Characterization of hepatitis C infection in tuberculosis patients in an urban city in the USA.

The impact of hepatitis C virus infection (HCI), the most common bloodborne virus infection in the USA, on outcome of active tuberculosis (TB) treatment is largely unknown. We aimed to describe characteristics of TB patients with hepatitis C virus infection (TB-HCI) in King County, Washington, including TB treatment duration and outcome. We reviewed 1510 records of patients treated for active TB at the Public Health - Seattle & King County Tuberculosis Control Program between 2000 and 2010, and identified 53 with HCI. Advanced age, being born in the USA, HIV infection, homelessness and injection drug use were independently associated with HCI in TB cases. Independent factors associated with increased treatment duration included HIV infection, excess alcohol use, extrapulmonary TB, and any drug-resistant TB disease. Our findings suggest that TB-HCI patients can be successfully treated for active TB without extending treatment duration.

Longitudinal determinants of consistent condom use by partner type among young injection drug users: the role of personal and partner characteristics.

We investigated the longitudinal influence of individual-, relationship- and social-level factors on condom use by partner type among young injections drug users (IDUs) enrolled in the Collaborative Injection Drug Users Study-III/Drug Users Intervention Trial (CIDUS-III/DUIT) from 2002 to 2004. Based on longitudinal analysis using generalized estimating equations (GEE), consistent condom use with main partners was more commonly reported among males and those with greater self-efficacy for condom use; main partner's desire for pregnancy and needle sharing were negatively associated with consistent condom use. Among those with casual partners, having fewer sex partners was associated with consistent condom use. Positive attitudes toward condom use and partner norms supporting condom use were associated with greater consistent condom use with both partner types. These findings suggest that intervention strategies targeting individual- and partner-level factors may provide avenues for intervening upon sexual risks among young IDUs.

Pharmacokinetics of intravenous mycophenolate mofetil after allogeneic blood stem cell transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) has shown synergistic effects in combination with cyclosporin A (CsA) in prevention of acute graft versus host disease (GvHD) after allogeneic blood stem cell transplantation (BSCT) in preclinical animal models. After having measured low plasma levels of the active metabolite mycophenolic acid (MPA) in recipients of allogeneic blood stem cell transplants after oral administration of MMF, we initiated a phase I/II study evaluating different dose levels of the intravenous (i.v.) formulation together with standard dose CsA. METHODS: A total of 15 patients received i.v. MMF in two split doses for 21 d after allogeneic BSCT from related (n=9) and unrelated (n=6) donors. Total daily doses of 25, 28, 31 and 34 mg/kg were investigated in 3-5 patients at each dose level. Plasma concentrations of MPA and its metabolite mycophenolic acid glucuronide (MPAG) were measured by high-performance liquid chromatography (HPLC). RESULTS: Mean trough blood levels of MPA ranged between 68.8 and 340 ng/mL with a median of 146.7 ng/mL. The mean MPA AUC0-12 h after first dose ranged between 19349+/-5087 ng * h/mL and 25705+/-3042 ng * h/mL and correlated with the dose level of MMF. The incidence of acute GvHD>grade I was 40%. No dose limiting toxicities were observed. CONCLUSIONS: The application of i.v. MMF is safe at a weight-adjusted dose between 25 and 34 mg/kg after allogeneic BSCT. The measured trough blood levels of MPA in patients after BSCT were ten times lower than in healthy volunteers. The toxicity induced by the conditioning therapy seems to negatively influence the pharmacokinetic behavior of MMF, MPA and MPAG.

Two decades after vaccine license: hepatitis B immunization and infection among young men who have sex with men.

OBJECTIVES: This study investigated hepatitis B immunization coverage and the extent of hepatitis B virus (HBV) infection among young men who have sex with men (MSM), a group for whom hepatitis B vaccine has been recommended since 1982. METHODS: We analyzed data from 3432 MSM, aged 15 to 22 years, randomly sampled at 194 gay-identified venues in 7 US metropolitan areas from 1994 through 1998. Participants were interviewed, counseled, and tested for serologic markers of HBV infection. RESULTS: Immunization coverage was 9% and the prevalence of markers of HBV infection was 11%. HBV infection ranged from 2% among 15-year-olds to 17% among 22-year-olds. Among participants susceptible to HBV infection, 96% used a regular source of health care or accessed the health care system for HIV or sexually transmitted disease testing. CONCLUSIONS: Despite the availability of an effective vaccine for nearly 2 decades, our findings suggest that few adolescent and young adult MSM in the United States are vaccinated against hepatitis B. Health care providers should intensify their efforts to identify and vaccinate young MSM who are susceptible to HBV.

Predictors of accidental fatal drug overdose among a cohort of injection drug users.

OBJECTIVES: This study evaluated factors associated with accidental fatal drug overdose among a cohort of injection drug users (IDUs). METHODS: In a prospective cohort study of 2849 IDUs in King County, Washington, deaths were identified by electronically merging subject identifiers with death certificate records. Univariate and multivariate Cox regression analyses were performed to identify predictors of overdose mortality. RESULTS: Thirty-two overdoses were observed. Independent predictors of overdose mortality were bisexual sexual orientation (relative risk [RR] = 4.86; 95% confidence interval [CI] = 2.30, 13.2), homelessness (RR = 2.30; 95% CI = 1.06, 5.01), infrequent injection of speedballs (RR = 5.36; 95% CI = 1.58, 18.1), daily use of powdered cocaine (RR = 4.84; 95% CI = 1.13, 20.8), and daily use of poppers (RR = 22.0; 95% CI = 1.74, 278). CONCLUSIONS: Sexual orientation, homelessness, and drug use identify IDUs who may benefit from targeted interventions.

Using a jail-based survey to monitor HIV and risk behaviors among Seattle area injection drug users.

Routine monitoring of human immunodeficiency virus (HIV) and risk behaviors among injection drug users (IDUs) is difficult outside drug treatment settings. We developed and implemented a survey of recently arrested IDUs to describe the prevalence of HIV, drug use, and sexual behaviors among them. A probability sampling survey was instituted in the King County Correctional Facility in Seattle, Washington, to sample recently arrested IDUs at the time of booking and in the jail health clinic between 1998 and 1999. Following HIV risk assessment and blood draw, additional information on drug use practices was gathered using a standardized questionnaire. Potential participants who were released from jail early could complete the study at a nearby research storefront office. Of the 4,344 persons intercepted at booking, 503 (12%) reported injection drug use, and 201 of the IDUs (40%) participated in the study. An additional 161 IDUs were enrolled in the study from the jail health clinic. Among the 348 unduplicated subjects, HIV prevalence was 2%; in the past 6 months, 69% reported two or more shooting partners, 72% used a cooker after someone else, 60% shared a syringe to divide up drugs, and 62% injected with used needles. Only 37% reported being hepatitis C seropositive, and 8% reported hepatitis B vaccination. It was feasible to conduct a jail-based survey of recently arrested IDUs that yielded useful information. The high prevalence of reported risky drug use practices warrants ongoing monitoring and illustrates the need for improving prevention programs for HIV and hepatitis B and C in this population, including expansion of hepatitis C screening and provision of hepatitis B vaccination at the jail health clinic.

Seroepidemiology of human herpesvirus 8 among young men who have sex with men.

BACKGROUND: The modes of transmission of human herpesvirus 8 (HHV-8) remain unclear. GOAL: To study HHV-8 seroprevalence and risk factors among young men. STUDY DESIGN: The Young Men's Survey was a multisite cross-sectional HIV seroprevalence and behavioral risk survey of men aged 15 to 22 years who attended public venues frequented by young men who have sex with men (MSM). Blood specimens were tested for HHV-8 by using an immunofluorescence assay at a 1:40 dilution among 488 participants in Seattle-King County, WA. RESULTS: Total HHV-8 seroprevalence was 6% among MSM and 5% among men who have sex only with women (MSW). In multivariate analysis, unprotected receptive anal sex during the past 6 months, injection drug use, and cytomegalovirus infection were associated with HHV-8 seropositivity in MSM. CONCLUSION: The HHV-8 seroprevalence among these young MSM was similar to the HHV-8 seroprevalence among young MSW, but lower than seroprevalence estimates in earlier studies of older MSM. The association of MSM between HHV-8 infection and unprotected receptive anal sex supports previous findings that HHV-8 is sexually transmitted. Although CMV infection and injection drug use may be markers for unsafe sexual practices, it is also possible that these are independent risk factors for acquiring HHV-8.

Sharing of drug preparation equipment as a risk factor for hepatitis C.

OBJECTIVES: This study investigated the sharing of drug preparation equipment as a possible route of hepatitis C virus (HCV) transmission. METHODS: HCV seroconversion was measured in a cohort of 317 injection drug users who tested negative for HCV antibody at recruitment. RESULTS: Cumulative HCV incidence was 16.7% per year. Among those who did not share syringes, HCV seroconversion was associated with sharing drug cookers and filtration cotton (adjusted risk ratio = 5.9; 95% confidence interval = 1.1, 31.7); 54% of HCV infections in injection drug users who did not share syringes were attributable to cooker/cotton sharing. CONCLUSIONS: Among injection drug users who do not share syringes, an important proportion of HCV infections may be attributed to cooker/cotton sharing.

Determination of mycophenolic acid and mycophenolate mofetil by high-performance liquid chromatography using postcolumn derivatization.

An efficient method to lower the optical detection limit is described using the displacement of an absorption and emission band of an analyte after a polarity change in different solvents. This solvatochromic effect was used in a RP-HPLC assay for the fluorescence detection of mycophenolic acid (6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl)-4-methyl-4-hexenoic acid, MPA) and the prodrug mycophenolate mofetil (MMF), the N-(2-hydroxyethyl)morpholino ester of MPA. The rational to use fluorescence detection is based on the behavior of MMF and MPA, which fluoresce in a basic medium (pH >9.5). Following a simple protein precipitation, the analytes were separated in an isocratic RP-HPLC system. The postcolumn generation of the phenolate anions of MPA and MMF was achieved by addition of an aqueous sodium hydroxide solution regulated by a newly developed continuous-flow liquid control system. MPAG, not directly accessible for fluorescence detection, was analyzed after enzymatic deglucuronidation to MPA. Compared to published quantification limits for MPA and MMF by UV detection, this method is more than 100-fold more sensitive, with a lower limit of quantification of 45 fmol for both MPA and MMF.

Reduced injection frequency and increased entry and retention in drug treatment associated with needle-exchange participation in Seattle drug injectors.

The association between needle exchange, change in drug use frequency and enrollment and retention in methadone drug treatment was studied in a cohort of Seattle injection drug users (IDUs). Participants included IDUs classified according to whether they had used a needle exchange by study enrollment and during the 12-month follow-up period. The relative risk (RR) and the adjusted RR (ARR) were estimated as measures of the association. It was found that IDUs who had formerly been exchange users were more likely than never-exchangers to report a substantial (> or= 75%) reduction in injection (ARR = 2.85, 95% confidence limit [CL] 1.47-5.51), to stop injecting altogether (ARR = 3.5, 95% CL 2.1-5.9), and to remain in drug treatment. New users of the exchange were five times more likely to enter drug treatment than never-exchangers. We conclude that reduced drug use and increased drug treatment enrollment associated with needle exchange participation may have many public health benefits, including prevention of blood-borne viral transmission.

Methadone treatment and HIV and hepatitis B and C risk reduction among injectors in the Seattle area.

Drug treatment has the potential to reduce incidence of blood-borne infections by helping injection drug users (IDUs) achieve abstinence or by decreasing the frequency of injection and sharing practices. We studied the associations between retention in methadone treatment and drug use behaviors and incidence of hepatitis B and C in a cohort of IDUs in the Seattle, Washington, area. Data on IDUs entering methadone treatment at four centers in King County, Washington, were collected through face-to-face interviews using a standardized questionnaire at baseline and 12-month follow-up between October 1994 and January 1998. Blood specimens were obtained and tested for human immunodeficiency virus (HIV) and hepatitis B and C. Drug treatment status at follow-up was analyzed in relation to study enrollment characteristics and potential treatment outcomes, including injection risk behaviors, cessation or reduced frequency of injection, and incidence of hepatitis B and C. Of 716 IDUs, 292 (41%) left treatment, 198 (28%) disrupted (left and returned) treatment, and 226 (32%) continued treatment throughout the 1-year follow-up period. Compared to those who left treatment, subjects who disrupted or continued were less likely to inject at follow-up (odds ratio [OR] = 0.5, 95% CI 0.3-0.7; and OR = 0.1, 95% CI 0.1-0.2, respectively). Among the 468 (65%) subjects who continued injecting, those who continued treatment injected less frequently, were less likely to pool money to buy drugs (OR = 0.5, 95% CI 0.3-0.8) and inject with used needles (OR = 0.5, 95% CI 0.2-0.8) compared to those who left treatment. Cooker or cotton sharing was not associated with retention in treatment, but hepatitis B incidence was lowest among those who continued treatment. The results of this study suggest drug use risk reduction is more likely to be achieved by those who remain in drug treatment and by those who stop injecting, but that those who drop out and return and those who continue to inject while in treatment may also benefit. This supports the role of consistent drug treatment in an overall harm-reduction strategy.

Changes in injection risk behavior associated with participation in the Seattle needle-exchange program.

We studied the influence of the Seattle, Washington, needle-exchange program on sharing of drug injection equipment (syringes, drug cookers, filtration cotton) to identify potential gaps in risk reduction and to understand in greater detail the lack of an association between exchange use and risk of hepatitis B or C virus transmission. In a cohort of 2,208 injection drug users who completed a 1-year follow-up visit, we measured the association between needle-exchange use at study enrollment (ever vs. never) and injection risk behavior at the follow-up. Control for confounding was carried out using both logistic regression and propensity score analytic methods to estimate the adjusted odds ratio (AOR). In both univariate and multivariate analyses, needle-exchange use was associated with a lower likelihood of injection with a used syringe (AOR = 0.7, 95% confidence limit 0.5, 0.9). There was no association between exchange use and cooker or cotton sharing (AOR = 0.8, 95% confidence limit 0.6, 1.1) or between exchange use and use of a common syringe to divide drugs (AOR = 0.9). This analysis suggests that risk reduction measures adopted by users of the Seattle exchange may not be sufficient to prevent transmission of all blood-borne viruses, including hepatitis C virus. Greater awareness of the infection risk associated with these practices may help curb this type of equipment sharing and ultimately prevent disease transmission.

HIV prevalence and associated risks in young men who have sex with men. Young Men's Survey Study Group.

CONTEXT: Studies conducted in the late 1980s on human immunodeficiency virus (HIV) infection among older men who have sex with men (MSM) suggested the epidemic had peaked; however, more recent studies in younger MSM have suggested continued high HIV incidence. OBJECTIVE: To investigate the current state of the HIV epidemic among adolescent and young adult MSM in the United States by assessing the prevalence of HIV infection and associated risks in this population in metropolitan areas. DESIGN: The Young Men's Survey, a cross-sectional, multisite, venue-based survey conducted from 1994 through 1998. SETTING: One hundred ninety-four public venues frequented by young MSM in Baltimore, Md; Dallas, Tex; Los Angeles, Calif; Miami, Fla; New York, NY; the San Francisco (Calif) Bay Area; and Seattle, Wash. SUBJECTS: A total of 3492 15- to 22-year-old MSM who consented to an interview and HIV testing. MAIN OUTCOME MEASURES: Prevalence of HIV infection and associated characteristics and risk behaviors. RESULTS: Prevalence of HIV infection was high (overall, 7.2%; range for the 7 areas, 2.2%-12. 1%) and increased with age, from 0% among 15-year-olds to 9.7% among 22-year-olds. Multivariate-adjusted HIV infection prevalence was higher among blacks (odds ratio [OR], 6.3; 95% confidence interval [CI], 4.1-9.8), young men of mixed or other race (OR, 4.8; 95% CI, 3. 0-7.6), and Hispanics (OR, 2.3; 95% CI, 1.5-3.4), compared with whites (referent) and Asian Americans and Pacific Islanders (OR, 1. 1; 95% CI, 0.5-2.8). Factors most strongly associated with HIV infection were being black, mixed, or other race; having ever had anal sex with a man (OR, 5.0; 95% CI, 1.8-13.8); or having had sex with 20 or more men (OR, 3.0; 95% CI, 2.0-4.7). Only 46 (18%) of the 249 HIV-positive men knew they were infected before this testing; 37 (15%) were receiving medical care for HIV, and 19 (8%) were receiving medical drug therapy for HIV. Prevalence of unprotected anal sex during the past 6 months was high (overall, 41%; range, 33%-49%). CONCLUSIONS: Among these young MSM, HIV prevalence was high, underscoring the need to evaluate and intensify prevention efforts for young MSM, particularly blacks, men of mixed race or ethnicity, Hispanics, and adolescents. JAMA. 2000;284:198-204

Volunteer bias in nonrandomized evaluations of the efficacy of needle-exchange programs.

OBJECTIVE: Nonrandomized comparisons of the incidence of HIV and hepatitis B and C between injection drug users (IDUs) who do and do not attend voluntary needle-exchange programs may be subject to bias. To explore possible sources of bias, we examined characteristics associated with voluntarily beginning or ceasing to participate in the Seattle needle exchange. METHODS: In a cohort of 2,879 IDUs, a standardized questionnaire measured characteristics present at enrollment. We examined the relation of these characteristics to the proportion of IDUs who began to use the program during the ensuing 12-month follow-up period and to the proportion of current exchangers who dropped out during that period of time. RESULTS: Of the 494 never-exchangers at baseline, 32% attended the exchange program during follow-up; those who reported sharing syringes or who were homeless at enrollment were more likely to become new exchange users (adjusted risk ratio [ARR] for becoming an exchange user = 1.8 for those who shared syringes, and ARR = 2.2 for those who were homeless). Of 1,274 current exchangers, 16% stopped using the exchange during followup, with daily injectors (ARR = 0.6) and those who reported backloading (ARR = 0.6) being relatively less likely to drop out of the exchange. CONCLUSIONS: The analysis suggests that IDUs participating in needle-exchange programs at a given point in time may include a particularly high proportion of those injectors whose pattern of drug use puts them at elevated risk of blood-borne viral infections.

Mycophenolate mofetil and cyclosporine as graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) is an inhibitor of purine nucleotide de novo synthesis leading to impaired proliferation of activated lymphocytes. Studies in animals show a synergistic effect of MMF and cyclosporine (CsA) in preventing acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation. We performed a pilot study evaluating the feasibility of the combined application of MMF and CsA as GVHD prophylaxis after allogeneic blood stem cell transplantation. Toxicity and the bioavailability of MMF in this setting were investigated. METHODS: Fourteen patients who had received grafts from HLA-compatible siblings received 2 g of oral MMF from day 1 to 14 combined with intravenous CsA at 4 mg/kg starting at day-1. Plasma levels of mycophenolic acid (MPA) and its glucoronide were measured by high-performance liquid chromatography. Fifteen patients treated with a combination of CsA and methotrexate at the same institution were referred to as the control group. RESULTS: Trilineage engraftment was achieved in all study and control patients. Acute GVHD > or = grade II was observed in 46.5% and 60% of the study and control patients, respectively. No major differences in the rate of acute toxicities were detectable. The mean trough blood level of MPA in 10 patients was 0.28 microg/ml, and 5.7 microg/ml for MPA glucoronide. Reduced peak levels of MPA indicate a reduced absorption rate of MMF in the early posttransplant phase. CONCLUSIONS: The combined administration of MMF and CsA was shown to be feasible in patients after allogeneic blood stem cell transplantation. Because of the decreased bioavailability of MMF, dose-finding studies for an intravenous formulation are warranted.

Syringe exchange and risk of infection with hepatitis B and C viruses.

The authors utilized a cohort study among Seattle injection drug users (IDUs) to assess whether participation in a syringe exchange program was associated with incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Susceptible IDU subjects (187 seronegative for antibody to HCV, and 460 seronegative for core antibody to HBV) were identified in drug treatment, corrections, and social service agencies from June 1994 to January 1996, and followed for seroconversion one year later. The subjects included in the analysis were Seattle-King County (Washington State) area IDUs enrolled in a larger multipurpose cohort study, the Risk Activity Variables, Epidemiology, and Network Study (RAVEN Study). There were 39 HCV infections (20.9/100/year) and 46 HBV infections (10.0/100/year). There was no apparent protective effect of syringe exchange against HBV (former exchange users, relative risk (RR) = 0.68, 95% confidence interval (CI) 0.2-2.5; sporadic exchange users, RR = 2.4, 95% CI 0.9-6.5; regular users, RR = 1.81, 95% CI 0.7-4.8; vs. RR = 1.0 for nonusers of the exchange; adjusted for daily drug injection). Neither did the exchange protect against HCV infection (sporadic users, RR = 2.6, 95% CI 0.8-8.5; regular users, RR = 1.3, 95% CI 0.8-2.2; vs. RR = 1.0 for nonusers; adjusted for recent onset of injection and syringe sharing prior to enrollment). While it is possible that uncontrolled confounding or other bias obscured a true beneficial impact of exchange use, these data suggest that no such benefit occurred during the period of the study.

AIDS surveillance: knowledge, attitudes, and practices of health care professionals in Washington State.

Health professionals in Washington State were surveyed in 1993 to assess acquired immunodeficiency syndrome (AIDS) reporting knowledge, attitudes, and practices. Seventy-five percent responded. Two thirds of previous reporters were informed about the 1993 AIDS case definition and reporting requirements, but 32 percent had neglected to report. Forty-eight percent were concerned about confidentiality of reported cases. Half favored human immunodeficiency virus reporting and 21 percent opposed it. In order to promote complete and timely AIDS reporting, current and future reporters need ongoing education on reporting requirements and methods. The importance of AIDS surveillance data for community planning as well as assurance of protection of confidentiality should be emphasized.

Inhibition of MAO and COMT by hypericum extracts and hypericin.

The influence of hypericin, hypericum total extract, and hypericum fractions on the activity of MAO and COMT, prepared in vitro from pork liver, were investigated in several concentration steps. An inhibition of MAO could be shown in the following concentrations (extract correlated to a mean molecular value of 500): hypericin to 10(-3) mol/L, hypericum total extract to 10(-4) mol/L, one extract fraction up to 10(-5). A COMT inhibition could not be shown for hypericin, with hypericum extract to 10(-4) mol/L and with two extract fractions also up to 10(-4) mol/L. The MAO inhibiting fraction contained hypericins as well as flavonols, the COMT-inhibition fraction being mainly flavonols and xanthones. The concentrations of inhibition shown might not be sufficient to explain the clinically proven antidepressive effect of hypericum particularly with regard to the inhibition of MAO activity.