Fat distribution and metabolic changes are strongly correlated and energy expenditure is increased in the HIV lipodystrophy syndrome.

OBJECTIVE: To examine the relationships between protease inhibitor (PI) therapy, body fat distribution and metabolic disturbances in the HIV lipodystrophy syndrome. DESIGN: Cross-sectional study. SETTING: HIV primary care practices. PATIENTS: PI-treated patients with lipodystrophy (n= 14) and PI-treated (n= 13) and PI-naive (n= 5) patients without lipodystrophy. MAIN OUTCOME MEASURES: Body composition was assessed by physical examination, dual-energy X-ray absorptiometry and computed tomography. Insulin sensitivity (SI) was measured using the insulin-modified frequently sampled intravenous glucose tolerance test. Lipid profiles, other metabolic parameters, duration of HIV infection, CD4 lymphocyte counts, HIV-1 RNA load and resting energy expenditure (REE) were also assessed. RESULTS: PI-treated patients with lipodystrophy were significantly less insulin sensitive than PI-treated patients and PI-naive patients without any changes in fat distribution (SI(22) x 10(-4) (min(-1)/microU/ml) versus 3.2 x 10(-4) and 4.6 x 10(-4) (min(-1)/microU/ml), respectively; P < 0.001). Visceral adipose tissue area and other measures of central adiposity correlated strongly with metabolic disturbances as did the percent of total body fat present in the extremities; visceral adipose tissue was an independent predictor of insulin sensitivity and high density lipoprotein cholesterol levels. REE per kg lean body mass was significantly higher in the group with lipodystrophy compared to the groups without lipodystrophy (36.9 versus 31.5 and 29.4 kcal/kg lean body mass; P < 0.001), and SI was strongly correlated with and was an independent predictor of REE in this population. CONCLUSIONS: Body fat distribution and metabolic disturbances are strongly correlated in the HIV lipodystrophy syndrome and REE is increased.

Clinical assessment of HIV-associated lipodystrophy in an ambulatory population.

OBJECTIVE: To identify clinical factors associated with prevalence of fat atrophy (lipoatrophy) and fat accumulation (lipoaccumulation) in HIV-1 infected patients. DESIGN: Evaluation of HIV-1 infected patients seen for routine care between 1 October and 31 December 1998 in the eight HIV Outpatient Study (HOPS) clinics. SETTING: Eight clinics specializing in the care of HIV-1 infected patients. PATIENTS: A total of 1077 patients were evaluated for signs of fat maldistribution. INTERVENTIONS: A standardized set of questions and specific clinical signs were assessed. Demographic, clinical and pharmacological data for each patient were also included in the analysis. MAIN OUTCOME MEASURES: Demographic, immunologic, virologic, clinical, laboratory, and drug treatment factors were assessed in stratified and multivariate analyses for their relationship to the presence and severity of fat accumulation and atrophy. RESULTS: Independent factors for moderate/severe lipoatrophy for 171 patients were increasing age, any use of stavudine, use of indinavir for longer than 2 years, body mass index (BMI) loss, and measures of duration and severity of HIV disease. Independent risk factors for moderate/severe fat accumulation for 104 patients were increasing age, BMI gain, measures of amount and duration of immune recovery, and duration of antiretroviral therapy (ART). The number of non-drug risk factors substantially increased the likelihood of lipoatrophy. If non-drug risk factors were absent, lipoatrophy was unusual regardless of the duration of drug use. CONCLUSIONS: HIV-associated lipodystrophy is associated with several host, disease, and drug factors. While prevalence of lipoatrophy increased with the use of stavudine and indinavir, and lipoaccumulation was associated with duration of ART, other non-drug factors were strongly associated with both fat atrophy and accumulation.

Factors associated with the successful modification of antiretroviral therapy. HIV Outpatient Study Investigators.

OBJECTIVES: To assess the characteristics of medication regimen modification and the influence of a commercial genotypic resistance assay on the short-term (3-12 weeks) viral load response (> or = 0.5 log reduction) in HIV-1-infected patients extensively treated with antiretroviral therapy (ART). METHODS: A nested cohort study was performed in two clinics from the HIV Outpatient Study of 96 persons with a HIV-1 viral load of 10(4) log copies/ml or greater taking at least two antiretroviral medications. RESULTS: Successful modification was associated with adding at least two new medications [relative risk (RR), 1.5; 95% confidence interval (CI), 1.1-2.2], adding a drug from a previously unused class of agents (RR, 2.0; CI, 1.4-2.9), the initiation of a non-nucleoside reverse transcriptase inhibitor (NNRTI) (RR, 1.7; CI, 1.2-2.4), but not substituting a protease inhibitor or the use of a commercial genotypic resistance assay. CONCLUSION: Incorporating a drug from a previously unused class or changing at least two new medications, but, within the confines of this study, not using a commercial genotypic resistance assay, was associated with the successful modification of ART as measured by a reduction in viral load.

Recurrent brainstem encephalitis associated with herpes simplex virus type 1 DNA in cerebrospinal fluid.

A 47-year-old man had recurrent signs and symptoms of brainstem encephalitis over a 4-year period. Although CSF viral cultures were repeatedly negative, herpes simplex virus type 1 (HSV-1) DNA was detected in CSF by polymerase chain reaction (PCR). HSV-1-specific antibodies were absent at the time of the first positive PCR test, but CSF seroconversion to high HSV-1-specific antibody titer subsequently occurred. CSF antibody to cytomegalovirus (CMV) and varicella-zoster virus (VZV) was not detectable, nor could CMV, VZV, or Epstein-Barr virus nucleic acid be detected by CSF by PCR. This is the first report of the use of CSF PCR for the rapid antemortem diagnosis of herpetic brainstem encephalitis.

The clinical significance of positive blood cultures: a comprehensive analysis of 500 episodes of bacteremia and fungemia in adults. I. Laboratory and epidemiologic observations.

Five hundred episodes of septicemia were reviewed, with emphasis on laboratory and epidemiologic findings. The isolation of facultative and anaerobic gram-negative bacilli, fungi, and gram-positive cocci (except viridans streptococci and Staphylococcus epidermidis) almost always indicated true bacteremia, whereas the isolation of aerobic and anaerobic gram-positive bacilli, including Clostridium species, often represented contamination. More than 99% of all episodes were detected when two samples of blood (a total of 30 ml) were cultured. The five most common isolates were Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The incidence of septicemia was highest among medical patients and lowest among obstetric-gynecologic patients. Two-thirds of all episodes were nosocomial; S. aureus, enterococci, facultative gram-negative bacilli, and fungi were especially common nosocomial pathogens. The microorganisms isolated varied with the hospital service; polymicrobial episodes were especially common among surgical patients and transplant recipients. The most common sources of bacteremia were the respiratory, genitourinary, and gastrointestinal tracts; however, the source was unknown in nearly one-third of episodes. Microorganisms causing septicemia in neutropenic and nonneutropenic patients were not different; however, polymicrobial infections were more frequent in the presence of neutropenia. After antimicrobial susceptibility data became available, therapy was appropriate greater than 90% of the time.

The clinical significance of positive blood cultures: a comprehensive analysis of 500 episodes of bacteremia and fungemia in adults. II. Clinical observations, with special reference to factors influencing prognosis.

Among 500 patients with bacteremia and fungemia, total mortality was 42%; about half of all deaths were attributable directly to infection. Mortality increased with age, but deaths unrelated to infection itself were responsible in part for this increase. Mortality was 2.6% among obstetric-gynecologic patients, 42% among medical patients, 49% among surgical patients, and 60% among transplant patients. The risk of death was especially high with enterococcal, facultative gram-negative, fungal, polymicrobial, or hospital-acquired sepsis; in the presence of shock, leukopenia, absolute granulocytopenia, or defined predisposing conditions (neoplasia, cirrhosis, and combinations of factors such as surgery and renal failure); and with a primary infected focus in the respiratory tract, the skin, a surgical wound, an abscess, or an unknown site. Body temperature was inversely related to mortality. Survival was increased by the use of appropriate antibiotics and, where applicable, additional therapeutic maneuvers (e.g., drainage). Multivariate analysis defined seven variables that independently influenced outcome: microorganism, blood pressure, body temperature, primary focus of infection, place of acquisition of infection, age, and predisposing factors. Although some adverse prognostic factors are not amenable to intervention, prevention of nosocomial bacteremia and fungemia and early reversal of hypotension may reduce the death rate from sepsis.

Granulomatous tenosynovitis and carpal tunnel syndrome caused by Sporothrix schenckii.

Although the usual form of sporotrichosis is a lymphocutaneous lesion, Sporothrix schenckii can cause articular disease that is difficult to diagnose. We describe two patients with sporotrichosis who presented with tenosynovitis and the carpal tunnel syndrome. A tissue specimen is required for a precise diagnosis; granulomatous tenosynovitis suggests an infectious cause. Unless appropriate cultures for bacteria, mycobacteria and fungi are obtained, the diagnosis may be missed or delayed. Mouse inoculations may be required to isolate S. schenckii from tissue, which rarely shows the delicate fungus in histologic sections. Our patients were cured by a combination of synovectomy and the intravenous administration of amphotericin B. Sporotrichosis should be considered in the differential diagnosis of the carpal tunnel syndrome, particularly when surgical exploration discloses a granulomatous tenosynovitis.