Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two patients presented with proximal muscle weakness, a normal or minor elevation of creatine phosphokinase (CPK) and normal findings on electromyography. Muscle biopsy in one patient revealed CD8+ polymyositis, and in the other showed ddI induced myopathy. These cases illustrate the importance of muscle biopsy in identifying the underlying pathology in HIV infected patients with muscle weakness and little or no abnormality in laboratory investigations.
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PMID:Unusual muscle disease in HIV infected patients. 1529 33

Amdoxovir [(-)-beta-D-2,6-diaminopurine dioxolane, DAPD], the prodrug of dioxolane guanosine (DXG), is currently in Phase I/II clinical development for the treatment of HIV-1 infection. In this study, we examined the phosphorylation pathway of DXG using 15 purified enzymes from human (8), animal (6), and yeast (1) sources, including deoxyguanosine kinase (dGK), deoxycytidine kinase (dCK), high Km 5'-nucleotidase (5'-NT), guanylate (GMP) kinase, nucleoside monophosphate (NMP) kinase, adenylate (AMP) kinase, nucleoside diphosphate (NDP) kinase, 3-phosphoglycerate (3-PG) kinase, creatine kinase, and pyruvate kinase. In addition, the metabolism of 14C-labeled DXG was studied in CEM cells. DXG was not phosphorylated by human dCK, and was a poor substrate for human dGK with a high Km (7 mM). Human 5'-NT phosphorylated DXG with relatively high efficiency (4.2% of deoxyguanosine). DXG-MP was a substrate for porcine brain GMP kinase with a substrate specificity that was 1% of dGMP. DXG-DP was phosphorylated by all of the enzymes tested, including NDP kinase, 3-PG kinase, creatine kinase, and pyruvate kinase. The BB-isoform of human creatine kinase showed the highest relative substrate specificity (47% of dGDP) for DXG-DP. In CEM cells incubated with 5 microM DXG for 24 h, 0.015 pmole/10(6) cells (approximately 7.5 nM) of DXG-TP was detected as the primary metabolite. Our study demonstrated that 5'-nucleotidase, GMP kinase, creatine kinase, and NDP kinase could be responsible for the activation of DXG in vivo.
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PMID:Anabolism of amdoxovir: phosphorylation of dioxolane guanosine and its 5'-phosphates by mammalian phosphotransferases. 1545 Sep 53

We compared the epidemiological data, clinical features and mortality of community-acquired pneumonia (CAP) by Streptococcus pneumoniae and Legionella in HIV-infected patients and determined discriminative features. An observational, comparative study was performed (January 1994 to December 2004) in 15 HIV patients with CAP by Legionella and 46 by S. pneumoniae. No significant differences were observed in delay until initiation of appropriate antibiotic therapy. Smoking, cancer and chemotherapy were more frequent in patients with Legionella pneumonia (p=0.03, p=0.00009 and p=0.01). Patients with Legionella pneumonia had a higher mean CD4 count (p=0.04), undetectable viral load (p=0.01) and received highly active antiretroviral therapy more frequently (p=0.004). AIDS was more frequent in patients with S. pneumoniae pneumonia (p=0.03). Legionella pneumonia was more severe (p=0.007). Extrarespiratory symptoms, hyponatraemia and increased creatine phosphokinase were more frequent in Legionella pneumonia (p=0.02, p=0.002 and p=0.006). Respiratory failure, need for ventilation and bilateral chest X-ray involvement were of note in the Legionella group (p=0.003, p=0.002 and p=0.002). Mortality tended to be higher in the Legionella group (6.7 vs 2.2%). In conclusion, CAP by Legionella has a higher morbimortality than CAP by S. pneumoniae in HIV-infected patients. Detailed analysis of CAP presentation features allows suspicion of Legionnaires' disease in this subset.
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PMID:Streptococcus pneumoniae and Legionella pneumophila pneumonia in HIV-infected patients. 1736 28

The use of highly active antiretroviral therapy (HAART) in HIV-infected patients has been associated with the development of risk factors for cardiovascular diseases (CD) including dyslipidemia and insulin resistance, hypertriglyceridemia being the most frequent metabolic disturbance in these patients. Fibrates are indicated when hypertriglyceridemia is accentuated and persists for over six months. We evaluated the efficacy and safety of bezafibrate for the treatment of hypertriglyceridemia in HIV-infected individuals on HAART. All patients received 400mg/day of bezafibrate and were evaluated three times: Mo (pre-treatment), M1 (one month after treatment), and M2 (six months after treatment). Fifteen adult individuals, eight males and seven females with mean age = 41.2 +/- 7.97 years and triglyceride serum levels > 400mg/dL were included in the study. Smoking, alcohol ingestion and sedentarism rates were 50%, 6.66% and 60%, respectively. Family history of CD, hypertension and diabetes mellitus was reported in 33.3%, 40% and 46.7% of the cases, respectively, while dyslipidemia was reported by only 13.3%. More than half of the patients were using a protease inhibitor plus a nucleotide analog transcriptase inhibitor. Eutrophy and tendency toward overweight were observed at all three study time points. There were significant reductions in triglyceride serum levels from Mo to M1 and from Mo to M2. No significant changes were observed in the serum levels of creatine phosphokinase, hepatic enzymes, CD4+, CD8+ and viral load. Therefore, bezafibrate seems to be safe and effective for the reduction of hypertriglyceridemia in HIV-infected patients on HAART.
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PMID:Bezafibrate for the treatment of hypertriglyceridemia in HIV1-infected patients on highly active antiretroviral therapy. 1756 45

Antiviral alpha-P-borano substituted NTPs are promising chain terminators targeting HIV reverse transcriptase (RT). Activation of antiviral nucleoside diphosphates (NDPs) to NTPs may be carried out by pyruvate kinase (PK) and creatine kinase (CK). Herein, are presented the effects of nucleobase, ribose, and alpha-phosphate substitutions on substrate specificities of CK and PK. Both enzymes showed two binding modes and negative cooperativity with respect to substrate binding. The stereospecificity and inhibition of ADP phosphorylation by alpha-P-borano substituted NDP (NDPalphaB) stereoisomers were also investigated. The Sp-ADPalphaB isomer was a 70-fold better substrate for CK than the Rp isomer, whereas PK preferred the Rp isomer of NDPalphaBs. For CK, the Sp-ADPalphaB isomer was a competitive inhibitor; for PK, the Rp-ADPalphaB isomer was a poor competitive inhibitor and the Sp-ADPalphaB isomer was a poor non-competitive inhibitor. Taken together, these data suggest that, although the Rp-NDPalphaB isomer would be minimally phosphorylated by CK or PK, it should not inhibit either enzyme.
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PMID:Stereospecificity, substrate, and inhibitory properties of nucleoside diphosphate analogs for creatine and pyruvate kinases. 1843 30

Ezetimibe (EZB) lowers cholesterol by blocking cholesterol absorption in the intestine. Data with EZB are limited in HIV-infected patients. We enrolled HIV-infected adults in this prospective, noncontrolled, single-center pilot study if their low-density lipoprotein (LDL) was not at goal despite therapy with a statin. Stable protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) and a low-dose statin were required for inclusion. The primary endpoint was LDL reduction at 18 weeks. In a subgroup of patients on lopinavir/ritonavir (LPV/r), trough concentrations were obtained before and after addition of EZB. Twenty patients were enrolled; 12 (60%) men, 18 (90%) African American. HAART included ritonavir (RTV)-boosted PIs in 17 (85%) patients; 3 (15%) were on nelfinavir. Mean percent changes from baseline in LDL were -10.9%, -12.2%, and -12.4% at weeks 6, 12, and 18, respectively (p < 0.05 for each time period vs. baseline). Mean percent changes from baseline in total cholesterol (TC) were -11.1%, -9.6%, and 9.1% at weeks 6, 12, and 18, respectively (p < 0.05 at each time period vs. baseline). No significant changes in triglycerides, high-density lipoprotein, and LPV/r concentrations were seen. One patient experienced elevated creatine phosphokinase possibly related to study medication; no other adverse effects were seen. Addition of EZB to low-dose statin effectively lowers LDL and TC and appears to be safe and well tolerated.
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PMID:Ezetimibe combined with low-dose statin effectively lowers LDL in protease inhibitor treated patients. 1846 73

Epilepsy is characterized by the presence of spontaneous episodes of abnormal neuronal discharges and its pathogenic mechanisms remain poorly understood. Recently, we found that the expression of creatine kinase (CK) was markedly decreased in an epilepsy animal model using proteomic analysis. A human CK gene was fused with a HIV-1 Tat peptide to generate an in-frame Tat-CK fusion protein. The purified Tat-CK fusion protein was efficiently transduced into PC12 cells in a time- and dose-dependent manner when added exogenously to culture media. Once inside the cells, the transduced Tat-CK fusion protein was stable for 48 h. Moreover, the Tat-CK fusion protein markedly increased endogenous CK activity levels within the cells. These results suggest that Tat-CK provides a strategy for the therapeutic delivery of proteins in various human diseases including the delivery of CK for potential epilepsy treatment.
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PMID:HIV-1 Tat-mediated protein transduction of human brain creatine kinase into PC12 cells. 1868 38

Due to the threat of bioterrorism, large-scale clinical trials of a new cell culture smallpox vaccine were conducted. Biologically false positive (BFR) serological reactions to viruses (hepatitis B and C, HIV) and syphilis were evaluated. BPR rapid reagin tests (RPR) to syphilis occurred in 19% and false positive tests for antibody to hepatitis B in 3.3% of 90 healthy adults undergoing primary vaccination. Most subjects (94%) were RPR-positive on Day 15 after vaccination and all seroreverted within 2 months thereafter. One subject with myocarditis was RPR-negative. One RPR-positive and 1 RPR-negative subject had elevated CK-MB enzymes without other evidence for myocarditis.
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PMID:Possible autoimmune reactions following smallpox vaccination: the biologic false positive test for syphilis. 1902 22

The aim of this review is to summarize the safety profile of the five approved oral nucleoside analogs used to treat chronic hepatitis B virus (HBV) infection, focusing on both the class adverse effects and those that have been reported with individual agents, as well as their safety in pregnancy. All nucleoside analogs have a "Black Box" warning because of their potential for inhibition of human DNA polymerase gamma involved in mitochondrial DNA replication. A reduction in intracellular mitochondrial DNA levels can lead to varying clinical manifestations of mitochondrial toxicity (i.e., neuropathy, myopathy, lactic acidosis), but these side effects are rarely reported with the oral antiviral agents active against HBV. Adefovir and tenofovir are associated with a dose-dependent but usually reversible proximal renal tubular toxicity. For these reasons, patients receiving these agents should be monitored for renal toxicity and the dose modified for renal insufficiency. Prolonged use of tenofovir has also been reported to lead to reduced bone mineral density in patients with human immunodeficiency virus infection, but prospective studies in patients with HBV infection are lacking. Telbivudine treatment is associated with moderate serum creatine phosphokinase elevations in up to 12% of patients. There have been few prospective studies on the safety of nucleoside analogs during pregnancy. According to the Antiretroviral Pregnancy Registry, the incidence of birth defects associated with lamivudine and tenofovir use during pregnancy is not increased. Studies on the safety of long-term therapy with the nucleoside analogs, alone and in combination, are needed as are further studies of children, the elderly, pregnant women, and patients with renal insufficiency.
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PMID:Side effects of long-term oral antiviral therapy for hepatitis B. 1939 2

Polymyositis in HIV-infected subjects, clinically and pathologically resemble polymyositis in non-HIV-infected subjects. We report 14 consecutive HIV-associated polymyositis cases and compare specific features with 25 polymyositis cases seen over the same 6.5 year period. The HIV-polymyositis cases were all female and compared to the polymyositis cases were younger (median age 33 years, interquartile range (IQR) 29; 37 vs. 46 years, IQR 38; 52, p=0.002), and with 4-fold lower serum creatine kinase (CK) values (median 1158 vs. 5153IU/l; p=0.019). A definite clinical improvement on prednisone therapy was documented in eight HIV-polymyositis cases and one improved with anti-retroviral therapy alone. The recognition of HIV-polymyositis which is treatable, but may present with serum CK elevations less than twofolds above normal, is clinically relevant in sub-Saharan Africa where electromyography and muscle biopsies are not readily available.
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PMID:Polymyositis in African HIV-infected subjects. 2063 Jul 56


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