Faculty Bibliography

Understanding drug interactions between antiretrovirals and opiate therapies may decrease toxicities and enhance adherence, with improved HIV outcomes in injection drug users. We report results of a clinical pharmacology study designed to examine the interaction of the protease inhibitor, nelfinavir, with methadone and LAAM (N = 48). Nelfinavir decreased methadone exposure, but no withdrawal was observed over the five day study period. LAAM and dinorLAAM concentrations were decreased, while norLAAM concentrations were increased, with minimal overall change in LAAM/metabolite exposure. Methadone and LAAM did not affect nelfinavir concentrations, but methadone decreased M8 metabolite exposure. While no toxicities were observed, clinicians should be aware of the potential for drug interactions when patients require treatment with nelfinavir and these opiate medications

BACKGROUND: Both diabetes mellitus and alcohol consumption are prevalent in the United States, yet physicians are poorly informed about how alcohol use affects risk for or management of diabetes. PURPOSE: To conduct a systematic review assessing the effect of alcohol use on the incidence, management, and complications of diabetes mellitus in adults. DATA SOURCES: English-language studies in persons 19 years of age or older that were identified by searching the MEDLINE database from 1966 to the third week of August 2003 and the reference lists of key articles. STUDY SELECTION: Two independent assessors reviewed 974 retrieved citations to identify all experimental, cohort, or case-control studies that assessed the effect of alcohol use on diabetes risk, control, self-management, adverse drug events, or complications. DATA EXTRACTION: Two independent reviewers extracted data and evaluated study quality on the basis of established criteria. DATA SYNTHESIS: Thirty-two studies that met inclusion criteria were reviewed. Compared with no alcohol use, moderate consumption (one to 3 drinks/d) is associated with a 33% to 56% lower incidence of diabetes and a 34% to 55% lower incidence of diabetes-related coronary heart disease. Compared with moderate consumption, heavy consumption (>3 drinks/d) may be associated with up to a 43% increased incidence of diabetes. Moderate alcohol consumption does not acutely impair glycemic control in persons with diabetes. CONCLUSIONS: Moderate alcohol consumption is associated with a decreased incidence of diabetes mellitus and a decreased incidence of heart disease in persons with diabetes. Further studies are needed to assess the long-term effects of alcohol consumption on glycemic control and noncardiac complications in persons with diabetes

OBJECTIVE: To define the prevalence of and factors associated with having a negative purified protein derivative (PPD) among persons who self-report a prior positive PPD and to define the safety of repeat testing in such persons. DESIGN: Observational cohort study. SETTING: Methadone maintenance program with onsite primary care. PATIENTS/PARTICIPANTS: Current or former drug users enrolled in methadone maintenance treatment. INTERVENTIONS: Structured interview, tuberculin skin testing regardless of self-reported PPD status, and anergy testing. MEASUREMENTS AND MAIN RESULTS: Nearly one third (31%) of participants who self-reported a prior positive PPD had a negative measured PPD, despite receipt of a 'booster' PPD. A single participant (0.5%) blistered in response to the PPD without lasting ill effect. Participants with PPD results discordant from their history were more likely to be HIV-seropositive and nonreactive to the anergy panel. The discordance rate among HIV-infected participants was 43%, and was largely attributable to immune dysfunction. Among HIV-seronegative participants, the discordance rate was 27%. Recent crack-cocaine use was independently associated with discordance in the absence of HIV infection. CONCLUSIONS: We confirmed that planting a PPD in patients who self-report a positive PPD history confers minimal risk. Substantial rates of discordance exist between self-reported history of a positive PPD and measured PPD status. Further research is needed to define the optimal management of PPD-negative patients who self-report a prior positive PPD and who have not received prior treatment for latent tuberculosis

OBJECTIVE: To identify gender differences in social and behavioral factors associated with antiretroviral adherence. DESIGN: Prospective cohort study. SETTING: Methadone maintenance program. PARTICIPANTS: One hundred thirteen HIV-seropositive current or former opioid users. MEASUREMENTS AND MAIN RESULTS: Participants were surveyed at baseline about social and behavioral characteristics and at monthly research visits about drug and alcohol use and medication side effects. Electronic monitors (MEMS) were used to measure antiretroviral adherence. Median adherence among women was 27% lower than among men (46% vs. 73%; P < .05). In gender-stratified multivariate models, factors associated with worse adherence in men included not belonging to an HIV support group (P < .0001), crack/cocaine use (P < .005), and medication side effects (P = .01). Among women, alcohol use (P = .005), heroin use (P < .05), and significant medication side effects (P < .005) were independently associated with worse adherence. In a model including both men and women, worse adherence was associated with lack of long-term housing (P < .005), not belonging to any HIV support groups (P < .0005), crack or cocaine use (P < .01), and medication side effects (P < .0005). In addition, worse adherence was associated with the interaction between female gender and alcohol use (P < or = .05). CONCLUSIONS: In this cohort of current and former opioid users, gender-stratified analysis demonstrated that different social and behavioral factors are associated with adherence in men and women. Among both men and women, worse adherence was associated with lack of long-term housing, not belonging to an HIV support group, crack/cocaine use, and medication side effects. Among women only, alcohol use was associated with worse adherence

Injection drug users (IDUs) were heavily affected by the tuberculosis (TB) resurgence in New York City in the 1990s. We assessed the effectiveness of screening for latent TB infection in methadone users and of selective treatment with isoniazid. Risk for future TB was classified as low or high on the basis of tuberculin, anergy, and HIV test results. The cohort of 2212 IDUs was followed up for a median of 4.2 years; 25 IDUs, of whom 20 (80%) were infected with human immunodeficiency virus (HIV), developed TB. In an adjusted Cox proportional hazards model of high-risk IDUs, the risk of TB was associated with HIV infection (HR 10.3; 95% CI, 3.4-31.3); receipt of <6 months of isoniazid therapy (HR 7.6; 95% CI, 1.02-57.1); a CD4+ T lymphocyte count of <200 cells/mm3 (HR 6.6; 95% CI, 1.7-25.9); and tuberculin positivity (HR 4.0; 95% CI, 1.6-10.2). Treatment with isoniazid was beneficial in HIV-infected, tuberculin-positive IDUs

We examined highly active antiretroviral therapy (HAART) era and pre-HAART era hospitalization rates among 604 HIV-infected drug users in a prospective study in Bronx, New York. Medical history and risk behaviors were elicited by semiannual interviews. Standardized medical record review abstracted discharge diagnoses for all hospitalizations. Hospitalization rates from January 1997 to December 2000 were compared with rates from January 1992 to December 1996. The rate of hospitalizations per 100 patient-years in the HAART era was 49.3 compared with 44.1 in the pre-HAART era (P = 0.13). Among women, the rate was significantly higher in the HAART era than in the pre-HAART era (68.1 vs. 49.4 hospitalizations per 100 patient-years, respectively; P = 0.01). In the second era, HAART users had lower rates than those who did not use HAART (37.2 vs. 83.4 hospitalizations per 100 patient-years, respectively; P < 0.001) for both HIV-associated and non-HIV-associated illnesses. Multivariate analysis revealed that in the HAART era, female gender (relative risk ratio = 1.72, P = 0.03) and not using HAART (relative risk ratio = 1.82, P = 0.02) independently predicted increased hospitalization risk. In the pre-HAART era, women were at independently higher risk of hospitalization (relative risk ratio = 1.36, P = 0.05). Among HIV-infected drug users, those who use HAART have a decreased risk of hospitalization; those who do not use HAART remain at high risk of continuing morbidity from both HIV-related and non-HIV-related illness and have high hospitalization rates

Injection drug use is an important factor in the spread of HIV infection, and strategies to enhance adherence to HIV therapeutics are critically important to controlling viral transmission and improving clinical outcomes. To this end, the authors sought (1) to enhance adherence to highly active antiretroviral therapy (HAART) among methadone-maintained injection drug users (IDUs) using modified directly observed therapy (MDOT), and (2) to define interactions between methadone and HAART and the potential contribution of drug interactions to adherence and HIV outcomes in this population. Adherence was explored here through a pilot, unblinded, 24-week study in a methadone maintenance program in which simplified HAART (efavirenz and didanosine [one daily] and a second nucleoside [twice daily]) was administered 6 days/week by clinic staff to HIV-infected IDUs (n = 5) with their methadone. Evening doses of riboflavin-tagged nucleoside and one full day of medication weekly were given as take home doses. As a result of HAART administration, four of five participants with mean viral load at baseline of 10(5) copies/ml had undetectable viral load by 8 weeks of treatment (p = .043). Methadone area under the curve (AUC) decreased by 55% (p = .007) within 2 weeks of initiating this HAART regimen, and a mean methadone dose increase of 52% was required. The authors conclude that MDOT is a promising intervention for the treatment of IDUs with HIV disease, though significant drug interactions must be monitored for carefully and rapidly addressed

Two-step tuberculin testing and standardized interviews of 793 current and former drug users were performed to determine the risk factors for tuberculin positivity. The prevalence of tuberculin positivity was 25%. Factors independently associated with tuberculin positivity among participants seronegative for human immunodeficiency virus (HIV) included crack cocaine use (adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.0-2.5), employment as a home health aide (adjusted OR, 2.1; 95% CI, 1.0-4.1), birth in Puerto Rico (adjusted OR, 2.2; 95% CI, 1.3-3.6), foreign birthplace (adjusted OR, 4.7; 95% CI, 1.6-13.6), African American race (adjusted OR, 2.5; 95% CI, 1.2-5.0), reported tuberculosis exposure (adjusted OR, 2.3; 95% CI, 1.2-4.4), and older age (adjusted OR, 2.9; 95% CI, 1.2-6.7). Additional risk factors among HIV-infected participants included alcoholism (adjusted OR, 2.4; 95% CI, 1.0-5.8) and high CD4(+) lymphocyte count. Identification of and administration of appropriate chemoprophylaxis to drug users with these risk factors should be given high priority