Grafting luminescent metal-organic species into mesoporous MCM-41 silica from europium(III)tetramethylheptanedionate, Eu(thd)3

Mixed systems with Eu(III) β-diketonates as optically active guest species, and mesoporous silicas MCM-41 as a host matrix have been investigated. The grafting of europium(III) onto the inner walls of unmodified MCM-41 has been achieved starting from Eu(thd)3 (thd = 2,2,6,6- tetramethyl-3,5-heptanedionate), using two routes: wet impregnation (WI) at room temperature,and chemical vapour infiltration (CVI) at 185 °C. In received hybrids, denoted Eu(thd)x@MCM- 41, the same maximum yield [Eu]/[Si] = 8.2 at% on average has been achieved with either methods. The molar ratio x = [thd]/[Eu] is 0.6 on average for WI samples, and 1.5 for CVI samples. In the latter, higher contents in thd compensate lower contents in silanols with respect to the former. Rationalizing the possible bonds exchanged at the silica surface leads to a great diversity of possible co-ordination schemes according to the expression Σ[Si(OH)nx (O)xEu(thd)3-x] (where Σ means that surface species are considered). Chromophore neutral ligands phenanthroline (phen) or bipyridine (bipy) have been added to induce efficient Eu3+ luminescence under 270–280 nm excitation, via the antenna effect. For the most favourable case, (phen)yEu(thd)x@MCM-41, the emission intensity at 612 nm under excitation at 270 nm is 2/3 that for the genuine heteroleptic complex Eu(thd)3(phen). Moreover the hybrid material is stable up to 440 °C

Hepatitis C viral evolution in genotype 1 treatment-naïve and treatment-experienced patients receiving telaprevir-based therapy in clinical trials

Background: In patients with genotype 1 chronic hepatitis C infection, telaprevir (TVR) in combination with peginterferon and ribavirin (PR) significantly increased sustained virologic response (SVR) rates compared with PR alone. However, genotypic changes could be observed in TVR-treated patients who did not achieve an SVR. Methods: Population sequence analysis of the NS3•4A region was performed in patients who did not achieve SVR with TVR-based treatment. Results: Resistant variants were observed after treatment with a telaprevir-based regimen in 12% of treatment-naïve patients (ADVANCE; T12PR arm), 6% of prior relapsers, 24% of prior partial responders, and 51% of prior null responder patients (REALIZE, T12PR48 arms). NS3 protease variants V36M, R155K, and V36M+R155K emerged frequently in patients with genotype 1a and V36A, T54A, and A156S/T in patients with genotype 1b. Lower-level resistance to telaprevir was conferred by V36A/M, T54A/S, R155K/T, and A156S variants; and higher-level resistance to telaprevir was conferred by A156T and V36M+R155K variants. Virologic failure during telaprevir treatment was more common in patients with genotype 1a and in prior PR nonresponder patients and was associated with higher-level telaprevir-resistant variants. Relapse was usually associated with wild-type or lower-level resistant variants. After treatment, viral populations were wild-type with a median time of 10 months for genotype 1a and 3 weeks for genotype 1b patients. Conclusions: A consistent, subtype-dependent resistance profile was observed in patients who did not achieve an SVR with telaprevir-based treatment. The primary role of TVR is to inhibit wild-type virus and variants with lower-levels of resistance to telaprevir. The complementary role of PR is to clear any remaining telaprevir-resistant variants, especially higher-level telaprevir-resistant variants. Resistant variants are detectable in most patients who fail to achieve SVR, but their levels decline over time after treatment

HIV and STI Prevalence among Female Sex Workers in Côte d'Ivoire: Why Targeted Prevention Programs Should Be Continued and Strengthened

Objective: To assess condom use and prevalence of STIs and HIV among female sex workers (FSWs), as part of a comprehensive monitoring and evaluation plan of a nationwide sex worker prevention project in Côte d’Ivoire. Design and Methods: Cross sectional surveys were conducted among FSWs attending five project clinics in Abidjan and San Pedro (2007), and in Yamoussoukro and Gagnoa (2009). A standardized questionnaire was administered in a face-toface interview, which included questions on socio-demographic characteristics, sexual behaviour and condom use. After the interview, the participants were asked to provide samples for STI and HIV testing. Results: A total of 1110 FSWs participated in the surveys. There were large differences in socio-demographic and behavioural characteristics between FSW coming for the first time as compared to FSW coming on a routine visit. The prevalence of N. gonorrhoeae or C.trachomatis was 9.1%, 11.8 % among first vs. 6.9 % routine attendees (p = 0.004). The overall HIV prevalence was 26.6%, it was lower among first time attendees (17.5 % as compared to 33.9 % for routine attendees, p,0.001). The HIV prevalence among first attendees was also lower than the proportion of HIV positive tests from routine testing and counselling services in the same clinics. Conclusions: The results show a relatively high STI and HIV prevalence among FSWs in different cities in Côte d’Ivoire. In th

Transmission of HIV-1 infection in sub-Saharan Africa and effect of elimination of unsafe injections

During the past year, a group has argued that unsafe injections are a major if not the main mode of HIV-1 transmission\ud in sub-Saharan Africa. We review the main arguments used to question the epidemiological interpretations on the lead\ud role of unsafe sex in HIV-1 transmission, and conclude there is no compelling evidence that unsafe injections are a\ud predominant mode of HIV-1 transmission in sub-Saharan Africa. Conversely, though there is a clear need to eliminate\ud all unsafe injections, epidemiological evidence indicates that sexual transmission continues to be by far the major\ud mode of spread of HIV-1 in the region. Increased efforts are needed to reduce sexual transmission of HIV-1

Estimating HIV Incidence among Adults in Kenya and Uganda: A Systematic Comparison of Multiple Methods

CITATION: Kim, A. A. et al. 2011. Estimating HIV incidence among adults in Kenya and Uganda : a systematic comparison of multiple methods. PLos ONE, 6(3): e17535, doi:10.1371/journal.pone.0017535.The original publication is available at http://journals.plos.org/plosoneBackground: Several approaches have been used for measuring HIV incidence in large areas, yet each presents specific challenges in incidence estimation. Methodology/Principal Findings: We present a comparison of incidence estimates for Kenya and Uganda using multiple methods: 1) Epidemic Projections Package (EPP) and Spectrum models fitted to HIV prevalence from antenatal clinics (ANC) and national population-based surveys (NPS) in Kenya (2003, 2007) and Uganda (2004/2005); 2) a survey-derived model to infer age-specific incidence between two sequential NPS; 3) an assay-derived measurement in NPS using the BED IgG capture enzyme immunoassay, adjusted for misclassification using a locally derived false-recent rate (FRR) for the assay; (4) community cohorts in Uganda; (5) prevalence trends in young ANC attendees. EPP/Spectrum-derived and survey-derived modeled estimates were similar: 0.67 [uncertainty range: 0.60, 0.74] and 0.6 [confidence interval: (CI) 0.4, 0.9], respectively, for Uganda (2005) and 0.72 [uncertainty range: 0.70, 0.74] and 0.7 [CI 0.3, 1.1], respectively, for Kenya (2007). Using a local FRR, assay-derived incidence estimates were 0.3 [CI 0.0, 0.9] for Uganda (2004/2005) and 0.6 [CI 0, 1.3] for Kenya (2007). Incidence trends were similar for all methods for both Uganda and Kenya. Conclusions/Significance: Triangulation of methods is recommended to determine best-supported estimates of incidence to guide programs. Assay-derived incidence estimates are sensitive to the level of the assay's FRR, and uncertainty around high FRRs can significantly impact the validity of the estimate. Systematic evaluations of new and existing incidence assays are needed to the study the level, distribution, and determinants of the FRR to guide whether incidence assays can produce reliable estimates of national HIV incidence.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0017535Publisher's versio

Transmitted drug resistance, selection of resistance mutations and moderate antiretroviral efficacy in HIV-2: Analysis of the HIV-2 Belgium and Luxembourg database

BACKGROUND: Guidelines established for the treatment of HIV-1 infection and genotype interpretation do not apply for HIV-2. Data about antiretroviral (ARV) drug efficacy and resistance mutations is scarce. METHODS: Clinical data about HIV-2 infected patients in Belgium and Luxembourg were collected and the effect of ARV therapy on plasma viral load and CD4 counts were analysed. Viral RNA encoding for protease (PR) and reverse transcriptase (RT) from ARV-naive and treated patients were sequenced. RESULTS: Sixty-five HIV-2 infected patients were included in this cohort. Twenty patients were treated with 25 different ARV combinations in a total of 34 regimens and six months after the start of ARV therapy, only one third achieved viral load suppression. All of these successful regimens bar one contained protease inhibitors (PIs). Mean CD4 gains in the group of viral load suppressors and the group of patients treated with PI-containing regimens were respectively significantly higher than in the group of non-suppressors and the group of PI-sparing regimens. The most frequent mutations selected under therapy (compared to HIV-2 ROD) were V71I, L90M and I89V within PR. Within RT, they were M184V, Q151M, V111I and K65R. All of these mutations, except K65R and M184V, were also found in variable proportions in ARV-naive patients. CONCLUSION: Despite a high rate of ARV treatment failure, better virological and immunological results were achieved with PI-containing regimens. The analysis of polymorphic positions and HIV-2 specific mutations selected during therapy showed for the first time that transmission of drug resistant viruses has occurred in Belgium and Luxembourg. The high heterogeneity in ARV combinations reflects a lack of guidelines for the treatment of HIV-2 infection

Week 48 resistance analyses of the once-daily, single-tablet regimen darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in adults living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is being investigated in two Phase III trials, AMBER (NCT02431247; treatment-naive adults) and EMERALD (NCT02269917; treatment-experienced, virologically suppressed adults). Week 48 AMBER and EMERALD resistance analyses are presented. Postbaseline samples for genotyping/phenotyping were analyzed from protocol-defined virologic failures (PDVFs) with viral load (VL) >= 400 copies/mL at failure/later time points. Post hoc analyses were deep sequencing in AMBER, and HIV-1 proviral DNA from baseline samples (VL = 3 thymidine analog-associated mutations (24% not fully susceptible to tenofovir) detected at screening. All achieved VL <50 copies/mL at week 48 or prior discontinuation. D/C/F/TAF has a high genetic barrier to resistance; no darunavir, primary PI, or tenofovir RAMs were observed through 48 weeks in AMBER and EMERALD. Only one postbaseline M184I/V RAM was observed in HIV-1 of an AMBER participant. In EMERALD, baseline archived RAMs to darunavir, emtricitabine, and tenofovir in participants with prior VF did not preclude virologic response

Grafting luminescent metal-organic species into mesoporous MCM-41 silica from europium(III)tetramethylheptanedionate, Eu(thd)3

International audienceMixed systems with Eu(III) β-diketonates as optically active guest species, and mesoporous silicas MCM-41 as a host matrix have been investigated. The grafting of europium(III) onto the inner walls of unmodified MCM-41 has been achieved starting from Eu(thd)3 (thd = 2,2,6,6- tetramethyl-3,5-heptanedionate), using two routes: wet impregnation (WI) at room temperature,and chemical vapour infiltration (CVI) at 185 °C. In received hybrids, denoted Eu(thd)x@MCM- 41, the same maximum yield [Eu]/[Si] = 8.2 at% on average has been achieved with either methods. The molar ratio x = [thd]/[Eu] is 0.6 on average for WI samples, and 1.5 for CVI samples. In the latter, higher contents in thd compensate lower contents in silanols with respect to the former. Rationalizing the possible bonds exchanged at the silica surface leads to a great diversity of possible co-ordination schemes according to the expression Σ[Si(OH)nx (O)xEu(thd)3-x] (where Σ means that surface species are considered). Chromophore neutral ligands phenanthroline (phen) or bipyridine (bipy) have been added to induce efficient Eu3+ luminescence under 270–280 nm excitation, via the antenna effect. For the most favourable case, (phen)yEu(thd)x@MCM-41, the emission intensity at 612 nm under excitation at 270 nm is 2/3 that for the genuine heteroleptic complex Eu(thd)3(phen). Moreover the hybrid material is stable up to 440 °C

Grafting of luminescent metalorganic species (europium (III) β-diketonates) into mesoporous MCM-41 silica

International audienc