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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the past 3 years, treatment for HIV infection has significantly improved the prognosis for HIV-infected persons. The administration of protease inhibitors for the treatment of HIV infection has had a significant role in the reduction of AIDS-related complications. Recent findings have indicated that protease inhibitors may significantly increase lipids to levels that pose a health risk that may be greater than the illness itself. This article reviews the initial findings of a study that investigated the impact of interventions for the treatment of protease inhibitor-related hyperlipidemia. The purpose of the study was to determine if initiation of interventions based on the National Cholesterol Education Program Guidelines would be effective in lowering protease inhibitor-related hyperlipidemia without disrupting the effectiveness of the HIV therapy. A total of 45 HIV-infected individuals who were taking a protease inhibitor and had abnormally elevated lipids were enrolled into this study. Mean serum cholesterol level prior to initiation of a protease inhibitor regimen was 170 mg/dl as compared to a mean cholesterol at time of enrollment of 289 mg/dl and triglycerides of 879 mg/dl. Interventions included diet and exercise and the prescription of gemfibrozil alone or in combination with atorvatstatin. During the course of the study, overall intervention significantly reduced serum cholesterol level to 201 mg/dl (p. 01) over a study period of ten months. Case studies of five medical events related to hyperlipidemia are included. Currently, 26 participants continue in the study. Sixteen participants discontinued protease inhibitor therapy during the course of the study and thus ended their participation.
J Assoc Nurses AIDS Care
PMID:Intervention for hyperlipidemia associated with protease inhibitors. 1039 60

Pneumocystis carinii is the paradigm of opportunistic infections in immunocompromised mammals. Prior to the acquired immunodeficiency syndrome (AIDS) pandemic and the use of immunosuppressive therapy in organ transplant and cancer patients, P. carinii was regarded as a curiosity, rarely observed clinically. Interest in this organism exploded when it was identified as the agent of P. carinii pneumonia (PcP), the direct cause of death among many AIDS patients. Aggressive prophylaxis has decreased the number of acute PcP cases, but it remains among the most prevalent opportunistic infections found within this patient population. The taxonomic assignment of P. carinii has long been argued; molecular genetics data now demonstrate that it is a fungus. Several antimycotic drugs are targeted against ergosterol or its biosynthesis, but these are not as effective against PcP as they are against other fungal infections. This can now be explained in part by the identification of the sterols of P. carinii. The organism lacks ergosterol but contains distinct C28 and C29 delta7 24-alkylsterols. Also, 24-methylenelanost-8-en-3beta-ol (C31) and pneumocysterol, (24Z)-ethylidenelanost-8-en-3beta-ol (C32) were recently identified in organisms infecting humans. Together, the delta7 24-alkylsterols and pneumocysterol are regarded as signature lipids of the pathogen that can be useful for the diagnosis of PcP, since no other lung pathogen is known to contain them. Cholesterol (C27), the dominant sterol component in P. carinii, is probably totally scavenged from the host. De novo synthesis of sterols has been demonstrated by the presence of lovastatin-sensitive 3-hydroxy-3-methylglutaryl-CoA reductase activity, the incorporation of radiolabeled mevalonate and squalene into P. carinii sterols, and the reduction in cellular ATP in cells treated with inhibitors of enzymes in sterol biosynthesis.
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PMID:C27 to C32 sterols found in Pneumocystis, an opportunistic pathogen of immunocompromised mammals. 1078 9

In a previous study we showed that budding of HIV-1 particles occurs at highly specialized membrane microdomains known as lipid rafts. These microdomains are characterized by a distinct lipid composition that includes high concentrations of cholesterol, sphingolipids, and glycolipids. Since cholesterol is known to play a key role in the entry of some other viruses, our observation of HIV budding from lipid rafts led us to investigate the role in HIV-1 entry of cholesterol and lipid rafts in the plasma membrane of susceptible cells. We have used 2-OH-propyl-beta-cyclodextrin (beta-cyclodextrin) to deplete cellular cholesterol and disperse lipid rafts. Our results show that removal of cellular cholesterol rendered primary cells and cell lines highly resistant to HIV-1-mediated syncytium formation and to infection by both CXCR4- and CCR5-specific viruses. beta-Cyclodextrin treatment of cells partially reduced HIV-1 binding, while rendering chemokine receptors highly sensitive to antibody-mediated internalization. There was no effect on CD4 expression. All of the above-described effects were readily reversed by incubating cholesterol-depleted cells with low concentrations of cholesterol-loaded beta-cyclodextrin to restore cholesterol levels. Cholesterol depletion made cells resistant to SDF-1-induced binding to ICAM-1 through LFA-1. Since LFA-1 contributes significantly to cell binding by HIV-1, this latter effect may have contributed to the observed reduction in HIV-1 binding to cells after treatment with beta-cyclodextrin. Our results indicate that cholesterol may be critical to the HIV-1 coreceptor function of chemokine receptors and is required for infection of cells by HIV-1.
AIDS Res Hum Retroviruses 2001 Jul 20
PMID:Lipid rafts and HIV pathogenesis: host membrane cholesterol is required for infection by HIV type 1. 1148 18

Human immunodeficiency virus (HIV) is a lipid enveloped virus. The lipid envelope differs significantly from the lipid membrane of normal human cells: it contains high amounts of cholesterol, that is of importance for the virus-cell interaction (for entry and exit of the virus) at so-called lipid rafts. Cholesterol, as a R-C=C-R compound possesses an oxidazable carbenic bond. The present work suggests the inactivation of HIV by oxidation of viral cholesterol and/or unsaturated fatty acids. For oxidation, the relatively mild oxidant singlet oxygen (1O(2)) might be used. 1O(2) is generated by redoxcyclers (e.g., of the quinone type, such as vitamin K) or by chloramines (e.g., taurine-chloramine). At the 1O(2) concentrations necessary to inactivate lipid enveloped virus in human blood the oxidation-sensible critical hemostasis parameters such as thrombocytes and fibrinogen are only partly inactivated. Therefore, it is proposed to consider generators of 1O(2) as a new form of AIDS therapy.
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PMID:Singlet oxygen (1O2)-oxidazable lipids in the HIV membrane, new targets for AIDS therapy? 1261 26

Hypertriglyceridemia has frequently been found both in subjects with AIDS and in asymptomatic HIV-positive ones. In order to evaluate the importance of hyperlipemia as an index of the clinical evolution of HIV infection, the levels of triglycerides, total cholesterol and CD4 lymphocytes were determined over a period of 2 years in 8 haemophiliacs with AIDS, 13 asymptomatic HIV-positive and 45 HIV-negative haemophiliacs attending the Operative Unit of Coagulation Disorders of the University of Pisa. The mean concentration of triglycerides and incidence of hypertriglyceridemia were significantly higher in haemophiliacs with AIDS, compared with HIV-negative subjects (p<0.0001), while the triglycerides values of asymptomatic HIV-positives fell between those of the other groups. Cholesterol levels were lower in HIV-positive haemophiliacs and in those with AIDS compared with HIV-negatives. No correlation was found between triglyceride levels and those of CD4 lymphocytes.
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PMID:[The behaviour of plasma triglycerides and cholesterol in HIV positive haemophiliacs] 1276 87

Lopinavir (LPV)/ritonavir (RTV) used in combination, is a potent antiretroviral drug. However, its benefit is limited by its inherent effect on lipid metabolism, causing dislypemia in a large proportion of treated patients. Fasting triglyceride (TG) and cholesterol levels were assessed in 126 HIV-infected patients who initiated salvage therapy based on LPV/RTV. Both TG and cholesterol significantly increased from baseline to month 3. A positive correlation was found between the percentage increase in TG and LPV trough levels (r = 0.32; p = 0.003). Moreover, patients with TG elevations above the median (27%) showed higher LPV Ctrough levels than those with lower TG elevations (7.1 vs. 4.7 microg/ml, p = 0.004). In contrast, no correlation was found between LPV Ctrough and increases in cholesterol levels. Cholesterol elevations were positively correlated with RTV Ctrough concentrations (r = 0.32; p = 0.003).
AIDS Patient Care STDS 2003 Sep
PMID:Correlation between lopinavir plasma levels and lipid abnormalities in patients taking lopinavir/ritonavir. 1458 81

Protease inhibitor (PI) treatment can result in dyslipidemia in a significant proportion of patients. Atazanavir (ATV) is a once-daily PI that has not been associated with clinically relevant increases in total cholesterol (TC), fasting low-density lipoprotein cholesterol (LDL-C), or fasting triglyceride (TG) concentrations. The objectives of this paper were to evaluate lipid profiles in untreated patients, and investigate the frequency and severity of dyslipidemia in the same individuals after treatment with ATV or nelfinavir (NFV) for 48 weeks. Two multinational, randomized, active-controlled, blinded trials compared the safety and efficacy of ATV and NFV in combination with two nucleoside reverse transcriptase inhibitors (NRTIs) in antiretroviral (ARV)-naive patients. Serum lipid concentrations were analyzed in patients who had available measurements both at baseline and at week 48. Patients who had missing data at either time point were not included. Lipid levels remained within baseline ranges at week 48 with ATV treatment, whereas clinically relevant elevations in TC, fasting LDL-C, and fasting TG concentrations occurred with NFV treatment. Mean changes from pre-treatment baseline in fasting LDL-C ranged from -6 percent to +6 percent in the ATV-treatment groups, and from +27 percent to +31 percent in the NFV-treatment groups. After 48 weeks, there was a substantive increase in the proportion of NFV-treated patients who would be recommended for lipid-lowering treatment by National Cholesterol Education Program (NCEP) guidelines, whereas a lesser proportion of ATV-treated patients would be recommended for lipid-lowering treatment. Atazanavir does not lead to dyslipidemia in ARV-naive patients, and may limit the need for lipid-lowering strategies to reduce the risk of cardiovascular disease.
J Int Assoc Physicians AIDS Care (Chic)
PMID:Atazanavir--a once-daily HIV protease inhibitor that does not cause dyslipidemia in newly treated patients: results from two randomized clinical trials. 1557 13

Pneumocystis can transiently colonize healthy individuals without causing adverse symptoms, and most people test positive for exposure to this organism early in life. However, it can cause Pneumocystis pneumonia (PcP) in people with impaired immune systems and is a major cause of death in HIV/AIDS. Although it has close affinities to the Ascomycetes, Pneumocystis has features unlike those of any single group of fungi. For example, Pneumocystis does not synthesize ergosterol, which is consistent with the inefficacy of amphotericin B and some triazoles in clearing PcP. Pneumocystis sterols include distinct delta7 24-alkylsterols. Metabolic radiolabeling experiments demonstrated that P. carinii synthesizes sterols de novo. Cholesterol is the most abundant sterol in Pneumocystis; most, if not all, is scavenged from the mammalian host lung by the pathogen. The P. carinii erg7, erg6, and erg11 genes have been cloned, sequenced, and expressed in heterologous systems. The recombinant P. carinii S-adenosyl-L-methionine:C-24 sterol methyl transferase (SAM:SMT) has a preference for lanosterol over zymosterol as substrate, and the enzyme can catalyze the transfer of either one or two methyl groups to the C-24 position of the sterol side chain. Two different sterol compositions were detected among human-derived P. jirovecii; one was dominated by C28 and C29 sterols, and the other had high proportions of higher molecular mass components, notably the C32 sterol pneumocysterol. The latter phenotype apparently represents organisms blocked at 14alpha-demethylation of the sterol nucleus. These studies suggest that SAM:SMT is an attractive drug target for developing new chemotherapy for PcP.
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PMID:Sterol metabolism in the opportunistic pathogen Pneumocystis: advances and new insights. 1563 43

Cholesterol-rich plasma membrane microdomains are important for entry of many viruses, including retroviruses. Depletion of cholesterol with 2-hydroxypropyl-beta-cyclodextrin inhibits entry of human T cell leukemia virus type I (HTLV-1) and HTLV-I envelope pseudotyped lentivirus particles. Using a soluble fusion protein of the HTLV-I surface envelope protein with the immunoglobulin Fc domain, the HTLV-I receptor was found to colocalize with a raft-associated marker and to cluster in specific plasma membrane microdomains. Depletion of cholesterol did not alter receptor binding activity, suggesting a requirement for cholesterol in a postbinding virus entry step.
AIDS Res Hum Retroviruses 2005 Jan
PMID:Cholesterol dependence of HTLV-I infection. 1566 43

There is a paucity of information on the safety and efficacy of lipid-lowering therapy for dyslipidemia associated with human immunodeficiency virus (HIV) and antiretroviral therapy. Our objective was to determine whether fenofibrate and pravastatin were equivalent for the treatment of combined dyslipidemia in HIV as measured by a composite of the National Cholesterol Education Project (NCEP) goals based on absolute values for low-density lipoprotein (LDL), triglycerides (TG), and high-density lipoprotein (HDL) and to compare the safety of these agents through 48 weeks. This was a randomized, open-label trial with subjects assigned to fenofibrate 200 mg (n = 88) or pravastatin 40 mg (n = 86) daily. Subjects who failed to reach the NCEP composite goal on monotherapy by week 12 received both drugs. The composite goal at week 12 was achieved in 1% of fenofibrate and 5% of pravastatin subjects. At week 16, 69/88 subjects on fenofibrate added pravastatin (FP) and 67/86 subjects on pravastatin added fenofibrate (PF). At week 48, 7% FP subjects and 3% PF subjects achieved the composite goal. Median changes in LDL/HDL/TG/non-HDL were -8/+5/-144/+50 and -14/+2/-66/+34 mg/dl in subjects receiving FP and PF, respectively. There were few adverse events and no rhabdomyolysis reported. Combination therapy with fenofibrate and pravastatin for HIV-related dyslipidemia provides substantial improvements in lipid parameters and appears safe, but is unlikely to achieve all NCEP targets for lipid levels.
AIDS Res Hum Retroviruses 2005 Sep
PMID:A randomized trial of the efficacy and safety of fenofibrate versus pravastatin in HIV-infected subjects with lipid abnormalities: AIDS Clinical Trials Group Study 5087. 1621 99


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