salicylates and HIV-Infections

In this 13-week, open-label, randomized study of the anti-inflammatory salsalate versus usual care, there were no significant improvements in flow-mediated dilation of the brachial artery, endothelial activation, inflammation or coagulation markers, homeostasis model assessment of insulin resistance or lipoproteins with salsalate or between groups in virologically suppressed, HIV-infected adults on antiretrovirals. Tinnitus and transaminitis occurred frequently in the salsalate group. Dose reduction due to toxicities encountered and low level of inflammation may explain these results.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Brachial Artery; Dose-Response Relationship, Drug; Endothelium, Vascular; Female; HIV Infections; Humans; Insulin Resistance; Male; Salicylates

Amyloid beta (Aβ) levels are increased in HIV-1 infected brains due to not yet fully understood mechanisms. In the present study, we investigate the role of lipid rafts, functional caveolae, and caveolae-associated signaling in HIV-1-induced Aβ accumulation in HBMEC. Both silencing of caveolin-1 (cav-1) and disruption of lipid rafts by pretreatment with beta-methyl-cyclodextrin (MCD) protected against Aβ accumulation in HBMEC. Exposure to HIV-1 and Aβ activated caveolae-associated Ras and p38. While inhibition of Ras by farnesylthiosalicylic acid (FTS) effectively protected against HIV-1-induced accumulation of Aβ, blocking of p38 did not have such an effect. We also evaluated the role of caveolae in HIV-1-induced upregulation of the receptor for advanced glycation end products (RAGE), which regulates Aβ transfer from the blood stream into the central nervous system. HIV-1-induced RAGE expression was prevented by infecting HBMEC with cav-1 specific shRNA lentiviral particles or by pretreatment of cells with FTS. Overall, the present results indicate that Aβ accumulation in HBMEC is lipid raft and caveolae dependent and involves the caveolae-associated Ras signaling.

Topics: Amyloid beta-Peptides; Brain; Caveolae; Cells, Cultured; Endothelial Cells; Enzyme Inhibitors; Farnesol; HIV Infections; HIV-1; Humans; Membrane Microdomains; ras Proteins; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Salicylates

Several HIV protease mutations, which are resistant to clinical HIV protease inhibitors (PIs), have been identified. There is a great need for second-generation PIs with different chemical structures and/or with an alternative mode of inhibition. Ginkgolic acid is a natural herbal substance and a major component of the lipid fraction in the nutshells of the Ginkgo biloba tree. The objective of this study was to determine whether ginkgolic acid could inhibit HIV protease activity in a cell free system and HIV infection in human cells.. Purified ginkgolic acid and recombinant HIV-1 HXB2 KIIA protease were used for the HIV protease activity assay. Human peripheral blood mononuclear cells (PBMCs) were used for HIV infection (HIV-1SF162 virus), determined by a p24gag ELISA. Cytotoxicity was also determined.. Ginkgolic acid (31.2 µg/ml) inhibited HIV protease activity by 60%, compared with the negative control, and the effect was concentration-dependent. In addition, ginkgolic acid treatment (50 and 100 µg/ml) effectively inhibited the HIV infection at day 7 in a concentration-dependent manner. Ginkgolic acid at a concentration of up to 150 µg/ml demonstrated very limited cytotoxicity.. Ginkgolic acid effectively inhibits HIV protease activity in a cell free system and HIV infection in PBMCs without significant cytotoxicity. Ginkgolic acid may inhibit HIV protease through different mechanisms than current FDA-approved HIV PI drugs. These properties of ginkgolic acid make it a promising therapy for HIV infection, especially as the clinical problem of viral resistance to HIV PIs continues to grow.

Topics: Cell Death; Cell-Free System; Dose-Response Relationship, Drug; Ginkgolides; HIV Infections; HIV Protease; HIV Protease Inhibitors; Humans; Jurkat Cells; Lactones; Salicylates

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Female; HIV Infections; Humans; Liver; Male; Middle Aged; Salicylates; Transaminases

The accessory glands of the male genital tract are the sites of several major health problems, including benign prostatic hyperplasia, prostate cancer, and human immunodeficiency virus (HIV) transmission. We aimed to validate and improve our noninvasive method for the quantitation of drug concentrations in these physiological subcompartments. Twenty-seven men were dosed with 100 mg desipramine (a weak base) and 975 mg aspirin (a weak acid) and ejaculated their semen in 1 pass across 5 compartments of a collection device 2.5 hours later. A Bayesian latent-variable model previously developed by our group was further advanced for the estimation of drug concentrations in prostate and seminal vesicles based on drug and biomarker concentrations in the split ejaculate. Under normality assumptions, desipramine concentration (with 95% credible intervals) in prostate and seminal vesicles were 27 (8.3-52) ng/mL and 7.6 (4.0-11) ng/mL, respectively; salicylate concentration in prostate and seminal vesicles were 2.0 (0.093-6.5) microg/mL, and 9.9 (8.2-12) microg/mL, respectively. The prostate-to-seminal vesicles concentration ratio was 0.20 (0.0087-0.75) for salicylate and 3.6 (0.91-9.9) for desipramine. We conclude that our quantitative analysis along with the split ejaculate method is sensitive, reproducible, and applicable for the assessment of pharmacokinetics of the accessory glands of the male genital tract.

Topics: Administration, Oral; Adolescent; Adult; Algorithms; Aspirin; Bayes Theorem; Biomarkers, Pharmacological; Chromatography; Desipramine; Ejaculation; Fructose; HIV Infections; Humans; Male; Middle Aged; Outpatients; Prostate; Prostate-Specific Antigen; Reproducibility of Results; Salicylates; Semen; Seminal Vesicles; Sexual Dysfunction, Physiological; Tandem Mass Spectrometry

We hypothesized that heightened systemic inflammation contributes to the increased rate of cardiovascular events in HIV-infected patients not receiving combination antiretroviral therapy. We performed a pilot trial to assess the effects of the nuclear factor-kappaB inhibitor salsalate on flow-mediated dilation of the brachial artery, a measure of endothelial function. Flow-mediated dilation significantly improved after 8 weeks of salsalate. However, hepatotoxicity occurred frequently. Research using alternative agents is warranted to examine the role of inflammation in HIV-related cardiovascular disease.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Brachial Artery; Cardiovascular Diseases; Endothelium, Vascular; Female; HIV Infections; Humans; Liver; Male; Middle Aged; NF-kappa B; Pilot Projects; Salicylates; Vasodilation

Topics: Administration, Cutaneous; Adult; Anti-Inflammatory Agents, Non-Steroidal; HIV Infections; Humans; Male; Psoriasis; Salicylates; Skin Absorption

Topics: Bismuth; Colon; HIV Infections; Humans; Male; Middle Aged; Organometallic Compounds; Pain; Radiography; Salicylates; Self Medication

To evaluate the efficacy of ultraviolet B (UVB) phototherapy for the treatment of psoriasis in patients infected with human immunodeficiency virus (HIV), the response of 14 patients was compared to that of matched seronegative control individuals. All patients were evaluated prior to treatment (baseline) and after 21 treatments for the extent of total body surface area (TBSA) involvement and the quantification of scale, erythema, and thickness of plaques using a scale of 0 (absent) to 4 (severe). The only concomitant medication allowed was salicylic acid in petrolatum. The cumulative score for scale, erythema, and thickness improved 1.9 +/- 0.5 [mean +/- standard error of mean (SEM)] in the HIV group and 2.4 +/- 0.3 in controls. There was 40.9 +/- 7.3% reduction of TBSA involvement in the former and 38.4 +/- 7.6% reduction in the latter group. None of the differences was statistically significant. There was no statistically significant difference in the response to therapy among various stages of immunosuppression in the HIV group. There was also no deterioration of immune status in this group. UVB phototherapy is an effective treatment for psoriasis in patients infected with HIV. The response is identical to that of matched control individuals.

Topics: Administration, Cutaneous; Adult; Antiviral Agents; Body Surface Area; Case-Control Studies; CD4 Lymphocyte Count; Dermatitis, Exfoliative; Erythema; HIV Infections; HIV Seronegativity; Humans; Immunocompromised Host; Keratolytic Agents; Male; Psoriasis; Salicylates; Salicylic Acid; Ultraviolet Rays; Ultraviolet Therapy; Zidovudine

Topics: Candida albicans; Candidiasis, Oral; Colony Count, Microbial; Drug Combinations; HIV Infections; Humans; Immune Tolerance; Ketoconazole; Mouthwashes; Salicylates; Terpenes