[What should we pay attention to in combination treatment of HIV infected patients? Interaction problems of protease inhibitors].
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Drug Therapy, Combination↗
Biomedical subjects
J C Wasmuth
Publications and source records attributed to J C Wasmuth.
Indication, outcome and follow up of intensive care in patients with HIV-infection.
BACKGROUND/AIM: The admission to intensive care is controversially discussed in patients with HIV infection, since life expectancy is limited. Therefore, we analyzed indications, outcomes and follow up of all patients with confirmed HIV-infection and Aids defining symptoms who had been admitted to the intensive care unit (ICU) of our department between 1985-1996. RESULTS: 49 patients were admitted to the ICU, 42 of them with CDC stage C of HIV infection before admission. The leading indications were pneumonia (n = 15; PCP: 10, bacterial: 5), acute bleedings (n = 14), acute neurological diseases (n = 6), and gastrointestinal perforation (n = 5). Overall mortality was 39% (19/49) with a higher mortality seen in patients with respiratory disorders (53%) compared to non-respiratory disorders (22%, n.s.). The only significant predictor of mortality was the serum creatinine (p = 0.001), while differences in the APACHE II score between survivors and non-survivors did not reach statistical significance (22 +/- 7, 16 +/- 5; p = 0.14). During follow up no difference was seen in the life expectancy of HIV-infected survivors of intensive care as compared to those patients with AIDS who had never been admitted to ICU (8.4 months versus 9 months). DISCUSSION: The need for intensive care in HIV infected patients does not accelerate the progression of HIV infection to death, if the complications requiring ICU intervention can be managed successfully. Respiratory infections and impaired renal function are risk factors for a fatal outcome. Thus, HIV infected patients benefit from intensive care therapy.
Adult↗
Prediction of imminent complications in HIV-1-infected patients by markers of lymphocyte apoptosis.
OBJECTIVE: The aim of the study was to compare accepted surrogate markers of HIV disease progression with markers of lymphocyte apoptosis in their ability to predict short-term disease progression. METHODS: In all, 40 HIV-positive patients were studied prospectively and observed during follow-up for HIV-related adverse clinical events. Ex vivo apoptosis was measured with the markers CD95 expression, annexin V binding, and Apostain dye uptake by flow cytometry at baseline. Established markers of disease progression (CD4 count, HIV-RNA level, and CD8/38 count), CD8, B-cell, and natural killer (NK) cell counts were determined by standard procedures at baseline and after 6 months. RESULTS: In HIV-infected patients, CD95 expression and annexin V binding showed significantly elevated apoptosis in peripheral blood lymphocytes and all lymphocyte subsets at baseline compared with HIV-negative, healthy controls. Apostain failed to differentiate between HIV-infected patients and healthy controls. HIV-related complications could be predicted by CD4 and CD8/38 counts, but not HIV viral load as assessed by relative operating characteristic (ROC) analysis (CD4, p = .003; CD8/38, p = .031). A similar or even better diagnostic accuracy was found for CD95 expression in total lymphocytes (p<.001), the CD4+ (p = .003) and CD8+ (p = .005) T-cell subsets and for annexin V binding in CD4+ T cells (p = .005). When patients with CD4 counts <200 cells/microl were analyzed separately, only annexin V binding in CD4+ T cells, but none of the other prognostic markers could predict complications (p = .001). CONCLUSION: Determination of annexin V binding on CD4+ T cells may be a useful tool to monitor HIV-infected patients with low (<200 cells/microl) CD4 counts, as it can reliably assess the risk for imminent complications in such patients.
AIDS-Related Opportunistic Infections↗
[Progressive multifocal leukoencephalopathy].
PATHOGENESIS: Progressive multifocal leukoencephalopathy is a demyelinating disease of the central nervous system caused by infection and reactivation of JC-virus. About 5% of all HIV-infected patients develop this fatal disease. Although pathogenesis is not completely understood, progressive multifocal leukoencephalopathy is thought to be a persistent infection. The kidneys, bone marrow, peripheral blood lymphocytes and the brain itself are candidates for latency sites of JC-virus. Loss of T-helper-cells in the course of HIV-infection or other immunosuppressive states result in reactivation of JC-virus. DIAGNOSIS: Progressive multifocal leukoencephalopathy can be diagnosed by focal neurological symptoms, radiographic signs in magnetic resonance imaging and detection of JC-virus in brain tissue or cerebrospinal fluid. TREATMENT: A specific therapy is not yet available or established. Highly active antiretroviral therapy (HAART) and cidofovir are promising and may prove useful in the near future.
AIDS-Related Opportunistic Infections↗
Influence of protease inhibitor therapy on lipoprotein metabolism.
OBJECTIVES: Protease inhibitors are efficient drugs as part of highly active antiretroviral therapy. They have been shown to cause hyper- and dyslipoproteinemia. Since antiretroviral therapy is able to delay disease progression and possibly extend life expectancy in HIV-infected individuals, the precise nature of serum lipid disturbances may become of clinical interest with respect to its atherogenicity and to finding treatment options. DESIGN: We investigated prospectively, in 19 subsequent HIV-positive male patients (mean age 42 +/- 13 years), multiple lipid parameters in plasma, before and during treatment with a protease inhibitor (nelfinavir, ritonavir, or indinavir) and two nucleoside analogue reverse transcriptase inhibitors (NRTI). The median (range) treatment duration was 22 (7-40) weeks. 12 patients were treatment-naive; 7 had already NRTI medication at baseline. RESULTS: Total cholesterol increased by 28 mg dL-1 (95% CI: + 7 to + 48, baseline 158 +/- 53, P = 0.01), triglycerides increased by 96 mg dL-1 (+ 22 to + 170, baseline 152 +/- 91, P = 0.014), HDL cholesterol was unchanged, LDL cholesterol was slightly but not significantly elevated, VLDL cholesterol increased by 20 mg dL-1 (+ 9 to + 31, baseline 33 +/- 21, P = 0.001), VLDL triglycerides increased by 86 mg dL-1 (+ 22 to + 150, baseline 128 +/- 91, P = 0. 01). The ratio of total cholesterol to HDL cholesterol increased by 1.2 (+ 0.7 to + 1.7, baseline 4.8 +/- 1.5, P = 0.0001) and the ratio of HDL2 to HDL3 decreased by 0.06 (-0.02 to -0.09, baseline 0.47 +/- 0.11, P = 0.005). (Conversion factors, mg dL-1 to mmol L-1: 0.0259 for cholesterol, 0.0114 for triglycerides.) CONCLUSIONS: The data indicate that the predominant feature of dyslipidemia under protease inhibitors is an increase in triglyceride-containing lipoproteins. This observation is in accordance with the hypothesis of increased apoptosis of peripheral adipocytes, release of free fatty acids and subsequent increased synthesis of VLDL. The lipid profile, based on the ratio of total cholesterol to HDL cholesterol and the ratio HDL2 to HDL3, is significantly more atherogenic.
Adult↗
Diurnal variation of corticotropin-releasing factor binding sites in the rat brain and pituitary.
1. Corticotropin-releasing factor (CRF) is thought to be involved in the regulation of the diurnal activity of the hypothalamus-pituitary-adrenal (HPA) axis and to act as a neurotransmitter in the brain. To date it is unknown whether the binding sites of the central CRF system are subject to diurnal variations. 2. We measured the number of CRF binding sites over the course of a complete 24-hr light-dark cycle in the pituitary, amygdala, bed nucleus of the stria terminalis (BNST), cingulate cortex, visceral cortex, paraventricular nucleus of the hypothalamus, hippocampus, and locus ceruleus of rats by in vitro receptor autoradiography with iodinated ovine CRF. A 24-hr time course was also established for plasma CRF and corticosterone. 3. The diurnal pattern of plasma CRF does not correlate with the pattern of plasma corticosterone. Within the brain, CRF binding in the basolateral nucleus of the amygdala showed a U-shaped curve with maximum levels in the morning and a wide hallow between 1500 and 0100. A biphasic profile with a small depression in the afternoon and a more pronounced depression in the second half of the activity period is characteristic for the other brain areas and the pituitary. The profile for the pituitary correlates with those for the BNST and the area of the locus ceruleus. Furthermore, the diurnal pattern of CRF binding sites in the BNST correlates with that of the hippocampus, and the daytime pattern of the visceral cortex is similar to that of both the hippocampus and the BNST. 4. Since the CRF-binding profiles in the brain and the pituitary clearly differ from the profiles of both plasma CRF and corticosterone, one may assume that the diurnal pattern of central CRF binding sites is not directly coupled to the activity of the HPA axis.
Animals↗