Dose adjustment of the non-nucleoside reverse transcriptase inhibitors during concurrent rifampicin-containing tuberculosis therapy: one size does not fit all

Importance of the field: HIV/tuberculosis (TB) co-infection is common and associated with high mortality. Simultaneous highly active antiretroviral therapy during TB treatment is associated with substantial survival benefit but drug–drug interactions complicate NNRTI dosing. Areas covered in this review: We reviewed the impact of rifampicin-containing TB therapy on the NNRTIs pharmacokinetics and clinical outcome. PubMed database was searched from 1966 to July 2009 using the terms efavirenz, rifampicin, nevirapine, pharmacokinetics, pharmacogenetics, HIV, TB, CYP2B6, CYP3A4 and metabolism. References from identified articles and abstracts from meetings were also reviewed. What the reader will gain: A comprehensive review of the literature on this subject including pharmacokinetic and clinical studies. Most studies were small, observational or underpowered to detect the true effect of rifampicin on NNRTI-based therapy. None of the studies were controlled for genetic factors and there were limited data on children. Take home message: There were insufficient data to make definitive recommendations about dose adjustment of the NNRTIs during rifampin-containing therapy. Current data suggest that the standard dose of efavirenz or nevirapine is adequate in most HIV/TB co-infected adults. However, more research is needed in pediatric populations as well as to define role of drug–gene interactions

Human trafficking and criminal proceedings in Portugal: discourses of professionals in the justice system

Author's personal copySince the adoption of the UN Trafficking Protocol in 2000, the predominant approach to combat human trafficking has been based on the criminalization of traffickers in conjunction with a concern for victims' protection. However, few empirical studies considered the effectiveness of those measures, which makes it difficult to understand why criminal cases of human trafficking generally result in few convictions. In Portugal, recent legislative changes have made the legal framework on human trafficking more comprehensive, inclusive and convergent with European directives. The effects of the implementation of those legislative changes on investigation and prosecution are still overlooked. The present study analyses the discourses of justice system professionals that concern the investigation and prosecution of human trafficking. It examines and identifies the factors that, in their perspective, block the recognition of the typifying elements of the crime of human trafficking and create obstacles to the prosecution and conviction of those crimes. Our findings suggest that legislative advances recognized by the participants need to be accompanied by other changes, some of a more systemic nature and others that are more specific. An efficient criminal procedure should include better legal phrasing of the means of evidence of human trafficking that is supported by objective instruments for this to be considered valid; the centralization of proof that the testimony of the victim has to overcome; specialized professional training of an ongoing nature; an efficient cooperation between the various law enforcement agencies at the national and international levels, with public prosecution services and magistrates; a greater clarification of the condition of the special vulnerability of victims and an informed perspective regarding the global nature of the phenomenon of human trafficking, one that is also sensitive towards the victim (e.g., in relation to the victims' vulnerability, illegal status, and their difficulties in teThis study was conducted at Psychology Research Centre, University of Minho, and supported by the Commission for Citizenship and Gender Equality (CIG), Presidency of the Council of Ministers. The authors also thank Eunice Seixas for technical support.info:eu-repo/semantics/publishedVersio

Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes

Background Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure. Methods We undertook collaborative joint analysis of 13 HIV cohorts from Europe, North America, and Australia, involving patients who had had three-class virological failure (viral load >1000 copies per mL for >4 months). Regression analyses were used to quantify the associations between CD4-cell-count slope, HIV-1 RNA concentration, treatment information, and demographic characteristics. Predictors of death were analysed by Cox's proportional-hazards models. Findings 2488 patients were included. 2118 (85%) had started antiretroviral therapy with single or dual therapy. During 5015 person-years of follow-up, 276 patients died (mortality rate 5.5 per 100 person-years; 3-year mortality risk 15.3% (95% Cl 13.5-17.3). Risk of death was strongly influenced by the latest CD4-cell count with a relative hazard of 15.8 (95% CI 9.28-27.0) for counts below 50 cells per muL versus above 200 cells per muL. The latest viral load did not independently predict death. For any given viral load, patients on treatment had more favourable CD4-cell-count slopes than those off treatment. For patients on treatment and with stable viral load, CD4-cell counts tended to be increasing at times when the current viral load was below 10 000 copies per mL or 1.5 log(10) copies per mL below off-treatment values. Interpretation In patients for whom viral-load suppression to below the level of detection is not possible, achievement and maintenance of a CD4-cell count above 200 per muL becomes the primary aim. Treatment regimens that maintain the viral load below 10 000 copies per mL or at least provide 1.5 log(10) copies per mL suppression below the off-treatment value do not seem to be associated with appreciable CD4-cell-count decline