indinavir-sulfate and Exanthema

Most of the studies evaluating rash in HIV-positive patients have focused on nonnucleoside reverse transcriptase inhibitors (NNRTI), particularly nevirapine, and little is known about the occurrence of rash and the risk factors for its development in patients receiving regimens not based on NNRTI.. We evaluated all cases of rash observed during a 48-week randomized multicentre trial in 1251 nucleoside-experienced patients who started treatment with protease inhibitors (ritonavir or indinavir) at CD4 counts below 50 cells/microL. Incidence rates for rash were calculated according to gender, clinical status, age, use of highly active antiretroviral therapy (HAART), Pneumocystis carinii pneumonia (PCP) prophylaxis and use of individual antiretroviral drugs at enrollment. Differences between groups defined according to the above characteristics were tested for statistical significance using the log-rank test in a Kaplan-Meier survival analysis. All factors that gave results in the univariate analyses below the significance level of 0.05 were included in a multivariate analysis using a Cox regression model.. During a follow-up period of 9690 person-months, 66 patients (5.3%) developed rash (0.68 events/100 person-months). In the univariate analyses, risk of rash did not differ with trial treatment (indinavir or ritonavir), clinical status, PCP prophylaxis, or age. During follow-up, rash was observed in 7.5% of enrolled women and in 4.5% of enrolled men (P=0.03). Serious rash occurred in 4.5% of enrolled women and in 1.6% of enrolled men (P=0.003). Use of HAART (P<0.001) and inclusion of zidovudine and of zalcitabine in the prescribed regimen (P=0.02) appeared to be associated with a lower risk of rash. In the multivariate analysis, the variables that remained significantly predictive of rash were gender (risk for women compared to men: 1.65, 95% confidence interval (CI): 1.00-2.72, P=0.048) and use of a non-HAART regimen (risk for non-HAART patients compared to HAART: 2.73, 95% CI: 1.49-5.02, P=0.001).. In our study, about 5% of HIV-positive patients who started treatment with protease inhibitors at very low CD4 counts developed rash, generally in the first few weeks after treatment. Risk was significantly higher in women and in patients who did not receive a HAART regimen. Our data indicate that women have a higher risk of rash than men, also with regimens that do not include NNRTI.

Topics: Adult; Aged; Antiretroviral Therapy, Highly Active; Drug Eruptions; Exanthema; Female; Follow-Up Studies; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Indinavir; Male; Middle Aged; Risk Factors; Ritonavir; Sex Factors; Viral Load

HBY-097 (HBY), an investigational nonnucleoside reverse transcriptase inhibitor (NNRTI), and indinavir (IDV) share a common metabolic pathway, cytochrome P4503A4 (CYP3A4), and may clinically be used together as well as with zidovudine (ZDV). Thus, the potential pharmacokinetic (PK) interaction between these drugs was evaluated. HBY (500 mg Q8H), IDV (800 mg Q8H), and ZDV (200 mg Q8H) were given to 8 HIV-infected subjects. Serial plasma samples were collected at baseline (ZDV and IDV alone) and day 11 (all 3 drugs) to determine PK parameters using noncompartmental analysis. PK parameters for ZDV in the presence and absence of HBY were not appreciably different. However, both the maximum (Cmax) and minimum (Cmin) concentrations of IDV were significantly reduced, from a mean of 7514 +/- 1636 and 146 +/- 81 mcg/L to 4725 +/- 2494 mcg/L and 54 +/- 24 mcg/L (p < .05) after addition of HBY. Furthermore, apparent clearance (CL/F) of IDV before and after 11 days of concomitant HBY administration was significantly higher, from 0.69 +/- 0.14 to 1.94 +/- 0.63 L/h/kg (p < .05) with an associated reduction in area under the curve (AUC0-8) from 16,034 +/- 4903 to 6134 +/- 2701 mg/L/h (p < .05). The increase in IDV CL/F is consistent with the observed metabolic induction effects of other NNRTIs. The results of this trial showed that HBY significantly alters the pharmacokinetic parameters of IDV at the dose studied.

Topics: Adult; Antiviral Agents; Area Under Curve; Drug Interactions; Drug Therapy, Combination; Exanthema; Female; Gastrointestinal Diseases; HIV Protease Inhibitors; HIV Seropositivity; Humans; Indinavir; Male; Middle Aged; Quinoxalines; Reverse Transcriptase Inhibitors; Zidovudine

Topics: Adult; Anti-HIV Agents; Chemoprevention; Exanthema; Female; General Surgery; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Neutropenia; Occupational Exposure

To characterize indinavir-associated rash using systematic data collection through postmarketing surveillance in a sample of HIV/AIDS patients.. HIV-infected patients identified through a medication counseling line who reported onset of a rash following initiation of indinavir therapy were included in this case series analysis. Pertinent information regarding onset, description, and management of rash; other medications initiated within two weeks of indinavir or rash onset; and medication allergy history was obtained through follow-up telephone contact. Patients were contacted weekly until the rash resolved or indinavir was discontinued.. Stadtlanders Drug Distribution Company, located in Pittsburgh, PA.. Of the 110 patients identified and followed, 67% reported rash onset within two weeks of initiating indinavir therapy. The rash was initially localized in all 110 patients and subsequently spread to other areas of the body in 77% of the patients. The rash spread to the full body in 44% (49) of the patients. The rash was accompanied by pruritus in 86% of the patients, and the majority of patients (87%) were afebrile. Eighty-one patients received treatment with medications such as antihistamines or oral or topical corticosteroids. Fifty percent of patients receiving treatment for the rash reported that these medications were helpful in relieving rash symptoms. Fifty-nine percent of the patients continued indinavir therapy despite the occurrence of rash.. Results from this study suggest that indinavir-associated rash occurs within two weeks of initiation of therapy for the majority of patients. Typically, the rash is localized with subsequent spread and is associated with pruritus. The majority of patients are able to continue indinavir therapy despite the occurrence of rash.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Anti-HIV Agents; Exanthema; Female; Humans; Indinavir; Male; Middle Aged