title: Efficacy of anti-leishmania therapy in visceral leishmaniasis among HIV infected patients: a systematic review with indirect comparison.
abstract: OBJECTIVE
  We conducted a systematic literature review with indirect comparison of studies evaluating therapeutic efficacy and toxicity associated to visceral leishmaniasis (VL) therapy among HIV infected individuals.
  
  
  METHODS
  The outcomes of interest were clinical and parasitological cure, mortality, and adverse events.
  
  
  METHODS
  PRISMA guidelines for systematic reviews and Cochrane manual were followed. Sources were MEDLINE, LILACS, EMBASE, Web of Knowledge databases and manual search of references from evaluated studies. We included all studies reporting outcomes after VL treatment, regardless of their design. Study quality was evaluated systematically by using the Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Comprehensive Meta-Analysis software v.2.2.048 was used to perform one-group meta-analysis of study arms with the same drug to estimate global rates of success and adverse events with each drug. These estimates were used, when possible, to indirectly compare treatment options, adjusted for CD4 count. Direct comparison was pooled when available.
  
  
  RESULTS
  Seventeen studies reporting five treatment regimens and outcome of 920 VL episodes occurring in HIV infected individuals were included. The main outstanding difference in outcome among the treatment regimens was observed in mortality rate: it was around 3 times higher with high-dose antimony use (18.4%, CI 95% 13.3-25%), indirectly compared to lipid formulations of amphotericin B treatment (6.1%, CI 95% 3.9-9.4%). It was observed, also by indirect comparison, higher rates of clinical improvement in study arms using amphotericin B than in study arms using pentavalent antimonial therapy (Sb(v)). The parasitological cure, an outcome that presented some degree of risk of selection and verification bias, had rates that varied widely within the same treatment arm, with high heterogeneity, hampering any formal comparison among drugs. One direct comparison of amphotericin and antimoniate was possible combining results of two studies and confirming the superiority of amphotericin.
  
  
  CONCLUSIONS
  Available evidence suggests that amphotericin is superior to antimony treatment. Death rate using antimoniate high dose is unacceptably high. Randomized controlled trials are necessary to compare different formulations and doses of amphotericin, alternative therapies and drug combinations.
authors: Laboratory of Clinical Research, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Fiocruz, Belo Horizonte, Minas Gerais, Brazil. glauciacota@uol.com.br
authors: Gláucia F
authors: GF
authors: Cota
authors: Marcos R
authors: MR
authors: de Sousa
authors: Tatiani Oliveira
authors: TO
authors: Fereguetti
authors: Ana
authors: A
authors: Rabello
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000627:therapeutic use; D000965:Antimony / Q000627:therapeutic use; D000981:Antiprotozoal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000981:Antiprotozoal Agents; D000666:Amphotericin B; D000965:Antimony
references: J Antimicrob Chemother. 2002 Feb;49 Suppl 1:21-30
references: 11801577
references: Clin Infect Dis. 2006 Aug 1;43(3):357-64
references: 16804852
references: J Antimicrob Chemother. 2007 Oct;60(4):837-42
references: 17684055
references: AIDS. 1999 Jun 18;13(9):1063-9
references: 10397536
references: Clin Infect Dis. 2011 Oct;53(7):e91-8
references: 21890763
references: Medicine (Baltimore). 2001 Jan;80(1):54-73
references: 11204503
references: J Glob Infect Dis. 2010 May;2(2):151-8
references: 20606971
references: Clin Microbiol Rev. 2008 Apr;21(2):334-59, table of contents
references: 18400800
references: Expert Rev Anti Infect Ther. 2006 Apr;4(2):187-97
references: 16597201
references: PLoS Negl Trop Dis. 2011 Jun;5(6):e1153
references: 21666786
references: Am J Trop Med Hyg. 2004 Dec;71(6):787-94
references: 15642973
references: Curr Pharm Des. 2002;8(4):319-42
references: 11860369
references: Am J Trop Med Hyg. 1999 Nov;61(5):766-9
references: 10586909
references: J Infect. 1996 Mar;32(2):133-7
references: 8708370
references: PLoS Med. 2009 Jul 21;6(7):e1000100
references: 19621070
references: Int J Technol Assess Health Care. 2008 Spring;24(2):170-7
references: 18400120
references: AIDS. 1999 Oct 1;13(14):1921-5
references: 10513651
references: Trans R Soc Trop Med Hyg. 1995 Mar-Apr;89(2):159-62
references: 7778140
references: Health Technol Assess. 2005 Jul;9(26):1-134, iii-iv
references: 16014203
references: BMJ. 2003 Mar 1;326(7387):472
references: 12609941
references: BMJ. 2011 Aug 16;343:d4909
references: 21846695
references: Enferm Infecc Microbiol Clin. 1995 Feb;13(2):73-9
references: 7711130
references: Eur J Clin Microbiol Infect Dis. 1997 Dec;16(12):898-903
references: 9495670
references: Future Microbiol. 2010 Sep;5(9):1301-3
references: 20860475
references: PLoS One. 2010 Nov 10;5(11):e11054
references: 21085712
references: Expert Opin Emerg Drugs. 2012 Dec;17(4):493-510
references: 23167833
references: Am J Med. 1996 May;100(5):496-501
references: 8644760
references: J Postgrad Med. 2003 Jan-Mar;49(1):39-49
references: 12865570
references: An Med Interna. 1997 Oct;14(10):506-10
references: 9424140
references: Molecules. 2009 Jun 30;14(7):2317-36
references: 19633606
references: Trans R Soc Trop Med Hyg. 2001 Nov-Dec;95(6):668-72
references: 11816442
references: Enferm Infecc Microbiol Clin. 1998 Mar;16(3):130-1
references: 9611875
references: Ann Trop Med Parasitol. 2003 Oct;97 Suppl 1:135-42
references: 14678640
references: J Int Assoc Physicians AIDS Care. 1997 Jun;3(6):22-39
references: 11364428
references: Am J Trop Med Hyg. 1992 Mar;46(3):296-306
references: 1313656
references: Clin Infect Dis. 2011 Dec;53(12):e152-8
references: 22016502
references: J Infect. 1990 Nov;21(3):261-70
references: 2273273
references: Clin Microbiol Infect. 2001 Jun;7(6):291-300
references: 11442562
references: J Clin Epidemiol. 2000 Nov;53(11):1119-29
references: 11106885