Jack Fuhrer

Bio: Jack Fuhrer is an academic researcher from Stony Brook University. The author has contributed to research in topics: Viral load & Acquired immunodeficiency syndrome (AIDS). The author has an hindex of 18, co-authored 32 publications receiving 10340 citations. Previous affiliations of Jack Fuhrer include Centers for Disease Control and Prevention & State University of New York System.

Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators.

Abstract: Background and Methods National surveillance data show recent, marked reductions in morbidity and mortality associated with the acquired immunodeficiency syndrome (AIDS). To evaluate these declines, we analyzed data on 1255 patients, each of whom had at least one CD4+ count below 100 cells per cubic millimeter, who were seen at nine clinics specializing in the treatment of human immunodeficiency virus (HIV) infection in eight U.S. cities from January 1994 through June 1997. Results Mortality among the patients declined from 29.4 per 100 person-years in 1995 to 8.8 per 100 person-years in the second quarter of 1997. There were reductions in mortality regardless of sex, race, age, and risk factors for transmission of HIV. The incidence of any of three major opportunistic infections (Pneumocystis carinii pneumonia, Mycobacterium avium complex disease, and cytomegalovirus retinitis) declined from 21.9 per 100 person-years in 1994 to 3.7 per 100 person-years by mid-1997. In a failure-rate model, increases in t...

Association of severe insulin resistance with both loss of limb fat and elevated serum tumor necrosis factor receptor levels in HIV lipodystrophy.

Abstract: Summary: HIV-lipodystrophy (HIV-LD) is characterized by the loss of body fat from the limbs and face, an increase in truncal fat, insulin resistance, and hyperlipidemia, factors placing affected patients at increased risk for vascular disease. This study evaluated insulin sensitivity and inflammatory status associated with HIV-LD and provides suggestions about its etiology. Insulin sensitivity and immune activation markers were assessed in 12 control subjects and 2 HIV-positive groups, 14 without and 15 with LD syndrome. Peripheral insulin sensitivity (mostly skeletal muscle) was determined with the hyperinsulinemic-euglycemic clamp. Circulating insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) and free fatty acid (FFA) levels, and their response to insulin infusion were indicative of insulin responsiveness of liver and adipose tissue, respectively. Serum levels of soluble type 2 tumor necrosis factor(TNF-) receptor (sTNFR2) were used as an indicator of immune activation. HIV-LD study subjects had significantly reduced (twofold) peripheral insulin sensitivity, but normal levels of FFA and reduced levels of IGFBP-1, relative to the nonlipodystrophy groups, indicating that the loss of insulin sensitivity was more pronounced in skeletal muscle than in liver or fat. The significant loss of peripheral fat in the HIV-LD group (34%; p < .05) closely correlated with the reduced peripheral insulin sensitivity (p .0001). Levels of sTNFR2 were elevated in all HIV-infected study subjects, but they were significantly higher in those with lipodystrophy than without, and sTNFR2 levels strongly correlated with the reduction in insulin sensitivity (p .0001). Loss of peripheral fat, normal levels of FFA, and reduced levels of IGFBP-1 indicate that insulin resistance in HIV-LD is distinct from type 2 diabetes and obesity. The relationship between the degree of insulin resistance and sTNFR2 levels suggests an inflammatory stimulus is contributing to the development of HIV-associated lipodystrophy. Key Words: Type 2 diabetes mellitus—Insulin resistance—Insulin-like growth factor binding protein—Free fatty acid—Tumor necrosis factor-— Lipodystrophy—Obesity—HIV/AIDS.

Incidence of and risk factors for lipoatrophy (abnormal fat loss) in ambulatory HIV-1-infected patients.

Abstract: To identify clinical factors associated with the incidence of HIV-1-associated lipoatrophy, HIV-1-infected patients in the HIV Outpatient Study (HOPS) were prospectively evaluated for clinical signs of lipoatrophy at two visits about 21 months apart. Development of lipoatrophy was analyzed in stratified and multivariate analyses for its relationship to immunologic, virologic, clinical, and drug treatment information for each patient. Of 337 patients with no lipoatrophy at Survey 1, 44 (13.1%) developed moderate or severe lipoatrophy between the two surveys. In multivariate analyses, significant risk factors for incident lipoatrophy were white race (OR = 5.2; 95% CI: 1.9-17.1; p =.003), CD4 T-lymphocyte count at Survey 2 less than 100 cells/mm 3 (OR = 4.2; 95% CI: 1.3-13.1; p =.013), and body mass index (BMI) less than 24 kg/m 2 (OR = 2.4; 95% CI: 1.1-5.4; p =.024). Analyses that controlled for the severity of HIV illness demonstrated no significant association with use of or time on any antiretroviral agent or class of agents and the development of lipoatrophy. Some host factors and factors associated with previous or current severity of HIV infection, especially CD4 T-lymphocyte cell count, appeared to have the strongest association with incidence of lipoatrophy.

Hepatitis A and B vaccination practices for ambulatory patients infected with HIV

Abstract: Few studies exist of adherence to guidelines for vaccination of persons infected with human immunodeficiency virus (HIV), especially in the era of highly active antiretroviral therapy (HAART). In a retrospective, cross-sectional analysis in the HIV Outpatient Study sites, 198 (32.4%) of 612 patients eligible for hepatitis B vaccine received at least 1 dose. In multivariate analysis, hepatitis B vaccination was associated with HIV risk category, education level, and number of visits to the HIV clinic per year. Among 716 patients eligible for hepatitis A vaccine, 167 (23.3%) received ⩾1 dose. Response to hepatitis B vaccination was associated with higher nadir CD4 + cell counts (P = .008) and HIV RNA levels less than the level of detection (P = .04), although some response was documented at all CD4 + levels. Although there were low rates of complete hepatitis vaccination in this cohort of ambulatory patients, prompt efforts to vaccinate patients entering care, receipt of antiretroviral therapy, and practice reminder systems may enhance vaccination practices.

Improved insulin sensitivity and body fat distribution in HIV-infected patients treated with rosiglitazone: a pilot study.

Abstract: The insulin-sensitizing drugs thiazolidinediones (TZDs), such as rosiglitazone, improve insulin sensitivity and also promote adipocyte differentiation in vitro. The authors hypothesized that TZDs might be beneficial to patients with HIV disease to improve insulin sensitivity and the distribution of body fat by increasing peripheral fat. The ability of rosiglitazone (8 mg/d) to improve insulin sensitivity (from hyperinsulinemic-euglycemic clamp) and to improve body fat distribution (determined from computed tomography measurements of visceral adipose tissue [VAT] and subcutaneous adipose tissue [SAT]) was determined in 8 HIV-positive patients. Before treatment, the insulin sensitivity of the patients was reduced to approximately 34% of that in control subjects. The rate of glucose disposal during a hyperinsulinemic-euglycemic clamp (Rd) was 3.8 +/-.4 (SEM) mg glucose/kg lean body mass/min compared with 11.08 +/- 1.1 (p<.001) in healthy age- and body mass index (BMI)-matched control subjects. After rosiglitazone treatment of 6 to 12 weeks, Rd increased to 5.99 +/-.9 (p=.02), an improvement of 59 +/- 22%. SAT increased by 23 +/- 10% (p=.05), and, surprisingly, VAT was decreased by 21 +/- 8% (p=.04) with a trend for increased SAT/VAT that failed to reach statistical significance. There were no significant changes in blood counts, viral loads, or CD4 counts with rosiglitazone treatment. The study demonstrates that rosiglitazone therapy improves insulin resistance and body fat distribution in some patients with HIV disease.

Actual causes of death in the United States, 2000.

Abstract: ContextModifiable behavioral risk factors are leading causes of mortality in the United States. Quantifying these will provide insight into the effects of recent trends and the implications of missed prevention opportunities.ObjectivesTo identify and quantify the leading causes of mortality in the United States.DesignComprehensive MEDLINE search of English-language articles that identified epidemiological, clinical, and laboratory studies linking risk behaviors and mortality. The search was initially restricted to articles published during or after 1990, but we later included relevant articles published in 1980 to December 31, 2002. Prevalence and relative risk were identified during the literature search. We used 2000 mortality data reported to the Centers for Disease Control and Prevention to identify the causes and number of deaths. The estimates of cause of death were computed by multiplying estimates of the cause-attributable fraction of preventable deaths with the total mortality data.Main Outcome MeasuresActual causes of death.ResultsThe leading causes of death in 2000 were tobacco (435 000 deaths; 18.1% of total US deaths), poor diet and physical inactivity (400 000 deaths; 16.6%), and alcohol consumption (85 000 deaths; 3.5%). Other actual causes of death were microbial agents (75 000), toxic agents (55 000), motor vehicle crashes (43 000), incidents involving firearms (29 000), sexual behaviors (20 000), and illicit use of drugs (17 000).ConclusionsThese analyses show that smoking remains the leading cause of mortality. However, poor diet and physical inactivity may soon overtake tobacco as the leading cause of death. These findings, along with escalating health care costs and aging population, argue persuasively that the need to establish a more preventive orientation in the US health care and public health systems has become more urgent.

Declining Morbidity and Mortality among Patients with Advanced Human Immunodeficiency Virus Infection

Abstract: To the Editor: Palella et al. (March 26 issue)1 reported that the use of more intensive antiretroviral therapies is responsible for declines in both morbidity and mortality in patients with AIDS. We conducted a study to evaluate the impact of protease inhibitors on the rates of selected opportunistic processes and mortality and found similar results. Our study population came from a public human immunodeficiency virus (HIV) outpatient clinic in New Orleans. All subjects and data were from the Adult Spectrum of Disease study, a prospective study funded by the Centers for Disease Control and Prevention examining the natural history of . . .

Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents

Abstract: SUMMARY The availability of an increasing number of antiretroviral agents and the rapid evolution of new information has introduced extraordinary complexity into the treatment of HIV-infected persons. In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for the clinical management of HIV-infected adults and adolescents. This report recommends that care should be supervised by an expert, and makes recommendations for laboratory monitoring including plasma HIV RNA, CD4 cell counts and HIV drug resistance testing. The report also provides guidelines for antiretroviral therapy, including when to start treatment, what drugs to initiate, when to change therapy, and therapeutic options when changing therapy. Special considerations are provided for adolescents and pregnant women. As with treatment of other chronic conditions, therapeutic decisions require a mutual understanding between the patient and the health care provider regarding the benefits and risks of treatment. Antiretroviral regimens are complex, have major side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance due to non-adherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic

Adherence to protease inhibitor therapy and outcomes in patients with HIV infection.

Abstract: Background: Combination antiretroviral therapy with protease inhibitors has transformed HIV infection from a terminal condition into one that is manageable. However, the complexity of regimens makes adherence to therapy difficult. Objective: To assess the effects of different levels of adherence to therapy on virologic, immunologic, and clinical outcome; to determine modifiable conditions associated with suboptimal adherence; and to determine how well clinicians predict patient adherence. Design: Prospective, observational study. Setting: HIV clinics in a Veterans Affairs medical center and a university medical center. Patients: 99 HIV-infected patients who were prescribed a protease inhibitor and who neither used a medication organizer nor received their medications in an observed setting (such as a jail or nursing home). Measurements: Adherence was measured by using a microelectronic monitoring system. The adherence rate was calculated as the number of doses taken divided by the number prescribed. Patients were followed for a median of 6 months (range, 3 to 15 months). Results: During the study period, 45 397 doses of protease inhibitor were monitored in 81 evaluable patients. Adherence was significantly associated with successful virologic outcome (P < 0.001) and increase in CD4 lymphocyte count (P 5 0.006). Virologic failure was documented in 22% of patients with adherence of 95% or greater, 61% of those with 80% to 94.9% adherence, and 80% of those with less than 80% adherence. Patients with adherence of 95% or greater had fewer days in the hospital (2.6 days per 1000 days of follow-up) than those with less than 95% adherence (12.9 days per 1000 days of follow-up; P 5 0.001). No opportunistic infections or deaths occurred in patients with 95% or greater adherence. Active psychiatric illness was an independent risk factor for adherence less than 95% (P 5 0.04). Physicians predicted adherence incorrectly for 41% of patients, and clinic nurses predicted it incorrectly for 30% of patients. Conclusions: Adherence to protease inhibitor therapy of 95% or greater optimized virologic outcome for patients with HIV infection. Diagnosis and treatment of psychiatric illness should be further investigated as a means to improve adherence to therapy.