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

Wasting and renal diseases are frequent complications of HIV (human immunodeficiency virus) infection and are associated with accelerated disease progression and increased mortality. Transgenic mice expressing HIV1 under control of the CD4 promoter develop an AIDS-like disease and were used in the present work to study HIV1-induced wasting and kidney pathology. In this study, we reported that disease evolution paralleled increases in serum urea and creatinine levels, indicating an early and progressive deterioration of kidney function; meanwhile the wasting syndrome characterized by up-regulation of the ubiquitine-proteasome pathway and increased level of serum 3-methyl-histidine levels occurred at later stages just prior to death. Further examination of kidney and muscle pathologies revealed a progressive accumulation of CD45(+) cells, first affecting the kidneys. In addition, the onset of disease is accompanied by elevated levels of circulating "regulated on activation, normal and secreted T cell expressed and secreted" (RANTES). These results prompted us to assess the effects of AS602868, a specific small molecule inhibitor of IkappaB kinase 2 (IKK2) on disease progression. Inhibition of the NF-kappaB pathway indeed resulted in increased lifespan, kidney and lean body mass preservation. These beneficial results were associated with a reduction of CD45(+) cells infiltrating the kidneys, amelioration of the renal architecture, and reduced level of circulating RANTES. Together our data provide evidence that IKK2 inhibitors have therapeutic relevance in the treatment of HIV1-associated disorders.
 ...
PMID:IKK2 inhibitor alleviates kidney and wasting diseases in a murine model of human AIDS. 1503 14

(1) Without treatment, between 15% and 25% of patients with chronic hepatitis B die prematurely, usually of cirrhosis or hepatocellular carcinoma. Two treatments are already available to prevent these complications, namely interferon alfa (2a and 2b), and lamivudine, a nucleotide analogue. (2) Marketing authorization has now been granted in the European Union for another antiviral agent, adefovir dipivoxil, a prodrug of the nucleotide analogue adefovir. (3) Two double-blind placebo-controlled trials in treatment-naive patients with active viral replication showed that adefovir dipivoxil 10 mg/day orally reduced viral load and improved hepatic histology. (4) In lamivudine-resistant patients with active viral replication, the preliminary results of two trials comparing adefovir dipivoxil with continued lamivudine therapy, and data from two non comparative trials (one in HIV-coinfected patients), showed that adefovir dipivoxil reduced viral load by about 4 log after 48 weeks. (5) In clinical trials, creatinine levels rose in 2-5% of patients treated with 10 mg/day adefovir dipivoxil, reflecting renal toxicity. Other possible risks, and especially lactic acidosis, must be monitored closely. (6) In practice, adefovir dipivoxil is currently a third-line option for patients with chronic hepatitis B, when interferon alfa-2 and lamivudine fail or are poorly tolerated.
 ...
PMID:Adefovir dipivoxil: new preparation. A third-line option in chronic hepatitis B. 1505 5

We describe 7 cases of renal tubular injury in HIV-infected patients receiving an antiretroviral regimen containing tenofovir. Our patients (5 women and 2 men) developed renal tubular dysfunction, with hypophosphatemia, normoglycemic glycosuria, proteinuria, and decrease of creatinine clearance. The first biologic signs of renal toxicity were observed after duration of tenofovir treatment from 5 weeks to 16 months, and they resolved less than 4 months after discontinuation of tenofovir. Six patients had a low body weight (<60 kg). Five patients received low doses of ritonavir, and 1 received didanosine. In 5 patients, the signs resolved with the discontinuation of only the tenofovir. A renal biopsy performed in 1 patient was consistent with tubulointerstitial injury. Proximal tubulopathy appears to be a rare adverse effect of long-term tenofovir therapy. In patients with low weight or mild preexisting renal impairment, regular monitoring of tubulopathy markers could lead to early detection of this dysfunction.
 ...
PMID:Renal tubular dysfunction associated with tenofovir therapy: report of 7 cases. 1507 41

Collapsing glomerulopathy (CG) has become an important cause of end-stage renal disease. Whether associated with HIV-1 or other potential etiologies, the pathogenesis of CG converges to induce aberrant proliferation of renal epithelium along the entire nephron. This raises the possibility that targeting cell-cycle progression may be an effective therapeutic strategy for CG. Here, we ask whether the cyclin-dependent kinase (CDK) inhibitor, CYC202 (R-roscovitine), could attenuate or reverse existing renal disease in Tg26 mice, a well characterized HIV-1 transgenic mouse model of CG. Tg26 mice were age and disease matched through analysis of urine (protein/creatinine) to generate 12 treatment pairs covering a range of mild to severe CG. One mouse from each pair received either vehicle or 75 mg/kg of CYC202 every 12 h for 20 d, a dose 20% above that needed to prevent the development of CG. After treatment, urinary, serologic, and histopathologic indices of nephrosis showed reversal of CG in 8 of 12 CYC202-treated mice compared with progression of CG in 10 of 12 vehicle-treated mice, demonstrating a significant therapeutic benefit from CYC202 (P < 0.05). Pharmacokinetic profiles showed that concentrations of CYC202 known to inhibit cell-cycle and transcriptional CDK in vitro were achieved in plasma at efficacious doses. However, amelioration of CG by CYC202 did not correlate with decreases in kidney HIV-1 transgene expression, indicating that suppression of HIV-1 transcription was not a prerequisite for the antiproliferative activity of CYC202. These results demonstrate a novel therapeutic strategy for CG.
 ...
PMID:Reversal of collapsing glomerulopathy in mice with the cyclin-dependent kinase inhibitor CYC202. 1510 Mar 81

Postinfectious proliferative glomerulonephritis may occur in HIV-infected patients, although it is not a common cause of severe acute renal failure in them. We report a woman with HIV infection, who developed hypocomplementemic acute nephritic syndrome 10 days after an upper respiratory infection. Systemic diseases were excluded. The serum creatinine level increased to 6.6 mg/dl. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis, with mesangial and capillary walls, granular deposits of IgG and C3 by immunofluorescence. She was given corticosteroids with progressive normalization of her renal function. No opportunistic infections have occurred during 1-year follow-up.
 ...
PMID:Postinfectious diffuse proliferative glomerulonephritis and acute renal failure in an HIV patient. 1512 34

Peritoneal dialysis (PD)for renal replacement therapy (RRT) is safe and effective in patients with end-stage renal disease (ESRD). Currently, no data exist for the same in patients at correctional institutions [Department of Corrections (DOC)]. We compared demographic characteristics of, and the efficacy and outcome of self-administered continuous ambulatory peritoneal dialysis (CAPD) in, DOC patients with data from the U.S. Renal Data System for the free-living population (FLP). We retrospectively reviewed the charts of DOC patients opting for CAPD (n = 10) in the last 7 years. Baseline data (age, race, cause of ESRD, serum chemistries, anemia, bone profiles, and Kt/V) were obtained for dialysis start and 6 - 12 months after dialysis start. Major events, including switches to hemodialysis (HD), hospitalizations, and deaths, were also studied. The median age of the DOC patients was 45 years. The group was 40% black, 30% white, and 30% Hispanic. Cause of renal failure was diabetes in 30%, HIV-associated nephropathy in 30%, primary glomerular disease in 20%, and hypertension or unknown in 20% of patients. The DOC patients had higher levels of blood urea nitrogen (BUN) at presentation, but better anemia profiles than did the FLP. Complications included peritonitis, fluid leaks, and cardiac events. Median age at dialysis start is lower for DOC patients, and HIV-associated nephropathy is more common than in the FLP. Levels of BUN/creatinine were much higher in DOC patients, but hemoglobin levels were similar to those in the FLP. Hospitalization rates for peritonitis were comparable; cardiac disease was common in both groups. Self-CAPD can be safely and effectively performed in DOC patients.
 ...
PMID:Self-performed peritoneal dialysis in prisoners. 1538 5

Increased lopinavir (LPV) exposure obtained in vivo through combination with low-dose ritonavir may overcome a certain grade of resistance but not all. We sought to analyze LPV variability and possible risk factors. LPV trough plasma concentrations were determined by high-performance liquid chromatography after 1, 4, and 12 weeks from salvage regimens and tested in both univariate and multivariate regression analyses with age, gender, weight, risk factors for HIV acquisition, hepatitis C virus reactivity, hepatitis B surface antigen positivity, baseline aspartate transferase (AST) or alanine transferase (ALT) levels, creatinine, non-nucleoside reverse transcriptase inhibitors (NNRTIs) or tenofovir as concomitant drugs, and NNRTIs administered in the previous regimen. Fifty-six patients were included into the study. Among them, 8 of 56 (14.3%) at week 1, 12 of 56 (21.4%) at week 4, and 9 of 56 (16.1%) at week 12 had suboptimal LPV plasma concentrations, defined as trough concentration less than 4 microg/mL. No correlation was found between LPV trough concentrations and assessed variables. In conclusion, pharmacokinetic variability and low LPV concentrations have been found, supporting the use of therapeutic drug monitoring in those starting this drug.
 ...
PMID:Lopinavir plasma levels in salvage regimes by a population of highly active antiretroviral therapy-treated HIV-1-positive patients. 1563 60

The use of folk remedies is widespread throughout Africa. Acute renal failure (ARF) is one of the most severe, but under-recognized, complications of folk remedy use. This report aims to describe the clinical presentation, outcomes, and nature of renal injury in patients with folk-remedy-associated ARF. Clinical data were evaluated retrospectively in 78 patients with ARF associated with recent folk remedy use. ARF was defined as elevated serum urea and creatinine above the age-appropriate normal ranges, persistent oligoanuria, worsening renal function with time, or need for dialysis. Overall mortality in patients with ARF was 41%. Mortality was higher in adults (45.5%) than in infants (36.6%), in patients with both renal and liver dysfunction (62.5%) than in those with renal dysfunction alone (22.6%), and in HIV-positive (44.4%) versus HIV-negative (34.6%) patients. Vomiting (51.3%) and diarrhea (43.6%) were the most frequent presenting symptoms. Metabolic acidosis (80.8%) and volume depletion (62.8%) were the most frequent clinical findings. The definable causes of ARF were pre-renal (26.9%), acute tubular necrosis (ATN; 26.9%), hepatorenal syndrome (6.4%), urinary tract infection/sepsis (7.7%), and primary renal disorders (7.7%). Twenty-seven patients had concomitant medical conditions unlikely primarily related to folk remedy ingestion. In conclusion, ARF occurring after use of folk remedies in South Africa is associated with significant morbidity and mortality. The most common contributors to ARF in this setting are volume depletion and ATN. Significantly, although a proportion of patients have underlying systemic or renal conditions that may contribute to renal dysfunction, in the majority of patients, folk remedy use appears to be the most likely proximate cause. In view of the large numbers of Africans living abroad, more widespread awareness of this important clinical problem needs to be raised.
 ...
PMID:Acute renal failure associated with the use of traditional folk remedies in South Africa. 1571 33

Tenofovir disoproxil fumarate (TDF) has been anecdotally associated with isolated hypophosphatemia (HP) as well as proximal tubular toxicity and renal dysfunction in which HP has consistently been a feature. Consequently, routine phosphate measurements in TDF recipients have been recommended. We identified and compared the frequency of HP in TDF recipients with that in non-TDF recipients; assessed the reproducibility of HP; identified the incidence of renal dysfunction in hypophosphatemic patients; and evaluated associations between HP and host, HIV infection, or treatment factors. This prospective observational study measured serum phosphate, urea, and creatinine in HIV-positive individuals among the following treatment groups: TDF-containing highly active antiretroviral therapy (HAART, group A), TDF-sparing HAART (group B), HAART naive (group C), and off HAART but treatment experienced (group D). Phosphate measurements were obtained in 252 patients. Seventy-two percent of patients prescribed TDF received a phosphate measurement. The frequency of HP in groups A, B, C, and D was 31%, 22%, 10%, and 14%, respectively. Seventy-eight percent of phosphate measurements were reproducible. Kaletra (P = 0.016) administration and duration of antiretroviral therapy (P = 0.023) were independently associated with HP, but elevated creatinine and urea or use of TDF was not. The etiology of HP seems to be multifactorial and unrelated to TDF or renal dysfunction. This questions the utility of routine phosphate testing, in isolation, in TDF recipients.
 ...
PMID:Serum hypophosphatemia in tenofovir disoproxil fumarate recipients is multifactorial in origin, questioning the utility of its monitoring in clinical practice. 1573 48

The efficacy and renal safety of amphotericin B lipid complex (ABLC) injection were assessed in 106 patients with cryptococcal infection. Eighty-three patients (78%) had a central nervous system (CNS) infection. Of these patients, 20 initiated azole therapy concomitantly with ABLC therapy, and 7 had received prior azole therapy, which continued during administration of ABLC. Clinical response (cured or improved) was achieved in 67 (66%) of 101 patients whose results could be evaluated. Response rates were 65% (51/78) for patients with a CNS infection and 70% (16/23) for patients without a CNS infection. The response rate for patients with HIV infection was 58% (30/52). Response rates were 56% (19/34) for patients who were refractory to prior antifungal therapy, 65% (11/17) for patients who were intolerant of prior antifungal therapy, 60% (3/5) for patients with underlying renal disease who received prior antifungal therapy, 76% (25/33) for patients with underlying renal disease who did not receive prior antifungal therapy, and 73% (8/11) for patients with no renal disease who did not receive prior antifungal therapy. A mean serum creatinine level decrease of 0.02 mg/dL occurred. ABLC was an effective treatment for cryptococcal infection in immunocompromised patients.
 ...
PMID:Successful use of amphotericin B lipid complex in the treatment of cryptococcosis. 1580 27


<< Previous 1 2 3 4 5 6 7 8 9 10