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.

Tuberculosis in drug users.

The rise in tuberculosis (TB) has disproportionately affected specific populations. Historically, many patients with TB became iatrogenic opiate addicts through therapeutic use of these drugs for symptom control. Demographic trends reshaped the relationship between drug use and TB into one in which drug use became a risk factor for tuberculosis as a result of the overlap of epidemiological and social factors associated with both drug use and TB. The spread of human immunodeficiency virus infection has amplified the spread of TB among drug users. We review the epidemiology of TB in drug users as well as the factors relevant to screening and compliance in drug-using populations. Drug users constitute a high-risk group for whom screening, prevention of infection, diagnosis, and treatment pose particular challenges. The development of TB services capable of engaging drug users (those both in and out of drug treatment programs) has potential for disrupting a significant chain of rapid TB transmission.

The number of CD1a+ large low-density cells with dendritic cell features is increased in the peripheral blood of HIV+ patients.

Employing a discontinuous Percoll gradient following Ficoll-Hypaque separation of peripheral blood mononuclear cells from normal subjects (n = 14) and patients with HIV-1 infection (n = 50), we separated a population of low-density cells consisting of monocytoid cells, lymphocytes, and some granulocytes. In cytospin preparations, less than 5% of the monocytoid cells were positive for nonspecific esterase and CD14. However, CD1a was positive in 5-20% of these cells. Ultrastructurally, CD1a-labeled immunogold particles were demonstrated on the monocytoid cells which bore some features of dendritic cells. Flow cytometry of the low-density cells identified a subset of buoyant, large cell population, which excluded lymphocytes. This large low-density cell (LLDC) population was significantly expanded in patients with HIV infection and comprised 32.3 +/- 21.3% of low-density cells compared to 7.0 +/- 2.8% in normal subjects (P < 0.0001). Of the LLDC population 45.2 +/- 23.4% were CD1a+ in patients compared to 17.5 +/- 13.3% in normal subjects (P < or = 0.0001). HLA-DR and HLA-DQ were coexpressed in approximately 70 and 50% of these CD1a+ LLDC, respectively. A simple nonculture assay method employed by us facilitates rapid screening of infected blood specimens for the CD1a+ large low-density cells with dendritic cell features, which could be an additional parameter to monitor HIV disease progression.

Continuity and change within an HIV epidemic. Injecting drug users in New York City, 1984 through 1992.

OBJECTIVES: To examine trends in acquired immunodeficiency syndrome (AIDS) risk behavior and human immunodeficiency virus (HIV) seroprevalence among injecting drug users (IDUs) in New York City from 1984 through 1992. DESIGN AND SETTING: Comparisons were made between two surveys of IDUs at the same hospital-based New York City drug abuse detoxification program: 141 IDUs in 1984 and 974 IDUs in 1990 through 1992. National Death Registry, New York City Health Department, and drug treatment program records were also used. PARTICIPANTS: Persons attending detoxification program randomly selected for participation. Eligibility was based on injection within previous 2 months; 99% acceptance rates were obtained. Participants in the 1984 and 1990 through 1992 surveys were 66% and 79% men, 21% and 19% white, 33% and 34% African American, and 45% and 46% Latin American, respectively. INTERVENTIONS: Community-based AIDS prevention programs, including underground syringe exchanges. MAIN OUTCOME MEASURES: Acquired immunodeficiency syndrome risk behaviors; HIV serostatus; CD4+ cell counts; death rates among 1984 subjects; and injection and intranasal routes of drug administration. RESULTS: The HIV seroprevalence remained stable at slightly more than 50%. Mean CD4+ cell counts declined from 0.716 x 10(9)/L (716/microL) to 0.575 x 10(9)/L (P < .009). Annual death rate among 1984 subjects was 3%, with a significantly higher rate among HIV-seropositive subjects (relative risk, 2.57; 95% exact binomial confidence interval, 1.12 to 6.61). Large-scale declines were observed in AIDS risk behaviors, eg, use of potentially contaminated syringes declined from 51% to 7% of injections (P < .001). Recent additional risk reduction was associated with use of the underground syringe exchanges. Intranasal heroin use was the primary route of drug administration for 46% of heroin admissions to New York City drug treatment programs. CONCLUSIONS: The HIV seroprevalence has remained stable among this population of New York City IDUs for almost a decade. Continuation of current trends should lead to further reduction in HIV transmission, although reversal of the trend to intranasal use could lead to substantially increased transmission.

CD4 lymphocytopenia among injecting drug users in New York City.

Recent cases of "AIDS-like" CD4 lymphocytopenia in the absence of HIV infection have generated considerable scientific and public interest. We studied CD4 cell counts and percentages from 1984 to 1992 among 1,246 HIV-seronegative injecting drug users in New York City, a population at very high risk for exposure to bloodborne pathogens. Severe CD4 lymphocytopenia was rare, and there was no evidence of an increase over time. Of 229 subjects with longitudinal data, only four met the surveillance definition for "idiopathic CD4 lymphocytopenia" (ICL). CD4 cell counts of < 500 cells/microliters were, however, associated with subsequent HIV seroconversion (12.7/100 person-years at risk, relative risk (RR) = 4.53, 95% exact binomial confidence interval (CI) 1.7-10.7, p = 0.002).

Implications of the revised surveillance definition: AIDS among New York City drug users.

The Centers for Disease Control (CDC) has proposed revising the AIDS surveillance definition to include any HIV-seropositive person with a CD4 cell count of less than 200 cells per microliter. Based on a study of persons receiving treatment for HIV infection, this new definition would lead to an estimated 50% increase in the number of persons recognized as living with AIDS. Among 440 HIV-seropositive research subjects recruited from drug treatment programs and through street outreach in New York City, 59 met this definition, yet only 25% of those had been reported to the New York City AIDS registry. The new definition, if combined with HIV and T-cell testing at drug treatment and street outreach programs, could thus yield very large increases in the number of injecting drug users meeting the new surveillance definition of AIDS.

A randomized trial of an interim methadone maintenance clinic.

BACKGROUND: Interim methadone maintenance has been proposed as a method of providing clinically effective services to heroin addicts waiting for treatment in standard comprehensive methadone maintenance programs. METHODS: A clinic that provided initial medical evaluation, methadone medication, and AIDS education, but did not include formal drug abuse counseling or other social support services was established in New York City. A sample of 301 volunteer subjects recruited from the waiting list for treatment in the Beth Israel methadone program were randomly assigned to immediate entry into the interim clinic or a control group. RESULTS: There were no differences in initial levels of illicit drug use across the experimental and control groups. One-month urinalysis follow-up data showed a significant reduction in heroin use in the experimental group (from 63% positive at intake to 29% positive) with no change in the control group (62% to 60% positive). No significant change was observed in cocaine urinalyses (approximately 70% positive for both groups at intake and follow-up). A higher percentage of the experimental group were in treatment at 16-month follow-up (72% vs 56%). CONCLUSIONS: Limited services interim methadone maintenance can reduce heroin use among persons awaiting entry into comprehensive treatment and increase the percentage entering treatment.

Prognostic significance of quantitative levels of HIV p24 binding capacity in HIV infection.

Human immunodeficiency virus, type 1 (HIV-1), produces a chronic infection with a long latency before clinical disease. We followed 214 untreated subjects for 12-42 months to study the natural history of HIV infection: 110 were classified as asymptomatic, 11 as AIDS-related complex (ARC), 15 as AIDS with Kaposi's sarcoma (KS), 31 as AIDS with opportunistic infections (AIDS/OI), and 47 were HIV-seronegative controls. The quantitative capacity of serum to complex HIV p24 antigen, termed the p24 binding capacity (p24 BC), and quantitative levels of HIV p24 antigen in serum were determined at regular intervals. For people in all diagnostic groups, a p24 BC below 31 ng/ml was more closely associated with progression to AIDS/OI than was p24 antigen positivity; 94% of AIDS/OI, 86% of ARC, 56% of AIDS/KS, and 19% of asymptomatic subjects had p24 BC less than 31 ng/ml during the study period, while 67% of AIDS/OI, 27% of ARC, 61% of AIDS/KS, and 20% of asymptomatic subjects were p24 antigenemic. Prospective analysis of 47 asymptomatic seropositive men followed for 3 years, who showed actuarial progression rates to ARC at 4%, 13%, and 23% and to AIDS at 5%, 8%, and 8% at 1, 2, and 3 years, indicated that entry levels of p24 BC below 31 ng/ml were as strongly associated with progression to ARC/AIDS as was p24 antigenemia (p = 0.0003 vs. p = 0.008). The p24 binding capacity assay is a new and convenient methodology to measure immunocomplexing antibody to HIV p24 and is a powerful indicator of progressive HIV disease.

HIV-1 infection among intravenous drug users in Manhattan, New York City, from 1977 through 1987.

Intravenous drug users are the second largest group to develop the acquired immunodeficiency syndrome, and they are the primary source for heterosexual and perinatal transmission in the United States and Europe. Understanding long-term trends in the spread of human immunodeficiency virus among intravenous drug users is critical to controlling the acquired immunodeficiency syndrome epidemic. Acquired immunodeficiency syndrome surveillance data and seroprevalence studies of drug treatment program entrants are used to trace seroprevalence trends among intravenous drug users in the borough of Manhattan. The virus entered this drug-using group during the mid-1970s and spread rapidly in 1979 through 1983. From 1984 through 1987, the seroprevalence rate stabilized between 55% and 60%--well below hepatitis B seroprevalence rates. This relatively constant rate is attributed to new infections, new seronegative persons beginning drug injection, seropositive persons leaving drug injection, and increasing conscious risk reduction.

Haemophilus influenzae pneumonia in young adults with AIDS, ARC, or risk of AIDS.

PURPOSE: Since the acquired immunodeficiency syndrome (AIDS) was first described in 1981, we have observed an increasing number of cases of Haemophilus influenzae pneumonia, particularly in young adult patients. To confirm this observation, we systematically identified and reviewed all cases of H. influenzae pneumonia that occurred in adult patients recently hospitalized at our institution. PATIENTS AND METHODS: Using a strict case definition, we identified all cases of adult H. influenzae pneumonia that were observed during a recent 32-month period at our institution, a large teaching hospital in New York City. We further reviewed each case record for evidence of AIDS, AIDS-related complex (ARC), or risk of AIDS. RESULTS: H. influenzae pneumonia was diagnosed in 51 adults. Thirty-four cases occurred in young adults (mean age = 33.9 years) with AIDS risk factors, including 23 (67 percent) intravenous drug abusers, six (18 percent) homosexual men, and five (15 percent) with both risks. Nine patients (26 percent) had a previous or concurrent diagnosis of AIDS, four (12 percent) developed AIDS later, and 13 (38 percent) others had ARC. The common presenting symptoms in young adult patients with H. influenzae pneumonia were fever (100 percent), productive cough (100 percent), chest pain (53 percent), and dyspnea (47 percent). Lung consolidation was detected on physical examination in 20 (59 percent), and chest radiograph demonstrated unilateral infiltrates in 18 (53 percent) and bilateral infiltrates in 16 (47 percent), with pleural effusions in three (nine percent). Most patients had an elevated white blood cell count (mean = 9.6 X 10(9)/liter) with a left shift in 22 (65 percent), and hypoxia on room air (mean partial pressure of oxygen = 69 mm Hg). Four patients with H. influenzae pneumonia and coexisting Pneumocystis carinii pneumonia had diffuse, bilateral infiltrates on chest radiograph, with significantly more dyspnea and a higher serum lactate dehydrogenase level than the others. All but one patient showed improvement with appropriate therapy. CONCLUSION: We conclude that potentially serious pneumonia caused by H. influenzae occurs in young adult patients with AIDS, ARC, or AIDS risk.

Treatment of cytomegalovirus retinitis with ganciclovir (9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl] guanine (BW B759U).

Six patients (11 eyes) with virologically confirmed cytomegalovirus (CMV) retinitis involving the posterior pole of the eye were treated with a new drug, ganciclovir. Treatment with intravenous ganciclovir consistently halted progression of retinitis and produced improvement in measures of visual function. However, within three weeks after cessation of therapy renewed CMV activity and worsening of visual function were observed in most cases. Maintenance therapy with ganciclovir extended the period of remission from CMV retinitis.

Clinical and demographic features of patients admitted to a new chemical dependency program in New York City.

We reviewed the clinical and demographic features of all 128 patients who were admitted to a new 28-day in-patient chemical dependency program in New York City during the first six months of operation. The medical records were reviewed retrospectively. Alcohol, cocaine, heroin, marijuana and diazepam were the most common substances abused. Parenteral drug abuse at any time was reported by 51 (40%) of the 128 patients, and 42 (33%) were current parenteral drug abusers. Abusers of alcohol only were significantly older than parenteral drug abusers or non-parenteral drug abusers. Patients who were employed at admission had a significantly longer mean length of stay and a higher rate of completion of the program than those who were not employed. We conclude that: (1) parenteral drug abuse is likely to be commonly seen in chemical dependency programs serving middle-income patients in urban areas, (2) alcohol abusers are older than abusers of other drugs, (3) a higher educational level is associated with successful completion of the chemical dependency program, and (4) evaluation programs are needed in all types of chemical dependency treatment.

Nonrandom development of immunologic abnormalities after infection with human immunodeficiency virus: implications for immunologic classification of the disease.

Blood specimens from 165 intravenous drug users who were seropositive for the human immunodeficiency virus (HIV), from 158 seropositive homosexual men with lymphadenopathy, and from 77 patients with acquired immunodeficiency syndrome (AIDS) were assessed immunologically. Immunologic parameters were analyzed by the Guttman scalogram technique to determine if immunologic abnormalities occurred in a nonrandom pattern. The following four patterns emerged: (i) seropositivity for HIV with no immunologic abnormalities; (ii) seropositivity for HIV with a depressed T4/T8 cell ratio; (iii) seropositivity with a depressed T4/T8 cell ratio and T4-cell depletion; and (iv) seropositivity with a depressed T4/T8 cell ratio, T4-cell depletion, and lymphopenia. Ninety-two to 100% of subjects in each of the three groups of patients were found "to scale" because the abnormalities occurred in the cumulative, ordered fashion described. This nonrandom occurrence of abnormalities indicates an ordered progression of immunologic abnormalities in individuals infected with HIV, a finding useful in the staging of both symptomatic and asymptomatic HIV-seropositive subjects.

Development of AIDS, HIV seroconversion, and potential co-factors for T4 cell loss in a cohort of intravenous drug users.

A cohort of 334 intravenous (IV) drug users from New York City drug treatment programs were followed over a mean 9-month period. Among the 165 who were seropositive at enlistment, four developed clinical AIDS, for an annual rate of 3%. Elevated IgA was a significant predictor of developing AIDS. Among 72 subjects who were initially seronegative and who were re-interviewed, four were seropositive at follow-up, for a seroconversion rate of 7% per year among seronegatives. Among seropositive subjects who did not develop AIDS or fatal AIDS related complex (ARC), continued drug injection was associated with rate of T4 cell loss, and there was a non-significant trend for males to lose T4 cells more rapidly than females. While it was not possible to distinguish the mechanism underlying the relationship between continued drug injection and T4 cell loss, seropositive IV drug users should be warned that continued injection may lead to increased HIV-related immunosuppression as well as, if injection equipment is shared, risking viral transmission to others.

Terminal ileitis associated with Mycobacterium avium-intracellulare infection in a homosexual man with acquired immune deficiency syndrome.

A 38-yr-old homosexual man developed fever, diarrhea, and weight loss. An upper gastrointestinal examination revealed terminal ileitis, and stains of stool revealed acid-fast bacilli that were subsequently identified as Mycobacterium avium-intracellulare. Antimycobacterial therapy was associated with weight gain and loss of fever and diarrhea. Several months later, cutaneous Kaposi's sarcoma was observed. When the patient developed strictures in the terminal ileum, a surgical resection was performed. Numerous granulomas and acid-fast bacilli, later identified as M. avium-intracellulare, were present in the resected terminal ileum. This report demonstrates that infection of the terminal ileum with M. avium-intracellulare in a patient with acquired immune deficiency syndrome can present with a clinical and radiologic picture resembling Crohn's disease. It also demonstrates symptomatic improvement of this infection temporally related to the administration of antimycobacterial therapy and the ability of an acquired immune deficiency syndrome patient to tolerate major abdominal surgery.

Risk factors for infection with human immunodeficiency virus among intravenous drug abusers in New York City.

We report here the results of a survey of 308 intravenous drug abusers recruited from hospital-based methadone maintenance or drug detoxification programmes located in Manhattan, New York City. Complete interviews and serological analyses for antibodies to human immunodeficiency virus (HIV) using both enzyme-linked immunosorbent and Western blot assays were obtained from 290 (94%) of the subjects. HIV antibodies were found by both assays in 147 (50.7%) of the tested subjects; conflicting results were found in three (1%) of the subjects; and negative results on both tests were found in 140 (48.3%) of the subjects. Logistic regression analysis identified significant relative risks for HIV infection associated with the frequency of drug injection and the proportion of injections in 'shooting galleries'. Additional risk among men was associated with a history of homosexual relations. Traditional efforts taken by subjects to clean syringes between uses, such as washing with water or alcohol, showed no evidence of being protective. Programmes aimed at prevention of HIV infection should focus on reducing use of shooting galleries and sharing of needles and syringes as well as reducing intravenous drug abuse generally.

Chronic liver disease in abusers of alcohol and parenteral drugs: a report of 204 consecutive biopsy-proven cases.

We studied a consecutive series of 204 patients who were admitted to a hospital for addictive diseases during 40 months and who had a liver biopsy. Parenteral drug abusers (n = 34) were significantly younger than alcohol abusers (n = 23) or abusers of both (n = 147) and had lower levels of serum alkaline phosphatase, total bilirubin, and aspartate aminotransferase than the other two groups. Chronic active hepatitis and chronic persistent hepatitis were more frequent (p less than 0.001) in abusers of parenteral drugs alone, whereas cirrhosis was found most often (p less than 0.001) in abusers of both alcohol and parenteral drugs. Cirrhosis was present in 10 of 39 (26%) simultaneous abusers of alcohol and parenteral drugs compared with 58 of 96 (60%) alcohol-abusing former parenteral drug abusers (p less than 0.001). Methadone maintenance treatment was not associated with cirrhosis. Thus, methadone-maintained patients who abuse alcohol and develop cirrhosis should remain in methadone maintenance treatment and receive concomitant alcoholism treatment. Also, these data further support the hypothesis that abusers of both alcohol and parenteral drugs have an increased risk of developing cirrhosis.