Evaluation of garlic plant and indinavir drug efficacy in the treatment of cryptosporidiosis in experimentally immumosuppressed rats.

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.

Prevention of vaginal simian immunodeficiency virus transmission in macaques by postexposure prophylaxis with zidovudine, lamivudine and indinavir.

OBJECTIVE: To evaluate the efficacy of postexposure prophylaxis with a combination of zidovudine (ZDV), lamivudine (3TC) and indinavir (IDV), after vaginal exposure to HIV. DESIGN: : Experimental intravaginal exposure of female cynomolgus macaques to SIVmac251. METHODS: ZDV/3TC/IDV treatment was initiated 4 h after exposure and continued for 28 days. Groups of six animals received a placebo or a combination of oral ZDV (4.5 mg/kg), 3TC (2.5 mg/kg) and IDV (20 mg/kg) twice daily or subcutaneous ZDV (4.5 mg/kg) and 3TC (2.5 mg/kg) twice daily, and a higher dose of IDV (60 mg/kg) administered orally twice daily. RESULTS: In the placebo group, all animals were infected. Antiretroviral association protected one of the six animals if all drugs were administered orally and four of the six animals if ZDV and 3TC were administered subcutaneously and IDV was given orally at triple dose. In infected animals, viremia was significantly delayed and lowered in treated animals than in animals given placebo, and high CD4 cell counts were maintained in the treated animals, at least in the medium term. Antiretroviral dosages made in macaques receiving the same treatments showed that protection efficacy could be linked to antiretroviral plasmatic concentration. CONCLUSION: This study shows, for the first time in macaques, that the postexposure prophylaxis recommended for humans may be effective after vaginal exposure. Improvements in pharmacokinetic parameters significantly increased treatment efficiency.

Novel therapeutic biosensor for indinavir-a protease inhibitor antiretroviral drug.

An amperometric drug metabolism biosensor consisting of cytochrome P450-3A4 (CYP3A4) encapsulated in a didodecyldimethylammonium bromide (DDAB) vesicular system on a Pt disk electrode was developed for the determination of indinavir, a protease inhibitor antiretroviral drug. Cyclic, square wave and pulse voltammetric responses of the bioelectrode showed quasi-reversible electrochemistry of the Fe(3+)/Fe(2+) redox species of the heme thiolate CYP3A4 enzyme under aerobic and anaerobic conditions. The biosensor exhibited excellent response to indinavir with a detection limit and response time of 6.158 x 10(-2)mgL(-1), and 40s, respectively. The detection limit is well below the plasma concentration of indinavir (8h after intake) which range from 0.13 to 8.6mgL(-1).

Evaluation of antitumoral properties of the protease inhibitor indinavir in a murine model of hepatocarcinoma.

PURPOSE: Accumulating evidences show a higher incidence of hepatic neoplasm in HIV/hepatitis C virus (HCV)-coinfected individuals compared with HCV-monoinfected patients. Treatment with HIV-1 protease inhibitors inhibited cancer-promoted angiogenesis in HIV-infected patients affected by Kaposi sarcoma. We aimed to evaluate the antineoplastic potential activities of the protease inhibitor indinavir (Crixivan) in in vitro and in vivo hepatocarcinoma models. EXPERIMENTAL DESIGN: We analyzed effects of indinavir on cell growth and invasiveness in Huh7 and SK-HEP-1 hepatocarcinoma cell lines and on in vivo tumor growth of the same cells in nude mice. Morphologic and molecular analyses on explanted tumors were carried out to evaluate vascularization and apoptosis. RESULTS: We observed a reduced ability to invade an in vitro extracellular matrix for both cell lines treated with indinavir compared with controls (P = 0,001). Moreover, indinavir treatment was able to inhibit matrix metalloproteinase-2 proteolytic activation, whereas there was no effect on cell proliferation. The drug was also able to delay in vivo tumor growth. The inhibition of tumor growth was statistically significant from days 6 to 21 (P = 0.004 and P = 0.003, respectively). Moreover, the drug showed antiangiogenic and proapoptotic actions, as revealed by vessel count and apoptotic index by terminal deoxynucleotide transferase-mediated nick end labeling in explanted tumors. Finally, treatment with indinavir did not block the production of vascular endothelial growth factor in the tumors. CONCLUSION: Indinavir could be helpful to prevent the development of hepatocarcinomas in HIV/HCV-coinfected individuals. In view of the current trend to substitute protease inhibitors with other antiretroviral agents, this information may have clinical implications.

Nutrición y SIDA / Nutrition and AIDS

La infección por el VIH en la infancia es un importante problema sanitario. Se calcula que cada año nacen 400-600 hijos de madres seropositivas.El diagnóstico precoz de la infección por el VIH en el niño, es de gran importancia para instaurar lo antes posible tratamiento antirretroviral, profilaxis de infecciones oportunistas, inmunización activa y pasiva, así como un soporte psicosocial y nutricional adecuado.Estos niños presentan una disregulación en el metabolismo de las citocinas que parecen jugar un importante papel en la malnutrición, la cual es de etiología multifactorial y puede presentarse en cualquier momento evolutivo de la enfermedad.Sería importante determinar los índices nutricionales con mayor poder discriminativo para valorar la malnutrición; pues se ha encontrado una correlación entre el deterioro de la situación clínica, inmunológica y nutricional.Las nuevas estrategias terapéuticas de la desnutrición en niños con infección por VIH, se basan en la administración de acetato de megestrol y hormona de crecimiento cuyo efecto parece ser beneficioso (AU)

When to switch and what to switch to: strategic use of antiretroviral therapy.

Clinical cohort studies suggest that as many as 60% of patients experience virologic failure of a first-line antiretroviral regimen. Second-line and rescue (or salvage) regimens have a poorer success record: Most studies presented to date show a short-term virologic response rate of only approximately 30% in treatment-experienced individuals. That rate will improve with better understanding of what causes initial virologic failure, continued development of new antiretroviral agents (including drugs with new mechanisms of action) and new treatment strategies (including dual-protease inhibitor regimens), and more widespread use of resistance testing. Further clinical research is needed to improve salvage options, and physicians should consider enrolling treatment-experienced patients in clinical trials.

Resolution of recalcitrant hand warts in an HIV-infected patient treated with potent antiretroviral therapy.

Human papilloma virus (HPV)-related cutaneous manifestations occur with increased frequency and severity among HIV-infected persons. In this report, we describe an HIV-infected man with persistent, severe cutaneous hand warts that did not respond to multiple therapies, including liquid nitrogen cryotherapy, topical dinitrochlorobenzene, topical podophyllin, and intralesional interferon-alfa injections. Approximately 1 year after starting a potent protease inhibitor-containing antiretroviral regimen, the patient's recalcitrant cutaneous warts markedly diminished in size, even though the patient did not receive any specific therapy for the warts after starting aggressive antiretroviral therapy. The patient continued on a potent protease inhibitor-containing antiretroviral regimen and, approximately 2 years later, the warts completely resolved. Our patient's dramatic clinical improvement of cutaneous HPV infection that followed protease inhibitor-containing antiretroviral therapy provides a clear-cut example that protease inhibitor-containing combination antiretroviral therapy can produce significant clinical benefit.

Antiviral update.

AIDS: Data collected from several studies can provide guidance on new therapies for treatment-experienced patients. A study comparing two different triple-drug combination therapies, both using Indinavir, showed no significant differences in antiviral activity. A study of a triple-drug regimen that included Delavirdine, produced more favorable results than two different dual combination regimens. A small study indicated that "recycling" previously used antiviral drugs with two new drugs into a 6-drug regimen had positive short-term effects as a salvage therapy. However, adherence to such a regimen may prove difficult. A larger study of another salvage therapy, which used Ritonavir plus Saquinavir plus two NARTIs, had different results depending on whether the patient had been treated previously with Ritonavir or with Saquinavir. Two other studies examined different dosages of Nelfinavir or Indinavir and found that twice-a-day dosing may be as effective as three times a day. More research is needed to supplement the available knowledge for treating patients who most need alternative therapies.^ieng