Diana Hartel

A Prospective Study of the Risk of Tuberculosis among Intravenous Drug Users with Human Immunodeficiency Virus Infection

To determine the risk of active tuberculosis associated with human immunodeficiency virus (HIV) infection, we prospectively studied 520 intravenous drug users enrolled in a methadone-maintenance program. Tuberculin skin testing and testing for HIV antibody were performed in all subjects. Forty-nine of 217 HIV-seropositive subjects (23 percent) and 62 of 303 HIV-seronegative subjects (20 percent) had a positive response to skin testing with purified protein derivative (PPD) tuberculin before entry into the study. The rates of conversion from a negative to a positive PPD test were similar for seropositive subjects (15 of 131; 11 percent) and seronegative subjects (26 of 202; 13 percent) who were retested during the follow-up period (mean, 22 months). Active tuberculosis developed in eight of the HIV-seropositive subjects (4 percent) and none of the seronegative subjects during the study period (P less than 0.002). Seven of the eight cases of tuberculosis occurred in HIV-seropositive subjects with a prior positive PPD test (7.9 cases per 100 person-years, as compared with 0.3 case per 100 person-years among seropositive subjects without a prior positive PPD test; rate ratio, 24.0; P less than 0.0001). We conclude that, although the prevalence and incidence of tuberculous infection were similar for both HIV-seropositive and HIV-seronegative intravenous drug users, the risk of active tuberculosis was elevated only for seropositive subjects. These data also suggest that in HIV-infected persons tuberculosis most often results from the reactivation of latent tuberculous infection; our results lend support to recommendations for the aggressive use of chemoprophylaxis against tuberculosis in patients with HIV infection and a positive PPD test.

Clinical Manifestations and Predictors of Disease Progression in Drug Users with Human Immunodeficiency Virus Infection

BACKGROUND AND METHODS To examine the clinical course of human immunodeficiency virus (HIV) infection in injection-drug users, we conducted a prospective study of a cohort of patients in a methadone-treatment program in New York City from July 1985 through December 1990. The patients underwent standardized evaluations at base line and semiannually thereafter and received on-site primary medical care. Rates of progression to the acquired immunodeficiency syndrome (AIDS) and major outcomes before the development of AIDS were examined by univariate analyses; the risk of AIDS was also assessed by product-limit survival analysis and proportional-hazards regression. RESULTS Of 318 HIV-seropositive patients who did not yet have AIDS (171 men and 147 women), 90 were black, 179 were Hispanic, and 49 were white; the median age was 33 years. Over a median of 3.0 years of follow-up, 55 (17 percent) received a diagnosis of AIDS (incidence per 100 person-years, 5.8). Major outcomes before the development of AIDS included oral candidiasis (incidence per 100 person-years, 11.2), pyogenic bacterial infections including pneumonia and sepsis (8.0), pulmonary tuberculosis (1.2), multiple constitutional symptoms (13.6), and herpes zoster (1.3). There were 41 deaths from AIDS, and 13 seropositive patients without AIDS (4.1 percent) died of bacterial infections, as compared with only 1 of 411 seronegative patients studied (P < 0.001). The incidence of AIDS was 62 percent lower among those who took zidovudine than among those who did not (P = 0.02). In the multivariate analysis, progression to AIDS was best predicted by low numbers and percentages of CD4+ lymphocytes, nonuse of zidovudine, and the presence of oral candidiasis, bacterial infections, or tuberculosis. There was no consistent relation between progression to disease and the continued use of injection drugs. CONCLUSIONS HIV-infected injection-drug users have progression to AIDS at rates comparable to those of other HIV-infected groups, but they have substantial pre-AIDS morbidity and mortality, particularly from bacterial infections, which also appear to predict disease progression.

Increased risk of bacterial pneumonia in HIV-infected intravenous drug users without AIDS.

Although patients with AIDS have been noted to be at risk for bacterial pneumonia as well as opportunistic infections, little is known about the risk of bacterial pneumonia in HIV-infected populations without AIDS. To determine the incidence of bacterial pneumonia in a well defined population of intravenous drug users (IVDUs), and to examine any association with HIV infection, we prospectively studied 433 IVDUs without AIDS, enrolled in a longitudinal study of HIV infection in an out-patient methadone maintenance program. At enrollment, 144 (33.3%) subjects were HIV-seropositive, 289 (66.7%) were seronegative. Over a 12-month period, 14 out of 144 (9.7%) seropositive subjects were hospitalized for community-acquired bacterial pneumonia, compared with six out of 289 (2.1%) seronegative subjects. The cumulative yearly incidence of bacterial pneumonia was 97 out of 1000 for seropositives and 21 out of 1000 for seronegatives (risk ratio = 4.7, P less than 0.001). Eleven out of 14 (78.6%) cases among the seropositive patients were due to either Streptococcus pneumoniae [5] or Hemophilus influenzae [6]. Two out of 14 (14.3%) cases among the seropositives were fatal. Stratifying by level of intravenous drug use indicated that even among subjects not reporting active intravenous drug use at study entry, eight out of 82 (9.8%) seropositives compared with three out of 211 (1.4%) seronegatives were hospitalized for bacterial pneumonia over the study period (risk ratio = 6.9, P less than 0.01). This study shows a markedly increased incidence of bacterial pneumonia associated with HIV infection in IVDUs without AIDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Heroin use during methadone maintenance treatment: the importance of methadone dose and cocaine use.

OBJECTIVES The purpose of this study was to examine factors associated with heroin use during methadone maintenance treatment. METHODS Logistic regression statistical models were used to examine data obtained in a cross-sectional sample of 652 methadone patients. RESULTS Heroin use during the 3 months prior to interview was shown to be greatest among (1) patients maintained on methadone dosages of less than 70 mg/day (adjusted odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.3, 3.4) and (2) patients who used cocaine during treatment (adjusted OR = 5.9, 95% CI = 3.8, 9.1). These results were independent of treatment duration, treatment compliance, alcohol use, and socioeconomic factors. Cocaine users were more likely than nonusers of cocaine to use heroin at all methadone dosage levels. CONCLUSIONS This study confirms and extends past research showing high-dose methadone maintenance to be important to heroin abstinence. Further investigation of the independent association between heroin use and cocaine use is needed.

Immigration generation status and its association with suicide attempts, substance use, and depressive symptoms among latino adolescents in the USA.

This study investigated the relation between suicide attempts and immigrant generation status using the Latino subset of the National Longitudinal Study of Adolescent Health, a school-based, nationally representative sample. This study also examined whether generation status predicted risk factors associated with elevated suicide behaviors, namely illicit substance use, problematic alcohol use, and depressive symptoms. Finally, hypothesizing that elevated depressive symptoms and substance use mediate the relation between immigrant generation status and suicide attempts among Latino adolescents, a path model was tested. Our findings revealed immigrant generation status was a determinant for suicide attempts, problematic alcohol use, repeated marijuana use, and repeated other drug use for Latino adolescents. US-born Latinos with immigrant parents (i.e., second-generation youth) were 2.87 (95% CI, 1.34, 6.14) times more likely to attempt suicide, 2.27 (95% CI, 1.53, 3.35) times more likely to engage in problematic alcohol use, 2.56 (95% CI, 1.62, 4.05) times more likely to engage in repeated marijuana use, and 2.28 (95% CI, 1.25, 4.17) times more likely to engage in repeated other drug use than were foreign-born youth (i.e., first-generation youth). Later-generations of US-born Latino youth with US-born parents were 3.57 (95% CI, 1.53–8.34) times more likely to attempt suicide, 3.34 (95% CI, 2.18–5.11) times more likely to engage in problematic alcohol use, 3.90 (95% CI, 2.46, 6.20) times more likely to engage in repeated marijuana use, and 2.80 (95% CI, 1.46, 5.34) times more likely to engage in repeated other drug use than were first-generation youth. Results from the path analysis indicated that repeated other drug use may mediate the effect of generation status on suicide attempts.

Impact of the AIDS epidemic on morbidity and mortality among intravenous drug users in a New York City methadone maintenance program.

To examine the impact of the AIDS epidemic on morbidity and mortality in a defined population of intravenous drug users, we analyzed overall and cause-specific death rates, AIDS incidence, and acute medical hospitalizations among patients in a long-term methadone maintenance program in New York City for the years 1984 through 1987 (midyear population for each year 828 to 891; demographic characteristics did not differ). The number of deaths while in treatment increased from 11 (13.3/1000) in 1984 to 39 (44.2/1000) in 1987. Deaths from AIDS increased from 3.6/1000 to 14.7/1000, deaths due to bacterial pneumonia/sepsis from 3.6/1000 to 13.6/1000; deaths from cirrhosis, drug overdose, trauma, and other causes remained relatively stable. AIDS incidence rose from six cases/1000 in 1984 to 20.4.1000 in 1987. Hospitalizations for AIDS, pneumonia, tuberculosis, and endocarditis/sepsis increased from 84.9/1000 in 1986 to 144.8/1000 in 1987. These data suggest that the AIDS epidemic has had a profound effect on patterns of morbidity and mortality among intravenous drug users in this methadone program population. Drug treatment programs may be important sites for targeting clinical services for drug users with AIDS, although the increasing burden of AIDS-related disease will require expansion of existing funding and treatment resources.

HIV infection, drug use, and onset of natural menopause.

OBJECTIVE To study the relationship of HIV infection and drug use with the onset of natural menopause. METHODS Our analyses used the World Health Organizations definition of menopause (i.e., the date of the last menstrual period is confirmed after 12 months of amenorrhea) and baseline data from a prospective study. Semiannual interviews were conducted. Levels of HIV antibody and CD4+ cell counts were obtained. Menopause was identified at baseline or during 12 months of follow-up. Women ingesting reproductive hormones were excluded. Logistic regression analyses were used to assess factors associated with menopause. RESULTS Of 571 women, 53% were HIV infected, and 52% had used heroin or cocaine in the previous 5 years. The median age was 43 years (interquartile range [IQR], 40-46 years); 48.9% of the women were black, 40.4% were Hispanic, and 10.7% were white. The median body mass index was 29.1 kg/m2, and 90.4% of participants were current or former cigarette smokers. Menopause was identified in 102 women: 62 HIV-infected women (median age, 46 years; interquartile range [IQR], 39-49 years) and 40 uninfected women (median age, 47 years; IQR, 44.5-48 years). Factors independently associated with menopause included HIV infection (adjusted odds ratio [OR], 1.73; 95% confidence interval [CI], 1.075-2.795), drug use (adjusted OR, 2.633; 95% CI, 1.610-4.308), and physical activity (adjusted OR, 0.895; 95% CI, 0.844-0.950). Among HIV-infected women, factors independently associated with menopause included CD4+ cell counts of >500 cells/mm3 (adjusted OR, 0.191; 95% CI, 0.076-0.4848) and 200-500 cells/mm3 (adjusted OR, 0.356; 95% CI, 0.147-0.813). CONCLUSION Our study shows that HIV infection and immunosuppression are associated with an earlier age at the onset of menopause. Whether early onset of menopause in HIV-infected women increases their risk of osteoporosis and heart disease requires further study.

Needle exchange use among a cohort of injecting drug users.

Objective: To study prospectively injection behavior of injecting drug users (IDU) who did and did not utilize a local needle exchange in the Bronx, New York City. Design: Since 1985, IDU attending a methadone maintenance program have been enrolled in a prospective study of HIV‐related risk behaviors. Since 1989, when a needle exchange opened near the methadone program, data have been collected from study participants regarding utilization of the exchange. Participants: Study participants (n = 904) who injected between 1985 and 1993. Results: Of 904 IDU, 21.9% used the needle exchange. Male gender [adjusted odds ratio (AOR), 1.57], HIV seropositivity (AOR, 1.39) and younger age (AOR per 10 years of age, 1.66) were independently associated with needle exchange attendance. The percentage injecting declined each year, preceding the opening of the needle exchange and concurrent with its operation (from 64.6% in 1985 to 43.6% in 1993). Among the 329 participants who injected in the year before the exchange opened, 1988, 53 out of 124 (42.7%) needle exchange users and 168 out of 205 (81.9%) nonusers reduced or stopped injecting by 1993 (P < 0.001). Exchange users shared needles less than non‐users (P < 0.05 in 1993). HIV infection was unrelated to these reductions in injection. Conclusions: Methadone‐treated IDU with access to a needle exchange reduced injecting and needle‐sharing. This pattern of harm reduction, which began at least 4 years before the needle exchange opened, occurred in both those who did and did not utilize the needle exchange. Needle exchange, as a strategy to reduce injection‐related harm, should not be viewed as discordant with methadone treatment.

Effectiveness of isoniazid chemoprophylaxis for HIV-infected drug users at high risk for active tuberculosis.

OBJECTIVE To define the effectiveness of chemoprophylaxis, outside of a clinical trial setting, in preventing tuberculosis among tuberculin-reactive and anergic HIV-infected drug users at high risk of developing active tuberculosis. DESIGN An observational cohort study. SETTING Methadone maintenance treatment program with on-site primary care. PARTICIPANTS Current or former drug users enrolled in methadone treatment. INTERVENTIONS Annual skin testing for tuberculosis infection and anergy was performed, and eligible patients were offered daily isoniazid for 12 months and followed prospectively. MAIN OUTCOME MEASURE The development of active tuberculosis. RESULTS A total of 155 persons commenced chemoprophylaxis. Among tuberculin reactors, tuberculosis rates were 0.51 and 2.07/100 person-years in those completing 12 months versus those not taking prophylaxis [rate ratio 0.25, 95% confidence interval (CI) 0.06-1.01]. Among anergic individuals, comparable rates were 0 and 1.44/100 person-years. Lower tuberculosis rates among completers were not attributable to differences in immune status between the treated and untreated groups. CONCLUSION The completion of isoniazid chemoprophylaxis was associated with a marked reduction in tuberculosis risk among tuberculin reactors and anergic persons in this high-risk population. These data support aggressive efforts to provide a complete course of preventative therapy to HIV-infected tuberculin reactors, and lend weight to the findings of others that isoniazid can reduce the rate of tuberculosis in high-risk anergic HIV-infected persons.

Staphylococcus aureus nasal colonization in HIV-seropositive and HIV-seronegative drug users

Nasal colonization plays an important role in the pathogenesis of Staphylococcus aureus infections. To identify characteristics associated with colonization, we studied a cross-section of a well-described cohort of HIV-seropositive and -seronegative active and former drug users considered at risk for staphylococcal infections. Sixty percent of the 217 subjects were Hispanic, 36% were women, 25% actively used injection drugs, 23% actively used inhalational drugs, 23% received antibiotics, and 35% were HIV-seropositive. Forty-one percent of subjects had positive nasal cultures for S. aureus. The antibiotic susceptibility patterns were similar to the local hospitals outpatient isolates and no dominant strain was identified by arbitrarily primed polymerase chain reaction (AB-PCR). Variables significantly and independently associated with colonization included antibiotic use (odds ratio [OR] = 0.37; confidence interval [CI] = 0.18-0.77), active inhalational drug use within the HIV-seropositive population (OR = 2.36; CI = 1.10-5.10) and female gender (OR = 1.97; CI = 1.09-3.57). Characteristics not independently associated included injection drug use, HIV status, and CD4 count. The association with active inhalational drug use, a novel finding, may reflect alterations in the integrity of the nasal mucosa. The lack of association between HIV infection and S. aureus colonization, which is contrary to most previous studies, could be explained by our rigorous control for confounding variables or by a limited statistical power due to the sample sizes.