title: Antimicrobial therapy for the treatment of opportunistic infections in HIV/AIDS patients: a critical appraisal.
abstract: The widespread use of antiretroviral therapy (ART) has entirely changed the management of human immunodeficiency virus (HIV) infection and dramatically reduced the rates of opportunistic infections (OI). However, OI continue to cause significant morbidity and mortality in both developed countries, where presentation with advanced HIV infection is common, and also in developing countries where ART is less widely available. Evidence to direct OI guidelines is partly limited by the fact that many large-scale studies date from the pre-ART era and more recent studies are sometimes poorly powered due to the falling rates of OI. Treatment of OI is now known to be as much about antimicrobials as about immune reconstitution with ART, and recent studies help guide the timing of initiation of ART in different infections. OI have also become complicated by the immune reconstitution inflammatory syndrome phenomenon which may occur once successful immune recovery begins. Trimethoprim-sulfamethoxazole has long been one of the most important antibiotics in the treatment and prevention of OI and remains paramount. It has a broad spectrum of activity against Pneumocystis jiroveci, toxoplasmosis, and bacterial infections and has an important role to play in preventing life-threatening OI. New advances in treating OI are coming from a variety of quarters: in cytomegalovirus eye disease, the use of oral rather than intravenous drugs is changing the face of therapy; in cryptococcal meningitis, improved drug formulations and combination therapy is improving clearance rates and reducing drug toxicities; and in gut disease, the possibility of rapid immune restitution with ART is replacing the need for antimicrobials against cryptosporidia and microsporidia.
authors.affiliation: Department of Infectious Diseases, Imperial College Healthcare NHS Trust, London, UK.
authors.forename: Jo
authors.initials: J
authors.lastname: Seddon
authors.forename: Sanjay
authors.initials: S
authors.lastname: Bhagani
references.citation: AIDS. 2001 Mar 30;15(5):645-7
references.pmid: 11317004
references.citation: J Acquir Immune Defic Syndr. 2002 Oct 1;31(2):183-7
references.pmid: 12394797
references.citation: Eur J Epidemiol. 1991 Nov;7(6):690-5
references.pmid: 1783064
references.citation: Clin Infect Dis. 2007 Feb 1;44(3):338-46
references.pmid: 17205438
references.citation: AIDS. 1991 Nov;5(11):1367-71
references.pmid: 1662959
references.citation: Clin Infect Dis. 2000 Oct;31(4):1084-92
references.pmid: 11049793
references.citation: J Infect Dis. 2008 Apr 1;197(7):1000-5
references.pmid: 18419536
references.citation: Retina. 1998;18(1):50-5
references.pmid: 9502281
references.citation: Am J Trop Med Hyg. 1990 Jan;42(1):83-8
references.pmid: 2301710
references.citation: N Engl J Med. 1997 Jul 3;337(1):15-21
references.pmid: 9203426
references.citation: Ann Intern Med. 1996 May 1;124(9):792-802
references.pmid: 8610948
references.citation: J Infect Dis. 1995 Oct;172(4):951-6
references.pmid: 7561215
references.citation: Ann Intern Med. 1986 Jul;105(1):37-44
references.pmid: 3521428
references.citation: AIDS. 1997 Mar;11(3):311-7
references.pmid: 9147422
references.citation: Lancet. 1998 Jan 24;351(9098):256-61
references.pmid: 9457096
references.citation: Eur J Ophthalmol. 1996 Apr-Jun;6(2):179-82
references.pmid: 8823593
references.citation: AIDS. 2002 Aug 16;16(12):1633-41
references.pmid: 12172085
references.citation: Clin Infect Dis. 1996 Feb;22(2):268-75
references.pmid: 8838183
references.citation: Ann Intern Med. 1994 Dec 15;121(12):905-11
references.pmid: 7978715
references.citation: Ophthalmology. 1994 Jul;101(7):1250-61
references.pmid: 8035989
references.citation: Arch Ophthalmol. 1996 Jul;114(7):815-20
references.pmid: 8660164
references.citation: J Acquir Immune Defic Syndr (1988). 1991;4 Suppl 1:S29-35
references.pmid: 1848619
references.citation: Am J Ophthalmol. 2001 Nov;132(5):700-10
references.pmid: 11704031
references.citation: J Infect. 2007 Oct;55(4):287-99
references.pmid: 17697716
references.citation: Clin Infect Dis. 1995 Aug;21 Suppl 1:S84-93
references.pmid: 8547518
references.citation: AIDS. 1995 Aug;9(8):881-5
references.pmid: 7576322
references.citation: J Infect Dis. 1993 Dec;168(6):1506-9
references.pmid: 8245536
references.citation: HIV Clin Trials. 2004 Mar-Apr;5(2):80-5
references.pmid: 15116283
references.citation: Gastroenterology. 1996 Jun;110(6):1803-9
references.pmid: 8964406
references.citation: Rev Infect Dis. 1990 Mar-Apr;12 Suppl 3:S364-8
references.pmid: 2184513
references.citation: Lancet. 1990 Sep 1;336(8714):545-9
references.pmid: 1975046
references.citation: J Infect Dis. 1994 Aug;170(2):419-24
references.pmid: 8035029
references.citation: AIDS. 1992 Mar;6(3):301-5
references.pmid: 1567574
references.citation: J Infect Dis. 1994 Jan;169(1):178-83
references.pmid: 8277179
references.citation: Clin Infect Dis. 2001 Feb 1;32(3):331-51
references.pmid: 11170940
references.citation: AIDS. 1997 Oct;11(12):1463-71
references.pmid: 9342068
references.citation: Clin Infect Dis. 2001 Mar 1;32(5):686-93
references.pmid: 11229835
references.citation: N Engl J Med. 1993 May 27;328(21):1514-20
references.pmid: 8479488
references.citation: N Engl J Med. 2002 Apr 11;346(15):1119-26
references.pmid: 11948271
references.citation: Clin Infect Dis. 2002 May 1;34(9):1243-50
references.pmid: 11941551
references.citation: J Fr Ophtalmol. 1998 Dec;21(10):723-6
references.pmid: 10052044
references.citation: Clin Infect Dis. 2010 Feb 1;50(3):291-322
references.pmid: 20047480
references.citation: J Clin Pathol. 1997 Jun;50(6):477-80
references.pmid: 9378812
references.citation: Clin Infect Dis. 2000 Nov;31(5):1245-52
references.pmid: 11073759
references.citation: Am J Med. 1998 Jan;104(1):33-9
references.pmid: 9528717
references.citation: AIDS. 2000 Mar 31;14(5):517-24
references.pmid: 10780714
references.citation: Ann Intern Med. 1992 Jan 1;116(1):33-43
references.pmid: 1727093
references.citation: Clin Infect Dis. 1999 Jan;28(1):136-8
references.pmid: 10028084
references.citation: Am J Med. 2002 Sep;113(4):294-9
references.pmid: 12361815
references.citation: J Infect Dis. 1998 May;177(5):1373-7
references.pmid: 9593027
references.citation: Clin Infect Dis. 2007 Sep 1;45(5):e60-7
references.pmid: 17682981
references.citation: N Engl J Med. 2010 Feb 25;362(8):697-706
references.pmid: 20181971
references.citation: Clin Infect Dis. 1999 May;28(5):1080-5
references.pmid: 10452638
references.citation: PLoS One. 2009;4(5):e5575
references.pmid: 19440326
references.citation: N Engl J Med. 1993 May 27;328(21):1521-7
references.pmid: 8479489
references.citation: Int J STD AIDS. 2007 May;18(5):321-3
references.pmid: 17524192
references.citation: Clin Infect Dis. 1998 Nov;27(5):1278-85
references.pmid: 9827282
references.citation: N Engl J Med. 1990 Nov 22;323(21):1451-7
references.pmid: 2233917
references.citation: J Infect Dis. 1998 Mar;177(3):770-3
references.pmid: 9498461
references.citation: Eur Respir J. 1994 Feb;7(2):235-9
references.pmid: 8162975
references.citation: Ann Intern Med. 1985 Feb;102(2):186-8
references.pmid: 3881072
references.citation: Cochrane Database Syst Rev. 2010 Aug 04;(8):CD006784
references.pmid: 20687081
references.citation: Clin Diagn Lab Immunol. 1994 Jul;1(4):450-63
references.pmid: 8556484
references.citation: AIDS. 2010 Mar 13;24(5):723-7
references.pmid: 20057312
references.citation: Br J Clin Pharmacol. 2007 Apr;63(4):387-93
references.pmid: 17335543
references.citation: Antimicrob Agents Chemother. 1996 Sep;40(9):2178-82
references.pmid: 8878602
references.citation: Lancet. 1989 Apr 8;1(8641):746-8
references.pmid: 2564563
references.citation: J Acquir Immune Defic Syndr. 2000 Oct 1;25(2):124-9
references.pmid: 11103042
references.citation: J Infect Dis. 1987 Dec;156(6):998-1002
references.pmid: 3680999
references.citation: N Engl J Med. 1996 Aug 8;335(6):377-83
references.pmid: 8676931
references.citation: Ann Intern Med. 1990 Jul 1;113(1):14-20
references.pmid: 2190515
references.citation: Am J Ophthalmol. 2001 Apr;131(4):457-67
references.pmid: 11292409
references.citation: Arch Ophthalmol. 1996 Jan;114(1):23-33
references.pmid: 8540847
references.citation: N Engl J Med. 1990 Nov 22;323(21):1500-4
references.pmid: 2136587
references.citation: Clin Infect Dis. 2004 Sep 15;39(6):770-5
references.pmid: 15472806
references.citation: Clin Infect Dis. 1999 Dec;29(6):1461-6
references.pmid: 10585796
references.citation: Antimicrob Agents Chemother. 1998 Jun;42(6):1346-9
references.pmid: 9624473
references.citation: N Engl J Med. 1997 Jul 10;337(2):83-90
references.pmid: 9211677
references.citation: PLoS One. 2010 Jul 01;5(7):e11416
references.pmid: 20617176
references.citation: Curr Opin Infect Dis. 2010 Oct;23(5):494-9
references.pmid: 20689422
references.citation: Clin Infect Dis. 2007 Feb 15;44(4):607-14
references.pmid: 17243069
references.citation: Cochrane Database Syst Rev. 2006 Jul 19;(3):CD005420
references.pmid: 16856096
references.citation: N Engl J Med. 1993 Sep 30;329(14):995-1000
references.pmid: 8366923
references.citation: J Infect Dis. 1998 Sep;178(3):900-3
references.pmid: 9728569
references.citation: N Engl J Med. 2002 Jun 20;346(25):1963-9
references.pmid: 12075057
references.citation: Am J Ophthalmol. 2001 Mar;131(3):396-7
references.pmid: 11239885
references.citation: N Engl J Med. 1991 Feb 28;324(9):580-4
references.pmid: 1992319
references.citation: Antimicrob Agents Chemother. 1998 Sep;42(9):2240-4
references.pmid: 9736542
references.citation: J Acquir Immune Defic Syndr (1988). 1993 Dec;6(12):1311-6
references.pmid: 8254467
references.citation: Ann Intern Med. 1990 Aug 1;113(3):183-7
references.pmid: 2197908
references.citation: Lancet. 1996 Mar 16;347(9003):718-23
references.pmid: 8602001
references.citation: Clin Infect Dis. 2004 Sep 15;39(6):842-9
references.pmid: 15472817
references.citation: Clin Infect Dis. 2010 Jul 15;51(2):225-32
references.pmid: 20536366
references.citation: N Engl J Med. 1984 Aug 9;311(6):354-8
references.pmid: 6738653
references.citation: N Engl J Med. 1992 Mar 19;326(12):793-8
references.pmid: 1538722
references.citation: Trans R Soc Trop Med Hyg. 1998 Nov-Dec;92(6):663-6
references.pmid: 10326116
references.citation: Clin Infect Dis. 2005 Dec 1;41(11):1621-7
references.pmid: 16267735
references.citation: Clin Infect Dis. 2010 Feb 1;50(3):338-44
references.pmid: 20038244
references.citation: Arch Intern Med. 2001 Jun 25;161(12):1529-33
references.pmid: 11427101
references.citation: Gastroenterology. 1996 Nov;111(5):1169-77
references.pmid: 8898629
references.citation: N Engl J Med. 1979 Jul 19;301(3):126-31
references.pmid: 449951
references.citation: Antimicrob Agents Chemother. 1993 Nov;37(11):2364-70
references.pmid: 8031351
references.citation: Am J Gastroenterol. 1994 Aug;89(8):1226-9
references.pmid: 8053439
references.citation: Am J Trop Med Hyg. 2009 Apr;80(4):583-7
references.pmid: 19346380
references.citation: Clin Infect Dis. 2010 Jun 1;50(11):1532-8
references.pmid: 20415574
references.citation: QJM. 1998 Dec;91(12):813-20
references.pmid: 10024946
references.citation: Antimicrob Agents Chemother. 1994 Sep;38(9):2215-7
references.pmid: 7811052
references.citation: Antimicrob Agents Chemother. 1999 Dec;43(12):2869-72
references.pmid: 10582873
references.citation: Clin Infect Dis. 2003 Nov 1;37(9):1234-43
references.pmid: 14557969
references.citation: J Infect Dis. 1998 Apr;177(4):914-20
references.pmid: 9534963
references.citation: Clin Infect Dis. 1994 Oct;19(4):741-5
references.pmid: 7803641
references.citation: Clin Infect Dis. 2003 May 1;36(9):1122-31
references.pmid: 12715306
references.citation: Clin Infect Dis. 2001 Feb 15;32(4):e81-2
references.pmid: 11181141
references.citation: Ann Intern Med. 1988 Aug 15;109(4):280-7
references.pmid: 3260759