indinavir-sulfate and Pancreatitis

To report on the incidence of clinical- and laboratory-defined pancreatitis in HIV-1-infected individuals treated with antiretrovirals (ARVs).. Pancreatitis incidence rates were calculated based on a Poisson distribution for subjects enrolled in 1 or more of 20 Adult AIDS Clinical Trials Group studies from October 1989 through July 1999.. A total of 8451 subjects were enrolled. The overall pancreatitis rates were 0.61 per 100 person-years (PYs) clinical and 2.23 per 100 PYs clinical/laboratory. Pancreatitis rates for single, dual, and triple nucleoside reverse transcriptase inhibitors (NRTIs) were similar. Rates of pancreatitis in didanosine (ddI) arms seemed to be dose dependent. Pancreatitis rates in ddI/hydroxyurea (HU) arms were not significantly different from the rates for ddI alone. Overall pancreatitis rates for ddI/stavudine (d4T) trials were high at 4.16 per 100 PYs clinical and 6.25 per 100 PYs clinical/laboratory. The highest rates were seen with the combination of indinavir (IDV)/ddI/d4T with or without HU.. The combination of NRTIs and definition has an impact on the incidence of pancreatitis. Standardization of definition and more comprehensive evaluations are needed to determine how much of this pancreatitis is directly caused by ARVs and how much is attributable to preexisting comorbidities and other known risk factors.

Topics: Acquired Immunodeficiency Syndrome; Didanosine; Drug Therapy, Combination; HIV-1; Humans; Hydroxyurea; Incidence; Indinavir; National Institutes of Health (U.S.); Pancreatitis; Reverse Transcriptase Inhibitors; Stavudine; United States

Virologic rebound can result from suboptimal antiviral potency in combination antiretroviral therapy.. Multicenter, partially blinded, prospective, randomized study of 202 HIV-infected subjects to determine whether therapy intensification improves long-term rates of virologic suppression.. Subjects had plasma HIV RNA < 200 copies/ml, CD4 cell count of > 200 x 10(6) cells/l, and treatment with indinavir (IDV) + zidovudine (ZDV) + lamivudine (3TC) for at least 6 months before randomization to stay on this regimen or to receive IDV + didanosine (ddI) + stavudine (d4T) plus or minus hydroxyurea (HU) (600 mg twice daily). Treatment failure was defined as either confirmed rebound of HIV RNA level to > 200 copies/ml or a drug toxicity necessitating treatment discontinuation.. Treatment failure occurred more frequently in subjects randomized to the HU-containing arm (32.4%), than in those taking IDV + ddI + d4T (17.6%) or IDV + ZDV + 3TC (7.6%). The time to treatment failure was shorter for the HU-containing arm compared with the IDV + ZDV + 3TC (P < 0.0001) or IDV + ddI + d4T arms (P = 0.032). Dose-limiting toxicities rather than virologic rebound accounted for the differences between treatment failure among the study arms. Pancreatitis led to treatment discontinuation in 4% of subjects in treatment arms containing ddI + d4T. Three subjects with pancreatitis died, all randomized to the HU-containing arm.. Switching to IDV + ddI + d4T + HU in patients treated with IDV + ZDV + 3TC was associated with a worse outcome, principally because of drug toxicity.

Topics: Adolescent; Adult; Anti-HIV Agents; Case-Control Studies; CD4 Lymphocyte Count; Drug Therapy, Combination; Enzyme Inhibitors; Female; HIV Infections; Humans; Hydroxyurea; Indinavir; Lamivudine; Male; Nucleic Acid Synthesis Inhibitors; Pancreatitis; Prospective Studies; Survival Analysis; Treatment Failure; Viral Load; Zidovudine

A new notice was distributed to health care providers cautioning of the increased risk of fatal and nonfatal pancreatitis for patients taking didanosine (Videx) from Bristol-Meyers Squibb. Several patients enrolled in the clinical trials died from pancreatitis. Any incidences of pancreatitis should be disclosed to Bristol-Meyers Squibb, and the FDA through MEDWATCH. Contact information is provided.

Topics: Anti-HIV Agents; Didanosine; Drug Therapy, Combination; HIV Infections; HIV Protease Inhibitors; Humans; Hydroxyurea; Indinavir; Nucleic Acid Synthesis Inhibitors; Pancreatitis; Stavudine