Combined HIV prevention, the New York City condom distribution program, and the evolution of safer sex behavior among persons who inject drugs in New York City.

Examine long term sexual risk behaviors among persons who inject drugs (PWID) in New York City following implementation of "combined" prevention programming, including condom social marketing. Quantitative interviews and human immunodeficiency virus (HIV) testing were conducted among PWID entering Beth Israel Medical Center drug treatment programs 1990-2012. Data were analyzed by four time periods corresponding to the cumulative implementation of HIV prevention interventions. 7,132 subjects were recruited from 1990 to 2012; little change in sexual behavior occurred among HIV seronegative subjects, while HIV seropositive subjects reported significant decreases in being sexually active and significant increases in consistent condom use. HIV transmission risk (being HIV positive and engaging in unprotected sex) declined from 14 % in 1990-1995 to 2 % in 2007-2012 for primary sexual partners and from 6 to 1 % for casual partners. Cumulative implementation of combined prevention programming for PWID was associated with substantial decreases in sexual risk behavior among HIV seropositives.

Clinical features and outcomes of HIV-related cytomegalovirus pneumonia.

OBJECTIVE: To describe the characteristics and outcomes of HIV-infected patients with biopsy-proven cytomegalovirus (CMV) pneumonia. DESIGN: Retrospective study. SETTING: A 900-bed acute facility in New York City. PATIENTS: Eighteen HIV-infected patients with pathologically confirmed CMV inclusions in lung tissue without other pathogens and 36 control patients with biopsy-proven Pneumocystis carinii pneumonia (PCP) selected for comparisons by computer-generated random sequential numbers. MAIN OUTCOME MEASURES: Demographic, clinical, laboratory, radiological findings, and in-hospital mortality. RESULTS: Eighteen HIV-infected patients were found to have CMV lung infection alone. Pathologic findings were pneumonitis (n = 11); pneumonitis and pulmonary vasculitis (n = 1); and CMV inclusions alone (n = 6). All presented with respiratory symptoms (cough or dyspnea), 89% had fever, 83% had radiological abnormalities, and 56% had severe hypoxemia. The pulmonary presentation was similar except for higher lactate dehydrogenase (median, 449 versus 329 IU/l; P = 0.03) and presence of pleural effusions (33 versus 0%; P = 0.001) in CMV patients. Multivariate analysis showed that CD4 counts < or = 12 x 10(6)/l (odds ratio; 9.2; P = 0.029) and extrapulmonary CMV (odds ratio, 20.4; P = 0.039) were independently associated with CMV pneumonia. Seventeen patients received specific anti-CMV therapy for a mean of 22 +/- 13 days. In-hospital mortality was higher in patients with CMV pneumonia (odds ratio, 11.9; P = 0.002). The median time from admission to death was 31 days. CONCLUSIONS: CMV lung infection was seen in severely immunosuppressed HIV-positive patients and associated with clinical pneumonitis with high early mortality. Although the clinical features resemble PCP, the presence of extrapulmonary CMV disease should suggest the diagnosis of CMV pneumonia.

Susceptibility to levofloxacin of Myocobacterium tuberculosis isolates from patients with HIV-related tuberculosis and characterization of a strain with levofloxacin monoresistance. Community Programs for Clinical Research on AIDS 019 and the AIDS Clinical Trials Group 222 Protocol Team.

OBJECTIVE: To characterize the susceptibility to levofloxacin of clinical isolates of Mycobacterium tuberculosis (MTB) obtained from patients with HIV-related tuberculosis and to characterize the molecular genetics of levofloxacin resistance. DESIGN AND METHODS: Isolates from culture-positive patients in a United States multicenter trial of HIV-related TB were tested for susceptibility to levofloxacin by minimum inhibitory concentration (MIC) determinations in Bactec 7H12 broth. Automated sequencing of the resistance determining region of gyrA was performed. RESULTS: Of the 135 baseline MTB isolates tested, 134 (99%; 95% exact binomial confidence interval, 95.9-99.9%) were susceptible to levofloxacin with an MIC < or = 1.0 microg/ml. We identified a previously unrecognized mis-sense mutation occurring at codon 88 of gyrA in a levofloxacin mono-resistant MTB isolate obtained from a patient with AIDS who had received ofloxacin for 8 months prior to the diagnosis of tuberculosis. CONCLUSIONS: Clinical MTB isolates from HIV-infected patients were generally susceptible to levofloxacin. However, the identification of a clinical isolate with mono-resistance to levofloxacin highlights the need for circumspection in the use of fluoroquinolones in the setting of potential HIV-related tuberculosis and for monitoring of rates of resistance of MTB isolates to fluoroquinolones.

Experience with a cross-study endpoint review committee for AIDS clinical trials. Terry Beirn Community Programs for Clinical Research on AIDS.

OBJECTIVES: To describe the methods and results of a standardized system for clinical endpoint determination for defining and reviewing endpoints in clinical trials for HIV-infected individuals. DESIGN: A system was developed utilizing standard definitions for the 24 diagnoses or clinical events that serve as trial endpoints and together define the combined endpoint 'progression of HIV disease. A common set of case report forms were used for all trials. Thus, an event of Pneumocystis carinii pneumonia (PCP), for example, for a subject co-enrolled in an antiretroviral trial and a PCP prophylaxis trial was only reported once. METHODS: A central committee was established to define clinical events and review endpoints across all studies. Events were classified according to established criteria for confirmed, probable and possible levels of certainty. RESULTS: This report describes the methods used to ascertain and review endpoints, and summarized 2299 clinical events for 8097 subjects enrolled in one or more of nine clinical trials. Data on the diagnostic certainty of events and agreement between site clinicians and the endpoint committee are presented. CONCLUSIONS: Uniform classification of endpoints across AIDS clinical trials can be accomplished by multicenter, multitrial organizations with standardized definitions and review of endpoint documentation. Our experience suggests that nurse coordinators reviewing all submitted endpoints for every trial are warranted and the need for external review by a clinical events committee may depend on the type of trial conducted.

Aspergillosis in the acquired immunodeficiency syndrome.

The role of Aspergillus species as a pathogen in acquired immunodeficiency syndrome (AIDS) has not been clearly defined. From 1984 to 1989, more than 2,000 AIDS patients were seen at Beth Israel Medical Center, New York. Aspergillus was isolated in ten patients; seven had invasive disease and three had noninvasive disease. Invasive pulmonary aspergillosis (IPA) was diagnosed in six patients and invasive renal aspergillosis was found in one patient. Five were homosexual men and two were intravenous drug users. At presentation, all ten had fever, seven had cough, eight had dyspnea, and five had pleuritic chest pain. Chest roentgenograms revealed focal infiltrates in six patients, bilateral interstitial infiltrates in two patients, and bilateral pneumothoraces in one patient. Predisposing conditions included corticosteroid therapy in four, granulocytopenia (less than 1,000/cu m) in two, and broad-spectrum antibiotic therapy in five. Three of the four patients receiving corticosteroids received them as adjuvant therapy for Pneumocystis carinii pneumonia (PCP). Aspergillus was identified antemortem in eight patients, in bronchoalveolar lavage (BAL) fluid in six, in transbronchial biopsy specimen in three, in open lung biopsy specimen in one, and postmortem in one patient. Six of seven patients had at least one concomitant pulmonary process. Six underwent necropsy and findings showed IPA in three, disseminated aspergillosis in two, and PCP in one. Invasive aspergillosis, although significant, is uncommon in AIDS. When Aspergillus is isolated in the setting of corticosteroid therapy, antibiotics, or granulocytopenia, one must suspect invasive disease.

Prevalence and risk factors for positive tuberculin skin tests among active drug users at a syringe exchange program.

OBJECTIVES: To evaluate the prevalence and predictors of tuberculin skin test (TST) reactions > or =10 mm among active injection drug users (IDUs) at a syringe exchange program in New York City. METHODS: From August 1995 to January 1996, participants were offered TB screening, an interview, and received $15.00 upon returning for skin test interpretation. RESULTS: 610/650 (94%) consented to screening. Of the 566 (93%) who returned for skin test readings, skin test data were available for 564 (99.8%); 14% (95% CI 11.6-17.4) had TSTs > or =10 mm. When the > or =5 mm threshold for interpretation of TST among HIV-infected persons was used, the prevalence of TST positivity increased by only 1%. In univariate analysis, the prevalence of TST > or =10 mm increased with age and with increasing years of IDU (both P = 0.001). Because of a strong correlation between age and duration of IDU, two logistic regression models were examined. In the model with age alone, a history of self-reported TST positivity (OR 8.88; 95% CI 4.9-16.09; P = 0.0001) and increasing age (OR per 10 years increase in age, 1.69; 95% CI 1.24-2.29; P = 0.0008) were independent predictors of TSTs > or =10 mm. In the model with duration of IDU, a history of TST positivity (OR 8.82; 95% CI 4.74-16.41; P = 0.0001) and duration of IDU (OR per 10 years of IDU, 1.46; 95% CI 1.10-1.94; P = 0.0081) were independent predictors of TST > or =10 mm. CONCLUSIONS: Use of the reduced cutoff point for TST positivity from 10 mm to 5 mm did not significantly affect the prevalence of positive TSTs in this cohort of active drug users. Increased prevalence of TB infection with age suggests a high annual incidence of TB infection in this population, and the increased risk of TB infection with increasing duration of IDU suggests that the duration spent in IDU environments may increase infection risk.

Implementation of universal directly observed therapy at a New York City hospital and evaluation of an out-patient directly observed therapy program.

SETTING: Directly observed therapy (DOT) program for tuberculosis (TB) at a New York City hospital. OBJECTIVE: To describe a specific TB DOT program model utilizing active prospective identification of inpatients, and identify factors associated with patient acceptance of voluntary DOT and with their retention in therapy. METHODS: Recruitment for DOT by daily surveillance of in-patients. DOT was offered as the patient's choice together with concrete services and incentives. On-site DOT was offered in an out-patient clinic. Outreach efforts were initiated when a patient missed one or more DOT visit. RESULTS: During the study period, 95% of 176 in-patients with TB were evaluated for DOT. Of the 137 who were eligible for DOT, 85% (95% confidence interval [CI], 77.5% to 90%) elected to receive DOT. Illicit drug use was independently associated with a higher likelihood of acceptance of DOT (odds ratio[OR], 4.88; 95% CI, 1.5-15.7). Among the 101 patients who received onsite DOT, illicit drug use (OR, 0.21; 95% CI, 0.08-0.6) and previous TB therapy (OR, 0.27; 95% CI, 0.27-0.7) were both independently associated with lower retention in therapy. However, with intensive case management, only 1% of this cohort was lost to follow-up and the overall treatment completion index was 98%. CONCLUSION: In-patient surveillance is a highly effective DOT recruitment strategy. A DOT model which elicits patient participation in discharge plans and offers incentives can yield a high rate of voluntary acceptance. Outpatient case management is a highly effective means of ensuring treatment completion, especially in those at risk for poor retention.

Predictors for multidrug-resistant tuberculosis among HIV-infected patients and response to specific drug regimens. Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) and the AIDS Clinical Trials Group (ACTG), National Institutes for Health.

SETTING: Mortality associated with human immunodeficiency virus (HIV) related multidrug-resistant tuberculosis (MDR-TB) is reduced with effective early therapy. Identifying predictors of, and effective regimens for, MDR-TB is critical. OBJECTIVE: A multicenter prospective study was initiated to 1) determine the demographic, behavioral, clinical and geographic risk factors associated with the occurrence of MDR-TB among HIV-infected patients, and 2) to evaluate the overall survival and clinical response of MDR-TB patients treated with specific drug regimens. METHODS: Patients were prospectively evaluated for MDR-TB. Information included history of prior treatment for tuberculosis, close contact with a known case of MDR-TB, and residence in a facility with known or suspected MDR-TB transmission. Patients with known MDR-TB, or those suspected to be at high risk, were offered enrollment in a treatment pilot study. Study drugs included levofloxacin and at least two additional drugs to which the patient's isolate was known, or most likely, to be susceptible. Survival was the primary endpoint. RESULTS: Complete data are available for 156 HIV-infected patients with confirmed tuberculosis. Sixteen (10%) had MDR-TB. Only a history of prior tuberculosis treatment was associated with MDR-TB in multivariate analysis (OR = 4.4, P < 0.02). Twelve patients with MDR-TB enrolled in the treatment pilot had a median CD4 cell count of 51/mm3. The cumulative probability of survival at one year was 75% (95% CI 50.5-99.5) and at 18 months, 65.6% (95% CI 38.1-93.1). Toxicity requiring discontinuation of medications occurred in two patients. CONCLUSIONS: A history of treatment for tuberculosis was the only predictor for MDR-TB in a cohort of HIV-infected patients with tuberculosis. In addition, this prospective study supports the results of prior retrospective studies that effective treatment impacts on mortality. Current second-line treatment, including high dose levofloxacin, appears to be reasonably well tolerated.

Doing a shotgun: a drug use practice and its relationship to sexual behaviors and infection risk.

There has been a rise in the frequency with which inhalational routes such as smoking are used for illicit drug use. A growing population of new inhalational drug users augments the pool of individuals at risk for transition to injection drug use. Further, illicit drug smoking has been implicated in the transmission of a variety of pathogens by the respiratory route, and crack smoking has been associated with an increased risk of HIV infection, particularly through the exchange of high-risk sex for drugs. Shotguns are an illicit drug smoking practice in which smoked drugs are exhaled or blown by one user into the mouth of another user. We conducted a series of ethnographic observations to attempt to characterize more fully the practice of shotgunning, the range of associated behaviors, and the settings and contexts in which this practice occurs. Shotguns may be seen as a form of drug use which has close ties to sexual behaviors, and which has both pragmatic and interpersonal motivations, combining in a single phenomenon the potential direct and indirect risk of disease transmission by sexual, blood borne and respiratory routes. These data support the need to develop and evaluate comprehensive risk reduction interventions, which take into consideration the relationships between interpersonal and sexual behaviors and specific forms of drug use.

Outcomes of granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor use in neutropenic patients infected with human immunodeficiency virus.

OBJECTIVE: To characterize the effects of granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) on clinical outcomes in neutropenic HIV-infected patients, by means of a retrospective cohort study at an urban teaching hospital. METHOD: Data were reviewed from all patients discharged between January 1, 1996, and August 31, 1997, with human immunodeficiency virus and neutropenia (absolute neutrophil count (ANC) <1000 cells/mL), with outcome measures of length of stay, infectious complications, and survival to discharge. RESULTS: Of the 228 discharged patients who met selection criteria, 71 had received G-CSF or GM-CSF; 157 controls had not. Cases had lower CD4+ cell counts (30 vs. 54 cells/mL; P = 0. 017) and lower nadir ANCs (372 vs. 579 cells/mL; P < 0.001). Granulocyte-CSF or GM-CSF usage was not associated with the frequency of site-related infections, fever, or sepsis (all P > 0. 20). No difference was found in duration of hospitalization (23 vs. 21 days; P > 0.20). In a logistic regression model for survival to discharge, higher nadir ANC and CSF use were independently associated with improved survival (P = 0.034 and P = 0.026, respectively). CONCLUSION: Use of G-CSF or GM-CSF was associated with improved survival to discharge among hospitalized HIV-infected patients with neutropenia.

Two-stage tuberculin skin testing in an HIV-infected population: a preliminary report.

To identify differences in purified protein derivative (PPD) tuberculin positivity rates and to assess the utility of sequential PPD testing among persons with HIV infection, we performed two sequential administrations of 5 tuberculin units of PPD in a group of persons with HIV infection. Eligible patients were skin-tested with the tuberculin using the Mantoux method. Patients who tested < 5 mm of induration were skin-tested seven days later along with Candida and mumps antigens. Of 37 tested patients, only 18 (49%) returned to have the first test read. Using a > or = 5 mm cutoff, 5 (28%) tested positive. Positivity varied markedly between patients with CD4+ cell counts under and at or over 400 cells/mm3 (0% vs. 56%). Among patients who had a reaction to the first test, the reaction was smaller in patients with CD4+ cell counts under 400 than in those with counts at or over 400 cells/mm3 (mean induration: 2.8 vs. 30.4 mm). Positivity was also less frequent in intravenous drug users than in nonusers (9% vs. 57%); these two groups did not differ with respect to CD4+ cell counts. Of the 13 patients who tested < 5 mm, only 8 (62%) kept their appointments to have the second test placed and read. Only 1 of these, a drug user with a CD4+ count of 6 cells/mm3, had a positive reaction with boosting from 4 mm on the first test to 10 mm on the second. These data indicate that PPD testing may be unreliable in screening for tuberculosis infection in persons with CD4+ counts < 400 cell/mm3.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug-resistant tuberculosis: factors associated with rise in resistance in an HIV-infected urban population.

Our objective was to characterize the population with tuberculosis (TB) and to identify factors predictive of resistance to anti-TB agents in an area of high prevalence of human immunodeficiency virus infection. We reviewed microbiology and clinical records from 1988 to 1991 at Beth Israel Medical Center, New York City, for patients with culture-proved TB and analyzed the frequency of resistance to anti-TB agents with respect to demographic and clinical variables. Of 360 patients with TB, 17.5% had drug-resistant isolates. Of the 333 patients on whom the information was available, 72% reported HIV risk factors, 54% injectable drug use, and nearly one-third homelessness. The majority (56%) had documented HIV infection. Between 1988 and 1991, acquired resistance to isoniazid (INH) alone rose from 5% to 21% and initial resistance to INH alone rose from 0% to 19%. Drug resistance was more likely in previously treated patients; 61% of the previously treated patients admitted noncompliance with therapy. Cavitary lung disease was the strongest predictor of acquired drug resistance. Initial drug resistance was more likely in patients with HIV infection. Among persons with HIV infection, none of the analyzed factors was found to be predictive of drug resistance. Noncompliance with therapy and the HIV epidemic played a major role in the rise of drug resistance in our population. HIV infection confounds the epidemiologic factors that might otherwise allow clinical prediction of resistance.

Provision of influenza and pneumococcal vaccines to injection drug users at a syringe exchange.

The objective of this study was to evaluate the feasibility, acceptance, and utility of administering influenza and pneumococcal vaccines to active injection drug users at a syringe exchange program (SEP) in New York City. Influenza and pneumococcal vaccines were offered for 1 month. Data on demographics, health status, vaccine awareness, and prior vaccination status were collected using a staff-administered questionnaire. Of 199 participants interviewed 167 (86%) agreed to one or both vaccinations; 24% of study participants had a chronic condition for which vaccination was indicated and 53% had no regular source of medical care; 95% were aware of influenza vaccine while 25% were aware of pneumococcal vaccine (p <.0001). Of those offered the influenza vaccine, 86% accepted it and 70% of those offered pneumococcal vaccine accepted it (p <.001). Influenza and pneumococcal vaccinations were well-accepted by active drug users at a syringe exchange although there was both greater awareness of and acceptance of influenza. Many SEP participants with chronic medical conditions for which these vaccines are indicated did not have a regular source of health care. Syringe exchange programs may be valuable sites to administer respiratory vaccines and other public health interventions to drug injectors not engaged in medical care in other settings.

"Shotgunning" as an illicit drug smoking practice.

There has been a rise in illicit drug smoking in the United States. "Shotgunning" drugs (or "doing a shotgun") refers to the practice of inhaling smoke and then exhaling it into another individual's mouth, a practice with the potential for the efficient transmission of respiratory pathogens. Three hundred fifty-four drug users (239 from a syringe exchange and 115 from a drug detoxification program) were interviewed about shotgunning and screened for tuberculosis (TB). Fifty-nine (17%; 95% CI 12.9%-20.9%) reported shotgunning while smoking crack cocaine (68%), marijuana (41%), or heroin (2%). In multivariate analysis, age < or = 35 years (OR 2.0, 95% CI 1.05-3.9), white race (OR 1.2, 95% CI 1.2-4.8), drinking alcohol to intoxication (OR 2.2, 95% CI 1.1-4.3), having engaged in high-risk sex (OR 2.6, 95% CI 1.04-6.7), and crack use (OR 6.0, 95% CI 3.0-12) were independently associated with shotgunning. Shotgunning is a frequent drug smoking practice with the potential to transmit respiratory pathogens, underscoring the need for education of drug users about the risks of specific drug use practices, and the ongoing need for TB control among active drug users.

Organizational issues in conducting tuberculosis screening at a syringe exchange program.

There has been a rise in tuberculosis (TB) cases in the United States and there is a potent link between human immunodeficiency virus (HIV) and tuberculosis. In New City it is estimated that 40% of the 200,000 injecting drug users are infected with HIV. In addition, the tuberculosis case rate is approximately four times the national average, and one third of these cases occurred in those persons infected with HIV. Drug users have a high prevalence of latent tuberculous infection and are at high risk for progression to active tuberculosis. Drug users are at high risk for both HIV and TB. Although studies have shown the value of incorporating TB services into drug treatment programs, the majority of drug users in the United States are not in drug treatment. We have been evaluating the feasibility of conducting TB screening and directly observed TB preventive therapy for active injecting drug users at a syringe exchange program in New York City. This paper describes issues relating to the implementation of the TB screening program and discusses general and operational issues relevant to integrating medical and public health programs into existing programs serving drug using individuals.

Knowledge of tuberculosis among drug users. Relationship to return rates for tuberculosis screening at a syringe exchange.

Tuberculosis is an important health issue among drug users. We sought to evaluate active drug users' (DUs) knowledge of tuberculosis (TB) and to assess the relationship between TB knowledge and attitudes and tuberculin skin test (TST) return rates at a syringe exchange program. DUs were recruited at a syringe exchange program in New York City, were interviewed and offered TSTs, and received $15.00 upon returning for TST reading. The questionnaire evaluated knowledge of TB transmission, prevention, and treatment. From March 13, 1995 to January 31, 1996, 610 of 650 (94%) of DUs approached agreed to participate. Of these, 80% had previous TSTs within the past 2 years and 20% were known to be HIV infected. Almost all knew that TB is contagious and more than two thirds knew that TB is treatable and that TB preventive therapy existed. However, fewer than half knew that HIV-related TB could be treated, 30% thought TB could be treated without a medical doctor, and the majority (70%) thought a reactive TST implied infectivity. The rate of return for TST reading was 93%. In multivariate analysis, those who knew that HIV-related TB was curable were more likely to return for TST reading (odds ratio 2.0; 95% confidence interval 1.04 to 3.95; p = .03). The high acceptance and return rates suggest that TB services can be incorporated into syringe exchange programs. However, several important gaps in TB knowledge existed in this population at high risk of TB, which may impact on adherence and which support the need for TB education for drug users.

Community-acquired methicillin-resistant Staphylococcus aureus infections in otolaryngology.

Soon after the introduction of methicillin, strains of Staphylococcus aureus resistant to methicillin were reported. Methicillin-resistant Staphylococcus aureus (MRSA) has become a common hospital pathogen, often resistant to multiple antibiotics, while causing significant morbidity and mortality. Community-acquired MRSA infections have been infrequently documented. Most reports have been associated with intravenous drug abuse. This report reviews 15 patients with community-acquired MRSA infections of the head and neck. None admitted to intravenous drug use. Additionally, no patient was known to be a healthcare worker. The MRSA strains showed antibiotic susceptibility and resistance profiles different from typical hospital-acquired MRSA isolates. All but one infection resolved with adequate surgical or appropriate antibiotic therapy. Clinicians should become aware of the possibility of community-acquired MRSA in the patient who has had continued infection despite antibiotic therapy.

The experience of respiratory isolation for HIV-infected persons with tuberculosis.

A recent resurgence of tuberculosis (TB) has been driven mostly by the HIV epidemic. The initial inpatient experience for individuals with HIV-related TB may be pivotal to the acceptance of and participation in ongoing TB care. The purpose of this study was to develop an understanding of the experience of respiratory isolation for HIV-infected patients with TB in order to identify strategies for enhancing quality of life and participation in care. Respondents (N = 18) identified 12 major themes related to the isolation and reported more mood disturbances during their confinement than the norm. This study suggests that staff behaviors which foster human connections may enhance the patient's quality of life and promote adherence to therapy.