Faculty Bibliography

To compare electronically monitored (MEMS) with self-reported adherence in drug users, including the impact of adherence on HIV load, we conducted a 6-month observational study of 67 antiretroviral-experienced current and former drug users. Adherence (percentage of doses taken as prescribed) was calculated for both the day and the week preceding each of 6 research visits. Mean self-reported 1-day adherence was 79% (median, 86%), and mean self-reported 1-week adherence was 78% (median, 85%). Mean MEMS 1-day adherence was 57% (median, 52%), and mean MEMS 1-week adherence was 53% (median, 49%). One-day and 1-week estimates were highly correlated (r>.8 for both measures). Both self-reported and MEMS adherence were correlated with concurrent HIV load (r=.43-.60), but the likelihood of achieving virologic suppression was greater if MEMS adherence was high than if self-reported adherence was high. We conclude that self-reported adherence is higher than MEMS adherence, but a strong relationship exists between both measures and virus load. However, electronic monitoring is more sensitive than self-report for the detection of nonadherence and should be used in adherence intervention studies

This study examined whether costs associated with tuberculosis (TB) screening and directly observed preventive therapy (DOPT) among drug injectors attending a syringe exchange are justified by cases and costs of active TB cases prevented and examined the impact of monetary incentives to promote adherence on cost-effectiveness. We examined program costs and projected savings using observed adherence and prevalence rates and literature estimates of isoniazid (INH) preventive therapy efficacy, expected INH hepatoxicity rates, and TB treatment costs; we conducted sensitivity analyses for a range of INH effectiveness, chest X-ray (CXR) referral adherence, and different strategies regarding anergy among persons affected with human immunodeficiency virus (HIV). For 1,000 patients offered screening, incorporating real observed program adherence rates, the program would avert $179,934 in TB treatment costs, for a net savings of $123,081. Assuming a modest risk of TB among HIV-infected anergic persons, all strategies with regard to anergy were cost saving, and the strategy of not screening for anergy and not providing DOPT to HIV-infected anergic persons resulted in the greatest cost savings. If an incentive of $25 per person increased CXR adherence from the observed 31% to 50% or 100%, over a 5-year follow-up the net cost savings would increase to $170,054 and $414,856, respectively. In this model, TB screening and DOPT at a syringe exchange is a cost-effective intervention and is cost-saving compared to costs of treating active TB cases that would have occurred in the absence of the intervention. This model is useful in evaluating the cost impact of planned program refinements, which can then be tested. Monetary incentives for those referred for screening CXRs would be justified on a cost basis if they had even a modest beneficial impact on adherence

SETTING: In persons infected with the human immunodeficiency virus (HIV), a decreased tuberculin reaction cut-point of > or = 5 mm induration is recommended. OBJECTIVE: To determine tuberculosis risk in non-anergic HIV-infected persons with 5-9 mm tuberculin reactions. DESIGN: A prospective study with semi-annual tuberculin and anergy testing, HIV antibody and T cell subset assays, and active surveillance for tuberculosis. RESULTS: Participants were 572 HIV-seronegative and 241 HIV-seropositive non-anergic drug users. No tuberculosis occurred in HIV-seronegative persons. Tuberculosis incidence among HIV-seropositive drug users was 3.3, 7.7, 0, and 0.34 per 100 person-years in those with tuberculin reaction sizes of > or = 10 mm, 5-9 mm, 1-4 mm, and 0 mm, respectively, and was significantly increased in persons with 5-9 mm induration compared with those with 0-4 mm induration (rate ratio 27.7, 95%CI 2.9-268). Among persons with reaction sizes of 5-9 mm, tuberculosis occurred exclusively in those with CD4+ lymphocyte counts <500/mm3 at the time of their 5-9 mm tuberculin reactions. CONCLUSION: HIV-infected persons with tuberculin reaction sizes of 5-9 mm are at increased risk for tuberculosis compared to non-anergic persons with smaller (0-4 mm) reaction sizes. However, this increased risk may be limited to those with low CD4+ lymphocyte counts at the time of tuberculin testing

CONTEXT: Patients and the public could benefit from identification of factors that prevent drug users' heavy reliance on inpatient care; however, optimal health care delivery models for illicit drug users remain ill-defined. OBJECTIVE: To evaluate associations of outpatient medical and drug abuse care with drug users' subsequent hospitalization rates. DESIGN AND SETTING: Retrospective cohort study of data from longitudinally linked claims for all ambulatory physician/clinic services and drug abuse services covered by the New York State Medicaid program. SUBJECTS: A total of 11 556 human immunodeficiency virus (HIV)-positive and 46 687 HIV-negative drug users. MAIN OUTCOME MEASURES: Hospitalization in federal fiscal year (FFY) 1997 compared by 4 patterns of care in FFY 1996: regular drug abuse care (>/=6 months in 1 program), regular medical care (>35% of care from 1 clinic, group practice, or individual physician), both, or neither. RESULTS: Hospitalization occurred in 55.6% of HIV-positive and 37.5% of HIV-negative drug users, with a mean of 27.5 and 24.5 inpatient days, respectively. In HIV-positive drug users, the adjusted odds ratio (AOR) for hospitalization was lowest among those with both regular medical and drug abuse care (AOR, 0.76; 95% confidence interval [CI], 0.67-0.85) followed by those with regular medical care alone (AOR, 0.82; 95% CI, 0.74-0.91) and regular drug abuse care alone (AOR, 0.85; 95% CI, 0.76-0.96) vs those with neither. In HIV-negative drug users, the AOR of hospitalization was lower for those with regular medical and drug abuse care (AOR, 0.73; 95% CI, 0.68-0.79), regular drug abuse care alone (AOR, 0.71; 95% CI, 0.66-0.76), and regular medical care (AOR, 0.91; 95% CI, 0.86-0.95) vs those with neither. Both types of care showed favorable effects for all but drug abuse-related hospitalizations. CONCLUSION: Our data indicate that regular drug abuse care with regular medical care for drug users is associated with less subsequent hospitalization

BACKGROUND: It is critical for providers caring for HIV-positive methadone recipients to have accurate information on pharmacologic interactions between methadone and antiretroviral therapy. If providers do not have these data, symptoms of narcotic withdrawal or excess due to medication interactions may be mismanaged, and antiretroviral regimens may be suboptimal in efficacy or associated with increased side effects and toxicities. This review was undertaken to clarify what is known about interactions between pharmacotherapies of opiate dependence and HIV-related medications, to suggest clinically useful approaches to these issues, and to outline areas which need further study. METHOD: A search for relevant published papers and abstracts presented at scientific meetings was conducted using electronic databases. These documents were obtained and reviewed, and additional publications referenced in them were also reviewed. RESULTS: Pharmacokinetic interactions between methadone and zidovudine, didanosine, stavudine, abacavir, nevirapine, efavirenz and nelfinavir have been documented. The mechanisms, clinical implications and management of these interactions are reviewed. CONCLUSIONS: Interactions between methadone and some HIV-related medications are known to occur, yet their characteristics cannot reliably be predicted based on current understanding of metabolic enzyme induction and inhibition, or through in vitro studies. Only carefully designed and conducted pharmacologic studies involving human subjects can help us define the nature of the interactions between methadone (and other pharmacotherapies for opiate dependence) and specific HIV-related medications. Clinicians must be aware of known interactions and be alert to the possibility that interactions which are still undocumented may be present among their patients

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

This study was done to determine whether there were any differences in subjective symptoms of opiate withdrawal or methadone pharmacodynamics among patients as they were switched between three different oral formulations of methadone. Patients enrolled in a three-way double-blind crossover trial of three methadone formulations. Subjective symptoms and pharmacodynamic measures were assessed throughout the study period. Eighteen patients were enrolled the study. No statistically significant differences in any of the pharmacodynamic parameters studied were found among the three methadone preparations. There was no significant difference among preparations in the rate and extent of rise and fall in plasma methadone levels during a 24-hour intensive sampling period. Subjective symptoms also did not correlate with methadone formulation. Intolerance to changes in methadone formulation, often observed clinically, do not appear to have a pharmacodynamic basis. Our findings support the notion that such change intolerance reflects factors other than the pharmacologic properties of the different formulations of methadone