Letter to the editor: Pre-exposure prophylaxis for HIV in Europe: The need for resistance surveillance

__To the editor:__ In a recent paper by Hauser et al. in this journal, a prevalence of 10.8% of transmitted drugresistant viruses was reported among newly diagnosed HIV cases in Germany in 2013 and 2014. The authors conclude that genotypic resistance testing remains important for treatment as well as HIV prevention. We comment on the use of pre-exposure prophylaxis (PrEP) in relation to drug resistance in HIV infections and the need for European surveillance of drug resistance

Partner notification for reduction of HIV-1 transmission and related costs among men who have sex with men: A mathematical modeling study

Background Earlier antiretroviral treatment initiation prevents new HIV infections. A key problem in HIV prevention and care is the high number of patients diagnosed late, as these undiagnosed patients can continue forward HIV transmission. We modeled the impact on the Dutch menwho-have-sex-with-men (MSM) HIV epidemic and cost-effectiveness of an existing partner notification process for earlier identification of HIV-infected individuals to reduce HIV transmission. Methods Reduction in new infections and cost-effectiveness ratios were obtained for the use of partner notification to identify 5% of all new diagnoses (Scenario 1) and 20% of all new diagnoses (Scenario 2), versus no partner notification. Costs and quality adjusted life years (QALYs) were assigned to each disease state and calculated over 5 year increments for a20 year period. Results Partner notification is predicted to avert 18-69 infections (interquartile range [IQR] 13-24; 51-93) over the course of 5 years countrywide to 221-830 (IQR 140-299; 530-1,127) over 20 years for Scenario 1 and 2 respectively. Partner notification was considered cost-effective in the short term, with increasing cost-effectiveness over time: from €41,476 -€41, 736 (IQR €40,529-€42,147; €40,791-€42,397) to €5,773 -€5,887 (€5,134-€7,196; €5,411-€6,552) per QAL

Self-reported adherence and pharmacy refill adherence are both predictive for an undetectable viral load among HIV-infected migrants receiving cART

HIV-infected migrants were shown to have poorer treatment outcomes than Dutch HIV-infected patients, often due to worse treatment adherence. Self-reported adherence would be an easy way to monitor adherence, but its validity relative to pharmacy refill adherence has not been extensively evaluated in migrants. All HIV-infected migrants older than 18 years and in care at the two Rotterdam HIV-treatment centers were eligible. Refill data with leftover medication (PRL) (residual pill count) were obtained from their pharmacies up to 15 months prior to inclusion. Self-reported adherence to combination Antiretroviral Therapy was assessed by four questions about adherence at inclusion. Additionally, risk factors for pharmacy refill non-adherence were examined. In total, 299 HIV-infected migrants were included. Viral load (VL) was detectable in 11% of the patients. Specificity of PRL was 53% for patients with an adherence of 100% and decreased with lower cut-off values. Sensitivity and negative predictive value (NPV) were 68% and 15% and increased with lower cut-off values. Positive predictive value (PPV) was around 93% for all cut-off values. Using the self-reported questions, 139 patients (47%) reported to be adherent. Sensitivity was 49% and specificity was 72%. PPV and NPV were 95% and 13%. No risk factors for pharmacy refill non-adherence were found in multivariable analyses. Both PRL and self-reported adherence, can predict undetectable VL in HIV-infected migrants. PPV and NPV are similar for both methods. This study shows that using four self-reported items is sufficient to predict adherence which is crucial for optimal clinical outcome in HIV-infected migrants

No serological evidence that harbour porpoises are additional hosts of influenza B viruses

Influenza A and B viruses circulate among humans causing epidemics almost annually. While various hosts for influenza A viruses exist, influenza B viruses have been detected only in humans and seals. However, recurrent infections of seals in Dutch coastal waters with influenza B viruses that are antigenetically distinct from influenza B viruses circulating among humans suggest that influenza B viruses have been introduced into this seal population by another, non-human, host. Harbour porpoises (Phocoena phocoena) are sympatric with seals in these waters and are also occasion

Characterization of the Mouse Neuroinvasiveness of Selected European Strains of West Nile Virus

West Nile virus (WNV) has caused outbreaks and sporadic infections in Central, Eastern and Mediterranean Europe for over 45 years. Most strains responsible for the European and Mediterranean basin outbreaks are classified as lineage 1. In recent years, WNV strains belonging to lineage 1 and 2 have been causing outbreaks of neuroinvasive disease in humans in countries such as Italy, Hungary and Greece, while mass mortality among birds was not reported. This study characterizes three European strains of WNV isolated in Italy (FIN and Ita09) and Hungary (578/10) in terms of in vitro replication kinetics on neuroblastoma cells, LD50 values in C57BL/6 mice, median day mortality, cumulative mortality, concentration of virus in the brain and spinal cord, and the response to infection in the brain. Overall, the results indicate that strains circulating in Europe belonging to both lineage 1 and 2 are highly virulent and that Ita09 and 578/10 are more neurovirulent compared to the FIN strain

Targeted HCV core antigen monitoring among HIV-positive men who have sex with men is cost-saving

Introduction: The World Health Organization declared the goal of hepatitis C virus (HCV) elimination by 2030. Microelimination, which is the reduction of incidence to zero in targeted populations, is less complex and costly and may be the first step to prove whether elimination is feasible. A suitable target group are HIV-positive men who have sex with men (MSM) because of their high-risk behaviour and high incidence rates. Moreover, HCV monitoring is integrated in HIV care. The current HCV monitoring approach is suboptimal and complex and may miss new HCV infections. Alternative monitoring strategies, based on alanine aminotransferase, HCV-PCR and HCV-core antigen (HCV-cAg), combined with immediate direct-acting antiviral (DAA) treatment, may be more effective in reducing new HCV infections. Methods: A deterministic mathematical transmission model was constructed representing the Dutch HCV epidemic among HIV-positive MSM to compare different HCV monitoring strategies from 2018 onwards. We evaluated the epidemiological impact of alternative and intensified monitoring in MSM with HCV. In addition, the cost-effectiveness was calculated over a lifetime horizon. Results: Current HCV monitoring and treatment is projected to result in an incidence of 1.1/1000 person-years, 0.24% prevalence, at a cost of €61.8 million (interquartile range 52.2–73.9). Compared with current monitoring, intensified monitoring will result in a maximum 27% reduction of incidence and 33% in prevalence at an increased cost. Conversely, compared with current monitoring, targeted HCV-cAg monitoring will result in a comparable incidence (1.1/1000 person-years) and prevalence (0.23%) but will be €1 million cheaper with increased quality-adjusted life year. Conclusion: Targeted monitoring reduces the HCV epidemic in a cost-saving manner; however, micro-elimination may not be obtained by 2030, highlighting the need for harm-reduction programmes

Risk factors for non-adherence to cART in immigrants with HIV living in the Netherlands: Results from the Rotterdam ADherence (ROAD) project

In the Netherlands, immigrant people living with HIV (PLWH) have poorer psychological and treatment outcomes than Dutch PLWH. This cross-sectional field study examined risk factors for non-adherence to combination Antiretroviral Therapy (cART) among immigrant PLWH. First and second generation immigrant PLWH attending outpatient clinics at two HIV-treatment centers in Rotterdam were selected for this study. Socio-demographic and clinical characteristics for all eligible participants were collected from an existing database. Trained interviewers subsequently completed questionnaires together with consenting participants (n = 352) to gather additional data on socio-demographic characteristics, psychosocial variables, and self-reported adherence to cART. Univariable and multivariable logistic regression analyses were conducted among 301 participants who had used cART 6 months prior to inclusion. Independent risk factors for self-reported non-adherence were (I) not having attended formal education or only primary school (OR = 3.25; 95%CI: 1.28-8.26, versus University), (II) experiencing low levels of social support (OR = 2.56; 95%CI: 1.37-4.82), and (III) reporting low treatment adherence self-efficacy (OR = 2.99; 95%CI: 1.59-5.64). Additionally, HIV-RNA >50 copies/ml and internalized HIV-related stigma were marginally associated (P<0.10) with non-adherence (OR = 2.53; 95%CI: 0.91-7.06 and OR = 1.82; 95%CI: 0.97-3.43). The findings that low educational attainment, lack of social support, and low treatment adherence self-efficacy are associated with non-adherence point to the need for tailored supportive interventions. Establishing contact with peer immigrant PLWH who serve as role models might be a successful intervention for this specific population

Dried blood spot cards: A reliable sampling method to detect human antibodies against rabies virus

Background Although preventable by vaccination for more than a century, rabies virus still causes numerous fatalities every year. To determine antibody levels in humans, blood collected with a finger prick and applied on dried blood spot (DBS) cards is an alternative for venipuncture. The use of DBS is specifically valuable in remote areas, as it is easy to perform, store and transport. Therefore, the technique is frequently used for epidemiological studies of tropical diseases. Up to present, determination of rabies virus antibody levels on human DBS has not been validated. Methodology/Principal findings We evaluated the use of human DBS for rabies serology and analyzed 99 pre- or post-vaccination serum and DBS samples with a fluorescent antibody virus neutralization test (FAVNt), which is the gold standard to detect protective antibody levels, and a Bio-Rad Platelia Rabies II ELISA. Sensitivity and specificity of DBS eluates tested with the FAVNt were 97% and 92%, respectively and 87% and 96% when tested with the Platelia-II ELISA. Antibody levels measured in serum with the FAVNt, correlated best with antibody levels measured in DBS with the FAVNt (R = 0.88). Conclusions/Significance This is the first study that applies DBS for reliable detection of human antibodies against rabies virus. Both the FAVNt and Platelia-II ELISA demonstrate an acceptable performance on DBS, providing opportunities for rabies serology in remote areas. This technique could drastically ease studies evaluating (novel) rabies vaccination strategies and monitoring persisting immunity in humans at risk, living in rabies endemic regions