indinavir-sulfate and Cryptosporidiosis

A substantial number of patients with advanced HIV infection suffer from intractable diarrhoea. The aim of this study was to evaluate whether potent antiretroviral therapy could alleviate such diarrhoea.. In an open randomized study the effect of the HIV protease inhibitor indinavir in combination with nucleoside analogue reverse transcriptase inhibitors on chronic HIV-related diarrhoea was investigated in 14 late-stage (CD4+ lymphocyte count < or = 50 x 10(6) cells/l) HIV-infected patients. Data concerning stool frequency, stool consistency and antidiarrhoeal drug use were collected in daily diaries over a 24-week period. Endpoints of the study were reduction of stool frequency, improvement of stool consistency, weight gain, and in case of diarrhoea due to Enterocytozoon bieneusi or Cryptosporidium sp. disappearance of these parasites from stool.. Thirteen patients started the study drug indinavir. One patient died after 1 week and one patient withdrew prematurely after 18 weeks. Median stool frequency declined from 5.8 daily at baseline to 2.3 daily after 24 weeks (P=0.04). Stool consistency improved considerably over the study period: before treatment 56% of stools were watery and 0% were formed; at week 24 these figures were 0 and 35%, respectively. Body weight increased significantly with a median increment of 6.6 kg at week 24 (P=0.0006). In two out of six patients with microsporidiosis and both patients with cryptosporidiosis, stools were free of parasites at week 24. Five out of six patients who used non-specific antidiarrhoeal medication on a regular basis prior to the study had ceased to do so at the end.. The use of potent antiretroviral therapy in patients with advanced HIV infection can improve chronic HIV-related diarrhoea and in some cases lead to disappearance of E. bieneusi and Cryptosporidium sp. from the stools.

Topics: Adult; AIDS-Related Opportunistic Infections; Body Weight; CD4 Lymphocyte Count; CD8-Positive T-Lymphocytes; Cryptosporidiosis; Feces; Female; Follow-Up Studies; HIV Enteropathy; HIV Protease Inhibitors; HIV-1; Humans; Indinavir; Lymphocyte Count; Male; Microsporidiosis; Middle Aged; RNA, Viral

The present study evaluated the efficacy of garlic plant and Indinavir on cryptosporidiosis in experimentally immunosuppressed infected rats. One hundred forty five Wister rats aging 3 weeks were divided into five groups: GI: normal control, GII: Indinavir treated control, GIII: immunosuppressed infected, GIV: immunosuppressed infected and treated with garlic and GV: immunosuppressed infected and treated with Indinavir. All were subjected to clinical, parasitological and histopathological examination at different days post infection (P.I.). The results showed that in GIII, all rats had diarrhea, loss of appetite, weakness and limited movement, with 51.4% death rate. In both treated groups, some rats regained activities, with death rate of 33.3% (GV) and non GIV. There was significant decrease in the number of excreted oocysts at 5th and 10th day post treatment (P.T.) in treated groups. One week P.T., in GIV, the number of excreted oocysts had continued in decreasing while in GV, it was insignificantly increased. No cure rate was detected in both treated groups as oocysts still excreted till the end of experiment. The histopathological changes improved in treated groups in spite of the presence of some parasites on the epithelial surfaces of ileum.

Topics: Animals; Antiprotozoal Agents; Cryptosporidiosis; Cyclophosphamide; Disease Models, Animal; Garlic; Immunosuppression Therapy; Immunosuppressive Agents; Indinavir; Male; Phytotherapy; Plant Extracts; Rats; Rats, Wistar

There is much evidence to indicate the ability of Indinavir (IND) to reduce Cryptosporidium parvum infection in both in vitro and in vivo models. However, there are limitations to the administration of IND as such, due to its renal toxicity and the high rate of metabolism and degradation. We aimed to encapsulate IND in biodegradable poly (D,L-lactide-co-glycolide) nanoparticles (Np) and to engineer their surface by conjugation with an anti-Cryptosporidium IgG polyclonal antibody (Ab). Tetramethylrhodamine-labelled Np were loaded with IND and modified by conjugation with an Ab. The IND-loaded modified Np (Ab-TMR-IND-Np) did not show any change, as demonstrated by chemical analysis studies. Simultaneous addition of 50μM Ab-TMR-IND-Np and excysted oocysts to the cell culture resulted in complete inhibition of the infection. In C. parvum-infected cells, the extent to which the infection decreased depended on the duration of treatment with the Ab-TMR-IND-Np. The antibody-engineered Np loaded with IND were able to target C. parvum in infected cells and therefore might represent a novel therapeutic strategy against Cryptosporidium sp. infection. Moreover, the use of Np as an IND delivery device, allows the development of a more appropriate dose formulation thereby reducing the IND side effects.

Topics: Animals; Antibodies, Protozoan; Biocompatible Materials; Cattle; Cell Line, Tumor; Chemistry, Pharmaceutical; Cryptosporidiosis; Cryptosporidium parvum; Drug Carriers; Drug Compounding; HIV Protease Inhibitors; Humans; Immunoconjugates; Indinavir; Lactic Acid; Microscopy, Fluorescence; Molecular Targeted Therapy; Nanoparticles; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rhodamines; Spectrum Analysis

In HIV infected persons, Cryptosporidium parvum causes chronic diarrhoea, which can be life-threatening in persons with AIDS and with a low CD4+ T cell count. However, a specific and effective therapy for this opportunistic infection does not yet exist. Since the use of a combination therapy with a highly active antiretroviral therapy (HAART), the prevalence of C. parvum infection in persons with AIDS has been strongly reduced. This favorable outcome was usually attributed to the recovery of the host immunity, however improvements from this opportunistic infection have been demonstrated even in the absence of immunological recovery. The aim of the present study was to determine whether HIV protease inhibitors (PIs) exert an anti-C. parvum activity. We selected the indinavir (an aspartyl protease inhibitor included in HAART) for our experiments, since a resolution of cryptosporidial enteritis in a person with AIDS after treatment with this drug has been reported. Human ileocecal adenocarcinoma tumor cells (HCT-8) were used as in vitro model. To determine whether or not indinavir had an effect on the parasite attachment to, or invasion of the HCT-8 cells, indinavir was added to the cultures at the same time as the infective dose (3 oocysts/cell) at one of the following concentrations: 0.1, 0.5, 5, 10, 20, and 50 microM (maximum DMSO content 0.5% vol/vol). To determine whether or not indinavir had an effect on established C. parvum infection, HCT-8 cells were infected with excysted oocysts at a ratio of 3 oocysts/cell at day 0, and then indinavir at a concentration of 50 microM was added to the cultures every 24 h for 4 days. The infection level was evaluated at 2, 3, 4 and 5 days p.i. using a flowcytometric assay. Three-day-old Balb/c mice were used as animal model, animals were infected per os with 50 microl of PBS containing 10(5) oocysts. The infected mice were divided into two groups (Group A and Group B), both of which received per os indinavir diluted in PBS with 0.1% DMSO at a concentration of 10 microM (24 mg/kg). For Group A, which consisted of 15 mice (3 litters), indinavir was administered at the same time that experimental infection was performed and then every day until the mice were sacrificed (i.e., 5 days p.i.), to determine the effect of indinavir on the attachment/invasion of the enterocytes. For Group B, which also consisted of 15 mice (3 litters), indinavir was administered after the infection was established (i.e., 72 h p.i.) and every

Topics: Adenocarcinoma; AIDS-Related Opportunistic Infections; Animals; Antiretroviral Therapy, Highly Active; Aspartic Acid Endopeptidases; Cell Line, Tumor; Coccidiostats; Cryptosporidiosis; Cryptosporidium parvum; Dose-Response Relationship, Drug; Enzyme Inhibitors; HIV Protease Inhibitors; Ileal Neoplasms; Indinavir; Mice; Mice, Inbred BALB C; Protozoan Proteins

The use of highly active antiretroviral therapy in persons with acquired immunodeficiency syndrome has reduced the prevalence of infection with Cryptosporidium parvum and the length and severity of its clinical course. This effect has in most cases been attributed to the recovery of the host immunity; however, some works suggest that human immunodeficiency virus protease inhibitors, indinavir in particular, which is one of the human immunodeficiency virus protease inhibitors used in highly active antiretroviral therapy, may be capable of controlling Microsporidia and Cryptosporidium infections, which are refractory to other treatments. The objective of the present study was to investigate the effect of human immunodeficiency virus protease inhibitors on C. parvum infections. Since preliminary experiments using ritonavir, saquinavir, and indinavir showed a drastic reduction of C. parvum infection both in vivo (neonatal Balb/c mice) and in vitro (human ileocecal adenocarcinoma tumour cell line) models, indinavir alone was tested in successive experiments. In vitro, the treatment of the sporulated oocysts with different concentrations of indinavir reduced the percentage of human ileocecal adenocarcinoma tumour cell line infected cells in a dose-dependent manner. For established infection, the treatment with 50 microM of indinavir decreased the percentage of infected cells in a time-dependent manner. In vivo, mice treated with indinavir at the same time they were infected with the oocysts showed a 93% reduction in the number of oocysts present in the entire intestinal contents and a 91% reduction in the number of intracellular parasites in the ileum. For established infection, indinavir treatment reduced the number of oocysts in the entire intestinal content by about 50% and the number of intracellular parasites in the ileum by about 70%. These data show that indinavir directly interferes with the cycle of C. parvum, resulting in a marked reduction in oocyst shedding and in the number of intracellular parasites. Protease inhibitors could be considered as good candidates for the treatment of cyptosporidiosis in immunosuppressed persons.

Topics: Animals; Animals, Newborn; Antiretroviral Therapy, Highly Active; Cell Cycle; Cryptosporidiosis; Cryptosporidium parvum; HIV Protease Inhibitors; Humans; Indinavir; Mice; Mice, Inbred BALB C; Models, Animal; Tumor Cells, Cultured

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; Cryptosporidiosis; Cryptosporidium parvum; HIV Protease Inhibitors; HIV-1; Humans; Indinavir; Male; Middle Aged; Remission Induction

Topics: AIDS-Related Opportunistic Infections; Cryptosporidiosis; HIV Infections; HIV Protease Inhibitors; HIV Seropositivity; Humans; Indinavir; Male; Middle Aged