Abstract
ABSTRACTIn 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.
Highlights
The human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS) are worldwide public health problems
Since the HIV is probably directly toxic to the pancreas, pancreatic involvement in patients with AIDS was a common finding in post-mortem studies in the pre-HAART era.[3,4,5,6,7,8] Chehter et al[9] found atrophy of acinar cells in 60% of samples from 109 post-mortem pancreas, in addition to decrease in zymogen granules (52%) and nucleus changes (64%), the question remaining if these changes were caused by the HIV virus or by malnutrition, and if they were really capable of leading to pancreas dysfunction
In the pre-HAART era, pentamidine and didanosine, drugs extensively used for AIDS patients, were associated with increased incidence of acute pancreatitis (AP),(8,11-19) mainly when there was a previous episode of AP, prolonged treatment with high doses and severe immunocompromised conditions.[20]. In the Cappell and Marks series,(10) among 18 patients with drug-related AP, pentamidine was responsible for 12 cases, followed by didanosine with 4, and sulfamethoxazole-trimethoprim with 2 cases
Summary
The human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS) are worldwide public health problems. Since the HIV is probably directly toxic to the pancreas, pancreatic involvement in patients with AIDS was a common finding in post-mortem studies in the pre-HAART era.[3,4,5,6,7,8] Chehter et al[9] found atrophy of acinar cells in 60% of samples from 109 post-mortem pancreas, in addition to decrease in zymogen granules (52%) and nucleus changes (64%), the question remaining if these changes were caused by the HIV virus or by malnutrition, and if they were really capable of leading to pancreas dysfunction. When compared to the control group, these patients were younger (mean age of 35.2 years versus 49.1 years) and, generally, men (77% versus 48%) and black individuals (77% versus 11%)
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