ABSTRACT
OBJECTIVE: To compare two reduced dose indinavir (IDV) + ritonavir (RTV) combinations guided by therapeutic drug monitoring (TDM) in treatment-naive HIV1-infected patients. METHODS: HIV1-infected treatment naive patients were prospectively randomized to treatment with IDV 600 mg or 400 mg BID each in combination with RTV 100 mg BID. Boosted IDV was combined with 2 NRTI, and patients were followed for 48 weeks. IDV-trough levels and initially also peak levels (C2h) were performed to allow dose modification of IDV following a specified protocol. RESULTS: 14 patients were randomized (age 38 +/- 10.4 years; mean +/- SD; 3 female, 11 male). 8 were treated with 600 mg (group 1), 6 with 400 mg IDV BID (group 2). Efficacy of treatment was good: CD4-cell count increased from 198/microl (14-523; median, range) to 371/microl (214-927) after 48 weeks (p<0.01). All but one patient with adherence problems achieved a viral load below the limit of detection. At the beginning two patients had plasma levels below 0.1 mg/l, most likely due to adherence problems. However, in the course of the observation period all patients had adequate plasma levels. 3 patients in group 1 could further reduce their IDV dose to 400 mg BID due to high plasma (peak and trough) levels. Rate of discontinuation was high (1: 4 pat., 2: 2 pat.), but only one discontinuation was possibly associated with IDV (alopecia; group 2). There were no significant changes in laboratory parameters (bilirubin, triglycerides, cholesterol) or suspicious urine results. Incidence and severity of adverse events was lower than in previous studies. CONCLUSION: Despite the low number of patients it seems reasonable to state, that boosted IDV may be used in significantly reduced dose. Efficacy seemed not to be altered, whereas tolerability was improved.
Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Drug Monitoring/methods , HIV Protease Inhibitors/therapeutic use , HIV-1/isolation & purification , Indinavir/therapeutic use , Ritonavir/therapeutic use , Adult , CD4 Lymphocyte Count , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , HIV Protease Inhibitors/pharmacokinetics , HIV-1/genetics , Humans , Indinavir/pharmacokinetics , Male , Middle Aged , Prospective Studies , RNA, Viral/analysis , Ritonavir/pharmacokinetics , Treatment OutcomeSubject(s)
Graft Rejection/diagnosis , Kidney Transplantation/physiology , Membrane Glycoproteins/analysis , Membrane Proteins/analysis , Proteins , RNA-Binding Proteins/analysis , Serine Endopeptidases/analysis , T-Lymphocytes, Cytotoxic/pathology , Biomarkers , Cytotoxicity, Immunologic , Graft Rejection/urine , Granzymes , Humans , Monitoring, Physiologic/methods , Perforin , Poly(A)-Binding Proteins , Pore Forming Cytotoxic Proteins , T-Cell Intracellular Antigen-1 , T-Lymphocytes, Cytotoxic/chemistry , Urine/cytologyABSTRACT
In a patient with metastatic melanoma transmitted by the renal allograft, HLA serves as an alloantigen per se and is associated with tumor antigens at the same time. The influence of this antigeneic pattern on the Vbeta T-cell repertoire in an allogeneic melanoma, allograft, and peripheral blood mononuclear cells (PBMC) was assessed by polymerase chain reaction. Vbeta13.1 and 19 were found in both the melanoma and the graft. Vbeta14 was detected only in the melanoma and Vbeta6 was detected only in the kidney. PBMC revealed an unrestricted Vbeta pattern. Markers for cytotoxic activity of T cells--granzyme B and perforin--were not expressed during immunosuppressive therapy as clinically reflected in a nonrejecting allograft and in a progressing melanoma. In vitro PBMC proliferated to recombinant interleukin-2, whereas recombinant interferon-gamma did not augment this response. Initiation of immune therapy, in addition to discontinuation of immunosuppression, might support the rejection of the allogeneic tumor by dominant Vbeta T cells.
