Prevalence of and viral outcomes associated with primary HIV-1 drug resistance.

Primary, or transmitted, HIV antiretroviral resistance is an ongoing concern despite continuing development of new antiretroviral therapies. We examined HIV surveillance data, including both patient demographic characteristics and laboratory data, combined with HIV genotypic test results to evaluate the comprehensiveness of drug resistance surveillance, prevalence of primary drug resistance, and impact, if any, of primary resistance on population-based virological outcomes. The King County, WA Variant, Atypical, and Resistant HIV Surveillance (VARHS) system increased coverage of eligible genotypic testing - within three months of an HIV diagnosis among antiretroviral naïve individuals -- from - 15% in 2003 to 69% in 2010. VARHS under-represented females, Blacks, Native Americans, and injection drug users. Primary drug resistance was more common among males, individuals aged 20 - 29 years, men who had sex with men, and individuals with an initial CD4+ lymphocyte count of 200 cells/µL and higher. High level resistance to two or three antiretroviral classes declined over time. Over 90% of sequences were HIV-1 subtype B. The proportion of individuals with a most recent viral load (closest to April 2011) that was undetectable (<50 copies/mL) was not statistically significantly associated with primary drug resistance. This was true for both number and type of antiretroviral drug class; although small numbers of specimens with drug resistance may have limited our statistical power. In summary, although we found disparities in testing coverage and prevalence of drug resistance, we were unable to detect a significantly deleterious impact of primary drug resistance based on a most recent viral load.

Low adherence to guidelines for preventing TB among persons with newly diagnosed HIV infection, United States.

SETTING: Persons infected with human immunodeficiency virus (HIV) are at risk for developing tuberculosis (TB) if latent TB infection remains untreated. OBJECTIVE: To assess missed opportunities for preventing TB by selecting a population-based sample of 1093 persons diagnosed with HIV from June 1995 to June 1997 in Seattle, WA, New Orleans, LA, and Jersey City, NJ. DESIGN: To determine the proportion of persons receiving a tuberculin skin test (TST) following HIV diagnosis, we conducted record reviews at providers and local TB control. RESULTS: An estimated 53.7% (95% CI 49.9-57.4) had a TST following HIV diagnosis; 6.6% (95% CI 4.3-8.9%) of TST-tested patients were reactive. Median time between HIV diagnosis and TST was 1 month (mean 5.7 months, 95% CI 4.8-6.5). Factors associated with TST included additional risk factors for TB (OR 1.76, 95% CI 1.17-2.63), history of HIV-related preventive treatment (OR 5.84, 95% CI 3.74-8.75), higher number of clinic visits (OR 4.16, 95% CI 2.01-8.02), and attendance at facilities with a written policy to provide TST for all persons with HIV (OR 2.54, 95% CI 1.28-4.88). CONCLUSION: About half of persons newly diagnosed with HIV infection had a TST following HIV diagnosis, with little variation by demographics, signaling a general need to improve interventions to prevent TB.

Low prevalence of antiretroviral resistance among persons recently infected with human immunodeficiency virus in two US cities.

Resistance testing for treatment-naïve, recently HIV-infected persons is not currently recommended; its clinical value will depend on the prevalence of resistance-associated mutations among recently infected persons. To estimate this prevalence, specimens were collected during 1997-1999 in Seattle and Los Angeles from drug-naïve, recently HIV-infected persons. HIV-1 protease and reverse transcriptase (RT) RNA sequences were amplified from plasma by RT-polymerase chain reaction (RT-PCR), sequenced, and analysed. Of 69 patients, five (7%) had resistance-associated mutations: three (4%) had primary mutations associated with resistance to nucleoside reverse transcriptase inhibitors (NRTI) or non-nucleoside-RTIs, and three patients (4%) had secondary NRTI mutations. No primary mutation associated with resistance to protease inhibitors was observed. Mean age of the five persons with resistance-associated mutations (38 years) was higher than that of the 64 persons without resistance-associated mutations (31 years, P=0.04). The findings suggest that the prevalence of resistance-associated mutations among persons recently infected with HIV in these cities is low.

Bordetella bronchiseptica infection in human immunodeficiency virus-infected patients.

Bordetella bronchiseptica is a pleomorphic gram-negative coccobacillus that commonly causes respiratory tract infections in dogs. We identified nine human immunodeficiency virus (HIV)-infected persons with culture-confirmed B. bronchiseptica infections (eight respiratory tract and one disseminated infection). The respiratory illnesses ranged in severity from mild upper respiratory tract infection to pneumonia. All nine patients had had at least one AIDS-defining condition before the B. bronchiseptica infection. Two patients had household contact with dogs before their illnesses, and one had household contact with cats. Infection due to B. bronchiseptica is uncommon in HIV-infected persons. Additional data are needed to fully define the spectrum of disease due to B. bronchiseptica infections and to evaluate the possibility that this infection may be acquired from pets. Treatment of B. bronchiseptica infection should be tailored to the patient and should be based on the results of susceptibility testing.

Hepatotoxicity associated with isoniazid preventive therapy: a 7-year survey from a public health tuberculosis clinic.

CONTEXT: Isoniazid preventive therapy for latent tuberculosis (TB) infection has been debated because of the risk of hepatotoxicity. The frequency of hepatotoxicity was 0.5% to 2.0% in early studies but may have changed with new criteria for diagnosis and patient selection. OBJECTIVE: To determine the rate of isoniazid hepatotoxicity in patients managed according to current guidelines and practice standards. DESIGN: Prospective cohort study. SETTING: A public health clinic operated by the TB control program of a city-county public health agency. PATIENTS: A total of 11141 consecutive patients who started a regimen of isoniazid preventive therapy for latent TB infection from January 1989 through December 1995. MAIN OUTCOME MEASURES: The rate of developing symptoms and signs of hepatotoxicity among all persons starting isoniazid preventive therapy, among all those completing therapy, and by age, sex, and race. RESULTS: Eleven patients (0.10% of those starting, and 0.15% of those completing treatment) had hepatotoxic reactions to isoniazid during preventive treatment. The rate of hepatotoxicity in persons receiving preventive therapy increased with increasing age (chi2 for linear trend = 5.22, P=.02) and there were trends toward increased rates in women (odds ratio [OR], 3.30; 95% confidence interval [CI], 0.87-12.45; chi2 = 3.28; P=.07) and in whites (OR, 2.60; 95% CI, 0.75-8.95; chi2 = 3.08; P=.08). CONCLUSIONS: The rate of isoniazid hepatotoxicity during clinically monitored preventive therapy was lower than has been reported previously. Clinicians should have greater confidence in the safety of isoniazid preventive therapy.

Effect of trimethoprim-sulfamethoxazole as Pneumocystis carinii pneumonia prophylaxis on bacterial illness, Pneumocystis carinii pneumonia, and death in persons with AIDS.

To measure the effect of trimethoprim-sulfamethoxazole (TMP-SMX) in preventing bacterial illness, Pneumocystis carinii pneumonia (PCP), and death in people with AIDS, we conducted a retrospective medical record review of 1078 persons who were observed for 3 years on average who attended nine outpatient facilities in Seattle, Washington between January 1990 and April 1996. We calculated relative risk estimates to measure the protective effect of TMP-SMX on the development of major bacterial illnesses, PCP, and death. Use of TMP-SMX decreased the risk of PCP (relative risk [RR] = 0.23; 95% confidence interval [CI], 0.14-0.36) and deaths not attributable to PCP (RR = 0.59; 95% CI, 0.47-0.73). Prevention of major bacterial illnesses of known etiology was of borderline significance (RR = 0.77; 95% CI, 0.57-1.05) and became statistically significant with the addition of patients with infections of unknown etiology (RR = 0.77; 95% CI 0.61-0.97). Use of TMP-SMX PCP prophylaxis significantly reduced the risks of death and of PCP and was associated with a trend toward reduced risk of major bacterial infections.

Tuberculosis in relation to a history of peptic ulcer disease and treatment of gastric hyperacidity.

Previous studies described an excess of tuberculosis among persons with a history of partial gastrectomy for the treatment of peptic ulcer disease. It is unknown if any contemporary therapies for peptic ulcer disease, such as histamine type 2 antagonists and antacids, are also associated with elevated risks of tuberculosis. A case-control study was conducted during 1988-1990 in the Seattle-King County Tuberculosis Clinic to address these questions. Self-administered questionnaires were completed by 135 cases with active tuberculosis and 380 controls. A history of daily antacid use was reported by 11 cases (8%) and 23 controls (6%), corresponding to an adjusted odds ratio of 0.9 (95% confidence interval 0.4-2.0). A history of daily histamine type 2 antagonist use was reported by nine cases (7%) and 18 controls (5%) with an adjusted odds ratio of 0.8 (95% confidence interval 0.3-2.1). Our results, while based on a relatively small number of subjects, suggest that treatment for peptic ulcer disease has no influence on the occurrence of tuberculosis.

Tuberculosis risk factors in adults in King County, Washington, 1988 through 1990.

OBJECTIVES: Tuberculosis has become a resurgent public health problem in the United States. Because resources are limited, control programs frequently must target populations at greatest risk. The purpose of the study was to examine risk factors for tuberculosis in adults. METHODS: In King County, Washington State, from 1988 through 1990, the characteristics of patients with tuberculosis were compared with census data, and a case-control study was conducted. Self-administered questionnaires were completed by 151 patients with active tuberculosis and 545 control subjects. RESULTS: Infection with the human immunodeficiency virus, non-White race/ethnicity, and foreign birthplace were each associated with a sixfold or greater increase in risk. Each of the following was associated with at least a doubled risk: history of selected underlying medical conditions; low weight for height; low socioeconomic status; and age 70 years or older. Men had 1.9 times the risk of women, smokers of 20 years' or more duration had 2.6 times the risk of nonsmokers, and heavy alcohol consumers had 2.0 times the risk of nondrinkers. CONCLUSIONS: Intervention targeting easily identified groups may be an effective way to reduce the incidence of tuberculosis.

Fatal injuries in the construction industry in Washington State.

Two hundred thirty-one deaths occurred in the construction industry in Washington State between 1973 and 1983, an average annual mortality rate of 27.5 per 100,000 workers. Falls, cave-ins, and electrocutions resulting from heavy equipment (boom type) contacting overhead power lines together accounted for 45.4% of the fatalities. Heavy construction had a death rate twice that of the other two construction subgroups (building and special trades construction). There was a significant trend towards increasing mortality with decreasing company size (p = 0.03). Drilling machine operators, welders, flamecutters, reinforcing-iron workers, and heavy-equipment operators had the highest proportionate mortality ratios (PMRs). PMRs for workers generally increased with age. Many of these fatal construction injuries would not have occurred had existing safety regulations been observed.