Enteroaggregative Escherichia coli as a Potential Cause of Diarrheal Disease in Adults Infected with Human Immunodeficiency Virus

Stools of 68 human immunodeficiency virus (HIV)-infected adults with diarrhea and 60 without diarrhea were examined for enteroaggregative Escherichia coli (EAggEc) by HeLa cell adherence assay. EAggEc were present in stools of 30 patients with and 18 without diarrhea (P = .05). CD4 cell counts of patients with EAggEc and diarrhea were significantly lower than those of patients with EAggEc without diarrhea (P = .02). There was no difference in the mean duration of diarrheal symptoms or in the number of stools per day between patients with EAggEc and those without. None of the EAggEc strains were positive by polymerase chain reaction for adherence fimbria, but 11 strains were positive for EAggEc heat-stable toxin EAST/1. Of the EAggEc strains, 51% were resistant to trimethoprim-sulfamethoxazole and 65% were resistant to ampicillin. EAggEc may be a pathogen in HIV-infected patients with diarrhea; HIV-infected patients with EAggEc appear to be more symptomatic when HIV disease is more advance

Urinary eicosanoid metabolites in HIV-infected women with central obesity switching to raltegravir: an analysis from the women, integrase, and fat accumulation trial.

Chronic inflammation is a hallmark of HIV infection. Eicosanoids reflect inflammation, oxidant stress, and vascular health and vary by sex and metabolic parameters. Raltegravir (RAL) is an HIV-1 integrase inhibitor that may have limited metabolic effects. We assessed urinary F2-isoprostanes (F2-IsoPs), prostaglandin E2 (PGE-M), prostacyclin (PGI-M), and thromboxane B2 (TxB2) in HIV-infected women switching to RAL-containing antiretroviral therapy (ART). Thirty-seven women (RAL = 17; PI/NNRTI = 20) with a median age of 43 years and BMI 32 kg/m(2) completed week 24. TxB2 increased in the RAL versus PI/NNRTI arm (+0.09 versus -0.02; P = 0.06). Baseline PGI-M was lower in the RAL arm (P = 0.005); no other between-arm cross-sectional differences were observed. In the PI/NNRTI arm, 24-week visceral adipose tissue change correlated with PGI-M (rho = 0.45; P = 0.04) and TxB2 (rho = 0.44; P = 0.005) changes, with a trend seen for PGE-M (rho = 0.41; P = 0.07). In an adjusted model, age ≥ 50 years (N = 8) was associated with increased PGE-M (P = 0.04). In this randomized trial, a switch to RAL did not significantly affect urinary eicosanoids over 24 weeks. In women continuing PI/NNRTI, increased visceral adipose tissue correlated with increased PGI-M and PGE-M. Older age (≥ 50) was associated with increased PGE-M. Relationships between aging, adiposity, ART, and eicosanoids during HIV-infection require further study

Pharmacy Adherence Measures to Assess Adherence to Antiretroviral Therapy: Review of the Literature and Implications for Treatment Monitoring

Prescription or pill-based methods for estimating adherence to antiretroviral therapy (ART), pharmacy adherence measures (PAMs), are objective estimates calculated from routinely collected pharmacy data. We conducted a literature review to evaluate PAMs, including their association with virological and other clinical outcomes, their efficacy compared with other adherence measures, and factors to consider when selecting a PAM to monitor adherence. PAMs were classified into 3 categories: medication possession ratio (MPR), pill count (PC), and pill pick-up (PPU). Data exist to recommend PAMs over self-reported adherence. PAMs consistently predicted patient outcomes, but additional studies are needed to determine the most predictive PAM parameters. Current evidence suggests that shorter duration of adherence assessment (≤6 months) and use of PAMs to predict future outcomes may be less accurate. PAMs which incorporate the number of days for which ART was prescribed without the counting of remnant pills, are reasonable minimum-resource methods to assess adherence to AR

Urinary Eicosanoid Metabolites in HIV-Infected Women with Central Obesity Switching to Raltegravir: An Analysis from the Women, Integrase, and Fat Accumulation Trial

Chronic inflammation is a hallmark of HIV infection. Eicosanoids reflect inflammation, oxidant stress, and vascular health and vary by sex and metabolic parameters. Raltegravir (RAL) is an HIV-1 integrase inhibitor that may have limited metabolic effects. We assessed urinary F2-isoprostanes (F2-IsoPs), prostaglandin E2 (PGE-M), prostacyclin (PGI-M), and thromboxane B2 (TxB2) in HIV-infected women switching to RAL-containing antiretroviral therapy (ART). Thirty-seven women (RAL = 17; PI/NNRTI = 20) with a median age of 43 years and BMI 32 kg/m2 completed week 24. TxB2 increased in the RAL versus PI/NNRTI arm (+0.09 versus −0.02; P=0.06). Baseline PGI-M was lower in the RAL arm (P=0.005); no other between-arm cross-sectional differences were observed. In the PI/NNRTI arm, 24-week visceral adipose tissue change correlated with PGI-M (rho=0.45; P=0.04) and TxB2 (rho=0.44; P=0.005) changes, with a trend seen for PGE-M (rho=0.41; P=0.07). In an adjusted model, age ≥ 50 years (N=8) was associated with increased PGE-M (P=0.04). In this randomized trial, a switch to RAL did not significantly affect urinary eicosanoids over 24 weeks. In women continuing PI/NNRTI, increased visceral adipose tissue correlated with increased PGI-M and PGE-M. Older age (≥50) was associated with increased PGE-M. Relationships between aging, adiposity, ART, and eicosanoids during HIV-infection require further study

Coccidioidomycosis among Workers at an Archeological Site, Northeastern Utah

In 2001, an outbreak of acute respiratory disease occurred among persons working at a Native American archeological site at Dinosaur National Monument in northeastern Utah. Epidemiologic and environmental investigations were undertaken to determine the cause of the outbreak. A clinical case was defined by the presence of at least two of the following symptoms: self-reported fever, shortness of breath, or cough. Ten workers met the clinical case definition; 9 had serologic confirmation of coccidioidomycosis, and 8 were hospitalized. All 10 were present during sifting of dirt through screens on June 19; symptoms began 9–12 days later (median 10). Coccidioidomycosis also developed in a worker at the site in September 2001. A serosurvey among 40 other Dinosaur National Monument workers did not find serologic evidence of recent infection. This outbreak documents a new endemic focus of coccidioidomycosis, extending northward its known geographic distribution in Utah by approximately 200 miles

Contribution of Genetic Background, Traditional Risk Factors, and HIV-Related Factors to Coronary Artery Disease Events in HIV-Positive Persons

We show in human immunodeficiency virus-positive persons that the coronary artery disease effect of an unfavorable genetic background is comparable to previous studies in the general population, and comparable in size to traditional risk factors and antiretroviral regimens known to increase cardiovascular ris

Effect of Levels of Acetate on the Mevalonate Pathway of Borrelia burgdorferi

Borrelia burgdorferi, the agent of Lyme disease, is a spirochetal pathogen with limited metabolic capabilities that survives under highly disparate host-specific conditions. However, the borrelial genome encodes several proteins of the mevalonate pathway (MP) that utilizes acetyl-CoA as a substrate leading to intermediate metabolites critical for biogenesis of peptidoglycan and post-translational modifications of proteins. In this study, we analyzed the MP and contributions of acetate in modulation of adaptive responses in B. burgdorferi. Reverse-transcription PCR revealed that components of the MP are transcribed as individual open reading frames. Immunoblot analysis using monospecific sera confirmed synthesis of members of the MP in B. burgdorferi. The rate-limiting step of the MP is mediated by HMG-CoA reductase (HMGR) via conversion of HMG-CoA to mevalonate. Recombinant borrelial HMGR exhibited a Km value of 132 µM with a Vmax of 1.94 µmol NADPH oxidized minute−1 (mg protein)−1 and was inhibited by statins. Total protein lysates from two different infectious, clonal isolates of B. burgdorferi grown under conditions that mimicked fed-ticks (pH 6.8/37°C) exhibited increased levels of HMGR while other members of the MP were elevated under unfed-tick (pH 7.6/23°C) conditions. Increased extra-cellular acetate gave rise to elevated levels of MP proteins along with RpoS, CsrABb and their respective regulons responsible for mediating vertebrate host-specific adaptation. Both lactone and acid forms of two different statins inhibited growth of B. burgdorferi strain B31, while overexpression of HMGR was able to partially overcome that inhibition. In summary, these studies on MP and contributions of acetate to host-specific adaptation have helped identify potential metabolic targets that can be manipulated to reduce the incidence of Lyme disease

Switch to Raltegravir From Protease Inhibitor or Nonnucleoside Reverse-Transcriptase Inhibitor Does not Reduce Visceral Fat In Human Immunodeficiency Virus-Infected Women With Central Adiposity.

Human immunodeficiency virus-infected women with central adiposity switched to raltegravir-based antiretroviral therapy immediately or after 24 weeks. No statistically significant changes in computed tomography-quantified visceral adipose tissue (VAT) or subcutaneous fat were observed, although 48 weeks of raltegravir was associated with a 6.4% VAT decline. Raltegravir for 24 weeks was associated with improvements in lipids

High-fat meals do not impair postprandial endothelial function in HIV-infected and uninfected men.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pagePrior studies have demonstrated impaired endothelium-dependent flow-mediated dilation (FMD) in healthy subjects following a high-fat meal. Compared to uninfected individuals, HIV-infected persons have been shown to have impaired FMD. We examined the effect of two different high-fat meals on endothelial function in HIV-infected and uninfected men. We performed a randomized, parallel group crossover study comparing 47 white men [18 HIV-uninfected, 9 HIV-infected and antiretroviral therapy (ART)-naïve, and 20 HIV-infected men on ART]. Fasting participants consumed one of two randomly assigned high-fat meals of either saturated or polyunsaturated fat, followed at least 24 h later by the other meal. Brachial artery ultrasound measurements to assess vascular reactivity were performed before and 3 h after each dietary challenge. There was no significant difference in mean baseline or postprandial FMD between HIV-infected and HIV-uninfected participants (mean baseline FMD±SD, 9.0%±5 vs. 9.2%±5, p=0.9; mean postprandial FMD±SD, 9.0%±4.7 vs. 9.1%±4.7, p=0.96, respectively). No significant difference in baseline or postprandial change in FMD was found between meals or HIV treatment groups. Fasting lipids and glucose, CD4(+) count, and viral load did not predict FMD in HIV-infected participants. In contrast to previous reports, this study did not demonstrate impaired endothelium-dependent vasodilation after high-fat meals in either HIV-infected or HIV-uninfected men. Moreover, HIV infection itself may not be the primary explanation for the abnormal endothelial function reported in HIV-infected individuals