Project description:BackgroundPeople living with HIV who use drugs (PLHWUD) face enormous challenges to access antiretroviral therapy (ART), addiction treatment, and other healthcare services. This study evaluated the effect of a community capacity-building approach on PLHWUD's access to healthcare services.MethodsA cluster randomized controlled trial was conducted in four provinces of Vietnam. Trained commune health workers in the intervention condition were encouraged to provide services to PLHWUD in the community and engage them in HIV/addiction treatment and care using learned knowledge and skills. A total of 241 PLHWUD participated in surveys at the baseline and every three months for one year. The primary outcome was PLHWUD's reported barriers to seeking healthcare. A linear mixed-effects regression model with a difference in difference approach was used to estimate the intervention effect on the primary outcome.ResultsAdjusted analyses indicated that significant intervention effects were observed at the Sixth and ninth month follow-ups for those on ART at the baseline and increased motivation to engage in treatment at the 3-month follow-up (60.2% vs 34.4% for the intervention and control groups, respectively).ConclusionsThe community capacity-building intervention had shown promising yet limited outcomes among a subset of PLHWUD in the community, that is, PLHWUD who had already initiated ART.
Project description:IntroductionIn Vietnam, people who inject drugs (PWID), who are the major population infected by hepatitis C virus (HCV), remain largely undiagnosed and unlinked to HCV prevention and care despite recommended universal hepatitis C treatment. The data on the outcomes of HCV treatment among PWID also remain limited in resource-limited settings. The DRug use & Infections in ViEtnam-hepatitis C (DRIVE-C) study examines the effectiveness of a model of hepatitis C screening and integrated care targeting PWID that largely uses community-based organisations (CBO) in Hai Phong, Vietnam. In a wider perspective, this model may have the potential to eliminate HCV among PWID in this city.Methods and analysisThe model of care comprises large community-based mass screening, simplified treatment with direct-acting antivirals (DAAs) and major involvement of CBO for PWID reaching out, linkage to care, treatment adherence and prevention of reinfection. The effectiveness of DAA care strategy among PWID, the potential obstacles to widespread implementation and its impact at population level will be assessed. A cost-effectiveness analysis is planned to further inform policy-makers. The enrolment target is 1050 PWID, recruited from the DRIVE study in Hai Phong. After initiation of pan-genotypic treatment consisting of sofosbuvir and daclatasvir administrated for 12 weeks, with ribavirin added in cases of cirrhosis, participants are followed-up for 48 weeks. The primary outcome is the proportion of patients with sustained virological response at week 48, that will be compared with a theoretical expected rate of 70%.Ethics and disseminationThe study was approved by Haiphong University of Medicine and Pharmacy's Ethics Review Board and the Vietnamese Ministry of Health. The sponsor and the investigators are committed to conducting this study in accordance with ethics principles contained in the World Medical Association's Declaration of Helsinki (Ethical Principles for Medical Research Involving Human Subjects). Informed consent is obtained before study enrolment. The data are anonymised and stored in a secure database. The study is ongoing. Results will be presented at international conferences and submitted to international peer-review journals.Trial registration numberNCT03537196.
Project description:BackgroundPeople who use drugs in Scotland are currently experiencing disproportionately high rates of drug-related deaths. Drug consumption rooms (DCRs) are harm reduction services that offer a safe, hygienic environment where pre-obtained drugs can be consumed under supervision. The aim of this research was to explore family member perspectives on DCR implementation in Scotland in order to inform national policy.MethodsScotland-based family members of people who were currently or formerly using drugs were invited to take part in semi-structured interviews to share views on DCRs. An inclusive approach to 'family' was taken, and family members were recruited via local and national networks. A convenience sample of 13 family members were recruited and interviews conducted, audio-recorded, transcribed, and analysed thematically using the Structured Framework Technique.ResultsFamily members demonstrated varying levels of understanding regarding the existence, role, and function of DCRs. While some expressed concern that DCRs would not prevent continued drug use, all participants were in favour of DCR implementation due to a belief that DCRs could reduce harm, including saving lives, and facilitate future recovery from drug use. Participants highlighted challenges faced by people who use drugs in accessing treatment/services that could meet their needs. They identified that accessible and welcoming DCRs led by trusting and non-judgemental staff could help to meet unmet needs, including signposting to other services. Family members viewed DCRs as safe environments and highlighted how the existence of DCRs could reduce the constant worry that they had of risk of harm to their loved ones. Finally, family members emphasised the challenge of stigma associated with drug use. They believed that introduction of DCRs would help to reduce stigma and provide a signal that people who use drugs deserve safety and care.ConclusionsReporting the experience and views of family members makes a novel and valuable contribution to ongoing public debates surrounding DCRs. Their views can be used to inform the implementation of DCRs in Scotland but also relate well to the development of wider responses to drug-related harm and reduction of stigma experienced by people who use drugs in Scotland and beyond.
Project description:Background and objectiveDrug use type and frequency may affect Anti-Retroviral Therapy (ART) uptake for HIV-infected people who inject drugs (PWID). This paper assesses the association between self-reported baseline drug use and ART among HIV-infected PWID in Indonesia, Ukraine and Vietnam.MethodsData on self-reported baseline drug use and ART among HIV-infected PWID at the 26- and 52-week follow-ups were extracted from the HIV Prevention Trials Network (HPTN) 074, a randomized, controlled vanguard study to facilitate HIV treatment for PWID in Indonesia, Ukraine, and Vietnam. Multivariable logistic regression models were fit by study site and the whole HPTN 074 sample, using a 0.5 type I error rate.ResultsThe response rate were 83.3% and 77.0% at 26th and 52th weeks. At 26-week, baseline use of over one non-opiate/non-stimulant drug was associated with lower odds of ART use among Indonesian participants (OR = 0.21, 95%CI: 0.05-0.82); and baseline injecting drugs for over 20 days in the previous month was associated with lower odds of ART use among all HPTN 074 sample (OR = 0.59, 95% CI: 0.36-0.97).ConclusionThe association of a specific drug use pattern with later ART uptake implies the importance of medication-assisted treatment to enhance ART uptake and adherence among participants.
Project description:The ROS1 tyrosine kinase is activated in lung cancer as a consequence of chromosomal rearrangement. Although high response rates and disease control have been observed in lung cancer patients bearing rearranged ROS1 tumors (ROS1+) treated with the kinase inhibitor crizotinib, many of these patients eventually relapse.To identify mechanisms of resistance to ROS1 inhibitors we generated resistant cells from HCC78 lung cancer cells bearing the SLC34A2-ROS1 rearrangement. We found that activation of the RAS pathway in the HCC78 cell model, due to either KRAS/NRAS mutations or to KRAS amplification, rendered the cells resistant to ROS1 inhibition. These cells were cross-resistant to different ROS1 inhibitors, but sensitive to inhibitors of the RAS signaling pathway. Interestingly, we identified focal KRAS amplification in a biopsy of a tumor from a patient that had become resistant to crizotinib treatment.Altogether our data suggest that the activation of members of the RAS family can confer resistance to ROS1 inhibitors. This has important clinical implications as: (i) RAS genetic alterations in ROS1+ primary tumors are likely negative predictors of efficacy for targeted drugs and (ii) this kind of resistance is unlikely to be overcome by the use of more specific or more potent ROS1 targeting drugs.
Project description:ObjectiveHIV has a profound impact on infected individuals and their families. This study evaluated the efficacy of an intervention aimed at improving the mental health of people living with HIV (PLH) and their family members.MethodA randomized controlled trial of 475 PLH and 522 family members was conducted in Anhui, China. The intervention comprised activities at individual, family, and community levels. The study outcomes, which included depressive symptoms and coping with illness for the PLH and depressive symptoms and caregiver burden for the family members, were assessed at baseline and at 6-, 12-, 18-, and 24-month follow-up. We used a mixed-effects regression model with village- and participant-level random effects to assess the intervention effect on the improvement of outcome measures.ResultsRelative to the control condition, the PLH and family members of the intervention group reported a significant reduction in depressive symptoms. The largest difference in depressive symptoms was observed at 6 months for the PLH and at 12 months for family members. Decreases in perceived caregiver burden over time were observed for family members in both conditions; however, the group difference did not reach statistical significance. Significant intervention effect on the coping with illness was reported by the PLH.ConclusionsThe study highlights the importance of empowering families affected by HIV to confront the challenges together rather than individually. It may be optimal for future programs to include both PLH and their family members to maximize intervention effects through strengthening interactions and support within a family. (PsycINFO Database Record
Project description:IntroductionModelling suggests that early diagnosis and immediate antiretroviral therapy (ART) among key populations would have a substantial impact in reducing HIV transmission and mortality in Vietnam. An implementation research project of "test-and-treat" among people who inject drugs (PWID) was developed to inform effective roll-out of such interventions.Methods"Test-and-treat" was offered to PWID in two high burden provinces, Thai Nguyen and Thanh Hoa. The interventions comprised the offer of biannual HIV testing and immediate ART, irrespective of CD4 count. PWID were enrolled between April 2014 and July 2015 and followed up for 12 months, and retention, HIV viral load (VL) and risk behaviours were assessed. Retention in care of this prospective cohort was compared with the retention among men enrolled in care in the preceding period (April 2012 to March 2013) at the same clinics when ART was initiated at CD4 cell count ≤350 cells/mm3 .ResultsIn total, 287 HIV positive PWID started immediate ART. The majority (98%) were men; median age was 34; and median (interquartile range) CD4 count was 199 (50 to 402) cells/mm3 . After 12 months, 238 participants (83%) were retained on ART, and 205 achieved viral suppression (<1000 copies/mL) (92% among those in whom VL was measured, 71% overall). Baseline CD4 count ≤100 cells/mm3 and history of imprisonment were associated with lower retention and viral suppression, while engagement in methadone maintenance was associated with higher retention. Retention in care was higher in the "test-and-treat" cohort (83%) compared with men enrolled in care in the preceding period (78%), primarily because lost-to-follow-up during pre-ART care was eliminated. No decline in consistent condom use and clean needle use was observed.ConclusionsEarly ART initiation resulted in successful treatment outcomes among PWID, with no observed increase in self-reported risk behaviours, suggesting feasibility and potential effectiveness of "test-and-treat" approach. The results also call for differentiated care for PWID, including promoting early diagnosis and engagement in methadone maintenance therapy while enhancing care for those with advanced HIV disease and history of imprisonment.
Project description:Development of drugs targeting Bcl-2 relatives and caspases, for treating diseases including cancer and inflammatory disorders, often involves measuring interactions with recombinant target molecules, and/or monitoring cancer cell killing in vitro. Here, we present yeast-based methods for evaluating drug-mediated inhibition of Bcl-2 relatives or caspases. Active Bax and caspases kill Saccharomyces cerevisiae, and pro-survival Bcl-2 proteins can inhibit Bax-induced yeast death. By measuring the growth or adenosine triphosphate content of transformants co-expressing Bax with pro-survival Bcl-2 relatives, we found that the Bcl-2 antagonist drugs ABT-737 or ABT-263 abolished Bcl-2 or Bcl-xL function and reduced Bcl-w activity, but failed to inhibit Mcl-1, A1 or the poxvirus orthologs DPV022 and SPPV14. Using this technique, we also demonstrated that adenoviral E1B19K was resistant to these agents. The caspase inhibitor Q-VD-OPh suppressed yeast death induced by caspases 1 and 3. Yeast engineered to express human apoptotic regulators enable simple, automatable assessment of the activity and specificity of candidate drugs targeting Bcl-2 relatives or caspases.
Project description:This proposed study will use previous study results to guide the development and evaluation of interventions to improve CRC screening acceptance. The proposed study will evaluate the impact of three interventions to promote CRC screening among siblings in this increased-risk group, who are not currently compliant with CRC screening guidelines: 1) a generic print intervention; 2) a tailored print intervention, and; 3) a tailored print plus tailored telephone counseling intervention.
Project description:IntroductionFamily-centered substance use treatment (FCSUT) approaches for pregnant and postpartum people have the potential to prevent intergenerational transmission of adverse childhood experiences (ACEs). Guided by two theoretical frameworks drawn from implementation science (the Consolidated Framework for Implementation Research [CFIR] and the Reach, Effectiveness, Adoption, Implementation and Maintenance [RE-AIM] framework), this study used a mixed methods approach to answer: (1) What is the extent to which FCSUT approaches are offered for pregnant and postpartum people seeking substance use disorder (SUD) treatment? and (2) How are FCSUT approaches for pregnant and postpartum people implemented?MethodsThis study utilized a sequential mixed methods design that began with quantitative data collection followed by qualitative data collection. The quantitative component consisted of service provision surveys of facilities that provided FCSUT to pregnant and postpartum people (n = 118). The qualitative component consisted of semi-structured in-depth interviews with administrators and providers working at FCSUT facilities (n = 26) and pregnant and postpartum people who were currently receiving or had previously received services in the last two years from FCSUT facilities (n = 27). The qualitative findings were used to deepen understanding of the quantitative findings.ResultsFindings from the quantitative survey of treatment facilities' FCSUT provision revealed that while most facilities offered services related to substance use treatment, behavioral health, and parenting skills development or parent training, a smaller proportion offered services related to prenatal and postpartum health, sexual and reproductive health, and family-related services. Qualitative in-depth interviews with program administrators and providers and pregnant and postpartum people who had participated in FCSUT programs revealed major themes around expanding reach of facilities by maintaining participants' familial connections, resources for implementation and maintenance of FCSUT, the importance of program adaptation, and gaps in service delivery.ConclusionsResults indicated there is a wide range of FCSUT services offered at treatment facilities across the United States. Furthermore, while many pregnant and postpartum people expressed positive experiences with FCSUT, there are some areas that should be considered for future progress to be made.