title: Antiretroviral drugs and acute pancreatitis in HIV/AIDS patients: is there any association? A literature review.
abstract: In HIV-seropositive individuals, the incidence of acute pancreatitis may achieve 40% per year, higher than the 2% found in the general population. Since 1996, when combined antiretroviral therapy, known as HAART (highly active antiretroviral therapy), was introduced, a broad spectrum of harmful factors to the pancreas, such as opportunistic infections and drugs used for chemoprophylaxis, dropped considerably. Nucleotide analogues and metabolic abnormalities, hepatic steatosis and lactic acidosis have emerged as new conditions that can affect the pancreas. To evaluate the role of antiretroviral drugs to treat HIV/AIDS in a scenario of high incidence of acute pancreatitis in this population, a systematic review was performed, including original articles, case reports and case series studies, whose targets were HIV-seropositive patients that developed acute pancreatitis after exposure to any antiretroviral drugs. This association was confirmed after exclusion of other possible etiologies and/or a recurrent episode of acute pancreatitis after re-exposure to the suspected drug. Zidovudine, efavirenz, and protease inhibitors are thought to lead to acute pancreatitis secondary to hyperlipidemia. Nucleotide reverse transcriptase inhibitors, despite being powerful inhibitors of viral replication, induce a wide spectrum of side effects, including myelotoxicity and acute pancreatitis. Didanosine, zalcitabine and stavudine have been reported as causes of acute and chronic pancreatitis. They pose a high risk with cumulative doses. Didanosine with hydroxyurea, alcohol or pentamidine are additional risk factors, leading to lethal pancreatitis, which is not a frequent event. In addition, other drugs used for prophylaxis of AIDS-related opportunistic diseases, such as sulfamethoxazole-trimethoprim and pentamidine, can produce necrotizing pancreatitis. Despite comorbidities that can lead to pancreatic involvement in the HIV/AIDS population, antiretroviral drug-induced pancreatitis should always be considered in the diagnosis of patients with abdominal pain and elevated pancreatic enzymes.
authors.affiliation: Faculdade de Medicina do ABC, Santo André, SP, Brazil.
authors.forename: Natalia Mejias
authors.initials: NM
authors.lastname: Oliveira
authors.affiliation: Faculdade de Medicina do ABC, Santo André, SP, Brazil.
authors.forename: Felipe Augusto Yamauti
authors.initials: FA
authors.lastname: Ferreira
authors.affiliation: Faculdade de Medicina do ABC, Santo André, SP, Brazil.
authors.forename: Raquel Yumi
authors.initials: RY
authors.lastname: Yonamine
authors.affiliation: Faculdade de Medicina do ABC, Santo André, SP, Brazil.
authors.forename: Ethel Zimberg
authors.initials: EZ
authors.lastname: Chehter
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy*; D000208:Acute Disease; D019380:Anti-HIV Agents / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D015897:Comorbidity; D005260:Female; D006801:Humans; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced*; D012307:Risk Factors
chemical_list: D019380:Anti-HIV Agents
references.citation: Dig Dis Sci. 2008 Oct;53(10):2616-20
references.pmid: 18288615
references.citation: Am J Med. 1995 Mar;98(3):243-8
references.pmid: 7872340
references.citation: J Clin Gastroenterol. 1993 Oct;17(3):254-63
references.pmid: 8228089
references.citation: J Clin Gastroenterol. 2005 Sep;39(8):709-16
references.pmid: 16082282
references.citation: Med Clin North Am. 1992 Jan;76(1):45-62
references.pmid: 1727541
references.citation: Eur J Clin Microbiol Infect Dis. 1998 Nov;17(11):810-1
references.pmid: 9923528
references.citation: J Infect. 2003 Aug;47(2):188-9
references.pmid: 12860159
references.citation: Lancet. 1988 Jan 2-9;1(8575-6):65-6
references.pmid: 2891934
references.citation: Rev Esp Enferm Dig. 1996 Feb;88(2):114-7
references.pmid: 8664067
references.citation: BMJ. 2001 Jan 13;322(7278):81
references.pmid: 11154621
references.citation: Lancet. 1990 Dec 15;336(8729):1515
references.pmid: 1979129
references.citation: AIDS Patient Care STDS. 2008 Feb;22(2):113-21
references.pmid: 18260802
references.citation: AIDS. 2008 Jan 2;22(1):47-56
references.pmid: 18090391
references.citation: AIDS. 2000 Sep 8;14(13):1879-86
references.pmid: 10997390
references.citation: N Engl J Med. 1998 Mar 26;338(13):853-60
references.pmid: 9516219
references.citation: Clin Infect Dis. 1999 Jan;28(1):161-2
references.pmid: 10028103
references.citation: Am J Gastroenterol. 1992 Jun;87(6):708-13
references.pmid: 1590305
references.citation: Lancet. 1987 Sep 5;2(8558):570-1
references.pmid: 2887861
references.citation: Clin Infect Dis. 2003 Sep 1;37(5):e57-62
references.pmid: 12942419
references.citation: S Afr J Surg. 2008 Aug;46(3):83-6
references.pmid: 18807304
references.citation: Ann Intern Med. 1993 Sep 15;119(6):539-40
references.pmid: 8395145
references.citation: Ann Pharmacother. 1994 Sep;28(9):1025-8
references.pmid: 7803875
references.citation: J Acquir Immune Defic Syndr. 2005 Jun 1;39(2):159-66
references.pmid: 15905731
references.citation: CMAJ. 2004 Jan 20;170(2):229-38
references.pmid: 14734438
references.citation: AIDS. 2007 Feb 19;21(4):532-3
references.pmid: 17301578
references.citation: J Antimicrob Chemother. 1999 Jul;44(1):137-8
references.pmid: 10459826
references.citation: J Clin Gastroenterol. 1997 Dec;25(4):640-5
references.pmid: 9451679
references.citation: Eur J Med Res. 2004 Dec 22;9(12):537-44
references.pmid: 15689299
references.citation: Int J STD AIDS. 2008 Feb;19(2):99-105
references.pmid: 18334062
references.citation: Drug Saf. 2008;31(10):823-37
references.pmid: 18759507
references.citation: Lancet. 2004 Jul 3-9;364(9428):65-7
references.pmid: 15234858
references.citation: AIDS. 2001 Mar 30;15(5):617-20
references.pmid: 11316999
references.citation: Pancreas. 2003 Jul;27(1):e1-5
references.pmid: 12826911
references.citation: J Clin Gastroenterol. 1991 Feb;13(1):58-64
references.pmid: 2007747
references.citation: Am J Gastroenterol. 2003 Jun;98(6):1278-83
references.pmid: 12818269
references.citation: J Emerg Med. 1995 Sep-Oct;13(5):633-7
references.pmid: 8530781
references.citation: Am J Gastroenterol. 1997 Nov;92(11):2044-8
references.pmid: 9362189
references.citation: Sex Transm Infect. 2002 Feb;78(1):58-9
references.pmid: 11872862
references.citation: AIDS. 1999 Jul 30;13(11):1421-3
references.pmid: 10449303
references.citation: Arch Pathol Lab Med. 1994 Sep;118(9):884-90
references.pmid: 8080357
references.citation: Mod Pathol. 1990 Jan;3(1):49-53
references.pmid: 2308920
references.citation: AIDS. 1999 Dec 24;13(18):2493-505
references.pmid: 10630518
references.citation: Gastroenterology. 1990 Jul;99(1):263-7
references.pmid: 2160899
references.citation: Pharmacotherapy. 2005 Aug;25(8):1044-54
references.pmid: 16207094
references.citation: Ann Pharmacother. 2004 Oct;38(10):1660-3
references.pmid: 15340130
references.citation: AIDS. 1992 Aug;6(8):831-5
references.pmid: 1418780