Correlates of drug use cessation among participants in the Canadian HIV-HCV Co-infection Cohort.

BACKGROUND: Ongoing drug use remains a barrier to HIV and HCV treatment. We examined the occurrence and correlates of drug use cessation among HIV-HCV co-infected drug users participating in HIV care. METHODS: Participants from the Canadian Co-infection Cohort reporting drug use (injecting drugs and/or smoking crack) with at least two follow-up visits were included (n=521 (43%), 1832 visits). Socio-demographics, behavioural, and health information were collected at each six-month visit. Associations with cessation (no drug use since last visit) were examined using non-linear mixed effects logistic regression models with random intercepts. RESULTS: During follow-up, 361 (69%) participants ceased using drugs. Having a fixed address (aOR [adjusted odds ratio] 1.73, CI [95% confidence interval] 1.02-2.96) and smoking crack without injecting drugs (aOR 3.10, CI 2.05-4.71) were positively associated. Living alone (aOR 0.47, CI 0.35-0.63), current tobacco use (aOR 0.41, CI 0.26-0.64), hazardous alcohol drinking (aOR 0.67, CI 0.49-0.91), snorting drugs (aOR 0.52, CI 0.37-0.74), having a greater exposure to addiction programmes (aOR 0.88, CI 0.81-0.94), having been recruited in Quebec or Nova Scotia (aOR 0.41, CI 0.25-0.66), and British Columbia or Alberta (aOR 0.51, CI 0.32-0.82) were negatively associated. Various socio-demographic (age, education) and health-related (HIV duration, care adherence) factors were not associated. CONCLUSION: Drug use cessation among HIV-HCV co-infected persons is relatively common in this cohort. Stable housing and supportive living situations seem to be important facilitators for drug use cessation in this population. Greater efforts should be made to retain patients in addiction treatment programmes.

Accuracy of physician reporting in routine public health surveillance for hepatitis C virus infection.

OBJECTIVE: From January 2007 to December 2008, the Montréal Public Health Department sent postal questionnaires to physicians and conducted patient interviews for all those newly diagnosed with hepatitis C virus (HCV) infection. We evaluated physician responses to risk factor questions for non-acute HCV cases. METHODS: We compared physician and patient responses with each of nine risk factor questions, determined the sensitivity and specificity of physician responses compared with patient responses, and evaluated agreement using Gwet's agreement coefficient (AC1). We ranked risk factors and compared the distributions by principal exposure category according to physician reporting vs. patient interview using the Chi-square test. RESULTS: The completeness of physicians' responses (yes, no, or unknown) varied by risk factor question from 90.8% to 96.7%. For risk factors present among more than 5% of cases, sensitivity of physician responses ranged from 26.9% to 87.7% and specificity ranged from 93.0% to 98.6%. The AC1 coefficients for agreement between physician and patient responses to lifetime risk factors considered most important in HCV acquisition were 0.80 for injection drug use, 0.95 for blood transfusion before 1990, and 0.86 for birth in a country with high HCV prevalence. Risk distributions by principal exposure category according to physician reporting vs. patient interview were not statistically different (χ(2)[4] = 2.17, p=0.704). CONCLUSION: Postal questionnaires completed by physicians appear valid for determining the principal exposure category among non-acute HCV cases. Physician reporting can be a useful and low-cost component of routine HCV surveillance.

Predictors of methadone program non-retention for opioid analgesic dependent patients.

This study evaluates loss to follow-up in a methadone maintenance treatment (MMT) program for patients dependent on opioid analgesics in a community in eastern Canada. Data were collected using the Addiction Severity Index Lite. The probability of loss to follow-up was evaluated using a time-to-event analysis. Involuntary and voluntary program discharges were treated separately as the outcomes of interest. Multivariate Cox proportional hazards models were used to explore the role of various patient-related attributes. The probabilities of involuntary and voluntary discharges at 1 year were 20% and 14%, respectively. In this exploratory analysis, determinants of loss to follow-up were characteristics related to drug use history (e.g., use of sedatives) and its consequences (e.g., number of lifetime arrests), and differed for each outcome. Some determinants of involuntary discharge were modified by sex. Understanding predictors of specific loss to follow-up outcomes may help MMT programs improve patient retention.

Human immunodeficiency virus type 1-anchored CD40 ligand induces secretion of the chemokine interleukin-8 by human primary macrophages.

CD40 ligand (CD40L) is mainly expressed in activated CD4(+)T cells and interacts with CD40 on antigen-presenting cells to regulate both humoral and cellular immune responses. We previously reported that CD40L is acquired by emerging HIV-1 particles. Here we demonstrate that both wild-type and a non-functional mutated form of CD40L are incorporated within HIV-1. Importantly, we show that wild-type CD40L remains functional since CD40L-bearing virions mediate NF-kappaB activation in a CD40-expressing reporter cell line and induce secretion of the chemokine IL-8 by monocyte-derived macrophages. These results suggest a possible means exploited by HIV-1 to attract susceptible target cells to the site of infection, a process that might promote viral dissemination.

LPS reduces HIV-1 replication in primary human macrophages partly through an endogenous production of type I interferons.

It has been proposed that the systemic immune activation state seen in HIV-1-infected patients is caused by circulating microbial products such as lipopolysaccharide (LPS). Given that macrophages play a key role in HIV-1 pathogenesis, we investigated the LPS-mediated effect on HIV-1 replication in cells of the myeloid lineage. We demonstrate that LPS promotes virus gene expression in a monocytic cell line while it diminishes virus production in primary human monocyte-derived macrophages (MDM). The incapacity of LPS to drive HIV-1 production in MDM was not due to its inability to activate the ubiquitous transcription factor NF-kappaB even in virus-infected cells. Neutralization of type I interferons (IFN) with B18R, a soluble vaccinia virus-coded type I IFN receptor, significantly but not totally diminished the antiviral activity of LPS. Therefore, inhibition of HIV-1 replication in MDM treated with microbial-derived LPS resulted from the induction of type I interferons and a yet to be defined soluble factor.