Search

Two commonly prescribed treatments for opioid addiction are methadone and buprenorphine. Although these drugs show some efficacy in treating opioid dependence, treatment response varies among individuals. It is likely that genetic factors have a role in determining treatment outcome. This study analyses the pharmacogenetic association of six polymorphisms in OPRD1, the gene encoding the delta-opioid receptor, on treatment outcome in 582 opioid addicted European Americans randomized to either methadone or buprenorphine/naloxone (Suboxone) over the course of a 24-week open-label clinical trial. Treatment outcome was assessed as the number of missed or opioid-positive urine drug screens over the 24 weeks. In the total sample, no single-nucleotide polymorphisms (SNPs) in OPRD1 were significantly associated with treatment outcome in either treatment arm. However, sex-specific analyses revealed two intronic SNPs (rs581111 and rs529520) that predicted treatment outcome in females treated with buprenorphine. Females with the AA or AG genotypes at rs581111 had significantly worse outcomes than those with the GG genotype when treated with buprenorphine (P=0.03, relative risk (RR)=1.67, 95% confidence interval (CI) 1.06-2.1). For rs529520, females with the AA genotype had a significantly worse outcome than those with the CC genotype when (P=0.006, RR=2.15, 95% CI 1.3-2.29). No significant associations were detected in males. These findings suggest that rs581111 and rs52920 may be useful when considering treatment options for female opioid addicts, however, confirmation in an independent sample is warranted.

Background: Previous reports on the pharmacokinetic of tipranavir (TPV) and buprenorphine (BUP)/ naloxone found that coadministration resulted in an 80% reduction in the area under the curve AUC of the primary BUP metabolite, norBUP, without any pharmacodynamic consequences. This study was conducted to characterize how tipranivir/ritonavir effects the glucuronide metabolites of BUP and may explain the reduction in the norBUP.Methods: HIV-seronegative subjects stabilized on at least 3 weeks of BUP/naloxone sequentially underwent baseline and steady-state pharmacokinetic evaluation of twice daily TPV 500?mg coadministered with ritonavir 200?mg (TPV/r).Results: Twelve subjects were enrolled and ten completed the study. The steady-state pharmacokinetics for BUP-3-glucuronide (BUP-3G) and norBUP-3-glucuronide (norBUP-3G) in the presence and absence of steady-state TPV/r were analyzed. The C(max) of BUP-3G was 8.78???5.23?ng/mL without TPV/r and increased to 12.7???11.7 after steady state of TPV/r was achieved. The AUC of BUP-3G was 31.1???19.4?(ng/mL)?(h) without TPV/r and increased to 58. 6???49.5 after steady state of TPV/r was achieved (p?=?.0966). In contrast, steady-state norBUP-3G AUC(0?24?h) (p?=?.0216) and C(max) (p?=?.0088) were significantly decreased in the presence of steady-state TPV/r.Conclusions and Scientific Significance: This study further elucidates the effects of TPV/r on glucuronidation. The current evaluation of glucuronide metabolites of BUP and norBUP are suggestive of combined inhibition of Uridine diphosphate (UDP)-glucuronosyltransferase of the 1A family and cytochrome P450 3A4 that spares UGT2B7 leading to a shunting of BUP away from production of norBUP and toward BUP-3G as seen by a statistically significant increase in the AUC of BUP-3G. [ABSTRACT FROM AUTHOR]

Background: Serum cystatin C was proposed as a potential replacement for serum creatinine in glomerular filtration rate (GFR) estimation. We report the development and evaluation of GFR-estimating equations using serum cystatin C alone and serum cystatin C, serum creatinine, or both with demographic variables.Study Design: Test of diagnostic accuracy.Setting& Participants: Participants screened for 3 chronic kidney disease (CKD) studies in the United States (n = 2,980) and a clinical population in Paris, France (n = 438).Reference Test: Measured GFR (mGFR).Index Test: Estimated GFR using the 4 new equations based on serum cystatin C alone, serum cystatin C, serum creatinine, or both with age, sex, and race. New equations were developed by using linear regression with log GFR as the outcome in two thirds of data from US studies. Internal validation was performed in the remaining one third of data from US CKD studies; external validation was performed in the Paris study.Measurements: GFR was measured by using urinary clearance of iodine-125-iothalamate in the US studies and chromium-51-EDTA in the Paris study. Serum cystatin C was measured by using Dade-Behring assay, standardized serum creatinine values were used.Results: Mean mGFR, serum creatinine, and serum cystatin C values were 48 mL/min/1.73 m(2) (5th to 95th percentile, 15 to 95), 2.1 mg/dL, and 1.8 mg/L, respectively. For the new equations, coefficients for age, sex, and race were significant in the equation with serum cystatin C, but 2- to 4-fold smaller than in the equation with serum creatinine. Measures of performance in new equations were consistent across the development and internal and external validation data sets. Percentages of estimated GFR within 30% of mGFR for equations based on serum cystatin C alone, serum cystatin C, serum creatinine, or both levels with age, sex, and race were 81%, 83%, 85%, and 89%, respectively. The equation using serum cystatin C level alone yields estimates with small biases in age, sex, and race subgroups, which are improved in equations including these variables.Limitations: Study population composed mainly of patients with CKD.Conclusions: Serum cystatin C level alone provides GFR estimates that are nearly as accurate as serum creatinine level adjusted for age, sex, and race, thus providing an alternative GFR estimate that is not linked to muscle mass. An equation including serum cystatin C level in combination with serum creatinine level, age, sex, and race provides the most accurate estimates. [ABSTRACT FROM AUTHOR]

Background: Injection drug use (IDU) accounts for 70 percent of HIV cases in Ukraine. Until buprenorphine maintenance therapy (BMT) was introduced, few effective strategies aimed at achieving reduction in illicit drug use were available as a conduit to anti-retroviral therapy (ARV) among IDUs.Description: In October 2005, BMT was scaled-up using Global Fund resources in six regions within Ukraine. Entry criteria included opioid dependence, HIV-1 seropositivity, age >or=18 years and reported interest in BMT. All sites included a multidisciplinary team. To date, 207 patients have been initiated on BMT.Lessons Learned: The existing infrastructure allows for further scale-up of and administration of BMT and the possibility of co-administration with ARV. The process for prescription and administration of buprenorphine and ARV is at times cumbersome and constrained by current regulations.Recommendations: More IDU need BMT to improve overall health outcomes. Central to expanding access will be legislative changes to existing drug policy. Moreover, the cost of buprenorphine is prohibitively expensive. Sustainable substitution therapy in Ukraine requires lower negotiated prices for buprenorphine, the addition of methadone, or both to the existing formulary for HIV+ drug users. [ABSTRACT FROM AUTHOR]

Chronic pain is common among older people with HIV. Etiologies of chronic pain are multifactorial in this population. A careful and thorough initial assessment of pain is important. Associated conditions that can contribute to pain should be explored and managed as indicated. Special consideration is warranted for some of the unique aspects of pain in people with HIV. Chronic pain management is multimodal; a variety of pharmacologic and nonpharmacologic strategies are effective. Among medications, opioids can be used but carry a risk of significant harms. The use and monitoring of opioids is discussed here, and recommendations are made for the safe prescribing of opioids for chronic pain.

Identifying candidates for HIV pre-exposure prophylaxis (PrEP) is a barrier to improving PrEP uptake in priority populations. Syphilis infection is an indication for PrEP in all individuals and can be easily assessed by primary care providers (PCP) and health systems. This retrospective study evaluated the impact of a multidisciplinary provider outreach intervention on PrEP uptake in patients with a positive syphilis test result in a safety-net hospital-based primary care practice. The PCPs of PrEP-eligible patients with a positive syphilis result were notified via the electronic medical record (EMR) about potential PrEP eligibility and institutional HIV PrEP resources. Rates of PrEP offers and prescriptions were compared in the pre (8/1/2018-12/31/2018, n  = 60) and post (1/1/2019-5/31/2019, n  = 86) intervention periods. Secondary analyzes evaluated receipt of appropriate syphilis treatment and contemporaneous screening for HIV, gonorrhea, and chlamydia. No significant differences in the overall proportion of patients offered (15% vs 19%) and prescribed (7% vs 5%) PrEP were observed between the pre- and post-periods. Overall, 7% of positive tests represented infectious syphilis. The rate of appropriate syphilis treatment was equivalent (57% vs 56%) and contemporaneous screening for other sexually transmitted infections was suboptimal across the entire study period. Although any positive syphilis test may be an easily abstracted metric from the EMR, this approach was inclusive of many patients without current HIV risk and did not increase PrEP uptake significantly. Future research into population health approaches to increase HIV prevention should focus on patients with infectious syphilis and other current risk factors for incident HIV infection.

Objective: To determine the prevalence of tuberculosis (TB) disease and infection as well as incident TB disease among people who use drugs (PWUD) attending Medication Assisted Treatment (MAT) clinics in Dar-es-Salaam, Tanzania., Methods: In this prospective cohort study, a total of 901 consenting participants were enrolled from November 2016 to February 2017 and a structured questionnaire administered to them through the open data kit application on android tablets. Twenty-two months later, we revisited the MAT clinics and reviewed 823 of the 901 enrolled participant's medical records in search for documentation on TB disease diagnosis and treatment. Medical records reviewed included those of participants whom at enrolment were asymptomatic, not on TB disease treatment, not on TB preventive therapy and those who had a documented tuberculin skin test (TST) result., Results: Of the 823 medical records reviewed 22 months after enrolment, 42 had documentation of being diagnosed with TB disease and initiated on TB treatment. This is equivalent to a TB disease incidence rate of 2,925.2 patients per 100,000 person years with a total follow up time of 1,440 person-years. At enrolment the prevalence of TB disease and TB infection was 2.6% and 54% respectively and the HIV prevalence was 44% and 16% among females and males respectively., Conclusion: PWUD attending MAT clinics bear an extremely high burden of TB and HIV and are known to have driven TB epidemics in a number of countries. Our reported TB disease incidence is 12 times that of the general Tanzanian incidence of 237 per 100,000 further emphasizing that this group should be prioritized for TB screening, testing and treatment. Gender specific approaches should also be developed as female PWUDs are markedly more affected with HIV and TB disease than male PWUDs., Competing Interests: The authors have declared that no competing interests exist.

Purpose of Review: Opioid use disorder (OUD) is a global phenomenon and is on the rise in Africa, denoting a shift from historical patterns of drug transport to internal consumption. In contrast, opioids for clinical pain management in Africa remain among the least available globally. This region also has the highest HIV and HCV disease burden, and the greatest shortages of health workers and addiction treatment. We undertook a systematic review of the literature to describe opioid use in Africa and how it is being addressed., Recent Findings: A total of 84 articles from 2000 to 2018 were identified. Descriptions of country-specific populations and patterns of opioid misuse were common. A smaller number of articles described interventions to address OUD., Summary: OUD occurs in sub-Saharan Africa, with attendant clinical and social costs. Evidence-based policies and health system resources are needed to promote OUD prevention and management, and infectious disease transmission reduction., Competing Interests: Competing interests The authors declare that they have no competing interests.

Available data indicate that opioid substitution treatment can successfully reduce rates of HIV transmission and that patients receiving such treatment can adhere to therapies for HIV, hepatitis C, and tuberculosis infection. Integration of opioid substitution treatment into the HIV clinic setting can make such treatment easier and improve retention in treatment. This article summarizes a presentation by R. Douglas Bruce, MD, MA, MS, at the IAS-USA continuing education program held in Chicago, Illinois, in May 2018.

Objective: To identify challenges that disadvantaged adults with asthma face in mitigating social and environmental factors associated with poor symptom control., Methods: Using a community-engaged approach, we partnered with a community health center in New Haven, CT to conduct in-person interviews and a written survey of asthmatic adults with poor symptom control. Using the constant comparative method, we analyzed participant interviews to establish emerging themes and identify common barriers to improved outcomes. Through a written survey utilizing clinically validated questions, we assessed information on access to medical care, asthma control, and selected social and environmental risk factors., Results: Twenty-one patients (mean age 47, 62% female, 71% Black, 95% insured by Medicaid) participated. The average Asthma Control Test (ACT) score was 11.6. Seventy-six percent of participants were currently employed and of those, 75% reported work-related symptoms. Among participants currently in housing, 59% reported exposure to domiciliary mice and 47% to mold. We identified three themes that summarize the challenges the study participants face: 1) Lack of knowledge about home and workplace asthma triggers; 2) Lack of awareness of legal rights or resources available to mitigate adverse conditions in the home or work environment; and 3) Fear of retaliation from landlords or employers, including threats of eviction, sexual assault, and job loss., Conclusion: Patients with poorly controlled asthma in a disadvantaged urban northeast community identified common barriers in both the domestic and work environments that impeded attainment of symptom control. These challenges may be best addressed through legal advocacy for those most at risk.

Pain has always been an important part of human immunodeficiency virus (HIV) disease and its experience for patients. In this guideline, we review the types of chronic pain commonly seen among persons living with HIV (PLWH) and review the limited evidence base for treatment of chronic noncancer pain in this population. We also review the management of chronic pain in special populations of PLWH, including persons with substance use and mental health disorders. Finally, a general review of possible pharmacokinetic interactions is included to assist the HIV clinician in the treatment of chronic pain in this population.It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. The Infectious Diseases Society of American considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Pain has always been an important part of human immunodeficiency virus (HIV) disease and its experience for patients. In this guideline, we review the types of chronic pain commonly seen among persons living with HIV (PLWH) and review the limited evidence base for treatment of chronic noncancer pain in this population. We also review the management of chronic pain in special populations of PLWH, including persons with substance use and mental health disorders. Finally, a general review of possible pharmacokinetic interactions is included to assist the HIV clinician in the treatment of chronic pain in this population.It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. The Infectious Diseases Society of American considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The intermediate filaments (IF) in trichocyte (hard α-) keratin are unique amongst the various classes of IF in having not one but two topologically-distinct structures. The first is formed at an early stage of hair development in a reducing environment within the cells in the lower part of the follicle. The second structure occurs at a later stage of hair development in the upper part of the follicle, where there is a transition to an oxidizing environment. Crosslinking studies reveal that molecular slippage occurs within the IF upon oxidation and that this results in many cysteine residues lying in near axial alignment, thereby facilitating disulphide bond formation. The disulphide bonds so formed stabilize the assembly of IF molecules and convert the keratin fibre into a tough, resilient and insoluble structure suitable for its function in vivo as a thermo-regulator and a protector of the animal against its external environment.

The Community Health Care Van (CHCV) is a mobile medical clinic (MMC) that has served vulnerable populations in New Haven, Connecticut since 1993. This study explores utilization patterns to understand if certain populations frequently rely upon non-traditional health care within a representative MMC. Patient characteristics, services used, and visitation frequency were described and compared for 8,415 unique clients making 29,728 visits. Negative binomial regression was used to model the impact of specific indicators on visitation. Clients receiving buprenorphine had the highest visitation rates, with 2.09 visits per person-year. Increased CHCV visitation was positively associated with being foreign-born (additional 3.42 visits on average, p < .001), injection drug use (additional 1.69 visits on average, p < .001) and having hypertension (additional 1.09 visits on average, p < .001). As the Affordable Care Act has increased health insurance coverage, MMCs will continue their role in assisting entry into continuous health care and offering low-threshold acute care for urban vulnerable populations.

The structures of avian and reptilian epidermal appendages, such as feathers, claws and scales, have been modelled using X-ray diffraction and electron microscopy data, combined with sequence analyses. In most cases, a family of closely related molecules makes up the bulk of the appendage, and each of these molecules contains a central β-rich 34-residue segment, which has been identified as the principal component of the framework of the 3.4 nm diameter filaments. The N- and C-terminal segments form the matrix component of the filament/matrix complex. The 34-residue β-rich central domains occur in pairs, related by either a parallel dyad or a perpendicular dyad axis, and form a β-sandwich stabilized by apolar interactions. They are also twisted in a right-handed manner. In feather, the filaments are packed into small sheets and it is possible to determine their likely orientation within the sheets from the low-angle X-ray diffraction data. The physical properties of the various epidermal appendages can be related to the amino acid sequence and composition of defined molecular segments characteristic of the chains concerned.

Prisoners bear much of the burden of the hepatitis C epidemic in the United States. Yet little is known about the scope and cost of treating hepatitis C in state prisons-particularly since the release of direct-acting antiviral medications. In the forty-one states whose departments of corrections reported data, 106,266 inmates (10 percent of their prisoners) were known to have hepatitis C on or about January 1, 2015. Only 949 (0.89 percent) of those inmates were being treated. Prices for a twelve-week course of direct-acting antivirals such as sofosbuvir and the combination drug ledipasvir/sofosbuvir varied widely as of September 30, 2015 ($43,418-$84,000 and $44,421-$94,500, respectively). Numerous corrections departments received smaller discounts than other government agencies did. To reduce the hepatitis C epidemic, state governments should increase funding for treating infected inmates. State departments of corrections should consider collaborating with other government agencies to negotiate discounts with pharmaceutical companies and with qualified health care facilities to provide medications through the federal 340B Drug Discount Program. Helping inmates transition to providers in the community upon release can enhance the gains achieved by treating hepatitis C in prison., (Project HOPE—The People-to-People Health Foundation, Inc.)

This study analyzed the quality of HIV screening at one of the largest community health centers in Connecticut. The data indicated that implementing universal HIV screening increased the proportion of underrepresented minorities and women tested, reducing the HIV testing disparities that previously existed at this center.

Introduction: People who inject drugs (PWID) and other individuals with opioid use disorders have a dramatically higher prevalence of hepatitis C virus (HCV) infection than the general population. The availability of novel direct acting antivirals (DAAs) for the treatment of HCV infection with very high efficacy, improved tolerability and shortened treatment durations have led to global efforts to ramp up treatment for all HCV-infected individuals to prevent or delay complications of the disease. Individuals with opioid use disorders, including those on medication-assisted therapy such as methadone or buprenorphine, are a key demographic group that can benefit from HCV treatment given their high HCV prevalence; however, pharmacokinetic and pharmacodynamic drug interactions could blunt their utility., Areas Covered: We performed a comprehensive literature review of published and unpublished data from PubMed database, relevant conference abstracts/proceedings and FDA approved drug package inserts, to review the pharmacokinetic (PK) profile and drug interactions between currently approved HCV DAAs and methadone and buprenorphine., Expert Opinion: The paper highlights specific drug combinations which result in altered opioid drug levels including telaprevir/methadone, daclatasvir/buprenorphine, and Abbvie 3D combination regimen (paritaprevir, ritonavir, ombitasvir and dasabuvir)/buprenorphine. However, concurrent pharmacodynamics assessments did not reveal significant signs and symptoms of opioid withdrawal or toxicity that would preclude concurrent administration.

Background: Despite dramatic improvement in antiretroviral therapy (ART) access globally, people living with HIV who inject drugs continue to face barriers that limit their access to treatment. This paper explores barriers and facilitators to ART initiation among clients attending a methadone clinic in Dar es Salaam, Tanzania., Methods: We interviewed 12 providers and 20 clients living with HIV at the Muhimbili National Hospital methadone clinic between January and February 2015. We purposively sampled clients based on sex and ART status and providers based on job function. To analyze interview transcripts, we adopted a content analysis approach., Results: Participants identified several factors that hindered timely ART initiation for clients at the methadone clinic. These included delays in CD4 testing and receiving CD4 test results; off-site HIV clinics; stigma operating at the individual, social and institutional levels; insufficient knowledge of the benefits of early ART initiation among clients; treatment breakdown at the clinic level possibly due to limited staff; and initiating ART only once one feels physically ill. Participants perceived social support as a buffer against stigma and facilitator of HIV treatment. Some clients also reported that persistent monitoring and follow-up on their HIV care and treatment by methadone clinic providers led them to initiate ART., Conclusion: Health system factors, stigma and limited social support pose challenges for methadone clients living with HIV to initiate ART. Our findings suggest that on-site point-of-care CD4 testing, a peer support system, and trained HIV treatment specialists who are able to counsel HIV-positive clients and initiate them on ART at the methadone clinic could help reduce barriers to timely ART initiation for methadone clients., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Injection of heroin has become widespread in Dar es Salaam, Tanzania and is spreading throughout the country. To prevent potential bridging of HIV epidemics, the Tanzanian government established a methadone maintenance treatment (MMT) clinic in February 2011. We assess the effect of MMT on health-related quality of life (HRQOL) and examine factors, particularly HIV infection and methadone dose, associated with changes in HRQOL., Methods: This study utilized routine data on clients enrolling in methadone from February 2011 to April 2012 at Muhimbili National Hospital. Change in physical (PCS) and mental health (MCS) composite scores, as measured by the SF-12 tool, were the primary outcomes. Backward stepwise linear regression, with a criterion of p<0.2 was used to identify baseline exposure variables for inclusion in multivariable models, while adjusting for baseline scores., Results: A total of 288 MMT clients received baseline and follow-up assessments. Mean methadone dose administered was 45mg (SD±25) and 76 (27%) were confirmed HIV-positive. Significant improvements were observed in PCS and MCS, with mean increases of 15.7 and 3.3, respectively. In multivariable models, clients who had previous poly-substance use with cocaine [p=0.040] had a significantly higher mean change in PCS. Clients who were living with HIV [p=0.002]; satisfied with current marital situation [p=0.045]; had a history of suicidal thoughts [p=0.021]; and previously experienced cognitive difficulties [p=0.012] had significantly lower mean change in PCS. Clients with shorter history of heroin use [p=0.012] and who received higher methadone doses [p=0.028] had significantly higher mean change in MCS, compared to their counterparts., Conclusion: Aspects of mental and physical health, risk behaviors and quality of life among drug users are intertwined and complex. Our research revealed positive short-term effects of MMT on HRQOL and highlights the importance of sustained retention for optimal benefits. Comprehensive supportive services in addition to provision of methadone are needed to address the complex health needs of people who inject drugs., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The effectiveness of interferon-free direct-acting antivirals (DAA) in treating chronic hepatitis C virus (HCV) is limited by low screening and treatment rates, particularly among people who inject drugs (PWIDs)., Methods: To evaluate the levels of screening and treatment with interferon-free DAAs that are required to control HCV incidence and HCV-associated morbidity and mortality, we developed a transmission model, stratified by age and by injection drug use, and calibrated it to epidemiological data in the United States from 1992 to 2014. We quantified the impact of administration of DAAs at current and at enhanced screening and treatment rates, focusing on outcomes of HCV incidence, prevalence, compensated and decompensated cirrhosis, hepatocellular carcinoma, liver transplants, and mortality from 2015 to 2040., Results: Increasing annual treatment of patients 4-fold-from the approximately 100 000 treated historically to 400 000-is predicted to prevent 526 084 (95% confidence interval, 466 615-593 347) cases of cirrhosis and 256 315 (201 589-316 114) HCV-associated deaths. By simultaneously increasing treatment capacity and increasing the number of HCV infections diagnosed, total HCV prevalence could fall to as low as 305 599 (222 955-422 110) infections by 2040. Complete elimination of HCV transmission in the United States through treatment with DAAs would require nearly universal screening of PWIDs, with an annual treatment rate of at least 30%., Conclusions: Interferon-free DAAs are projected to achieve marked reductions in HCV-associated morbidity and mortality. Aggressive expansion in HCV screening and treatment, particularly among PWIDs, would be required to eliminate HCV in the United States., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Heroin trafficking and consumption has increased steadily over the past decade in Tanzania, but limited information regarding HIV and drug use exists for the city of Mwanza. Our study investigates the epidemiology of drug use, and HIV risk behaviors among drug users in the northwestern city of Mwanza. Using a combination of targeted sampling and participant referral, we recruited 480 participants in Mwanza between June and August 2014. The sample was 92% male. Seventy-nine (16.4%) participants reported injecting heroin, while 434 (90.4%) reported smoking heroin. Unstable housing and cohabitation status were the only socioeconomic characteristics significantly associated with heroin injection. More than half of heroin injectors left syringes in common locations, and half reported sharing needles and syringes. Other risk behaviors such as lack of condom use during sex, and the use of illicit drugs during sex was widely reported as well. Among the study sample, there was poor awareness of health risks posed by needle/syringe sharing and drug use. Our results show that heroin use and HIV risk related behaviors are pressing problems that should not be ignored in Mwanza. Harm reduction programs are urgently needed in this population.

TRP (Transient Receptor Potential) cation channels of the TRPM subfamily have been found to be critically important for the regulation of Mg2+ homeostasis in both protostomes (e.g., the nematode, C. elegans, and the insect, D. melanogaster) and deuterostomes (e.g., humans). Although significant progress has been made toward understanding how the activities of these channels are regulated, there are still major gaps in our understanding of the potential regulatory roles of extensive, evolutionarily conserved, regions of these proteins. The C. elegans genes, gon-2, gtl-1 and gtl-2, encode paralogous TRP cation channel proteins that are similar in sequence and function to human TRPM6 and TRPM7. We isolated fourteen revertants of the missense mutant, gon-2(q338), and these mutations affect nine different residues within GON-2. Since eight of the nine affected residues are situated within regions that have high similarity to human TRPM1,3,6 and 7, these mutations identify sections of these channels that are potentially critical for channel regulation. We also isolated a single mutant allele of gon-2 during a screen for revertants of the Mg2+-hypersensitive phenotype of gtl-2(-) mutants. This allele of gon-2 converts a serine to phenylalanine within the highly conserved TRP domain, and is antimorphic against both gon-2(+) and gtl-1(+). Interestingly, others have reported that mutation of the corresponding residue in TRPM7 to glutamate results in deregulated channel activity.

Hepatitis C virus (HCV) infection is common among people who inject drugs, including those managed with maintenance opioids. Pharmacokinetic interactions between opioids and emerging oral HCV antivirals merit evaluation. Daclatasvir is a potent pangenotypic inhibitor of the HCV NS5A replication complex recently approved for HCV treatment in Europe and Japan in combination with other antivirals. The effect of steady-state daclatasvir (60 mg daily) on stable plasma exposure to oral opioids was assessed in non-HCV-infected subjects receiving methadone (40 to 120 mg; n = 14) or buprenorphine plus naloxone (8 to 24 mg plus 2 to 6 mg; n = 11). No relevant interaction was inferred if the 90% confidence interval (CI) of the geometric mean ratio (GMR) of opioid area under the plasma concentration-time curve over the dosing interval (AUCτ) or maximum concentration in plasma (C max) with versus without daclatasvir was within literature-derived ranges of 0.7 to 1.43 (R- and S-methadone) or 0.5 to 2.0 (buprenorphine and norbuprenorphine). Dose-normalized AUCτ for R-methadone (GMR, 1.08; 90% CI, 0.94 to 1.24), S-methadone (1.13; 0.99 to 1.30), and buprenorphine (GMR, 1.37; 90% CI, 1.24 to 1.52) were within the no-effect range. The norbuprenorphine AUCτ was slightly elevated in the primary analysis (GMR, 1.62; 90% CI, 1.30 to 2.02) but within the no-effect range in a supplementary analysis of all evaluable subjects. Dose-normalized C max for both methadone enantiomers, buprenorphine and norbuprenorphine, were within the no-effect range. Standardized assessments of opioid pharmacodynamics were unchanged throughout daclatasvir administration with methadone or buprenorphine. Daclatasvir pharmacokinetics were similar to historical data. Coadministration of daclatasvir and opioids was generally well tolerated. In conclusion, these data suggest that daclatasvir can be administered with buprenorphine or methadone without dose adjustments., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Background: The first methadone maintenance treatment clinic in Tanzania was launched in February 2011 to address an emerging HIV epidemic among people who inject drugs. We conducted a retrospective cohort study to understand factors associated with linkage to HIV care and explore how a methadone maintenance treatment clinic can serve as a platform for integrated HIV care and treatment., Methods: This study used routine programmatic and clinical data on clients enrolled in methadone at Muhimbili National Hospital from February 2011 to January 2013. Multivariable proportional hazards regression model was used to examine time to initial CD4 count., Results: Final analyses included 148 HIV-positive clients, contributing 31.7 person-years. At 30, 60, and 90 days, the probability of CD4 screening was 40% [95% confidence interval (CI): 32% to 48%], 55% (95% CI: 47% to 63%), and 63% (95% CI: 55% to 71%), respectively. Clients receiving high methadone doses (≥ 85 mg/d) [adjusted hazard ratio (aHR): 1.68, 95% CI: 1.03 to 2.74] had higher likelihood of CD4 screening than those receiving low doses (<85 mg/d). Clients with primary education or lower (aHR: 1.62, 95% CI: 1.05 to 2.51) and self-reported poor health (aHR: 1.96, 95% CI: 1.09 to 3.51) were also more likely to obtain CD4 counts. Clients with criminal arrest history (aHR: 0.56, 95% CI: 0.37 to 0.85]) were less likely to be linked to care. Among 17 antiretroviral therapy eligible clients (CD4 ≤ 200), 12 (71%) initiated treatment, of which 7 (41%) initiated within 90 days., Conclusions: Levels of CD4 screening and antiretroviral therapy initiation were similar to Sub-Saharan programs caring primarily for people who do not inject drugs. Adequate methadone dosing is important in retaining clients to maximize HIV treatment benefits and allow for successful linkage to services.

Purpose: Intravenous opioid use is a common route of hepatitis C virus (HCV) infection; consequently, the prevalence of HCV is high among patients on methadone or buprenorphine/naloxone. The authors evaluated the pharmacokinetic interaction of boceprevir with methadone or buprenorphine/naloxone in patients on stable maintenance therapy., Methods: This was a two-center, open-label, fixed-sequence study in 21 adult volunteers on stable maintenance therapy. Oral methadone (20-150 mg once daily) or sublingual buprenorphine/naloxone (8/2-24/6 mg once daily) was administered alone or in combination with boceprevir (800 mg every 8 h) on days 2-7. Pharmacokinetic sampling occurred before and up to 24 h after the dose on days 1 and 7., Results: Coadministration of boceprevir reduced the area under the concentration-time curve during a dosing interval τ (AUC τ ) and maximum observed plasma (or serum) concentration (C max) of R-methadone (geometric mean ratios (GMRs) [90 % confidence intervals (CIs)], 0.85 [0.74, 0.96] and 0.90 [0.71, 1.13]) and S-methadone (GMRs [90 % CIs], 0.78 [0.66, 0.93] and 0.83 [0.64, 1.09]). Boceprevir increased the AUC τ and C max of buprenorphine (GMRs [90 % CIs], 1.19 [0.91, 1.58] and 1.18 [0.93, 1.50]) and naloxone (GMRs [90 % CIs], 1.33 [0.90, 1.93] and 1.09 [0.79, 1.51]). Boceprevir exposure upon methadone or buprenorphine/naloxone coadministration was not clinically different from historical controls and there was no evidence of opioid withdrawal or excess., Conclusions: There was no clinically meaningful impact of boceprevir on methadone or buprenorphine pharmacokinetics, suggesting that methadone/buprenorphine dose adjustments are not required upon coadministration with boceprevir. Individual patients may differ in their clinical experience and clinicians should maintain vigilance when coadministering these medications.

Avian and reptilian epidermal appendages such as feathers, claws and scales exhibit a filament-matrix texture. Previous studies have established that both components reside within the same single-chain molecule. In the present study the homology in a wide range of aligned sequences is used to gain insights into the structure and function of the molecular segments associated with the filament and with the matrix. The notion that all molecules contain a β-rich 34-residue segment associated with the framework of the filament is reinforced by the present study. In addition, the residues involved in the polymerization of the molecules to form filaments are identified. In the Archosaurs (birds, crocodiles and turtles), and the Squamates (snakes and lizards) segments rich in glycine and tyrosine can be identified in the C-terminal domain. In Rhynocephalians (tuataras) and Squamates a similar segment is inserted at a specific point in the N-terminal domain. In some Archosaurian appendages (both avian and reptilian) segments rich in charged residues and cysteine are found in the N-terminal domain. The likely effect of these segments will be to soften the tissue without compromising its insolubility. The structure and role of the various molecular segments identified in this study and the way in which they might manifest themselves in terms of the physical properties of the particular epidermal appendage in which they appear are also discussed., (Copyright © 2014 Elsevier Inc. All rights reserved.)

While there have been significant advances in curbing the HIV disease epidemic worldwide, there continues to be significant number of incident cases with 2.3 million new infections in the year 2012 alone. Treatment as prevention (TasP), which involves the use of antiretroviral drugs to decrease the likelihood of HIV illness, death and transmission from infected individuals to their noninfected sexual and /or drug paraphernalia-sharing injecting partners, must be incorporated into any HIV prevention strategy that is going to be successful on a large scale. Especially in resource-limited settings, the focus of the prevention approach should be on high-risk groups who contribute disproportionately to community HIV transmission, including people who inject drugs (PWID), men who have sex with men (MSM) and sex workers. Innovative strategies including integrated care services adapted to different patient care settings have to and can be employed to reach these at-risk populations.

Background: People who inject drugs (PWID) in Dar es Salaam, Tanzania, have an estimated human immunodeficiency virus (HIV) prevalence of 42%-50% compared with 6.9% among the general population. Extensive evidence supports methadone maintenance to lower morbidity, mortality, and transmission of HIV and other infectious diseases among PWID. In 2011, the Tanzanian government launched the first publicly funded methadone clinic on the mainland of sub-Saharan Africa at Muhimbili National Hospital., Methods: We conducted a retrospective cohort study of methadone-naive patients enrolling into methadone maintenance treatment. Kaplan-Meier survival curves were constructed to assess retention probability. Proportional hazards regression models were used to evaluate the association of characteristics with attrition from the methadone program., Results: Overall, 629 PWID enrolled into methadone treatment during the study. At 12 months, the proportion of clients retained in care was 57% (95% confidence interval [CI], 53%-62%). Compared with those receiving a low dose (<40 mg), clients receiving a medium (40-85 mg) (adjusted hazard ratio [aHR], 0.50 [95% CI, .37-.68]) and high (>85 mg) (aHR, 0.41 [95% CI, .29-.59]) dose of methadone had a lower likelihood of attrition, adjusting for other characteristics. Older clients (aHR, 0.53 per 10 years [95% CI, .42-.69]) and female clients (aHR, 0.50 [95% CI, .28-.90]) had a significantly lower likelihood of attrition, whereas clients who reported a history of sexual abuse (aHR, 2.84 [95% CI, 1.24-6.51]) had a significantly higher likelihood of attrition., Conclusions: Patient retention in methadone maintenance is comparable to estimates from programs in North America, Europe, and Asia. Future implementation strategies should focus on higher doses and flexible dosing strategies to optimize program retention and strengthened efforts for clients at higher risk of attrition., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objectives: We evaluated the efficacy of a mobile medical clinic (MMC) screening program for detecting latent tuberculosis infection (LTBI) and active tuberculosis., Methods: A LTBI screening program in a MMC in New Haven, Connecticut, used medical surveys to examine risk factors and tuberculin skin test (TST) screening eligibility. We assessed clinically relevant correlates of total (prevalent; n = 4650) and newly diagnosed (incident; n = 4159) LTBI from 2003 to 2011., Results: Among 8322 individuals, 4159 (55.6%) met TST screening eligibility criteria, of which 1325 (31.9%) had TST assessed. Similar to LTBI prevalence (16.8%; 779 of 4650), newly diagnosed LTBI (25.6%; 339 of 1325) was independently correlated with being foreign-born (adjusted odds ratio [AOR] = 8.49; 95% confidence interval [CI] = 5.54, 13.02), Hispanic (AOR = 3.12; 95% CI = 1.88, 5.20), Black (AOR = 2.16; 95% CI = 1.31, 3.55), employed (AOR = 1.61; 95% CI = 1.14, 2.28), and of increased age (AOR = 1.04; 95% CI = 1.02, 1.05). Unstable housing (AOR = 4.95; 95% CI = 3.43, 7.14) and marijuana use (AOR = 1.57; 95% CI = 1.05, 2.37) were significantly correlated with incident LTBI, and being male, heroin use, interpersonal violence, employment, not having health insurance, and not completing high school were significantly correlated with prevalent LTBI., Conclusions: Screening for TST in MMCs successfully identifies high-risk foreign-born, Hispanic, working, and uninsured populations and innovatively identifies LTBI in urban settings.

Setting: Active case finding is a World Health Organization (WHO) endorsed strategy for improving tuberculosis (TB) case detection. Despite WHO recommendations for active case finding among people who inject drugs (PWID), few studies have been published. The historical focus of case finding has been in populations that are human immunodeficiency virus-positive, incarcerated or at higher occupational risk., Objective: We sought to examine the yield of active case finding among PWID newly started on methadone in Tanzania., Design: Of 222 methadone clients, 156 (70%) met with study administrators; 150 consented to participate, 139 (93%) of whom were male. The median age was 34 years. A symptom-based questionnaire was developed by the investigators and administered to every consenting patient by a native Swahili speaker., Results: Of the 150 patients surveyed, 16 (11%) had one or more TB symptoms and were referred for laboratory testing. Six new TB cases were identified in this active case finding program, with a prevalence of 4%., Conclusion: This study presents the first data on TB prevalence in a population of PWID in Tanzania. This prevalence is 23 times that of the general Tanzanian TB prevalence of 0.2%. These results have significant implications for TB control.

Previous studies have shown that a strong interaction exists between oppositely directed 1B molecular segments in the intermediate filaments of trichocyte keratins. A similar interaction has been identified as having a significant role in the formation of unit-length filaments, a precursor to intermediate filament formation. The present study is concerned with the spatial relationship of these interacting segments and its dependence on differences in the amino acid sequences of the two-chain regions that constitute the 1B molecular segment. It is shown that along a particular line of contact both chain segments possess an elevated concentration of residues with a high propensity for dimer formation. The transition from the reduced to the oxidized state involves a simple axial displacement of one molecular segment relative to the other, with no attendant rotation of either segment. This changes the inter-relationship of the two 1B molecular segments from a loosely packed form to a more compact one. After the slippage eight of the cysteine residues in the dimer are precisely aligned to link up and form the disulfide linkages as observed. The two remaining cysteine residues are located on the outside of the dimer and are presumably involved in inter-dimer bonding. The existence of a unique line of contact requires that two chains in the molecule have different amino acid compositions with the clustering of dimer-favoring residues phased by half the pitch length of the coiled coil., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Previous studies have shown that a strong interaction exists between oppositely directed 1B molecular segments in the intermediate filaments of trichocyte keratins. A similar interaction has been identified as having a significant role in the formation of unit-length filaments, a precursor to intermediate filament formation. The present study is concerned with the spatial relationship of these interacting segments and its dependence on differences in the amino acid sequences of the two-chain regions that constitute the 1B molecular segment. It is shown that along a particular line of contact both chain segments possess an elevated concentration of residues with a high propensity for dimer formation. The transition from the reduced to the oxidized state involves a simple axial displacement of one molecular segment relative to the other, with no attendant rotation of either segment. This changes the inter-relationship of the two 1B molecular segments from a loosely packed form to a more compact one. After the slippage eight of the cysteine residues in the dimer are precisely aligned to link up and form the disulfide linkages as observed. The two remaining cysteine residues are located on the outside of the dimer and are presumably involved in inter-dimer bonding. The existence of a unique line of contact requires that two chains in the molecule have different amino acid compositions with the clustering of dimer-favoring residues phased by half the pitch length of the coiled coil., (Copyright © 2013 Elsevier Inc. All rights reserved.)

To successfully address HIV and TB in the world, we must address the healthcare needs of key populations, such as drug users, and we must do this urgently. Currently in Tanzania, as in many countries, the care for these medical disorders is separated into disease specific clinical environments. Our consortium began working to integrate HIV and TB clinical services into the methadone program in Dar es Salaam, Tanzania. We present the key lessons learned in this process of integration and the importance of integrating HIV/TB into the methadone program, which serves as a critical anchor for adherence to clinical services. Integrated healthcare for people who use drugs is clearly a long-term goal and different health systems will progress upon this continuum at different rates. What is clear is that every health system that interacts with drug users must aspire to achieve some level of integrated healthcare if the incidence rates of HIV and TB are to decline., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Interactions between HIV and opioid dependence therapies are known to occur. We sought to determine if such interactions occurred between methadone and elvitegravir boosted with cobicistat (EVG/COBI). We performed a within-subject open-label pharmacokinetic and pharmacodynamic study of 11 HIV-seronegative subjects stabilized on at least 2 weeks of methadone. Subjects underwent baseline and steady-state evaluation of the effect of elvitegravir 150 mg once a day (QD) boosted with 150 mg QD of cobicistat (EVG/COBI) on methadone pharmacokinetic parameters. Safety and pharmacodynamics were monitored throughout the study. Compared to baseline values, the R-methadone mean area under the concentration-time curve to the end of the dosing period (AUCtau) (5,550 versus 6,210 h · ng/ml) and mean maximum concentration of drug in serum (Cmax) (316 versus 337 ng/ml) did not significantly increase in the presence of EVG/COBI. Compared to baseline values, the S-methadone mean AUCtau (7,040 versus 7,540 h · ng/ml) and mean Cmax (446 versus 452 ng/ml) did not significantly increase in the presence of EVG/COBI. The AUCtau, Cmax, and Ctau of elvitegravir and cobicistat did not significantly differ from those of historical controls. Opioid withdrawal or overdose was not observed among subjects in this study. The addition of EVG/COBI to stabilized patients receiving methadone did not affect methadone pharmacokinetics and pharmacodynamics. These two agents can be safely coadministered.

Despite its benefit for treating active tuberculosis, directly observed therapy (DOT) for latent tuberculosis infection (LTBI) has been largely understudied among challenging inner city populations. Utilizing questionnaire data from a comprehensive mobile healthcare clinic in New Haven, CT from 2003 to July 2011, a total of 2,523 completed tuberculin skin tests (TSTs) resulted in 356 new LTBIs. Multivariate logistic regression correlated covariates of the two outcomes (a) initiation of isoniazid preventative therapy (IPT) and (b) completion of 9 months of IPT. Of the 357 newly positive TSTs, 86.3 % (n = 308) completed screening chest radiographs (CXRs): 90.3 % (n = 278) were normal, and 0.3 % (n = 1) had active tuberculosis. Of those completing CXR screening, 44.0 % (n = 135) agreed to IPT: 69.6 % (n = 94) selected DOT, and 30.4 % (n = 41) selected self-administered therapy (SAT). Initiating IPT was correlated with undocumented status (AOR = 3.43; p < 0.001) and being born in a country of highest and third highest tuberculosis prevalence (AOR = 14.09; p = 0.017 and AOR = 2.25; p = 0.005, respectively). Those selecting DOT were more likely to be Hispanic (83.0 vs 53.7 %; p < 0.0001), undocumented (57.4 vs 41.5 %; p = 0.012), employed (p < 0.0001), uninsured (p = 0.014), and have stable housing (p = 0.002), no prior cocaine or crack use (p = 0.013) and no recent incarceration (p = 0.001). Completing 9 months of IPT was correlated with no recent incarceration (AOR 5.95; p = 0.036) and younger age (AOR 1.03; p = 0.031). SAT and DOT participants did not significantly differ for IPT duration (6.54 vs 5.68 months; p = 0.216) nor 9-month completion (59.8 vs 46.3 %; p = 0.155). In an urban mobile healthcare sample, screening completion for LTBI was high with nearly half initiating IPT. Undocumented, Hispanic immigrants from high prevalence tuberculosis countries were more likely to self-select DOT at the mobile outreach clinic, potentially because of more culturally, linguistically, and logistically accessible services and self-selection optimization phenomena. Within a diverse, urban environment, DOT and SAT IPT models for LTBI treatment resulted in similar outcomes, yet outcomes were hampered by differential measurement bias between DOT and SAT participants.

Although buprenorphine and methadone are both effective treatments for opioid dependence, their efficacy can vary significantly among patients. Genetic differences may explain some of the variability in treatment outcome. Understanding the interactions between genetic background and pharmacotherapy may result in more informed treatment decisions. This study is a pharmacogenetic analysis of the effects of genetic variants in OPRD1, the gene encoding the δ-opioid receptor, on the prevalence of opioid-positive urine tests in African-Americans (n=77) or European-Americans (n=566) undergoing treatment for opioid dependence. Patients were randomly assigned to treatment with either methadone or buprenorphine/naloxone (Suboxone) over a 24-week open-label clinical trial, in which illicit opioid use was measured by weekly urinalysis. In African-Americans, the intronic SNP rs678849 predicted treatment outcome for both medications. Methadone patients with the CC genotype were less likely to have opioid-positive urine tests than those in the combined CT and TT genotypes group (relative risk (RR)=0.52, 95% confidence interval (CI)=0.44-0.60, p=0.001). In the buprenorphine treatment group, however, individuals with the CC genotype were more likely to have positive opioid drug screens than individuals in the combined CT and TT genotypes group (RR=2.17, 95% CI=1.95-2.68, p=0.008). These findings indicate that the genotype at rs678849 predicts African-American patient response to two common treatments for opioid dependence, suggesting that matching patients to treatment type based on the genotype at this locus may improve overall treatment efficacy. This observation requires confirmation in an independent population.

Background: Interactions between HIV and opioid-dependence therapies are known to occur. We sought to determine if such interactions occurred between buprenorphine/naloxone and elvitegravir boosted with cobicistat., Methods: We performed a within-subject open-labeled pharmacokinetic and pharmacodynamic study in 17 HIV-seronegative subjects stabilized on at least 2 weeks of buprenorphine/naloxone therapy. Subjects underwent baseline and steady state evaluation of the effect of elvitegravir 150 mg once daily boosted with 150 mg once daily of cobicistat (EVG/COBI) on buprenorphine/naloxone parameters. Safety was monitored throughout the study., Results: Compared with baseline values, buprenorphine mean AUCtau (69.0 versus 95.6 hr*ng/mL) and mean Cmax (8.4 versus 9.3 ng/mL) increased significantly in the presence of EVG/COBI. Compared with baseline values, norbuprenorphine mean AUCtau (103.4 versus 163.4 hr*ng/mL) and mean Cmax (6.9 versus 9 ng/mL) also increased significantly after achieving steady state EVG/COBI. Naloxone mean AUCtau (0.57 versus 0.45 hr*ng/mL) and mean Cmax (0.25 versus 0.16 ng/mL) decreased after the addition of EVG/COBI. The AUCtau, Cmax and Ctau of EVG and cobicistat did not significantly differ from historical controls. Opioid withdrawal or overdose was not observed among subjects in this study., Conclusion: The addition of EVG/COBI to stabilized patients receiving buprenorphine/naloxone modestly increased buprenorphine and norbuprenorphine levels without affecting the opioid pharmacodynamics.

Background: Universal Human Immunodeficiency Virus (HIV) testing and treatment are strategies to decrease AIDS-related morbidity and mortality and to reduce HIV transmission., Objective: This study examined the feasibility and effectiveness of routine HIV rapid testing implemented in the largest New York City (NYC) Methadone Maintenance Treatment Program (MMTP)., Methods: A routine HIV rapid testing program performed by medical providers without pretest counseling or the provision of incentives was compared to HIV rapid testing done by referral to HIV counselors with pretest counseling and incentives over the prior 12 months., Results: Routine HIV rapid testing proved feasible and effective when performed by the medical staff in the setting of a large urban MMTP. The program increased HIV testing in all genders, race/ethnicities, and ages. HIV-positive individuals were diagnosed and successfully linked to care. The elimination of HIV prevention counseling may have facilitated expanded testing., Conclusion: This study confirms that routine HIV rapid testing without HIV-prevention counseling or the provision of incentives for patients is feasible on a large scale in a busy, urban methadone clinic.

Addiction to prescription opioids is prevalent in primary care settings. Increasing prescription opioid use is largely responsible for a parallel increase in overdose nationally. Many patients most at risk for addiction and overdose come into regular contact with primary care providers. Lack of routine addiction screening results in missed treatment opportunities in this setting. We reviewed the literature on screening and brief interventions for addictive disorders in primary care settings, focusing on opioid addiction. Screening and brief interventions can improve health outcomes for chronic illnesses including diabetes, hypertension, and asthma. Similarly, through the use of screening and brief interventions, patients with addiction can achieve improved health outcome. A spectrum of low-threshold care options can reduce the negative health consequences among individuals with opioid addiction. Screening in primary care coupled with short interventions, including motivational interviewing, syringe distribution, naloxone prescription for overdose prevention, and buprenorphine treatment are effective ways to manage addiction and its associated risks and improve health outcomes for individuals with opioid addiction., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: Current estimates suggest an HIV prevalence of 42% among people who inject drugs (PWIDs) in Dar es Salaam, while HIV prevalence is estimated to be 8.8% among the general population in the city. To address the HIV epidemic in this population, the government of Tanzania began establishing HIV prevention, treatment and care services including outreach and medication assisted treatment (MAT) for PWIDs in 2010. We assessed gender inequities in utilization of outreach and MAT services and evaluated differences in HIV risk behaviors between female and male PWIDs., Materials and Methods: Routine outreach data between December 2010 to mid-August 2012 and baseline data on clients enrolling in methadone from February 2011 to August 2012 were utilized. Binomial regression was used to estimate adjusted relative risk estimates comparing females to males., Results: From December 2010 to August 2012, 8,578 contacts were made to drug users; among them 1,898 were injectors. A total of 453 injectors were eligible and referred to MAT, of which, 443 enrolled in treatment. However, regarding total outreach contacts, outreach to PWID, referral to MAT and enrollment in MAT, 8% or less of drug users accessing services were women. In contrast, weighted estimations from surveys suggest that 34% of PWIDs are female, and this approximation is similar to recent population size estimations. Overall, 43% of traditional outreach workers conducting outreach with drug users were female. Though reporting higher levels of condom usage, female PWID were more likely to report multiple sex partners, anal sex, commercial sex work and struggle under a higher burden of addiction, mental disorders and abuse., Conclusions: Services have not been mobilized adequately to address the clear needs of females who inject drugs. A clear and urgent need exists for women-centered strategies that effectively engage female PWID into HIV prevention services.

Global access to opioid agonist therapy and HIV/hepatitis C virus (HCV) treatment is expanding but when used concurrently, problematic pharmacokinetic and pharmacodynamic interactions may occur. Articles published from 1966 to 2012 in Medline were reviewed using the following keywords: HIV, AIDS, HIV therapy, HCV, HCV therapy, antiretroviral therapy, highly active antiretroviral therapy, drug interactions, methadone and buprenorphine. In addition, a review of abstracts from national and international meetings and conference proceedings was conducted; selected reports were reviewed as well. The metabolism of both opioid and antiretroviral therapies, description of their known interactions and clinical implications and management of these interactions were reviewed. Important pharmacokinetic and pharmacodynamic drug interactions affecting either methadone or HIV medications have been demonstrated within each class of antiretroviral agents. Drug interactions between methadone, buprenorphine and HIV medications are known and may have important clinical consequences. Clinicians must be alert to these interactions and have a basic knowledge regarding their management.

Hepatitis C virus (HCV) is the most common chronic blood-borne infection in the United States, with the majority of patients becoming chronically infected and a subset (20%) progressing to cirrhosis and hepatocellular carcinoma. Individual variations in immune responses may help define successful resistance to infection with HCV. We have compared the immune response in primary macrophages from patients who have spontaneously cleared HCV (viral load negative [VL-], n = 37) to that of primary macrophages from HCV genotype 1 chronically infected (VL+) subjects (n = 32) and found that macrophages from VL- subjects have an elevated baseline expression of Toll-like receptor 3 (TLR3). Macrophages from HCV patients were stimulated ex vivo through the TLR3 pathway and assessed using gene expression arrays and pathway analysis. We found elevated TLR3 response genes and pathway activity from VL- subjects. Furthermore, macrophages from VL- subjects showed higher production of beta interferon (IFN-β) and related IFN response genes by quantitative PCR (Q-PCR) and increased phosphorylation of STAT-1 by immunoblotting. Analysis of polymorphisms in TLR3 revealed a significant association of intronic TLR3 polymorphism (rs13126816) with the clearance of HCV and the expression of TLR3. Of note, peripheral blood mononuclear cells (PBMCs) from the same donors showed opposite changes in gene expression, suggesting ongoing inflammatory responses in PBMCs from VL+ HCV patients. Our results suggest that an elevated innate immune response enhances HCV clearance mechanisms and may offer a potential therapeutic approach to increase viral clearance.

Background: Buprenorphine/naloxone (BUP) and methadone (MET) are efficacious treatments for opioid dependence, although concerns about a link between BUP and drug-induced hepatitis have been raised. This study compares the effects of BUP and MET on liver health in opioid-dependent participants., Methods: This was a randomized controlled trial of 1269 opioid-dependent participants seeking treatment at 8 federally licensed opioid treatment programs and followed for up to 32 weeks between May 2006 and August 2010; 731 participants met "evaluable" criteria defined as completing 24 weeks of medication and providing at least 4 blood samples for transaminase testing. Participants were randomly assigned to receive BUP or MET for 24 weeks. Shift table analysis determined how many evaluable participants moved between categories of low and elevated transaminase levels. Predictors of moving from low to high transaminase levels were identified., Results: Changes in transaminase levels did not differ by medication condition. Baseline infection with hepatitis C or B was the only significant predictor of moving from low to elevated transaminase levels; 9 BUP and 15 MET participants showed extreme liver test elevations and were more likely than those without extreme elevations to have seroconverted to both hepatitis B and C during the study, or to use illicit drugs during the first 8 weeks of treatment. MET participants were retained longer in treatment than BUP participants., Conclusions: This study demonstrated no evidence of liver damage during the initial 6 months of treatment in either condition. Physicians can prescribe either medication without major concern for liver injury., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)