The effect of initiation of antiretroviral therapy on monocyte, endothelial and platelet function in HIV-1 infection.

OBJECTIVES: Monocyte activation, endothelial dysfunction and platelet activation all potentially contribute to the increased risk of cardiovascular disease (CVD) reported in those with HIV-1 infection. To date, no study has examined how initiation of antiretroviral therapy (ART) affects markers of all three processes. We aimed to compare markers of monocyte, endothelial and platelet function between untreated HIV-positive subjects and HIV-negative controls and to examine the early effects of ART initiation on these markers. METHODS: We measured monocyte [soluble CD14 (sCD14) and sCD163], endothelial [von Willebrand factor (vWF), intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1)] and platelet [soluble P-selectin (sP-selectin), soluble CD40 ligand (sCD40L) and soluble glycoprotein VI (sGPVI)] biomarkers before and at weeks 4 and 12 post ART initiation in HIV-positive and well-matched HIV-negative controls. RESULTS: We examined 40 subjects, 25 HIV-positive subjects and 15 controls, with a median age of 34 years [interquartile range (IQR) 31, 40 years], of whom 60% were male and 47.5% Caucasian. Pre-ART, all biomarkers (monocyte, endothelial and platelet) were significantly higher in HIV-positive patients versus controls (all P < 0.05) and decreased with ART initiation, except for sCD14, which remained unchanged [median 1680 (IQR 1489, 1946) ng/mL at week 12 versus 1570 (IQR 1287, 2102) ng/mL at week 0; P = 0.7]. Although platelet activation markers reduced to levels comparable to those in controls, endothelial dysfunction markers remained elevated, as did sCD163 [at week 12, median 1005 (IQR 791, 1577) ng/mL in HIV-positive patients versus 621 (IQR 406, 700) ng/mL in controls; P < 0.0001]. CONCLUSIONS: ART initiation resulted in reductions in levels of CVD-associated biomarkers; however, although they improved, markers of endothelial dysfunction and monocyte activation remained elevated. How these persistent abnormalities affect CVD risk in HIV infection remains to be determined.

Characterization of associations and development of atazanavir resistance after unplanned treatment interruptions.

OBJECTIVES: Although current guidelines recommend resistance testing prior to antiretroviral therapy (ART) reinitiation after treatment interruptions, virological failure of first-line ritonavir-boosted, protease-inhibitor (PI/r)-containing ART is associated with low emergent PI resistance. In patients experiencing unscheduled treatment interruptions (UTrIs) on ritonavir-boosted atazanavir (ATV/r) ART regimens, we hypothesized low emergence of PI mutations conferring resistance to ATV/r. METHODS: In a retrospective assessment of HIV-infected patients initiating ATV/r-containing ART, using logistic regression we determined factors associated with UTrI, the prevalence of emergent resistance mutations and virological response after ART reinitiation. RESULTS: A total of 202 patients [median age 33 years (interquartile range (IQR) 29-40 years); 52% female; median CD4 count 184 cells/µL (IQR 107-280 cells/µL); median HIV RNA 4.6 log10 HIV-1 RNA copies/mL (IQR 3.2-5.1 copies/mL)] initiated ATV/r between 2004 and 2009; 80 (43%) were ART naïve. One hundred and ten patients (55%) underwent 195 UTrIs after a median (IQR) 25 (10-52) weeks on ART, with a median (IQR) UTrI duration of 10 (3-31) weeks. Fifty-four of 110 patients (49%) underwent more than one UTrI. The commonest reasons for UTrI were nonadherence (52.7%) and drug intolerance (20%). Baseline HIV RNA > 100 000 copies\mL [odds ratio (OR) 3.6; 95% confidence interval (CI) 1.3-9.95] and being HCV positive, an injecting drug user or on methadone (OR 2.4; 95% CI 1.3-4.4) were independently associated with UTrI. In 39 patients with at least two resistance assays during UTrIs, 72 new mutations emerged; four nucleoside reverse transcriptase inhibitor (NRTI), two nonnucleoside reverse transcriptase inhibitor (NNRTI) and 66 protease inhibitor (PI) resistance mutations. All emergent PI resistance mutations were minor mutations. At least 65% of patients were re-suppressed on ATV/r reinitiation. CONCLUSIONS: In this PI-treated cohort, UTrIs are common. All emergent PI resistance mutations were minor and ATV/r retained activity and efficacy when reintroduced, even after several UTrIs, raising questions regarding the need for routine genotypic resistance assays in PI/r-treated patients prior to ART reinitiation after UTrI.

Human immunodeficiency virus and hepatitis--implications for operating room personnel.

Human Immunodeficiency Virus, Hepatitis B and C are important blood borne viruses and pose occupational risks for operating room personnel. Increasing numbers of patients with these infections are appearing in Irish hospitals. In this review we describe in detail the occupational risks of these blood borne viruses for operating room personnel and how best to minimise them.

Colonoscopy-associated listeriosis: report of a case.

We report a case of meningitis due to Listeria monocytogenes that occurred following colonoscopy. The patient had cirrhosis, a portosystemic shunt, and diarrhea for which she was being evaluated. Only one previous report has linked colonoscopy to listeriosis. We review the pathogenesis of listeriosis and, in particular, the evidence that prior fecal colonization is followed by bacteremia in a susceptible host. The findings in this case are consistent with this pathogenetic sequence.

Urinary schistosomiasis: a report of four cases and a review.

Urinary schistosomiasis is a common cause of hematuria in tropical regions, where it most often affects teenage boys. Children presenting with hematuria in the developed world are usually considered to have bacterial cystitis or a structural lesion and are investigated and treated accordingly. The authors report on a family recently returned to Canada from Nigeria in which all four children had urinary schistosomiasis. Nocturnal enuresis was the presenting symptom in the index case; this patient also had hematuria and dysuria. Nocturia occurred in a second child, and the other two children were asymptomatic. All four were cured by a single dose of praziquantel, a new schistosomicide. The life cycle of the causative organism, the clinical manifestations of schistosomiasis, the host response and treatment with praziquantel are reviewed.

Intraabdominal infection: a review.

Significant advances in our understanding of the pathogenesis and microbiology of intraabdominal sepsis have been made over the past 15 years. There has also been progress in various aspects of diagnosis and treatment of these infections. Computed tomography and ultrasonography have simplified the diagnosis of an intraabdominal abscess, and percutaneous drainage of abscesses has become an acceptable alternative to surgery. Novel surgical approaches have been tried, but their true role is not yet defined. A broader selection of less-toxic antimicrobial agents is now available as treatment for intraabdominal infection. The role of superinfecting pathogens is more clearly defined. Patients who would have died of this infection in a previous era now survive because of an array of supportive therapies.

A phenomenology of scut.

OBJECTIVE: To identify, describe, and quantify the night-call duties that residents in internal medicine call "scutwork" and to compare faculty and residents' perceptions of scutwork. DESIGN: Prospective, cross-sectional study. SETTING: General internal medicine training program at a university-affiliated tertiary care hospital. PARTICIPANTS: Forty-eight residents who spent 3 months or more on an internal medicine teaching unit during the previous year and 41 faculty members who spent 2 months or more on one of these units. INTERVENTIONS: Postcall surveys and night-call diaries were used to analyze residents' activities, to derive a definition of scutwork, and to estimate its prevalence. Residents and faculty then completed a detailed questionnaire that included ratings of the educational value, "scut content," and residents' responsibility for 20 specific tasks. MAIN RESULTS: Eighty-three percent of residents found scutwork and education to be mutually exclusive for the 20 tasks, although 20% indicated that scutwork was an appropriate task for residents. Residents' ratings of tasks as scut varied according to the context of the task. For example, obtaining routine consent from someone else's patient was considered scutwork by 98% of residents, whereas obtaining such consent from the residents's own patient was rated as scutwork by only 52% (P less than 0.01). Similarly, performing intravenous cannulation at the request of ward staff was rated as scut by 94% of residents, whereas performing cannulation at another resident's request was rated as scut by 56% (P less than 0.01). Night-time admission of a patient for an elective procedure was rated as scut by 75% of residents, whereas admission of such a patient after discussion with a faculty member was labeled scut by only 44% (P less than 0.01). Faculty ratings of such admissions did not show the same variation (24% for both). Faculty were more likely than residents to assess tasks as educational (50% compared with 26%, P less than 0.01) but were less likely to consider tasks as scutwork (47% compared with 62%, P = 0.12) or as work that should be done by nonresidents (35% compared with 46%, P greater than 0.2). CONCLUSIONS: Our results suggest that the characteristics of scutwork can be identified, that the perception of scut varies between faculty and residents, and that the context of a task often determines whether residents perceive it as scut.

Double-blind, randomized comparison of 24 weeks of norfloxacin and 12 weeks of norfloxacin followed by 12 weeks of placebo in the therapy of complicated urinary tract infection.

We evaluated the benefits of prolonging norfloxacin therapy from 12 to 24 weeks for complicated urinary tract infection in a double-blind, randomized, placebo-controlled study. During the second 12 weeks, norfloxacin was superior to placebo (P less than 0.05) in suppressing bacteriuria. Adverse effects were common but mostly confined to the initial 12 weeks.