title: Evolving uses of oral reverse transcriptase inhibitors in the HIV-1 epidemic: from treatment to prevention.
abstract: The HIV epidemic continues unabated, with no highly effective vaccine and no cure. Each new infection has significant economic, social and human costs and prevention efforts are now as great a priority as global antiretroviral therapy (ART) scale up. Reverse transcriptase inhibitors, the first licensed class of ART, have been at the forefront of treatment and prevention of mother to child transmission over the past two decades. Now, their use in adult prevention is being extensively investigated. We describe two approaches: treatment as prevention (TasP) - the use of combination ART (2NRTI and 1NNRTI) following HIV diagnosis to limit transmission and pre-exposure prophylaxis (PrEP) -the use of single or dual oral agents prior to sexual exposure. Prevention of mother-to-child transmission using NRTI has been highly successful, though does not involve sustained use of NRTI to limit transmission. Despite theoretical and preliminary support for TasP and PrEP, data thus far indicate that adherence, retention in care and late diagnosis are the major barriers to their successful, sustained implementation. Future advances in drug technologies will be needed to overcome the issue of drug adherence, through development of drugs that involve both less frequent dosing as well as reduced toxicity, possibly through specific targeting of infected cells.
authors.affiliation: Division of Infection and Immunity, University College, 90 Gower St, London WC1E 6BT, UK. rebmrag@ucl.ac.uk
authors.forename: Ravindra K
authors.initials: RK
authors.lastname: Gupta
authors.forename: David A M C
authors.initials: DA
authors.lastname: Van de Vijver
authors.forename: Sheetal
authors.initials: S
authors.lastname: Manicklal
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wainberg
mesh_terms: D000284:Administration, Oral; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018890:Chemoprevention / Q000379:methods*; D018562:Disease Transmission, Infectious / Q000517:prevention & control; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control* / Q000635:transmission; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors
references.citation: Lancet. 2008 Mar 1;371(9614):752-9
references.pmid: 18313504
references.citation: N Engl J Med. 2012 Aug 2;367(5):423-34
references.pmid: 22784038
references.citation: Clin Infect Dis. 2009 Dec 15;49(12):1928-35
references.pmid: 19911963
references.citation: J Infect Dis. 2004 Mar 1;189(5):837-46
references.pmid: 14976601
references.citation: N Engl J Med. 1994 Nov 3;331(18):1173-80
references.pmid: 7935654
references.citation: PLoS One. 2008 May 07;3(5):e2077
references.pmid: 18461185
references.citation: AIDS. 2012 Aug 24;26(13):1679-84
references.pmid: 22739389
references.citation: PLoS One. 2009;4(1):e4096
references.pmid: 19119321
references.citation: J Infect Dis. 2009 Nov 15;200(10):1503-8
references.pmid: 19835478
references.citation: J Acquir Immune Defic Syndr. 2007 Feb 1;44(2):148-53
references.pmid: 17117145
references.citation: Antimicrob Agents Chemother. 1993 Apr;37(4):875-81
references.pmid: 7684216
references.citation: Lancet Infect Dis. 2009 Jul;9(7):409-17
references.pmid: 19555900
references.citation: AIDS. 2006 Apr 24;20(7):995-1002
references.pmid: 16603851
references.citation: AIDS. 2008 Aug 20;22(13):1679-81
references.pmid: 18670232
references.citation: AIDS. 2011 Mar 27;25(6):843-50
references.pmid: 21192233
references.citation: PLoS Med. 2011 Mar;8(3):e1000430
references.pmid: 21468304
references.citation: J Infect Dis. 2013 May 1;207(9):1359-69
references.pmid: 23382571
references.citation: J Acquir Immune Defic Syndr. 2002 Apr 15;29(5):484-94
references.pmid: 11981365
references.citation: Clin Infect Dis. 2012 May;54 Suppl 4:S280-9
references.pmid: 22544188
references.citation: N Engl J Med. 2012 Aug 2;367(5):411-22
references.pmid: 22784040
references.citation: Ann Intern Med. 2011 Apr 5;154(7):445-56
references.pmid: 21320923
references.citation: N Engl J Med. 2011 Aug 18;365(7):637-46
references.pmid: 21848464
references.citation: N Engl J Med. 2010 Dec 30;363(27):2587-99
references.pmid: 21091279
references.citation: Antivir Ther. 2008;13(2):189-97
references.pmid: 18505170
references.citation: J Infect Dis. 2003 Oct 1;188(7):992-1000
references.pmid: 14513419
references.citation: Curr HIV/AIDS Rep. 2013 Jun;10(2):142-51
references.pmid: 23494772
references.citation: Lancet. 2012 Oct 6;380(9849):1250-8
references.pmid: 22828485
references.citation: Pediatr Infect Dis J. 2013 Apr;32(4):e164-9
references.pmid: 23249916
references.citation: PLoS Med. 2011 Jul;8(7):e1001056
references.pmid: 21811403
references.citation: AIDS. 2007 Mar 30;21(6):665-75
references.pmid: 17413687
references.citation: Lancet Infect Dis. 2011 May;11(5):363-71
references.pmid: 21354861
references.citation: N Engl J Med. 1998 Mar 26;338(13):853-60
references.pmid: 9516219
references.citation: J Antimicrob Chemother. 2009 Jan;63(1):170-7
references.pmid: 18974161
references.citation: Antimicrob Agents Chemother. 2012 May;56(5):2305-13
references.pmid: 22330916
references.citation: AIDS. 2012 Jun 1;26(9):1131-9
references.pmid: 22382143
references.citation: AIDS. 2009 Jun 1;23(9):1127-34
references.pmid: 19417582
references.citation: N Engl J Med. 2010 Jun 17;362(24):2271-81
references.pmid: 20554982
references.citation: J Intern Med. 2011 Dec;270(6):532-49
references.pmid: 21929723
references.citation: Clin Infect Dis. 2007 Feb 1;44(3):447-52
references.pmid: 17205457
references.citation: AIDS. 2006 May 12;20(8):1163-9
references.pmid: 16691068
references.citation: J Infect Dis. 2007 Apr 1;195(7):951-9
references.pmid: 17330784
references.citation: Clin Infect Dis. 2010 Jan 1;50(1):98-105
references.pmid: 19951169
references.citation: J Infect Dis. 2005 Jul 1;192(1):24-9
references.pmid: 15942890
references.citation: PLoS Med. 2012;9(7):e1001245
references.pmid: 22802730
references.citation: AIDS Res Hum Retroviruses. 2013 May;29(5):746-54
references.pmid: 23289671
references.citation: N Engl J Med. 1987 Jul 23;317(4):185-91
references.pmid: 3299089
references.citation: N Engl J Med. 2006 Jan 19;354(3):251-60
references.pmid: 16421366
references.citation: Lancet Infect Dis. 2010 Mar;10(3):155-66
references.pmid: 20185094
references.citation: Mol Cell. 1999 Jul;4(1):35-43
references.pmid: 10445025
references.citation: Lancet. 1999 Sep 4;354(9181):795-802
references.pmid: 10485720
references.citation: Antimicrob Agents Chemother. 2009 Mar;53(3):1170-6
references.pmid: 19114673
references.citation: PLoS One. 2010 Jul 09;5(7):e11505
references.pmid: 20634893
references.citation: PLoS Med. 2004 Oct;1(1):e19
references.pmid: 15526045
references.citation: Lancet Infect Dis. 2011 Mar;11(3):171-80
references.pmid: 21237718
references.citation: Lancet. 2004 Jul 3-9;364(9428):29-34
references.pmid: 15234853
references.citation: JAMA. 2001 Mar 7;285(9):1155-63
references.pmid: 11231744
references.citation: Clin Infect Dis. 2012 Jun;54(11):1660-9
references.pmid: 22474222
references.citation: Clin Infect Dis. 2011 Dec;53(12):1265-70
references.pmid: 21976467
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):317-22
references.pmid: 17179211
references.citation: N Engl J Med. 2010 Jun 17;362(24):2282-94
references.pmid: 20554983
references.citation: AIDS. 2012 Jul 31;26(12):1491-500
references.pmid: 22555161
references.citation: Arch Intern Med. 2010 Aug 9;170(15):1347-54
references.pmid: 20696960
references.citation: JAMA. 2004 Jul 14;292(2):191-201
references.pmid: 15249568
references.citation: JAMA. 2010 Sep 8;304(10):1082-90
references.pmid: 20823434
references.citation: N Engl J Med. 2004 Jul 15;351(3):229-40
references.pmid: 15247339
references.citation: N Engl J Med. 1997 Sep 11;337(11):734-9
references.pmid: 9287228
references.citation: Lancet. 2009 Jan 3;373(9657):48-57
references.pmid: 19038438
references.citation: Clin Infect Dis. 2010 May 15;50(10):1397-404
references.pmid: 20377404
references.citation: J Infect Dis. 2009 May 1;199(9):1310-7
references.pmid: 19301982
references.citation: J Virol. 1997 Nov;71(11):8893-8
references.pmid: 9343254
references.citation: J Acquir Immune Defic Syndr. 2009 Apr 1;50(4):397-402
references.pmid: 19214119
references.citation: J Acquir Immune Defic Syndr. 2010 Mar;53(3):283-4
references.pmid: 19901845
references.citation: JAMA. 2006 Aug 16;296(7):794-805
references.pmid: 16905785
references.citation: Clin Infect Dis. 2011 Apr 15;52(8):1069-76
references.pmid: 21460326
references.citation: AIDS. 2001 Oct 19;15(15):1951-7
references.pmid: 11600822
references.citation: JAMA. 2012 Jul 25;308(4):387-402
references.pmid: 22820792
references.citation: AIDS. 2010 Mar 13;24(5):723-7
references.pmid: 20057312
references.citation: Science. 2013 Feb 22;339(6122):961-5
references.pmid: 23430655
references.citation: Clin Infect Dis. 2009 Feb 15;48(4):462-72
references.pmid: 19133804
references.citation: AIDS Rev. 2012 Jan-Mar;14(1):17-27
references.pmid: 22297501
references.citation: N Engl J Med. 2011 Aug 11;365(6):493-505
references.pmid: 21767103
references.citation: Lancet Infect Dis. 2012 Apr;12(4):307-17
references.pmid: 22036233
references.citation: PLoS One. 2012;7(2):e30216
references.pmid: 22348000
references.citation: PLoS Med. 2007 Dec;4(12):e335
references.pmid: 18052601
references.citation: Pediatr Infect Dis J. 2012 Sep;31(9):999; author reply 1000
references.pmid: 22609611
references.citation: Lancet. 2012 Jan 21;379(9812):221-8
references.pmid: 22196945
references.citation: N Engl J Med. 1992 Aug 27;327(9):581-7
references.pmid: 1353607
references.citation: Lancet. 2010 Jan 9;375(9709):123-31
references.pmid: 20004464
references.citation: J Infect Dis. 2013 Jul 15;208(2):224-34
references.pmid: 23570850
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14410-5
references.pmid: 12386343
references.citation: BMJ. 2011 Nov 09;343:d6792
references.pmid: 22074711
references.citation: Lancet. 2008 Jul 26;372(9635):300-13
references.pmid: 18657709
references.citation: Lancet. 2008 Apr 26;371(9622):1417-26
references.pmid: 18387667
references.citation: Science. 2013 Feb 22;339(6122):966-71
references.pmid: 23430656
references.citation: Clin Infect Dis. 2008 Sep 1;47(5):712-22
references.pmid: 18662137
references.citation: AIDS. 2001 Nov 23;15(17):2287-92
references.pmid: 11698702
references.citation: J Infect Dis. 2013 Apr 15;207(8):1216-20
references.pmid: 23315324
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10943-8
references.pmid: 18667707
references.citation: J Infect Dis. 2013 Jun 15;207 Suppl 2:S78-84
references.pmid: 23687293
references.citation: PLoS Med. 2009 Oct;6(10):e1000172
references.pmid: 19859531
references.citation: N Engl J Med. 2008 Jul 10;359(2):119-29
references.pmid: 18525035
references.citation: AIDS. 2013 Jun 1;27(9):1403-12
references.pmid: 23343913
references.citation: Clin Infect Dis. 2010 Jun 1;50(11):1512-20
references.pmid: 20415573
references.citation: N Engl J Med. 2004 Jul 15;351(3):217-28
references.pmid: 15247338
references.citation: Clin Infect Dis. 2013 Jun;56(12):1789-96
references.pmid: 23487387
references.citation: Wkly Epidemiol Rec. 1998 Oct 9;73(41):313-20
references.pmid: 9795578
references.citation: N Engl J Med. 1998 Nov 12;339(20):1409-14
references.pmid: 9811915
references.citation: N Engl J Med. 2012 Aug 2;367(5):399-410
references.pmid: 22784037
references.citation: HIV Med. 2004 May;5(3):180-4
references.pmid: 15139985
references.citation: Antimicrob Agents Chemother. 2005 Mar;49(3):1139-44
references.pmid: 15728915
references.citation: PLoS One. 2011;6(7):e21919
references.pmid: 21799755
references.citation: J Exp Med. 2003 Nov 17;198(10):1551-62
references.pmid: 14623909
references.citation: J Acquir Immune Defic Syndr Hum Retrovirol. 1995;10 Suppl 1:S57
references.pmid: 8595510
references.citation: Lancet. 1999 Mar 6;353(9155):773-80
references.pmid: 10459957
references.citation: J Acquir Immune Defic Syndr. 2013 Sep 1;64(1):87-94
references.pmid: 23481668
references.citation: J Nanosci Nanotechnol. 2012 Nov;12(11):8513-21
references.pmid: 23421238
references.citation: AIDS Res Hum Retroviruses. 2011 Aug;27(8):823-9
references.pmid: 21241214
references.citation: Lancet. 2004 Apr 17;363(9417):1253-63
references.pmid: 15094269
references.citation: PLoS One. 2012;7(8):e42834
references.pmid: 22905175
references.citation: N Engl J Med. 2007 Jan 11;356(2):135-47
references.pmid: 17215531
references.citation: Science. 2010 Sep 3;329(5996):1168-74
references.pmid: 20643915
references.citation: Clin Infect Dis. 2011 Feb 15;52(4):514-21
references.pmid: 21258105
references.citation: PLoS One. 2010 Nov 05;5(11):e13646
references.pmid: 21079767
references.citation: Int J Epidemiol. 2007 Oct;36(5):1009-21
references.pmid: 17533166
references.citation: HIV Med. 2008 Jul;9(6):332-5
references.pmid: 18705758
references.citation: AIDS. 2012 Oct 23;26(16):2039-52
references.pmid: 22951634
references.citation: J Infect Dis. 1992 Jan;165(1):105-10
references.pmid: 1370174
references.citation: Curr Opin Infect Dis. 2010 Dec;23(6):621-7
references.pmid: 20847692
references.citation: Antimicrob Agents Chemother. 1992 Nov;36(11):2423-31
references.pmid: 1283296
references.citation: PLoS One. 2013;8(3):e59549
references.pmid: 23527217
references.citation: Ann Intern Med. 1997 Mar 1;126(5):355-63
references.pmid: 9054279
references.citation: AIDS. 2008 May 11;22(8):973-81
references.pmid: 18453857
references.citation: Antimicrob Agents Chemother. 2006 Dec;50(12):4182-5
references.pmid: 17015626