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Query: UMLS:C0019693 (HIV)
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Background: We recently observed that a short course of trimethoprim 300 mg b.i.d. in healthy volunteers can cause a substantial increase in fasting plasma homocysteine levels, up to concentrations reportedly associated with atherothrombotic complications. The purpose of this study was to determine whether primary Pneumocystis carinii prophylaxis (PCP) with trimethoprim-sulphamethoxazole (TMP-SMX) adversely affects serum homocysteine levels in HIV-positive patients. Methods: We studied 34 subjects [29 male, 5 female, mean age 36.8+/-7.9 (S.D.) years] with no prior AIDS-defining disease who required primary PCP prophylaxis (CD4+ T-cell count <200/mm(3)). The common dose of TMP-SMX was 80/400 mg (80 mg trimethoprim and 400 mg sulphamethoxazole) once daily. Serum total homocysteine levels were determined in four samples: two collected prior to the start of TMP-SMX and two collected on average 2.6+/-2.2 and 5.3+/-3.5 months into the first year of prophylactic therapy. Results: Mean serum homocysteine was 13.9+/-3.7 &mgr;mol/l pre-treatment and 14.4+/-5.0 &mgr;mol/l during treatment with TMP-SMX, a non-significant increase of 0.5 &mgr;mol/l (95% CI: -0.5 to +1.4, P=0.34). Folate levels were equally unaffected by TMP-SMX (13.1+/-6.5 nmol/l versus 13.3+/-5.3 nmol/l, before and during therapy, respectively). Baseline folate levels did not predict the response of homocysteine to TMP-SMX, and neither did age, gender, or serum creatinine. Conclusion: Long-term therapy with 80/400 mg TMP-SMX does not adversely affect homocysteine levels.
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PMID:Trimethoprim-sulphamethoxazole as primary Pneumocystis carinii prophylaxis does not increase serum homocysteine levels in HIV-positive subjects. 1139

The pharmacology, bioavailability and pharmacokinetics, clinical efficacy, and adverse effects of caspofungin acetate are reviewed. Caspofungin acetate is an echinocandin with fungicidal activity against a wide range of pathogens, including Candida spp., Aspergillus spp., and Histoplasma spp. It is active against fluconazole-resistant and fluconazole-susceptible strains of Candida albicans. Caspofungin acetate irreversibly inhibits the enzyme 1,3-beta-D-glucan synthase, preventing the formation of glucan polymers and disrupting the integrity of the fungal cell wall. Caspofungin acetate has an elimination half-life of 9-10 hours and is suitable for once-daily regimens. Data from animal and human studies demonstrate that the drug is 80-96% protein bound. Less than 3% of the dose is eliminated unchanged in the urine, and the proposed route of elimination is hepatic. In a trial of 128 patients with Candida esophagitis, clinical response rates were higher with caspofungin acetate 50 or 70 mg/day (85%) than with amphotericin B 0.5 mg/kg/day (67%). Most enrolled patients had HIV infection, and almost half had CD4+ lymphocyte counts of less than 50 cells/microL in another study, 56 immunocompromised patients with aspergillosis were treated with one 70-mg dose of caspofungin acetate, then 50 mg once a day. All patients had refractory invasive aspergillosis or were intolerant of amphotericin B, liposomal amphotericin B, or azole therapy. In patients who received at least one dose of caspofungin acetate, a favorable response was reported in 41%. In 128 patients who received either caspofungin acetate or amphotericin B, fewer caspofungin acetate recipients (1.4%) had elevated serum creatinine levels and discontinued therapy because of adverse effects (4%) than amphotericin B recipients (15% and 22%, respectively). The manufacturer's recommended dose for infections caused by Candida or Aspergillus spp. has not been determined. Caspofungin acetate appears to be fungicidal, with a wide spectrum of antifungal activity and a good safety profile. The lack of adequate efficacy and safety data in humans makes a recommendation to add this drug to the formulary premature. Pending advanced clinical trials and cost information, caspofungin acetate may be a reasonable addition to the formulary, particularly in hospitals with large immunocompromised patient populations.
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PMID:Caspofungin acetate: an antifungal agent. 1181 74

HIV-associated nephropathy (HIVAN) is the most common cause of renal failure in patients infected with type 1 human immunodeficiency virus (HIV-1). The renal prognosis for HIVAN is poor and is typically associated with rapid progression to renal death. We report a patient with biopsy-proven HIVAN who was successfully treated with corticosteroids and review the currently available evidence supporting the specific treatments of this condition. A 34-year-old African-American male with a 2-year history of uncomplicated HIV disease developed progressive azotemia despite treatment with highly active antiretroviral therapy (HAART). He was treated with an uncomplicated 4-month course of prednisone, which improved his serum creatinine from 2.9 to 1.9 mg/dl and decreased his degree of proteinuria from 8 to 2.1 g/day. Two years post-steroid treatment his renal function remains stable. Increasing evidence supports that both ACE inhibitors and HAART are effective in preventing and in some cases of reversing HIVAN induced renal failure. In selected patients who progress despite these measures, a limited course of corticosteroid may achieve long-standing disease remissions. In general, with adequate supervision, corticosteroid therapy appears to be well tolerated and has an acceptable side effect profile. Although persuasive in view of the abysmal natural history of HIVAN, the currently available studies are subject to major methodological limitations. Appropriate randomized controlled trials are urgently required in order to further examine the efficacy, optimal timing, and potential side effects of these treatments.
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PMID:Treatment of HIV-associated nephropathy. 1148 63

We report a urinary tract infection (UTI) with erythrovirus B19 in an HIV-1-positive homosexual man persisting for more than 7 months after the decline of viremia after a primary infection. During the course of the UTI, the patient complained of soreness in the kidney region and suffered from transient episodes of edema and hematuria. Proteinuria and elevated serum concentrations of creatinine further substantiated the hypothesis of a renal focus of a persistent erythrovirus B19 infection.
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PMID:Persistent erythrovirus B19 urinary tract infection in an HIV-positive patient. 1167 36

BACKGROUND: Amphotericin B deoxycholate remains the treatment of choice for most systemic fungal infections; however, its clinical use can be limited by infusion-related side effects and nephrotoxicity. New formulations of amphotericin in lipid compounds have been shown to decrease toxicity. We previously showed that a lipid emulsion preparation of amphotericin B deoxycholate was better tolerated than the conventional preparation in dextrose. Therefore, we have now studied the clinical tolerance, renal toxicity and efficacy of higher doses of amphotericin B deoxycholate prepared and infused in a fat emulsion (Intralipid 20%). Thus, this report adds information to the previous publication. METHODS: Forty-two patients infected with HIV and suffering oral candidosis entered the study. The patients received either amphotericin B deoxycholate---glucose 1 mg/kg/day or amphotericin B deoxycholate---lipid emulsion 1 mg/kg/day for 4 days (randomized phase), or amphotericin B deoxycholate---lipid emulsion 2 mg/kg/day or 3 mg/kg/day (escalating-dose phase) for 5 days. Clinical (immediate) side effects and renal (creatinine) tolerance were assessed daily; efficacy against oral candidosis was measured by using a simple clinical score. Serum levels of amphotericin B were also measured. RESULTS: None of the patients receiving amphotericin B deoxycholate---lipid emulsion had treatment interrupted, as compared to four (36%) in the amphotericin B deoxycholate---glucose group (pless-than-or-equal0.01); chills during or after the infusions were significantly less frequent in the amphotericin B deoxycholate---lipid emulsion groups than in the amphotericin B deoxycholate-glucose group (p=0.03). The increase of creatininemia during treatment was significantly higher for patients receiving amphotericin B deoxycholate---glucose than for those receiving amphotericin B deoxycholate---lipid emulsion (p=0.001). The number of patients who had a creatininemia greater-than-or-equal18 mg/L during treatment was significantly higher in both the amphotericin B deoxycholate---glucose group (36%) and in the group receiving the highest dose of amphotericin B deoxycholate---lipid emulsion than in other groups (pless-than-or-equal0.06). The serum concentrations of amphotericin B were lower for the amphotericin B deoxycholate---lipid emulsion regimen than for the amphotericin B deoxycholate---glucose regimen at the same dose of 1 mg/kg/day, but increased with the dose. The change of the oral candidosis score was similar for the same dose of 1 mg/kg/day of amphotericin B deoxycholate infused in either glucose or lipid emulsion; higher doses of amphotericin B deoxycholate---lipid emulsion were more efficacious (p=0.009) and this efficacy seemed to increase with the dose (p=0.06). CONCLUSIONS: The clinical and renal tolerance of amphotericin B deoxycholate are improved when the drug is directly prepared and infused in lipid emulsion (Intrapid) and this preparation allows for greater dosage, up to 3 mg/kg/day, with resultant greater efficacy. This preparation is simple and cost-effective (approximately 7 US $ per 50 mg of amphotercin B) and could be clinically compared to other formulations of amphotericin B.
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PMID:Toxicity and efficacy of conventional amphotericin B deoxycholate versus escalating doses of amphotericin B deoxycholate---fat emulsion in HIV-infected patients with oral candidosis. 1186 56

HIV/AIDS is a multifactorial and multi-step disease. No single treatment against AIDS can save a patient. Our last report showed that vitamin A, vitamin E and beta-carotene were decreased while malondialdehyde (MDA) was increased. This report aims to evaluate biochemical and hematological parameters in HIV/AIDS patients in Chiang Mai, Thailand by holistic approaches. Sera from HIV/AIDS patients were examined for sugar, cholesterol, uric acid, total protein, albumin, urea, creatinine, AST, ALT, ALP, total/direct bilirubin, vitamin E, MDA, total antioxidant capacity (TAC), beta-carotene, complete blood cell counts, platelet count, CD4 count, prothrombin time, partial prothrombin time and soluble Fas (sFas). The results found that sFas levels in sera prior to holistic approach was not different from reference values and not significantly correlate with CD4 and absolute lymphocyte count. sFas could not serve as putative marker for CD4 destruction. After 3 months CD4 count, MDA, vitamin E and TAC did not change statistically. This approach had no effect on liver and kidney functions, red blood cell, white blood cell, platelet counts, and blood clotting factors. This presentation may be some alternative approaches to combat HIV infections and AIDS, leading to stabilize or extend survival time which should further be elucidated.
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PMID:Biochemical and hematological manifestations of HIV/AIDS in Chiang Mai, Thailand. 1194 6

The main objective of this study was to analyze the influence of nutritional state among HIV-1 infected people, according to the different clinical stages referred by the CDC (Control Disease Center of the United States) in 1987, as well as the changes in the concentrations of some biochemical markers linked to nutritional state. A similar study was carried out in a control group with UltramicroELISA non-reagent healthy individuals, anthropometrically classified. Concentrations of total proteins, albumin, cholesterol, triglycerides, urea, uric acid and creatinine were analyzed by sex and clinical group, comparing the levels obtained through a variance study. When comparing HIV-1 asymptomatic infected patients to HIV-1 and HIV-2 non infected people, the results showed a non significant increase in the level of total proteins with a significant decrease of albumin and creatinine, the latter observed only in male patients. In stage IV patients, an important decrease of cholesterol and a significant increase of the triglycerides were found, as well as the lowest albumin levels. Urea and uric acid levels did not experience statistically significant changes. It was concluded that the study of biochemical markers is advisable, since it contributes to the detection by default of malnutrition marginal states in infected individuals.
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PMID:[Influence of HIV/AIDS infection on some biochemical indicators of the nutritional status]. 1215 77

In this 6-month prospective study, we compared the efficacy of two treatment regimens: double-drug therapy with zidovudine (ZDV) and lamivudine (3TC) and triple-drug therapy with ZDV plus 3TC plus nelfinavir (NFV), in the treatment of asymptomatic and early symptomatic HIV-infected children. Twenty-five children were enrolled in this study and were divided into 2 groups: group A, consisting of 13 children who were given ZDV+3TC; group B, consisting of 12 children who were given ZDV+3TC+NFV. Serial determinations of weight, CD4-cell count, HIV RNA or plasma viral load (VL) and complete blood counts (CBC), liver function tests (LFT), blood urea nitrogen (BUN) tests, creatinine and serum amylase tests were performed at study entry and at 1, 3 and 6 months. The side-effects of drugs were recorded. Over the 6-month period, the median weight increase in group B (24%) was higher than in group A (2%). The median CD4-cell count increase from baseline in group B (94.5%) was better than in group A (9.4%). The reduction of VL below baseline in group B (1.2 log10; 20.8%) was also better than in group A (0.72 log10; 13.8%). However, these differences were not statistically significant (p>0.05). Both combination regimens could not completely suppress HIV RNA below detectable limits (<400 copies/ml). Both groups tolerated the regimens well; no side-effects or toxicities occurred. The efficacy levels of triple-drug therapy (ZDV+3TC+NFV) and double-drug therapy (ZDV+3TC) were not different. There were no side-effects and no deaths during the 6-month study period.
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PMID:The efficacy of combined zidovudine and lamivudine compared with that of combined zidovudine, lamivudine and nelfinavir in asymptomatic and early symptomatic HIV-infected children. 1223 26

Plasma cell neoplasia occurs much less frequently than high-grade B-cell non-Hodgkins lymphoma in HIV-infected patients, but is nevertheless an AIDS-associated malignancy. In this report, we describe the fine-needle aspiration (FNA) findings of a mass in the left parotid region with plasmablastic features that occurred in a 41-yr-old HIV-infected homosexual man whom we diagnosed as having anaplastic myeloma. The patient had normochromic, normocytic anemia with a hematocrit of 21%, a white blood count of 2.2 x 10(9)/l with 76% neutrophils, and a CD4 count of 31%. He also had elevated levels of calcium (13.2 mg/dl), alkaline phosphatase (25,400 IU/l), blood urea nitrogen (2,600 mg/dl), and creatinine (2.5 mg/dl). Serum protein electrophoresis showed polyclonal hypergammaglobulinemia without any monoclonal component. A bone survey revealed multiple punched-out lytic lesions. FNA smears showed large plasmacytoid cells with eccentrically placed nuclei, prominent nucleoli, and moderate amounts of basophilic cytoplasm. By immunocytochemical staining, tumor cells were negative for CD19, CD20, and leukocyte-common antigen (LCA), but strongly positive for CD38 and kappa light chain. Anaplastic myeloma and plasmablastic lymphoma were considered in the differential diagnosis. Although the cytomorphologic and immunophenotypic findings of our case overlapped with those of plasmablastic lymphoma, the pattern of bone involvement with punched-out lytic lesions and absence of localization of the tumor to the mucosa of the oral cavity led us to a diagnosis of anaplastic myeloma. The patient initially received antiretroviral therapy followed by thalidomide and pulse dexamethasome therapy, but his response was poor. His HIV load increased, and his malignancy rapidly progressed with the development of multiple vertebral lesions, extraosseous extension, and eventually cord compression. He died of the disease less than 2 mo after presentation.
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PMID:Fine-needle aspiration cytology of a case of HIV-associated anaplastic myeloma. 1235 99

Summary Forty (40) HIV positive patients with CD4 cell counts between 100 - 500 cellh/mm3 were recruited from 8 different centres in Nigeria including a research centre and specialist and teaching hospitaLs They were enrolled into an open, non-comparative study of a triple combination regimen containing the Protease Inhibitor (PI), Nelfinavir and two Reverse Transcriptase Inhibitors (RTIs), Zakitabine (Hivid) and Zidovudine for a period of 24 weeks. Thirty-one (31) patients completed the study. Nine (9) patients withdrew from the study. Two of these because of Adverse Events (AE), 2 others because they developed tuberculosis and had to withdraw because of rifampicin therapy. The remaining five (5), withdrew voluntarily. Efficacy of the PI containing triple regimen was evaluated using viral load and absolute CD4 changes, weight gain and clinical response during the course of the triaL Twenty-two (22) patients had plasma viral loads measured at the beginning and at the end of the trial (24 weeks). Seventeen (17) out of the 22 patients (77%), experienced a significant reduction in their plasma viral loads (p<0.05 There was 1 log reduction in plasma viral load in 6 patients (25%), 2 log in 4 patients (17%). In 2 patients (8%), plasma viral load was reduced below the level of detection. The viral load increased over the treatment period in five patients (21%). Similarly 22 out of the 26 patients (85%) experienced increase in the level of their CD4 lymphocyte counts at the end of the study. The average CD4 counts of all 26 patients rose from 272.94 +/- 137.71/dl to 414 +/- 243.71/ul over 24 weeks (p<0.05). There was monthly rise of 27 CD4 cells/microl. Four (4) patients (15%) had a fall in their CD4 lymphocyte counts. Twenty (20) out of the 26 patients (77%), who completed the study were observed to have weight gains ranging from 1.5 to 31 kilograms over the 24 week study period. In 4 patients, there was no weight gain during the study period. Two patients (5%) were withdrawn due to adverse events from the viracept combination. One of these was because of life threatening diarrhoea while the other patient had severe peripheral neuropathy and severe weakness in the lower limbs. Eight (8) other patients had diarrhoea but not severe enough to stop them from continuing with the triaL Other adverse events seen include anaemia (1 patient), pancytopenia (1 patient), and transient elevation of serum urea and creatinine (1 patient). None of these adverse events was severe enough to warrant withdrawal from therapy. The study has therefore demonstrated the significant efficacy and tolerability of (Nelfinavir/Zalcitabine/ Zidovudine combination in suppressing viral replication, increasing the CD4 cell counts and improving the quality of life in Nigeria patients with HIV.
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PMID:A multicentre study to determine the efficacy and tolerability of a combination of nelfinavir (VIRACEPT), zalcitabine (HIVID) and zidovudine in the treatment of HIV infected Nigerian patients. 1240 23


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