indinavir-sulfate and Diarrhea

A double-blind, randomized study of zidovudine-experienced, PI- and lamivudine-naive adults with baseline CD4 cell counts of < or =50 cells/mm3 had demonstrated that the HIV suppression achieved with zidovudine, lamivudine, and indinavir therapy was superior to that achieved with dual-nucleoside or indinavir-only regimens after 24 weeks of therapy. In a 192-week extension of the study, 371 participants received open-label indinavir with or without other antiretroviral drugs. One hundred and eight subjects were originally randomized to receive triple therapy. After 216 weeks, the proportion of subjects with HIV RNA levels of <500 copies/mL were 34%, according to a general estimating equation analysis, 92%, according to an observed data analysis, and 24%, according to an intention-to-treat analysis counting noncompleters as failures; the proportions of subjects with HIV RNA levels of <50 copies/mL were 31%, 85%, and 22%, respectively. Hyperbilirubinemia (experienced by 31% of subjects), nausea (17%), abdominal pain (14%), and nephrolithiasis (13%) were the most common drug-related adverse events during the extension.

Topics: Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Diarrhea; Double-Blind Method; Drug Therapy, Combination; Fatigue; Female; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Indinavir; Lamivudine; Male; Middle Aged; RNA, Viral; Zidovudine

This study evaluates the safety and potential pharmacokinetic interaction between indinavir and trimethoprim/sulfamethoxazole (TMP/SMZ). In a randomized, three-period crossover fashion, 12 healthy adults received 1 week of indinavir sulfate 400 mg orally every 6 hours with placebo, TMP 160 mg/SMZ 800 mg orally every 12 hours with placebo, and indinavir sulfate with TMP/SMZ. Plasma indinavir, SMZ, and TMP concentrations were determined after the last dose of each treatment period. Concomitant administration resulted in a 17% decrease in geometric mean trough plasma indinavir concentrations (p = 0.032), an 18% increase in geometric mean AUC0-12 h and Cmax TMP values (p = 0.031 and 0.030, respectively), and a 5% increase in geometric mean AUC0-12 h SMZ values (p = 0.039). None of these effects was considered clinically significant. The combination of indinavir sulfate and TMP/SMZ is generally well tolerated, with no clinically significant pharmacokinetic interaction being noted.

Topics: Abdominal Pain; Administration, Oral; Adolescent; Adult; Anti-Infective Agents; Area Under Curve; Bilirubin; Cross-Over Studies; Diarrhea; Drug Interactions; Female; Headache; HIV Protease Inhibitors; Humans; Indinavir; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Colon; Diarrhea; HIV Protease Inhibitors; HT29 Cells; Humans; Indinavir; Intestinal Absorption; Intestinal Mucosa; Nelfinavir; Ritonavir; Saquinavir

Diarrhea due to infection with Microsporidium (M) or Cryptosporidium (C) raises significant therapeutic challenges in HIV-infected patients. The usefulness of protease inhibitor therapy was evaluated in 20 HIV-positive patients with positive tests for M and/or C. There were 17 men and three women with a mean age of 42.5 years (range, 26-64 years). Two patients had category B disease and 18 category C disease according to the 1993 CDC classification scheme (CD4 count before therapy, 72/mm3; mean viral burden, 4.6 log). Seventeen patients had chronic diarrhea (due to M in 12 cases and to C in five), and the remaining three patients were asymptomatic M carriers. Clinical symptoms resolved after addition to the antiretroviral regimen of indinavir (n = 17) or saquinavir (n = 3). Mean weight gain was 10.5 kg. Karnofsky's index improved. Twelve patients, including one of the three who were asymptomatic at baseline, had negative follow-up stool cultures. The mean CD4 count increase was 125/mm3, and the mean viral burden decrease was 1.285 log. These data suggest that protease inhibitors may be capable of eradicating M and/or C infection refractory to other treatments. The reason for this effect may involve partial restoration of immune function due to inhibition of HIV replication.

Topics: Adult; AIDS-Related Opportunistic Infections; Animals; Anti-HIV Agents; Cryptosporidiosis; Diarrhea; Drug Therapy, Combination; Feces; Female; HIV Infections; HIV Protease Inhibitors; Humans; Immunocompetence; Indinavir; Male; Microsporida; Microsporidiosis; Middle Aged; Reverse Transcriptase Inhibitors; Saquinavir; Treatment Outcome

Topics: AIDS-Related Opportunistic Infections; Animals; Anti-HIV Agents; Diarrhea; Follow-Up Studies; HIV Protease Inhibitors; Humans; Indinavir; Intestinal Diseases, Parasitic; Male; Microsporida; Microsporidiosis; Remission Induction; Retrospective Studies; Ritonavir

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Delavirdine; Diarrhea; Didanosine; Drug Interactions; Drug Therapy, Combination; HIV Infections; Humans; Indinavir; Lamivudine; Nelfinavir; Nevirapine; Protease Inhibitors; Reverse Transcriptase Inhibitors; Ritonavir; Saquinavir; Virus Replication; Zalcitabine; Zidovudine