Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since the adoption of highly active antiretroviral therapy (HAART) in the mid-1990s, certain metabolic toxicities have been increasingly recognized. These include a fat redistribution syndrome (lipohypertrophy, lipoatrophy), hyperlipidaemia, altered glucose metabolism and insulin resistance, mitochondrial toxicity (presenting as anaemia, myopathy, pancreatitis, neuropathy, hepatic steatosis and lactic acidosis), and bone density abnormalities (osteoporosis and osteonecrosis). Metabolic complications are principally reported with protease inhibitors and nucleoside reverse transcriptase inhibitors, but may be seen with all classes of antiretroviral therapy. In this review, we summarize the epidemiology, pathogenesis and management of these various toxicities.
Int J STD AIDS 2001 Sep
PMID:The metabolic toxicities of antiretroviral therapy. 1151 63

The safety and efficacy of hydroxyurea with didanosine in combination with stavudine in nucleoside reverse-transcriptase inhibitor (NRTI)-experienced patients was investigated. Entry criteria included HIV-1 infected, NRTI-experienced adults, with CD4(+) counts 50-550 cells/mm(3) and viral loads >or=12,500 copies/mL. Subjects were treated with didanosine 200 mg twice a day (BID), stavudine 40 mg BID, and hydroxyurea 1000 mg daily for 16 weeks. Thirty-one HIV-1 subjects with mean bDNA viral load 1x10(5) log(10) copies/mL and mean CD4(+) T-cell counts of 231 cells/mm(3) were enrolled. A 1.3 log(10) decrease in mean viral load was seen at 12 weeks of therapy. Prior didanosine use resulted in a more rapid response to therapy compared with prior zidovudine use. Side effects consisting of neutropenia, pancreatitis, and peripheral neuropathy occurred in four subjects and resolved upon withdrawal of therapy. This non-randomized study in subjects with a mean CD4(+) T-cell count of 230 cells/mm(3) demonstrates the antiviral activity of hydroxyurea+didanosine and stavudine. Toxicities related to therapy need to be followed closely. The results support the need for a randomized, prospective study to determine the safety and efficacy of hydroxyurea plus didanosine in antiretroviral-experienced patients with CD4(+) cell counts below 300 cells/mm(3).
Int J STD AIDS 2003 May
PMID:Hydroxyurea in combination with didanosine and stavudine in antiretroviral-experienced HIV-infected subjects with a review of the literature. 1280 44

Lactic acidosis (LA), a rare but life-threatening adverse effect associated with antiretroviral therapy, has been reported with an increasing frequency since the mid-1990s. From June 1994 to June 2002, a total of six patients, four males and two females with a median age of 43 years (range, 30 to 74 years), had been diagnosed with LA. The estimated incidence of LA was 5.1 per 1000 patient-years (PYs) on highly active antiretroviral therapy (HAART) (95% confidence interval [95% CI], 4.5-5.5 per 1000 PYs) and 4.4 per 1000 PY on nucleoside analogues (NAs) (95% CI, 3.9-4.7 per 1000 PYs). Their median body mass index at diagnosis of LA was 17.6 kg/m(2) (range 16.3 to 22.6 kg/m(2)). The median CD4+ lymphocyte count at the initial diagnosis of HIV infection and at the onset of LA was 38 cells/ micro L (range, 4 to 103 cells/ micro L) and 108 cells/ micro L (range, 79 to 224 cells/ micro L), respectively. The most common symptoms were nausea, vomiting, and dyspnoea. All of the patients had findings suggestive of NA-related mitochondrial toxicity, such as myositis, pancreatitis, fatty hepatitis, peripheral neuropathy or lipodystrophy. The prescribed NA related to LA were stavudine in six patients, lamivudine, five, and didanosine, one. Despite treatment, all patients died of persistent circulatory collapse following LA. The median duration from diagnosis to death was eight days (range, 4-17 days). Our report highlights that clinicians caring for patients with AIDS should be alerted to the potentially fatal LA associated with antiretroviral therapy when patients present with low body mass index, lipodystrophy, unexplained abdominal symptoms, dyspnoea, or elevated aminotransferases.
Int J STD AIDS 2004 Apr
PMID:Fatal lactic acidosis associated with highly active antiretroviral therapy in patients with advanced human immunodeficiency virus infection in Taiwan. 1507 19

One thousand and eighty-one evaluable HIV-infected patients were assessed for pancreatic abnormalities in a prospective case-control study including the whole follow-up period of each patient (minimum 12 months). The 435 patients (40.2%), who experienced at least one episode of confirmed pancreatic laboratory abnormality had a longer duration of seropositivity, exposure to protease inhibitors, a more frequent immunodeficiency, AIDS, chronic liver and/or biliary disease and hypertriglyceridaemia, while no relation was found with antiretroviral administration, and the duration of type of nucleoside analogues, when compared with the 646 controls. High and prolonged laboratory alterations eventually associated with signs of organ involvement occurred in 166 cases (38.2%), and were related to the administration of didanosine, stavudine, lamivudine, pentamidine, cotrimoxazole or antitubercular/antimycobacterial therapy, cytotoxic chemotherapy, illicit substance or alcohol abuse, opportunistic infections, chronic liver and/or biliary disease, a protease inhibitor-based highly active antiretroviral therapy (HAART) and hypertriglyceridaemia (usually associated with HAART administration). No difference was noticed between the 46 patients with clinical and/or imaging evidence of pancreatic involvement and the 120 asymptomatic subjects. Although recurrences of enzyme alterations involved 69.6% of patients, only in 30.1% of cases did a change of the underlying antiretroviral or antimicrobial therapy become necessary. An acute, uncomplicated pancreatitis occurred in nine of the 46 symptomatic subjects (19.6%). A two to four week gabexate and/or octreotide administration (performed in 79 cases of 166, 47.6%), achieved a significant laboratory, clinical and imaging cure or improvement in 82.3% of cases, with a better success rate of combined (gabexate mesilate plus octreotide) vs. single (gabexate mesilate or ocreotide) therapy. Reduced disease recurrences and a better tolerability of antiretroviral regimens, were also noticed.
Int J STD AIDS 2008 Feb
PMID:HIV infection and the pancreas: risk factors and potential management guidelines. 1833 62