Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.16 (HIV-1 protease)
 2,107 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper describes a case report of an HIV-infected patient with mucocutaneous Kaposi's sarcoma (KS) with oral involvement, which presented complete clinical resolution of lesions on antiretroviral treatment with ritonavir, an HIV-1 protease inhibitor. Although it has still not been demonstrated that ritonavir has a specific antiviral action against HHV-8, a gamma herpesvirus probably involved in KS aetiopathogenesis, it has been proven that it reduces the HIV load significantly. This affects certain growth factors of KS, such as Tat protein and cytokines, and favours recovery of immune function, which correlates with protection against AIDS-defining conditions.
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PMID:Regression of AIDS-related Kaposi's sarcoma following ritonavir therapy. 969 61

Human herpesvirus 8 (HHV-8) is believed to play a role in the pathogenesis of Kaposi's sarcoma (KS) and possibly in other proliferative disorders often associated with human immunodeficiency virus type 1 (HIV-1) infection. Recent case reports have indicated resolution of KS and clearance of HHV-8 DNA from peripheral blood mononuclear cells (PBMC) in HIV-1-infected subjects following highly effective antiretroviral therapy, including HIV-1 protease inhibitors (PI), suggesting a possible activity for these compounds on HHV-8 replication. In the present study, the time course of PBMC HHV-8 DNA levels, plasma HIV-1 RNA load, and CD4+ T-cell counts were followed up in six coinfected subjects (four with and two without KS) under antiretroviral therapy with PI. A specific anti-HHV-8 role for PI was not consistently found, since fluctuation of HHV-8 viral load over time appeared to be independent of treatment. Nevertheless, our data support the hypothesis that KS patients may significantly benefit from PI therapy as an indirect consequence of partial restoration of immune functions following effective anti-HIV-1 combination therapy.
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PMID:Antiretroviral therapy with protease inhibitors in human immunodeficiency virus type 1- and human herpesvirus 8-coinfected patients. 989 98

Treatment with HIV-1 protease inhibitors (PI) is associated with a reduced incidence or regression of Kaposi sarcoma (KS). Here we show that systemic administration of the PIs indinavir or saquinavir to nude mice blocks the development and induces regression of angioproliferative KS-like lesions promoted by primary human KS cells, basic fibroblast growth factor (bFGF), or bFGF and vascular endothelial growth factor (VEGF) combined. These PIs also block bFGF or VEGF-induced angiogenesis in the chorioallantoic membrane assay with a potency similar to paclitaxel (Taxol). These effects are mediated by the inhibition of endothelial- and KS-cell invasion and of matrix metalloproteinase-2 proteolytic activation by PIs at concentrations present in plasma of treated individuals. As PIs also inhibit the in vivo growth and invasion of an angiogenic tumor-cell line, these data indicate that PIs are potent anti-angiogenic and anti-tumor molecules that might be used in treating non-HIV KS and in other HIV-associated tumors.
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PMID:HIV protease inhibitors are potent anti-angiogenic molecules and promote regression of Kaposi sarcoma. 1187 92

Infection by human immunodeficiency virus (HIV) is associated with an increased risk of certain tumours, particularly Kaposi's sarcoma, non-Hodgkin's lymphomas and cervical cancer. However, the incidence of these tumours in HIV-infected patients has decreased significantly since the widespread use of highly active antiretroviral therapy (HAART). This effect cannot be solely explained by the ability of these drugs to suppress HIV replication and thereby reconstitute the immune system. Recent studies have shown that inhibitors of the HIV aspartyl protease, which are widely used in HAART, have direct anti-angiogenic and antitumour effects that are unrelated to their antiviral activity. So these drugs might be used to treat cancer in patients who are not infected with HIV.
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PMID:Antitumour effects of antiretroviral therapy. 1551 59

A patient with human immunodeficiency virus infection and end-stage renal disease received a renal transplant. At the time of surgery, the patient was on quadruple antiretroviral therapy (lamivudine, zidovudine, and amprenavir/ritonavir). Immunosuppression was initiated with basiliximab, corticosteroid, mycophenolate mofetil, and a single 0.5 mg dose of tacrolimus. In the following days, an increase in tacrolimus concentration was observed with a peak of 37 ng/mL. Tacrolimus half-life was 6.5 days and tacrolimus maintenance dose was 0.5 mg every 4 days. Eleven months later, the patient had developed Kaposi sarcoma. Tacrolimus was replaced by sirolimus (first dose 1 mg), and the patient was stabilized with 1.5 mg of sirolimus once a week. Increased tacrolimus half-life and increased dose interval of sirolimus and tacrolimus were due to CYP3A4/5 and/or P-glycoprotein inhibition by protease inhibitors. Close monitoring is required in the management of tacrolimus and sirolimus dosing regimens when combined with ritonavir boosted HIV-1 protease inhibitors.
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PMID:Effect of coadministered HIV-protease inhibitors on tacrolimus and sirolimus blood concentrations in a kidney transplant recipient. 1970 21