Skin-Test Screening and Tuberculosis Transmission among the Homeless1

We describe the implementation of a mandatory tuberculosis (TB) screening program that uses symptom screening and tuberculin skin testing in homeless shelters. We used the results of DNA fingerprinting of Mycobacterium tuberculosis isolates to evaluate the effect of the program on TB incidence and transmission. After the program was implemented, the proportion of cases among homeless persons detected by screening activities increased, and the estimated TB incidence decreased from 510 to 121 cases per 100,000 population per year. Recent transmission, defined by DNA fingerprinting analysis as clustered patterns occurring within 2 years, decreased from 49% to 14% (p=0.03). Our results suggest that the shelter-based screening program decreased the incidence of TB by decreasing its transmission among the homeless

The AMT: What’s Wrong and How to Fix It

The alternative minimum tax (AMT) is a complex, unfair, and inefficient shadow tax system that threatens to affect 32 million taxpayers by 2010, many of them solidly middle class. Under current law, repealing the AMT without offsets would cost more than $850 billion through 2017. This paper summarizes the current and projected effects of the AMT and considers options to finance repeal. One attractive option we consider would be to combine AMT repeal with a four percent tax on AGI in excess of$200,000 for married couples and $100,000 for others

The AMT: What’s Wrong and How to Fix It

The alternative minimum tax (AMT) is a complex, unfair, and inefficient shadow tax system that threatens to affect 32 million taxpayers by 2010, many of them solidly middle class. Under current law, repealing the AMT without offsets would cost more than $850 billion through 2017. This paper summarizes the current and projected effects of the AMT and considers options to finance repeal. One attractive option we consider would be to combine AMT repeal with a four percent tax on AGI in excess of$200,000 for married couples and $100,000 for others

The 'Antiretrovirals, Sexual Transmission Risk and Attitudes' (ASTRA) study. Design, methods and participant characteristics.

Life expectancy for people diagnosed with HIV has improved dramatically however the number of new infections in the UK remains high. Understanding patterns of sexual behaviour among people living with diagnosed HIV, and the factors associated with having condom-less sex, is important for informing HIV prevention strategies and clinical care. In addition, in view of the current interest in a policy of early antiretroviral treatment (ART) for all people diagnosed with HIV in the UK, it is of particular importance to assess whether ART use is associated with increased levels of condom-less sex. In this context the ASTRA study was designed to investigate current sexual activity, and attitudes to HIV transmission risk, in a large unselected sample of HIV-infected patients under care in the UK. The study also gathered background information on demographic, socio-economic, lifestyle and disease-related characteristics, and physical and psychological symptoms, in order to identify other key factors impacting on HIV patients and the behaviours which underpin transmission. In this paper we describe the study rationale, design, methods, response rate and the demographic characteristics of the participants. People diagnosed with HIV infection attending 8 UK HIV out-patient clinics in 2011-2012 were invited to participate in the study. Those who agreed to participate completed a confidential, self-administered pen-and-paper questionnaire, and their latest CD4 count and viral load test results were recorded. During the study period, 5112 eligible patients were invited to take part in the study and 3258 completed questionnaires were obtained, representing a response rate of 64% of eligible patients. The study includes 2248 men who have sex with men (MSM), 373 heterosexual men and 637 women. Future results from ASTRA will be a key resource for understanding HIV transmission within the UK, targeting prevention efforts, and informing clinical care of individuals living with HIV

Discontinuation of Prophylaxis against Mycobacterium avium Complex Disease in HIV-Infected Patients Who Have a Response to Antiretroviral Therapy

BACKGROUND Several agents are effective in preventing Mycobacterium avium complex disease in patients with advanced human immunodeficiency virus (HIV) infection. However, there is uncertainty about whether prophylaxis should be continued in patients whose CD4+ cell counts have increased substantially with antiviral therapy. METHODS We conducted a multicenter, double-blind, randomized trial of treatment with azithromycin (1200 mg weekly) as compared with placebo in HIV-infected patients whose CD4+ cell counts had increased from less than 50 to more than 100 per cubic millimeter in response to antiretroviral therapy. The primary end point was M. avium complex disease or bacterial pneumonia. RESULTS A total of 520 patients entered the study; the median CD4+ cell count at entry was 230 per cubic millimeter. In 48 percent of the patients, the HIV RNA value was below the level of quantification. The median prior nadir CD4+ cell count was 23 per cubic millimeter, and 65 percent of the patients had had an acquired immunodeficiency syndrome-defining illness. During follow-up over a median period of 12 months, there were no episodes of confirmed M. avium complex disease in either group (95 percent confidence interval for the rate of disease in each group, 0 to 1.5 episodes per 100 person-years). Three patients in the azithromycin group (1.2 percent) and five in the placebo group (1.9 percent) had bacterial pneumonia (relative risk in the azithromycin group, 0.60; 95 percent confidence interval, 0.14 to 2.50; P=0.48). Neither the rate of progression of HIV disease nor the mortality rate differed significantly between the two groups. Adverse effects led to discontinuation of the study drug in 19 patients assigned to receive azithromycin (7.4 percent) and in 3 assigned to receive placebo (1.1 percent; relative risk, 6.6; P=0.002). CONCLUSIONS Azithromycin prophylaxis can safely be withheld in HIV-infected patients whose CD4+ cell counts have increased to more than 100 cells per cubic millimeter in response to antiretroviral therapy

Randomized Trials to Optimize Treatment of Multidrug-Resistant Tuberculosis: The time for action is now

The time is now right for randomized trials of MDR-TB, say the authors, as the expansion of MDR-TB programs provides the setting in which trials can be implemented

Acquired Rifamycin Resistance with Twice-Weekly Treatment of HIV-related Tuberculosis

Rationale: Rifabutin was recommended in place of rifampin during treatment of HIV-related tuberculosis (TB) to facilitate concomitant potent antiretroviral therapy, but this approach has not been evaluated in a prospective study. Objective: To evaluate the activity of intermittent rifabutin-based therapy. Methods: Patients with culture-confirmed TB were treated under direct supervision with 2 mo of rifabutin, isoniazid, pyrazinamide, and ethambutol (given daily, thrice-weekly, or twice-weekly per the local tuberculosis control program), followed by 4 mo of twice-weekly rifabutin plus isoniazid. Measurements: Culture-positive treatment failure or relapse. Main Results: A total of 169 eligible patients were enrolled. Most had advanced HIV disease; the median CD4 cell count and HIV-RNA level were 90 cells/mm3 (interquartile range, 35–175) and 5.3 log10 copies/ml (interquartile range, 4.8–5.7), respectively. Nine (5.3%) patients had culture-positive treatment failure (n = 3) or relapse (n = 6). Eight of these nine (89%) cases had isolates with acquired rifamycin resistance. Treatment failure or relapse was associated with baseline CD4 lymphocyte count, being 12.3% (9/73; 95% confidence interval, 6.5–22.0%) among patients with CD4 < 100 cells/mm3 versus 0% (0/65; 95% confidence interval, 0.0–4.5%) among those with higher CD4 lymphocyte counts (p < 0.01). One hundred thirty-seven (81%) patients received antiretroviral therapy during TB treatment. Adverse events were common, but only two patients (1%) permanently discontinued study drugs

Drug-resistance mechanisms and tuberculosis drugs.

This publication presents independent research supported by the Health Innovation Challenge Fund (HICF-T5-342 and WT098600), a parallel funding partnership between the UK Department of Health and Wellcome Trust.This is the final version of the article. It first appeared at http://dx.doi.org/10.1016/S0140-6736(14)62450-8

Daily Dosing of Rifapentine Cures Tuberculosis in Three Months or Less in the Murine Model

Eric Nuermberger and colleagues found that after two months of treatment, mice with lung cultures positive for tuberculosis that received daily doses of rifapentine- and moxifloxacin-containing regimens converted to negative lung cultures. This finding could make possible the development of shorter treatment regimens for humans