Impact of drug consumption rooms on non-fatal overdoses, abscesses and emergency department visits in people who inject drugs in France: results from the COSINUS cohort.

BACKGROUND: The effectiveness of drug consumption rooms (DCRs) for people who inject drugs (PWID) has been demonstrated for HIV and hepatitis C virus risk practices, and access to care for substance use disorders. However, data on other health-related complications are scarce. Using data from the French COSINUS cohort, we investigated the impact of DCR exposure on non-fatal overdoses, abscesses and emergency department (ED) visits, all in the previous 6 months. METHODS: COSINUS is a 12-month prospective cohort study of 665 PWID in France studying DCR effectiveness on health. We collected data from face-to-face interviews at enrolment, and at 6 and 12 months of follow-up. After adjusting for other correlates (P-value < 0.05), the impact of DCR exposure on each outcome was assessed using a two-step Heckman mixed-effects probit model, allowing us to adjust for potential non-randomization bias due to differences between DCR-exposed and DCR-unexposed participants, while taking into account the correlation between repeated measures. RESULTS: At enrolment, 21%, 6% and 38% of the 665 participants reported overdoses, abscesses and ED visits, respectively. Multivariable models found that DCR-exposed participants were less likely to report overdoses [adjusted coefficient (95% CI): -0.47 (-0.88; -0.07), P = 0.023], abscesses [-0.74 (-1.11; -0.37), P < 0.001] and ED visits [-0.74 (-1.27; -0.20), P = 0.007]. CONCLUSION: This is the first study to show the positive impact of DCR exposure on abscesses and ED visits, and confirms DCR effectiveness in reducing overdoses, when adjusting for potential non-randomization bias. Our findings strengthen the argument to expand DCR implementation to improve PWID injection environment and health.

Efficacy, safety and patient-reported outcomes of ledipasvir/sofosbuvir in NS3/4A protease inhibitor-experienced individuals with hepatitis C virus genotype 1 and HIV coinfection with and without cirrhosis (ANRS HC31 SOFTRIH study).

OBJECTIVES: Studies evaluating the efficacy and safety of the fixed-dose combination ledipasvir (LDV)/sofosbuvir (SOF) in patients coinfected with HIV-1 and hepatitis C virus (HCV) have mainly included treatment-naïve patients without cirrhosis. We aimed to evaluate the efficacy and safety of this combination in treatment-experienced patients with and without cirrhosis. METHODS: We conducted a multicentre, open-label, double-arm, nonrandomized study in patients coinfected with HIV-1 and HCV genotype 1 with and without cirrhosis, who had good viral suppression on their antiretroviral regimens. All patients were pretreated with a first-generation NS3/4A protease inhibitor (PI) plus pegylated interferon/ribavirin. Patients received a fixed-dose combination of LDV/SOF for 12 weeks, or for 24 weeks if cirrhosis was present. The primary endpoint was a sustained virological response (SVR) 12 weeks after the end of therapy. Secondary endpoints included safety, pharmacokinetics and patient-reported outcomes. RESULTS: Of the 68 patients enrolled, 39.7% had cirrhosis. Sixty-five patients [95.6%; 95% confidence interval (CI): 87.6-99.1%; P < 0.0001] achieved an SVR, with similar rates of SVR in those with and without cirrhosis. Tolerance was satisfactory, with mainly grade 1 or 2 adverse events. Among patient-reported outcomes, only fatigue significantly decreased at the end of treatment compared with baseline [odds ratio (OR): 0.36; 95% CI: 0.14-0.96; P = 0.04]. Mean tenofovir area under the plasma concentration-time curve (AUC) at week 4 was high, with mean ± SD AUC variation between baseline and week 4 higher in cirrhotic than in noncirrhotic patients (3261.57 ± 1920.47 ng/mL vs. 1576.15 ± 911.97 ng/mL, respectively; P = 0.03). Mild proteinuria (54.4%), hypophosphataemia (50.0%), blood bicarbonate decrease (29.4%) and hypokalaemia (13.2%) were reported. The serum creatinine level was not modified. CONCLUSIONS: LDV/SOF provided a high SVR rate in PI-experienced subjects coinfected with HCV genotype 1 and HIV-1, including patients with cirrhosis.

Factors Associated with HIV Status Disclosure in HIV-Infected Sub-Saharan Migrants Living in France and Successfully Treated with Antiretroviral Therapy: Results from the ANRS-VIHVO Study.

To estimate rates and identify correlates of HIV disclosure in migrants from sub-Saharan Africa (SSA) successfully treated, a sub-analysis was conducted in HIV-1 native SSA migrants, living in France with undetectable viral load on antiretroviral, included in the VIHVO adherence study. Logistic regression models assessed factors associated with HIV disclosure. Among 246 individuals (40 % male, median age 41), 79 % of those in a steady heterosexual partnership (n = 167) had disclosed their status to their partner, 55 % of the total 246 to a relative, and 33 % to (an)other person(s). Disclosure to one's steady partner was associated with a follow-up duration since HIV diagnosis of more than 5 years, a higher literacy level, a better social context and marital status. Women were more likely to disclose their HIV status to relatives. Interventions targeting this population should be provided to improve disclosure which in turn ensures better social support, testing of the partner and lower rates of undiagnosed HIV.

Psychiatric and substance use disorders in HIV/hepatitis C virus (HCV)-coinfected patients: does HCV clearance matter? [Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) HEPAVIH CO13 cohort].

OBJECTIVES: The objective of this nested study was to assess the prevalence of psychiatric disorders in a sample of HIV/hepatitis C virus (HCV)-coinfected patients according to their HCV status. METHODS: The nested cross-sectional study, untitled HEPAVIH-Psy survey, was performed in a subset of HIV/HCV-coinfected patients enrolled in the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) CO13 HEPAVIH cohort. Psychiatric disorders were screened for using the Mini International Neuropsychiatric Interview (MINI 5.0.0). RESULTS: Among the 286 patients enrolled in the study, 68 (24%) had never received HCV treatment, 87 (30%) were treatment nonresponders, 44 (15%) were currently being treated and 87 (30%) had a sustained virological response (SVR). Of the 286 patients enrolled, 121 patients (42%) screened positive for a psychiatric disorder other than suicidality and alcohol/drug abuse/dependence, 40 (14%) screened positive for alcohol abuse/dependence, 50 (18%) screened positive for drug abuse/dependence, 50 (17.5%) were receiving an antidepressant treatment and 69 (24%) were receiving an anxiolytic. Patients with an SVR did not significantly differ from the other groups in terms of psychiatric disorders. Patients receiving HCV treatment screened positive less often for an anxiety disorder. The highest rate of drug dependence/abuse was among HCV treatment-naïve patients. CONCLUSIONS: Psychiatric disorders were frequent in HIV/HCV-coinfected patients and their rates were comparable between groups, even for patients achieving an SVR. Our results emphasize the need for continuous assessment and care of coinfected patients, even after HCV clearance. Drug addiction remains an obstacle to access to HCV treatment. Despite the recent advent and continued development of directly acting antiviral agents (DAAs), it is still crucial to offer screening and comprehensive care for psychiatric and addictive disorders.

HCV seropositivity in inmates and in the general population: an averaging approach to establish priority prevention interventions.

OBJECTIVES: Despite the fact that a considerable portion of hepatitis C virus (HCV) positive individuals are viraemic, the risk of transmitting HCV to others is context dependent. Prison is a particularly risky environment as HCV prevention tools are often unavailable. Using data from a cross-sectional study conducted in centres for HCV testing in southeastern France, we aimed to compare the patterns of risk factors in HCV-positive inmates with those in the general population. SETTING: 26 centres for HIV/HCV testing in southeastern France (23 in the general population and 3 in prison). PRIMARY OUTCOME MEASURE: HCV seropositivity measured with ELISA test. METHODS: A propensity score method to ensure that the general and inmate populations could be compared and a multimodel averaging to estimate the degree (strong, weak, none) of the association of a number of specific factors with HCV seropositivity in each group. RESULTS: Among the 52,082 participants, HCV infection prevalence was 1.5% and 5.2% in the general (n=46,125) and inmate (n=5957) populations, respectively. In both populations, 'drug injection without snorting' and 'drug injection with snorting' were very strongly associated with HCV seropositivity. Among inmates, 'drug snorting alone' (OR (95% CI) 2.21 (1.39 to 3.52) was also a strong correlate while tattoos, piercings (OR (95% CI) 1.22 (0.92 to 1.61)) and the sharing of toiletry items (OR (95% CI) 1.44 (0.84 to 2.47)) were weak correlates. CONCLUSIONS: The pattern of risk factors associated with HCV seropositivity is different between the general and prison populations, injection and snorting practices being more prevalent in the latter. Access to prevention measures in prisons is not only a public health issue but also a human right for inmates who deserve equity of care and prevention.

Patterns of adherence to antiretroviral therapy and HIV drug resistance over time in the Stratall ANRS 12110/ESTHER trial in Cameroon.

OBJECTIVES: The emergence of HIV drug resistance is a crucial issue in Africa, where second-line antiretroviral therapy (ART) is limited, expensive and complex. We assessed the association between adherence patterns and resistance emergence over time, using an adherence measure that distinguishes low adherence from treatment interruptions, in rural Cameroon. METHODS: We performed a cohort study among patients receiving nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART in nine district hospitals, using data from the Stratall trial (2006-2010). Genotypic mutations associated with antiretroviral drug resistance were assessed when 6-monthly HIV viral loads were > 5000 HIV-1 RNA copies/mL. ART adherence data were collected using face-to-face questionnaires. Combined indicators of early (1-3 months) and late (6 months to t - 1; t is the time point when the resistance had been detected) adherence were constructed. Multivariate logistic regression and Cox models were used to assess the association between adherence patterns and early (at 6 months) and late (after 6 months) resistance emergence, respectively. RESULTS: Among 456 participants (71% women; median age 37 years), 45 developed HIV drug resistance (18 early and 27 late). Early low adherence (< 80%) and treatment interruptions (> 2 days) were associated with early resistance [adjusted odds ratio (95% confidence interval) 8.51 (1.30-55.61) and 5.25 (1.45-18.95), respectively]. Early treatment interruptions were also associated with late resistance [adjusted hazard ratio (95% confidence interval) 3.72 (1.27-10.92)]. CONCLUSIONS: The emergence of HIV drug resistance on first-line NNRTI-based regimens was associated with different patterns of adherence over time. Ensuring optimal early adherence through specific interventions, adequate management of drug stocks, and viral load monitoring is a clinical and public health priority in Africa.

Adjuvant endocrine therapy with tamoxifen in young women with breast cancer: determinants of interruptions vary over time.

BACKGROUND: In premenopausal women with hormone receptor-positive breast cancer (BC), 5 years of tamoxifen is recommended. Little is known about reasons for interruption in this population. The aim was to estimate the incidence of tamoxifen interruption and its correlates among younger women. PATIENTS AND METHODS: Using a prospective cohort Elippse 40 of women with BC aged ≤ 40 diagnosed between 2005 and 2008, we studied 196 women. Tamoxifen interruption was defined as two or more consecutive months without dispensed prescription of tamoxifen, based on pharmacy refill database. Two periods were studied: between tamoxifen initiation and 16 months after BC diagnosis, and between 16 and 28 months. RESULTS: Among women treated with tamoxifen, 42% interrupted within the first 2 years of treatment. During the first period, treatment interruptions were associated with a lack of understandable information about endocrine treatment and insufficient social support. During the second period, another set of factors were associated with interruption: treatment side-effects, no longer fearing cancer relapse, lack of social support, no opportunity to ask questions at the time of diagnosis, and fewer treatment modalities. CONCLUSIONS: Improving information and patient-provider relationship might prevent interruption. Particular attention should be paid to women with little social support.

Determinants of the underreporting of alcohol consumption by HIV/HCV co-infected patients during face-to-face medical interviews: the role of the physician.

OBJECTIVES: The objective of this study was to assess to what extent HIV/HCV co-infected patients underreport alcohol use to their physician with respect to self-reports from self-administered questionnaires (SAQ) and identify correlates of alcohol underreporting during face-to-face medical interviews (FMI). DESIGN: ANRS-CO13-HEPAVIH is a French multi-center cohort of HIV/HCV co-infected patients. METHODS: Data were collected at enrolment using both SAQ and FMI while clinical data were retrieved from medical records. Alcohol consumption was assessed through SAQ and compared with FMI patient reports. Correlates of underreporting alcohol consumption during FMI with respect to SAQ were identified using logistic regression analysis. RESULTS: Among 544 patients, 37% were classified as alcohol abusers according to AUDIT-C in the SAQ. During FMI, 14% underreported alcohol consumption. The following correlates were independently associated with underreporting alcohol consumption in FMI: not receiving HIV treatment, being followed up by a hepatologist for HCV infection and reporting a history of injecting drug use. CONCLUSIONS: These results highlight the difficulties in alcohol consumption assessment which HCV specialists may face when suggesting to their HIV/HCV co-infected patients that they cease drinking completely. Patient awareness about the real need to reduce their alcohol use before starting HCV therapy may also contribute to underreporting. Innovative strategies for alcohol risk-reduction, including the promotion of controlled consumption and access to multidisciplinary teams, should be implemented for HIV/HCV co-infected patients in order to reduce barriers to HCV treatment.

Role of treatment for depressive symptoms in relieving the impact of fatigue in HIV-HCV co-infected patients: ANRS Co13 Hepavih, France, 2006-2008.

Fatigue is a major component of quality of life (QOL) and is associated with depression in HIV-HCV co-infected individuals. We investigated whether treating depressive symptoms (DS) could mitigate the impact of fatigue on daily functioning in co-infected patients, even those at an advanced stage of disease. The analysis was conducted on enrollment data of 328 HIV-HCV co-infected patients recruited in the French nationwide ANRS CO 13 HEPAVIH cohort. Data collection was based on medical records and self-administered questionnaires which included items on socio-behavioural data, the fatigue impact scale (FIS) in three domains (cognitive, physical and social functioning), depressive symptoms (CES-D classification) and use of treatments for depressive symptoms (TDS). After multiple adjustment for gender and unemployment, CD4 cell count <200 per mm(3) was associated with a negative impact of fatigue on the physical functioning dimension (P = 0.002). A higher number of symptoms causing discomfort significantly predicted a higher impact of fatigue on all three dimensions (P < 0.001). This was also true for patients with DS receiving TDS when compared with those with no DS but receiving TDS. A significant decreasing linear trend (P < 0.001) of the impact of fatigue was found across the categories 'DS/TDS', 'DS/no TDS', 'no DS/TDS' and 'no DS/no TDS'. Despite limitations related to the cross-sectional nature of this study, our results suggest that routine screening and treatment for DS can reduce the impact of fatigue on the daily functioning of HIV-HCV co-infected patients and relieve the burden of their dual infection.

Immunosuppression and cancer: A comparison of risks in recipients of organ transplants and in HIV-positive individuals.

The comparison of cancers occurring excessively among HIV-infected and transplanted individuals may help to elucidate the relationship between immune surveillance, viral infections, and cancer. A longitudinal study was conducted on 2002 HIV-infected Italian subjects, 6072 HIV-infected French individuals, and 2878 Italian recipients of solid organ transplants. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were computed to quantify the risk for cancer, compared with the French and Italian general populations. The SIRs for all cancers were 9.8 (95% CI: 9.0-10.6) for HIV-infected individuals versus 2.2 (95% CI: 1.9-2.5) for transplant recipients. In both groups, most of the excess risk was attributable to virus-related cancers, such as Kaposi's sarcoma (KS; SIR = 451 in HIV-positive individuals, 125 in transplant recipients), non-Hodgkin's lymphoma (NHL; SIR = 62.1 and 11.1, respectively), and liver cancer (SIR = 9.4 and 4.1, respectively). Significantly increased SIRs for anal cancer and Hodgkin's lymphoma were found only among HIV-positive individuals. Among women younger than 40 years of age, a more than 10-fold increase in cervical cancer risk was found in both groups. Among HIV-infected individuals treatment with highly active antiretroviral therapies drastically reduced SIRs for KS and NHL only. These results show that HIV-infected individuals and transplant recipients share a similar pattern of cancer risk, largely due to virus-related cancers.

[Health related quality of life among HIV-HCV co-infected patients]. / La qualité de vie des patients co-infectés par le VIH et le VHC.

BACKGROUND: To assess factors associated with higher levels of health-related quality-of-life among HIV-HCV co-infected injecting drug users and more specifically, to explore the role of injecting drug status and drug maintenance treatment on health-related quality-of-life. METHODS: The two hundred and forty participants were patients enrolled in the MANIF cohort of HIV-HCV patients infected through injecting drug use who completed a self-administered questionnaire that included a health-related quality-of-life evaluation at the 42 month follow-up. A self-administered questionnaire collected information about socio-demographic characteristics, health-related quality-of-life (as measured by SF-12), injecting drug status and drug maintenance treatment, depressive symptoms, self-reported symptoms related to HIV treatment; clinical characteristics were obtained from medical records. RESULTS: Higher levels of both mental and physical health-related quality-of-life were found in patients with no depressive symptoms, abstinent from drugs and experiencing few drug related problems. Patients on drug maintenance treatment who stopped injecting drugs had better mental health-related quality-of-life than injectors but lower levels of mental health-related quality-of-life than abstinent patients. Mental health-related quality-of-life was also independently higher in patients receiving high social support. Physical health-related quality-of-life was independently higher for patients who stopped injection, whether on drug maintenance treatment or not, for patients on anti-retroviral treatment and for patients who remained in clinical stage A. CONCLUSIONS: Drug maintenance treatment seems to be associated with higher health-related quality-of-life among patients HIV-HCV co-infected by drug use, but it is still necessary to help patients cope with the mental impact of drug cessation. These results underline the need to provide regular psychological support and counselling for HIV-HCV co-infected injecting drug users during the medical follow-up for HIV-disease.

Oral contraception and unprotected sex with occasional partners of women HIV-infected through injection drug use.

Among HIV-infected women, unprotected sex with the main sexual partner is common practice. Conversely, studies about condom use with sexual partners of unknown HIV sero-status are sparsely reported. We aimed to assess the impact of oral contraception on unsafe sexual behaviours with occasional partners in women HIV-infected through injection drug use. The analysis focused on 90 women, enrolled in the French cohort MANIF 2000 and reported having engaged in sexual relationships with occasional partners during a 48-month period. Visits where women reported unprotected sex with occasional partners in the prior 6 months were compared to visits where they reported protected sex using a logistic model based on Generalised Estimating Equations. Unprotected sex with occasional partners was independently associated with oral contraception (OR[95%CI] = 3.2[1.4-7.2]), reporting only one occasional partner (OR[95%CI] = 3.1[1.6-6.2]) and antiretroviral treatment receipt. No significant association was found between unprotected sex and CD4 level or plasma viral load. With the growing population of people living with HIV as a chronic infection, the development and evaluation of HIV-prevention interventions tailored toward women remain a public health priority. Risk reduction counselling and interventions are needed to promote either the use of dual contraception or, alternatively, that of female condom.

Failure to maintain adherence to HAART in a cohort of French HIV-positive injecting drug users.

The study, carried out in the French MANIF 2000 cohort of HIV positive patients contaminated through injecting drug use, assessed the impact of patients' sociodemographic and psychological characteristics, behaviors toward drug abuse, and antiretroviral treatment characteristics on the maintenance of adherence to HAART (highly active antiretroviral therapies). A total of 96 patients (30 men and 66 women), who were initially adherent at their first visit after HAART prescription, were considered for analysis. Among these 96 patients, 22 (22.9%) experienced adherence failure defined as a self-reported, non-adherence behavior at any visit before the 18th month of treatment. Logistic regression showed that lack of a stable relationship, active drug injection, and depression were independently associated with adherence failure. Patients' counseling for facilitating maintenance of adherence to HAART over time should focus on prevention of drug use, provision of social support and consider the potential impact of difficulties with treatment on psychological well-being.