ptak RG, Chow E, Yan JM, Russell JD, Mankowski MK, et al.In vitro resistance development for RO-0335, a novel diphenyl ether nonnucleoside reverse transcriptase inhibitor. Antiviral Res 2010; 86:212-9.
65. Cohen CJ, Andrade-Villanueva J, Clotet B, Fourie J, Johnson MA, RuxrungthamK, et al. On behalf of the THRIVE Study Group, Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial. Lancet 2011; 378:229-37.
66. Azijn H, Tirry I, Vingerhoets J, de Béthune MP, Kraus G, Boven K, et al. TMC278, a next generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1. Antimicrob Agents Chemother 2010; 54:718-27.
67. Asahchop EL, Wainberg MA, Oliveira M, Xu H, Brenner BG, Moisi D, et al. Distinct resistance patterns to etravirine and rilpivirine in viruses containing NNRTI mutations at baseline. AIDS 2012; http://dx.doi.org/10.1097/QAD.0b013e32835d9f6d.
68. Corbau R, Mori J, Phillips C, Fishburn L, Martin A, Mowbray C, et al. Lersivirine, a nonnucleoside reverse transcriptase inhibitor with activity against drug-resistant human immunodeficiency virus type 1. Antimicrob Agents Chemother 2010; 54:4451-63.
69. Vernazza P, Wang C, Pozniak A, Weil E, Pulik P, Cooper DA, et al. Efficacy and safety of lersivirine (UK-453,061) versus efavirenz in antiretroviral treatment-naïve HIV-1-infected patients: week 48 primary analysis results from an ongoing, multicenter, randomized, double-blind, phase IIb trial. J Acquir Immune Defic Syndr 2013; 62:171-9.
70. Boyer J, Arnoult E, Médebielle M, Guillemont J, Unge J, Jochmans D. Difluoromethylbenzoxazole pyrimidine thioether derivatives: a novel class of potent non-nucleoside HIV-1 reverse transcriptase inhibitors. J Med Chem 2011; 54:7974-85.
71. Pohlmann S, Reeves JD. Cellular entry of HIV: Evaluation of therapeutic targets. Curr Pharm Des 2006; 12:1963-73.
72. Greenberg ML, Cammack N. Resistance to enfuvirtide, the first HIV fusion inhibitor. J Antimicrob Chemother 2004; 54:333-40.
73. Greenberg ML, Sista P, Miralles G. Melby T, Davison D, Jin L, et al. Enfuvirtide (T-20) and T-1249 resistance: observations from Phase II clinical trials of enfuvirtide in combination with oral antiretrovirals (ARVs) and a Phase I/II dose-ranging monotherapy trial of T-1249. Antivir Ther 2002; 7:S106.
74. Mink M, Greenberg ML, Mosier S, Janumpalli S. Impact of HIV-1 gp41 amino acid substitutions (positions 36-45) on susceptibility to T-20 (enfuvirtide) in vitro: Analysis of primary virus isolates recovered from patients during chronic enfuvirtide treatment and site directed mutants in NL4-3. Antivir Ther 2002; 7:S24.
75. Lederman MM, Penn-Nicholson A, Cho M, Mosier D. Biology of CCR5 and its role in HIV infection and treatment. JAMA 2006; 296:815-26.
76. Kwong P. Human immunodeficiency virus: refolding the envelope. Nature 2005; 433:815-6.
77. Wood A, Armour D. The discovery of the CCR5 receptor antagonist, UK-427, 857, a new agent for the treatment of HIV infection and AIDS. Prog Med Chem 2005; 43:239-71.
78. Gorry PR, Ellett A, Lewin SR. Maraviroc. In Kucers’ The Use of Antibiotics. In: Grayson L, Crowe S, McCarthy J, Mills J, Mouton J, Norrby SR, Paterson D, Pfaller M, editors. 6th Ed. London: Hodder & Stoughton Ltd. 2010, pp. 2869-76.
79. Roche M, Salimi H, Duncan R, Wilkinson BL, Chikere K, Moore MS, et al. A common mechanism of clinical HIV-1 resistance to the CCR5 antagonist maraviroc despite divergent resistance levels and lack of common gp120 resistance mutations. Retrovirol 2013; 10:43-62.
80. Hazuda DJ, Felock P, Witmer M, Wolfe A, Stillmock K, Grobler JA, et al. Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. Science 2000; 287:646-50.
81. Eron JJ, Cooper DA, Steigbigel RT, Clotet B, Gatell JM, Kumar PN, et al. Efficacy and safety of raltegravir for treatment of HIV for 5 years in the BENCHMRK studies: final results of two randomised, placebo-controlled trials. Lancet Infect Dis 2013; 13:587-96.
82. Delelis O, Thierry S, Subra F, Simon F, Malet I, Alloui C, et al. Impact of Y143 HIV-1 integrase mutations on resistance to raltegravir in vitro and in vivo. Antimicrob Agents Chemother 2010; 54:491-501.
83. Dunn BM. Structure and mechanism of the pepsin-like family of aspartic peptidases. Chem Rev 2002; 102:4431-58.
84. De Clercq E. Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. Int J Antimicrob Agents 2009; 33:307-20.
85. Alfonso Y, Monzote L. HIV Protease Inhibitors: Effect on the opportunistic protozoan parasites. Open Med Chem J 2011; 5:40-50.
86. Vella S, Floridia M. Saquinavir. Clinical pharmacology and efficacy. Clin Pharmacokinet 1998; 34:189-201.
87. Hsu A, Granneman GR, Bertz RJ. Ritonavir. Clinical pharmacokinetics and interactions with other anti-HIV agents. Clin Pharmacokinet 1998; 35:275-91.
88. Dieleman JP, Salahuddin S, Hsu YS, Burger DM, Gyssens IC, Sturkenboom MC, et al. Indinavir crystallization around the loop of henle: Experimental evidence. J Acquir Immune Defic Syndr 2001; 28:9-13.
89. Wensing AM, van Maarseveen NM, Nijhuis M. Fifteen years of HIV protease inhibitors: Raising the barrier to resistance. Antiviral Res 2010; 85:59-74.
90. Fernández Montero JV, Barreiro P, Soriano V. HIV protease inhibitors: recent clinical trials and recommendations on use. Expert Opin Pharmacother 2009; 10:1615-29.
91. Eron JJ, Haubrich R, Lang W, Pagano G, Millard J, Wolfram J, et al. A phase II trial of dual protease inhibitor therapy: Amprenavir in combination with indinavir, nelfinavir, or saquinavir. J Acquir Immune Defic Syndr 2001; 26:458-61.
92. Rivas P, Morello J, Garrido C, Rodríguez-Nóvoa S, Soriano V. Role of atazanavir in the treatment of HIV infection. Ther Clin Risk Manag 2009; 5:1-18.
93. Möbius U, Lubach-Ruitman M, Castro-Frenzel B, Stoll M, Esser S, Voigt E, et al.Switching to atazanavir improves metabolic disorders in antiretroviral-experienced patients with severe hyperlipidemia. J Acquir Immune Defic Syndr 2005; 39:174-80.
94. Piacenti FJ. An update and review of antiretroviral therapy. Pharmacother 2006; 26:1111-33.
95. Shen CH, Wang YF, Kovalevsky AY, Harrison RW, Weber IT. Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. FEBS J 2010; 277:3699-714.
96. McKeage K, Perry CM, Keam SJ. Darunavir: A review of its use in the management of HIV infection in adults. Drugs 2009; 69:477-503.
97. Johnson VA, Calvez V, Günthard HF, Paredes R, Pillay D, Shafer R, et al. 2011 update of the drug resistance mutations in HIV-1. Top Antivir Med. 2011; 19:156–164.
98. Sugiura W, Matsuda Z, Yokomaku Y, Hertogs K, Larder B, Oishi T, et al. Interference between D30N and L90M in selection and development of protease inhibitor-resistant human immunodeficiency virus type 1. Antimicrob Agents Chemother 2002; 46:708-15.
99. Fun A, Wensing AMJ, Verheyen J, Nijhuis M. Human immunodeficiency virus gag and protease: partners in resistance. Retrovirol 2012; 9:63.
100. Rhee SY, Taylor J, Fessle WJ, Kaufman D, Towner W, Troia P, et al. HIV-1 protease mutations and protease inhibitor cross-resistance. Antimicrob Agents Chemother 2010; 54:4253-61.
101. Ide K, Aoki M, Amano M, Koh Y, Yedidi RS, Das D, et al. Novel HIV-1 protease inhibitors (PIs) containing a bicyclic P2 functional moiety, tetrahydropyrano-tetrahydrofuran, that are potent against multi-PI-resistant HIV-1 variants. Antimicrob Agents Chemother 2011; 55:1717-27.
102. Dierynck I, van Marck H, van Ginderen M, Jonckers THM, Nalam MNL, Schiffer CA, et al. TMC310911, a novel human immunodeficiency virus type 1 protease inhibitor, shows in vitro an improved resistance profile and higher genetic barrier to resistance compared with current protease inhibitors. Antimicrob Agents Chemother 2011; 55:5723-31.
103. Vidal JE, Wan Songa AT, Matosa ML, Bartmanna D, dos Anjosa G, de Mirandaa EJP, et al. High rate of virologic suppression with darunavir/ritonavir plus optimized background therapy among highly antiretroviral-experienced HIV-infected patients: results of a prospective cohort study in São Paulo, Brazil. Braz J Infect Dis 2013; 17:41-7.
104. Feng JY, Ly JK, Myrick F, Goodman D, White KL, Svarovskaia ES, et al. The triple combination of tenofovir, emtricitabine and efavirenz shows synergistic anti-HIV-1 activity in vitro: a mechanism of action study. Retrovirol 2009; 6:44.
105. Schader SM, Colby-Germinario SP, Schachter JR, Xu H, Wainberg MA. Synergy against drug-resistant HIV-1 with the microbicide antiretrovirals, dapivirine and tenofovir, in combination. AIDS 2011; 25:1585-94.
106. Kulkarni R, Feng JY, Miller MD, White KL. Dead-end complexes contribute to the synergistic inhibition of HIV-1 RT by the combination of rilpivirine, emtricitabine, and tenofovir. Antiviral Res 2014; 101:131-5.
107. Llibre JM, Clotet B. Once-daily single-tablet regimens: a long and winding road to excellence in antiretroviral treatment. AIDS Rev 2012; 14:168-78.
108. Thompson MA, Aberg JA, Hoy JF, Telenti A, Benson C, Cahn P, et al. Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA Panel. JAMA 2012; 308:387-402.
109. A Phase I, open label dose escalation study to evaluate safety of iHIVARNA-01 in chronically HIV-infected patients under stable combined antiretroviral therapy. Available from https://clinicaltrials.gov/ct2/show/NCT02413645.
110. Immunotherapy of HIV-infected patients an open, dose-escalating assessment of Vacc-C5 with either GM-CSF or Alhydrogel as adjuvant in HIV-1-infected subjects on antiretroviral therapy (ART). Available from https://clinicaltrials.gov/ct2/show/NCT01627678.
111. A Phase I randomized, double-blind, placebo-controlled study of a multi-antigen DNA vaccine prime delivered by in vivo electroporation, rVSV booster vaccine in HIV-infected patients who began antiretroviral therapy during acute/early infection. Available from https://clinicaltrials.gov/ct2/show/NCT01859325.
112. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R, et al.Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 2009; 361:2209-20.
113. Williams WB, Liao HX, Moody MA, Kepler TB, Alam SM, Gao F, et al. Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies. Science 2015; 349(6249):aab1253. doi: 10.1126/science.aab1253.
114. Walker LM, Phogat SK, Chan-Hui PY, Wagner D, Phung P, Goss JL, et al. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 2009; 326:285-9.
115. Wu X, Yang ZY, Li Y, Hogerkorp CM, Schief WR, Seaman MS, et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 2010; 329:856-61.
116. Zhou T, Georgiev I, Wu X, Yang ZY, Dai K, Finzi A, et al.Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science 2010; 329:811-7.
117. Arthos J, Cicala C, Martinelli E, Macleod K, Van Ryk D, Wei D, et al. HIV-1 envelope protein binds to and signals through integrin α4β7, the gut mucosal homing receptor for peripheral T cells. Nat Immunol 2008; 9:301-9.
118. Honnen WJ, Krachmarov C, Kayman SC, Gorny MK, Zolla-Pazner S, Pinter A. Type-specific epitopes targeted by monoclonal antibodies with exceptionally potent neutralizing activities for selected strains of human immunodeficiency virus type 1 map to a common region of the V2 domain of gp120 and differ only at single positions from the clade B consensus sequence. J Virol 2007; 81:1424-32.
119. Kwong PD, Mascola JR, Nabel GJ. Rational design of vaccines to elicit broadly neutralizing antibodies to HIV-1. Cold Spring Harbor Perspectives Med 2011; doi: 10.1101/cshperspect.a007278.
120. Ackerman M, Alter G. Mapping the Journey to an HIV Vaccine. N Engl J Med 2013; 369(4):389-391.
121. Mikell I, Sather DN, Kalams SA, Altfeld M, Alter G, Stamatatos L. Characteristics of the earliest cross-neutralizing antibody response to HIV-1. PLoS Pathog 2011; 7(1):e1001251.
122. Jardine J, Julien JP, Menis S, Ota T, Kalyuzhniy O, McGuire A, et al. Rational HIV immunogen design to target specific germline B cell receptors. Science 2013; 340, 711-6.
123. AS Fauci and HD Marston. Ending the HIV-AIDS pandemic-Follow the science. N Engl J Med 2015; 373(23):2197-9.
124. Implementation of HIV pre exposure prophylaxis with antiretroviral medications among people at high risk for HIV infection: A demonstration project. Available from https://clinicaltrials.gov/ct2/show/NCT02206555.
125. A pilot trial evaluating maintenance therapy with lamivudine and dolutegravir in HIV-1 infected patients virologically suppressed with triple HAART - ANRS 167 lamidol. Available from https://clinicaltrials.gov/ct2/show/NCT02527096.
126. Outcomes of HIV infected individuals after ten years on antiretroviral treatment. Available from https://clinicaltrials.gov/ct2/show/NCT02514707.
127. An interventional, one-arm, open label pilot study to assess the feasibility of dolutegravir monotherapy in virologically suppressed patients on conventional triple antiretroviral therapy of dolutegravir plus two nucleoside reverse transcriptase inhibitors. Available from https://clinicaltrials.gov/ct2/show/NCT02572947.
128. Safety and efficacy of the histone deacetylase inhibitor chidamide in combination with antiretroviral therapy for eradication of the latent HIV-1 reservoir (CHARTER). Available from https://clinicaltrials.gov/ct2/show/NCT02513901.
129. A phase 3b, randomized, double-blind, switch study to evaluate F/TAF in HIV-1 infected subjects who are virologically suppressed on regimens containing ABC/3TC. Available from https://clinicaltrials.gov/ct2/show/NCT02469246.
130. Clotet B, Feinberg J, van Lunzen J, Khuong-Josses MA, Antinori A, Dumitru I, et al.Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomized open-label phase 3b study. Lancet 2014; 383:2222-31.
Published
01-11-2015
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“PROGRESS AND PROSPECTS IN THERAPEUTICS AGAINST HIV INFECTION”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 7, no. 6, Nov. 2015, pp. 432-43, https://doi.org/10.25004/IJPSDR.2015.076501.
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Review Article
How to Cite
“PROGRESS AND PROSPECTS IN THERAPEUTICS AGAINST HIV INFECTION”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 7, no. 6, Nov. 2015, pp. 432-43, https://doi.org/10.25004/IJPSDR.2015.076501.
