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.

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.

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.

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.

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.

Salmonella bacteremia associated with the acquired immunodeficiency syndrome (AIDS).

Six cases of bacteremia due to serotypes of Salmonella enteritidis are described in patients with the acquired immunodeficiency syndrome (AIDS). In four instances the bacteremia was recurrent despite appropriate antimicrobial treatment. Neither a gastrointestinal tract source nor any other focus of infection could be identified in four of the six patients. In one patient an unusual Salmonella infection, ie, pyelonephritis, was noted. The discovery of Salmonella sepsis led in four cases to the initial diagnostic consideration of AIDS, which was ultimately confirmed. When unexplained Salmonella bacteremia occurs in populations known to be at high risk for the development of AIDS, a thorough evaluation for this disorder should be undertaken.

Effect of severe alcoholic liver disease on the disposition of methadone in maintenance patients.

We studied methadone disposition in 11 maintenance patients with alcoholic liver disease of such severity that liver biopsy was contraindicated. Nine methadone-maintained patients with recent alcohol abuse but minimal or no evidence of liver disease served as controls. Most kinetic indices, including the apparent oral clearance and area under the concentration-time curves, were similar in patients and controls. Although the apparent terminal half-life of methadone was longer (p = 0.04) in the patients with liver disease, the peak plasma methadone level was lower (p = 0.03). None of the patients had signs or symptoms of methadone overdosage or abstinence at the time of study. Six patients and one control had flattened plasma methadone concentration-time curves. We hypothesize that, in severe liver disease, damage to hepatic drug-metabolizing systems is offset by damage to the capacity of the liver to store and release unchanged methadone. The usual methadone maintenance dose may be continued in stable patients with severe alcoholic cirrhosis.

Isolation of lymphadenopathy-associated virus (LAV) and detection of LAV antibodies from US patients with AIDS.

A human retrovirus was isolated from the peripheral blood of three American patients newly diagnosed with the acquired immunodeficiency syndrome (AIDS). In each case the major core viral protein (p25) was shown to be antigenically identical to that of the prototype lymphadenopathy-associated virus (LAV). Two of the viral isolates were derived from intravenous narcotics abusers, the first demonstration of LAV isolation from this risk group. Antibody to LAV was detected by an IgG enzyme-linked immunosorbent assay in the serum samples of these and 14 additional American patients with AIDS and in none of 12 hospital worker controls. These findings provide support for the etiologic association of LAV and AIDS.

Hepatic cirrhosis in young adults: association with adolescent onset of alcohol and parenteral heroin abuse.

Hepatic cirrhosis is infrequently diagnosed in young adults. In a hospital for addictive diseases in New York City, we found cirrhosis in 53 patients under age 35 within just 40 months. The cirrhosis was biopsy-proven in 37 patients (group I) and diagnosed clinically in 16 patients with severe liver disease (group II). Alcohol abuse was found in 51 patients (96%), and parenteral heroin abuse was seen in 52 (98%). The duration of alcohol abuse was seven or fewer years in 24 patients (45%) and 10 or fewer in 39 (74%). In 44 (83%), the substance abuse began in adolescence. Comparison of group I cirrhotic patients with 65 non-cirrhotic biopsied patients showed that cirrhosis was significantly associated with abuse of both alcohol and parenteral heroin (p less than 0.001). The distribution of 66 HLA antigens from A, B, C, and DR loci showed no differences when 42 patients were compared with 42 ethnically-matched control substance abusers. The early development of cirrhosis in these young patients may be related to multiple hepatic injuries induced by alcohol and parenteral heroin abuse and to the onset of addictive diseases during adolescence or early adult life.

Longitudinal study of persistent generalised lymphadenopathy in homosexual men: relation to acquired immunodeficiency syndrome.

42 homosexual or bisexual men with persistent generalised lymphadenopathy not attributable to an identifiable cause have been followed longitudinally since February, 1981. Lymphadenopathy was accompanied by fatigue, low-grade fever and/or night sweats (57%), splenomegaly (29%), leucopenia (40%), hypergamma - globulinaemia (76%), and diminished proportion and absolute numbers of helper T cells (95%). Of the 26 patients who had lymph node biopsy, all showed benign reactive hyperplasia. After 15-30 (median 22) months, 8 patients have met criteria for the diagnosis of acquired immunodeficiency syndrome (AIDS). This outcome was associated with previous heavy nitrite inhalant use, with the presence of night sweats, with leucopenia, and with the triad of constitutional symptoms, splenomegaly, and leucopenia. In addition, a lower mean absolute helper T cell count and an increased frequency of anergy to mumps intradermal antigen and of herpes simplex virus isolation distinguished these patients from those remaining in the cohort, who seem to be stable and in some cases to have improved.

Methadone disposition in patients with chronic liver disease.

Chronic liver disease is common in methadone-maintained patients. We studied the disposition of this drug in 14 patients with biopsy-proved chronic liver disease and five otherwise healthy subjects receiving methadone maintenance treatment. The patients were divided into three groups based on the severity of liver disease, with group I having the most severe disease. The apparent terminal half-life of methadone was longer in group I than in group II and III (moderate and mild chronic liver disease, P less than 0.01) and the contrast group (P less than 0.05). All other kinetic indices determined for group I and all kinetic indices in groups II and III were essentially the same as those in the contrast subjects or in the other patient groups. Seven patients, including al five in group I, had flattened plasma methadone concentration-time curves. The data suggest that the maintenance dosage of methadone need not be changed in stable chronic liver disease.