Prevalence and predictive factors of stigmatizing attitudes towards people living with HIV in the remote villages on the Maroni River in French Guiana

The Maroni basin, an isolated region which lies between Suriname and French Guiana, has been affected by the HIV epidemic 10 years after coastal French Guiana. However, the rise in HIV prevalence was sharp with a prevalence exceeding 1% within 10 years. Stigma and discrimination towards people living with HIV (PLWHIV) or “suspected to have HIV” is rampant as reported by health professionals or non-governmental organisations. The objective of this article is to present the first quantitative data from the general population of this region on stigma towards people living with HIV. Data were collected in 2012 by a structured questionnaire among a random sample of 896 individuals residing in remote villages on the Maroni River. Proportion comparisons between the Maroni sample and the sample from the general population on the coastline in 2011 were conducted. Simple and multivariate logistic regression models were used to predict stigmatising attitudes. For all situations involving PLWHIV, the proportion of negative attitudes was significantly higher on the Maroni than in coastal French Guiana (p < 0.001). Findings indicate that the different levels of knowledge, erroneous beliefs and poor situation (not having electricity in one's home; not having French health insurance) were associated with stigmatising attitudes. The present data could help both sides coordinate interventions both at the individual level by improving knowledge and at the community level to change norms in order to reduce stigma and discrimination aiming for increased impact.     

Exposure of Staphylococcus aureus to Subinhibitory Concentrations of β-Lactam Antibiotics Induces Heterogeneous Vancomycin-Intermediate Staphylococcus aureus

Glycopeptides are known to select for heterogeneous vancomycin-intermediate Staphylococcus aureus (h-VISA) from susceptible strains. In certain clinical situations, h-VISA strains have been isolated from patients without previous exposure to glycopeptides, such as cystic fibrosis patients, who frequently receive repeated treatments with beta-lactam antibiotics. Our objective was to determine whether prolonged exposure to beta-lactam antibiotics can induce h-VISA. We exposed 3 clinical vancomycin-susceptible methicillin-resistant Staphylococcus aureus (MRSA) strains to ceftazidime, ceftriaxone, imipenem, and vancomycin (as a control) at subinhibitory concentrations for 18 days in vitro. Population analyses showed progressive increases in vancomycin resistance; seven of the 12 derived strains obtained after induction were classified as h-VISA according to the following criteria: area under the curve (AUC) on day 18/AUC of Mu3 of ≥90% and/or growth on brain heart infusion (BHI) agar with 4 mg/liter vancomycin. The derived isolates had thickened cell walls proportional to the level of glycopeptide resistance. Genes known to be associated with glycopeptide resistance (vraSR, yvqF, SA1703, graRS, walKR, and rpoB) were PCR sequenced; no de novo mutations were observed upon beta-lactam exposure. To determine whether trfA, a gene encoding a glycopeptide resistance factor, was essential in the selection of h-VISA upon beta-lactam pressure, a trfA-knockout strain was generated by allelic replacement. Indeed, beta-lactam exposure of this mutated strain showed no capacity to induce vancomycin resistance. In conclusion, these results showed that beta-lactam antibiotics at subinhibitory concentrations can induce intermediate vancomycin resistance in vitro. This induction required an intact trfA locus. Our results suggest that prior use of beta-lactam antibiotics can compromise vancomycin efficacy in the treatment of MRSA infections.     

Immunoregulation of Dendritic Cell Subsets by Inhibitory Receptors in Urothelial Cancer

Blockade of inhibitory receptors (IRs) overexpressed by T cells can activate antitumor immune responses, resulting in the most promising therapeutic approaches, particularly in bladder cancer, currently able to extend patient survival. Thanks to their ability to cross-present antigens to T cells, dendritic cells (DCs) are an immune cell population that plays a central role in the generation of effective antitumor T-cell responses. While IR function and expression have been investigated in T cells, very few data are available for DCs. Therefore, we analyzed whether DCs express IRs that can decrease their functions. To this end, we investigated several IRs (PD-1, CTLA-4, BTLA, TIM-3, and CD160) in circulating CD1c⁺ DCs, CD141⁺ DCs, and plasmacytoid DCs from healthy donors and patients with urothelial cancer (UCa). Different DC subsets expressed BTLA and TIM-3 but not other IRs. More importantly, BTLA and TIM-3 were significantly upregulated in DCs from blood of UCa patients. Locally, bladder tumor–infiltrating DCs also overexpressed BTLA and TIM-3 compared to DCs from paired nontumoral tissue. Finally, in vitro functional experiments showed that ligand-mediated engagement of BTLA and TIM-3 receptors significantly reduced the secretion of effector cytokines by DC subpopulations. Our findings demonstrate that UCa induces local and systemic overexpression of BTLA and TIM-3 by DCs that may result in their functional inhibition, highlighting these receptors as potential targets for UCa treatment.

Willingness to receive intravenous buprenorphine treatment in opioid-dependent people refractory to oral opioid maintenance treatment: results from a community-based survey in France

Background

Injectable opioids are an interesting option for people who inject drugs (PWID) that do not respond to oral Opioid Maintenance Treatment (OMT). To date, intravenous (IV) buprenorphine - a safer drug than full-opioid agonists in terms of overdose risk - has never been tested in a clinical trial on opioid dependence. We designed a survey to better understand the profile of PWID eligible for IV buprenorphine, and their willingness to receive it.

Methods

This cross-sectional community-based national survey was conducted through face-to-face interviews (in low-threshold and addiction care services) and online questionnaires (on https://psychoactif.org and other websites). Among the 557 participants, we selected those who were eligible for IV buprenorphine treatment (history of oral OMT, regular opioid injection) (n = 371). We used regression models to study factors associated with willingness to receive IV buprenorphine treatment among those with data on willingness (n = 353). In those who were willing (n = 294), we subsequently studied their willingness to receive daily supervised IV buprenorphine treatment.

Results

Among the selected 353 participants, 59% mainly injected buprenorphine, 15% heroin, 16% morphine sulfate and 10% other opioids. Eighty-three percent of the sample reported willingness to receive IV buprenorphine treatment. Factors associated with willingness were: more than 5 injection-related complications, regular buprenorphine injection, no lifetime overdose, and completion of the questionnaire online. Factors associated with unwillingness to receive daily supervised treatment were younger age (OR[IC95%]=1.04[1.01; 1.07]) and stable housing (OR[IC95%]=0.61[0.37;1.01]) while regular heroin injectors were more willing to receive daily supervision (OR[IC95%]=2.94 [1.42; 6.10]).

Conclusions

PWID were very willing to receive intravenous buprenorphine as a treatment, especially those with multiple injection-related complications. In addition, our findings show that IV buprenorphine may be less acceptable to PWID who inject morphine sulfate. Young PWID and those with stable housing were unwilling to receive IV buprenorphine if daily supervision were required. This preliminary study provides useful information for the development of a clinical trial on IV buprenorphine treatment.

     

Buprenorphine sniffing as a response to inadequate care in substituted patients: results from the Subazur survey in south-eastern France

Background

Despite the safety profile of buprenorphine, which makes this treatment highly acceptable for many countries, the risk of its diversion raises several public health and drug policy concerns. Although buprenorphine injection has been investigated quite extensively, diversion by sniffing has been overlooked. The Subazur survey gave us the opportunity to identify factors associated with buprenorphine sniffing in patients receiving buprenorphine in primary care.

Methods

We studied a population of 111 stabilized patients receiving office-based buprenorphine in south-eastern France. The design of the study consisted of two longitudinal assessments by phone interviews (at enrolment and 6 months later) detailing patients' socio-demographic characteristics, addictive behaviors, treatment experience and general health status. We used a logistic regression based on generalized estimating equations (GEE) to identify factors associated with buprenorphine sniffing at any interview.

Results

Among the 111 interviewed subjects, 33 (30%) patients reported sniffing buprenorphine after having initiated treatment. After multivariate analysis, 4 variables remained significantly associated with buprenorphine sniffing: not living in a stable relationship, having had only one or no parents during childhood, a history of drug sniffing and dissatisfaction with buprenorphine treatment.

Conclusions

Our findings underline the need to address these patients to appropriate social and mental services as well as diversifying therapeutic options, in order to provide them with adequate care and minimize diversion. The issues highlighted in the study reflect the need for recommendations for physicians prescribing OST in primary care to consider buprenorphine diversion during treatment more as non-adherence behavior than an abuse.