[Perception of problem-based learning among student nurses in Lebanon]. / Perception des étudiants infirmiers au Liban de l'apprentissage par problème.

Introduction : Problem-based learning (PBL) has been introduced in university nursing programs following the implementation of the competency-based approach (CBA). This innovation required a pedagogical reform, hence the interest in this method. PBL stimulates students to develop critical thinking, identified as the most important challenge for nursing education in the twenty-first century.Background : Several studies have been conducted to understand undergraduate nursing students' perceptions of the use of PBL in the learning process. The results have highlighted the positive and negative aspects of this method.Objective : The purpose of this article is to explore student nurses' perceptions of the evaluation of PBL in their learning process.Method : A descriptive qualitative study of twenty student nurses was carried out using semi-structured individual interviews.Results : The results of the study highlighted the positive and negative aspects of PBL, as perceived by the students. Positive aspects include the development of friendly relationships in subgroups, behavioral changes in learning, and the development of student autonomy. Negative aspects include a feeling of having insufficient knowledge, time management difficulties during learning, and the lack of cohesion in the group.Conclusion : Results from this study would help develop learning promotion strategies in order to help students become more active in their learning process.

Therapeutic Immune Recovery and Reduction of CXCR4-Tropic HIV-1.

BACKGROUND: In the absence of therapy, CXCR4 (X4)-tropic human immunodeficiency virus type 1 (HIV-1) increases over time, associated with accelerated disease progression. In contrast, the majority of patients receiving long-term combination antiretroviral therapy (cART) present with CCR5 (R5)-tropic HIV-1 variants. It is unclear whether cART itself mediates the reduction of X4-tropic HIV-1. The current study aimed at assessing the tropism of viral integrates in patients' blood during fully suppressive cART. METHODS: The relative frequencies of X4-tropic proviral HIV-1 variants were determined by means of next-generation sequencing (False Positive Rate (FPR), 3.5%; R5- or X4 tropic variants occurring at less than 2% of the total virus population) for 35 treated patients in the Swiss HIV Cohort Study and followed longitudinally over time. Full viral suppression and a continuous CD4 T-cell recovery during cART were documented for all patients. Viral phylogenetic changes and sequence evolution were analyzed. RESULTS: The majority of patients (80%) experienced no frequency increase in X4-tropic proviruses during therapy. Although some proviral sequence evolution was demonstrable in >50% of these patients during therapy, this growing viral diversity was in no case paralleled by the emergence or expansion of X4-tropic provirus variants. In the remaining 20% of patients, the documented expansion of X4-tropic provirus was based on the outgrowth of single viral variants from minority populations already present before therapy initiation. CONCLUSION: Our study demonstrates that X4-tropic HIV sharply declines in most patients during successful therapy, which indicates a preferential tropism-dependent provirus elimination in the immunocompetent host. The recently implemented World Health Organization strategies of immediate therapy initiation are fully in line with this gradual loss of X4 tropism during therapy. Moreover, the early use of coreceptor antagonists against the remaining CCR5-tropic viruses may be indicated.

Alcohol use and depression: link with adherence and viral suppression in adult patients on antiretroviral therapy in rural Lesotho, Southern Africa: a cross-sectional study.

BACKGROUND: Depression and alcohol use disorder have been shown to be associated with poor adherence to antiretroviral therapy (ART). Studies examining their association with viral suppression in rural Africa are, however, scarce. METHODS: This study reports prevalence of depressive symptoms and alcohol use disorder, and their potential association with adherence and viral suppression in adult patients on ART in ten clinics in rural Lesotho, Southern Africa. RESULTS: Among 1,388 adult patients (69 % women), 80.7 % were alcohol abstinent, 6.3 % were hazardous drinkers (men: 10.7 %, women: 4.4 %, p < 0.001). The prevalence of depressive symptoms was 28.8 % (men 20.2 %, women 32.7 %, p < 0.001). Both alcohol consumption (adjusted odds-ratio: 2.09, 95 % CI: 1.58-2.77) and alcohol use disorder (2.73, 95 % CI: 1.68-4.42) were significantly associated with poor adherence. There was, however, no significant association with viral suppression. CONCLUSIONS: Whereas the results of this study confirm previously reported association of alcohol use disorder with adherence to ART, there was no association with viral suppression. TRIAL REGISTRATION: April 28th 2014; NCT02126696 .

A diagnostic HIV-1 tropism system based on sequence relatedness.

Key clinical studies for HIV coreceptor antagonists have used the phenotyping-based Trofile test. Meanwhile various simpler-to-do genotypic tests have become available that are compatible with standard laboratory equipment and Web-based interpretation tools. However, these systems typically analyze only the most prominent virus sequence in a specimen. We present a new diagnostic HIV tropism test not needing DNA sequencing. The system, XTrack, uses physical properties of DNA duplexes after hybridization of single-stranded HIV-1 env V3 loop probes to the clinical specimen. Resulting "heteroduplexes" possess unique properties driven by sequence relatedness to the reference and resulting in a discrete electrophoretic mobility. A detailed optimization process identified diagnostic probe candidates relating best to a large number of HIV-1 sequences with known tropism. From over 500 V3 sequences representing all main HIV-1 subtypes (Los Alamos database), we obtained a small set of probes to determine the tropism in clinical samples. We found a high concordance with the commercial TrofileES test (84.9%) and the Web-based tool Geno2Pheno (83.0%). Moreover, the new system reveals mixed virus populations, and it was successful on specimens with low virus loads or on provirus from leukocytes. A replicative phenotyping system was used for validation. Our data show that the XTrack test is favorably suitable for routine diagnostics. It detects and dissects mixed virus populations and viral minorities; samples with viral loads (VL) of <200 copies/ml are successfully analyzed. We further expect that the principles of the platform can be adapted also to other sequence-divergent pathogens, such as hepatitis B and C viruses.

Is zidovudine first-line therapy virologically comparable to tenofovir in resource-limited settings?

OBJECTIVE: To compare virologic success between adult patients on tenofovir (TDF) and zidovudine (AZT)-containing first-line antiretroviral (ART) regimens in 10 rural clinics in Lesotho, Southern Africa. METHODS: Multicentre cross-sectional study, patients ≥16 years, on first-line ART ≥6 months, receiving AZT/lamivudine (3TC) or TDF/3TC combined with efavirenz (EFV) or nevirapine (NVP). Patient characteristics and clinical/therapeutic history were collected on the day of blood draw for viral load (VL). Analysis was stratified for non-nucleoside reverse transcriptase inhibitor (EFV or NVP). A logistic regression model weighted for patients' baseline characteristics was used to assess the likelihood of virologic success (<80 copies/ml) in patients with TDF- as compared to AZT-backbones. RESULTS: In total 1539 patients were included in the analysis. Most were clinically and immunologically stable (clinical failure: 2.7% (AZT) and 2.8% (TDF); immunological failure: 4.6% (AZT) and 4.8% (TDF)). In EFV-based regimens (n = 1162), TDF was significantly associated with higher rates of virologic suppression than AZT (93.8% vs. 88.1%; weighted odds ratio: 2.15 (95% CI: 1.29-3.58; P = 0.003)). In NVP-based regimens, a similar trend was observed, but not significant (89.4% vs. 86.7%; 1.99 (0.83-4.75, P = 0.121)). CONCLUSION: These findings support the WHO recommendation to use TDF/3TC/EFV as first-line regimen. They do, however, not support the recommendation that patients who are clinically stable on AZT should continue on this first-line regimen.

Phenotypic co-receptor tropism and Maraviroc sensitivity in HIV-1 subtype C from East Africa.

Genotypic tropism testing (GTT) for co-receptor usage is a recommended tool for clinical practice before administration of the CCR5-antagonist maraviroc. For some isolates, phenotypic tropism testing (PTT) revealed discordant results with GTT. In this study, we performed a comparative study between GTT and PTT in HIV-1C from East Africa (HIV-1CEA) and compared the data with HIV-1B and 01_AE and described the maraviroc susceptibility in the CCR5-tropic strains. Patient-derived HIV-1 envgp120 region was cloned into a modified pNL4-3 plasmid expressing the luciferase gene. rPhenotyping dissected single clones from 31 HIV-1CEA infected patients and four strains with known phenotype. Additionally, 68 clones from 18 patients (HIV-1B: 5, 01_AE: 7, HIV-1CEA: 6) were used to determine the PTT in GHOST cell line. The respective V3-sequences were used for GTT. R5-tropic strains from HIV-1CEA (n = 20) and non-C (n = 12) were tested for maraviroc sensitivity in TZMbl cell line. The GTT falsely called a higher proportion of X4-tropic strains in HIV-1CET compared to PTT by both rPhenotyping and the GHOST-cell assay. When multiple clones were tested in a subset of patients' samples, both dual-tropic and R5-tropic strains were identified for HIV-1C. Relatively higher EC50 values were observed in HIV-1C strains than the non-C strains (p = 0.002).

Should viral load thresholds be lowered?: Revisiting the WHO definition for virologic failure in patients on antiretroviral therapy in resource-limited settings.

The World Health Organization (WHO) guidelines on antiretroviral therapy (ART) define treatment failure as 2 consecutive viral loads (VLs) ≥1000 copies/mL. There is, however, little evidence supporting 1000 copies as an optimal threshold to define treatment failure. Objective of this study was to assess the correlation of the WHO definition with the presence of drug-resistance mutations in patients who present with 2 consecutive unsuppressed VL in a resource-limited setting.In 10 nurse-led clinics in rural Lesotho children and adults on first-line ART for ≥6 months received a first routine VL. Those with plasma VL ≥80 copies/mL were enrolled in a prospective study, receiving enhanced adherence counseling (EAC) and a follow-up VL after 3 months. After a second unsuppressed VL genotypic resistance testing was performed. Viruses with major mutations against ≥2 drugs of the current regimen were classified as "resistant".A total of 1563 adults and 191 children received a first routine VL. Of the 138 adults and 53 children with unsuppressed VL (≥80 copies/mL), 165 (116 adults; 49 children) had a follow-up VL after EAC; 108 (74 adults; 34 children) remained unsuppressed and resistance testing was successful. Ninety of them fulfilled the WHO definition of treatment failure (both VL ≥1000 copies/mL); for another 18 both VL were unsuppressed but with <1000 copies/mL. The positive predictive value (PPV) for the WHO failure definition was 81.1% (73/90) for the presence of resistant virus. Among the 18 with VL levels between 80 and 1000 copies/mL, thereby classified as "non-failures", 17 (94.4%) harbored resistant viruses. Lowering the VL threshold from 1000 copies/mL to 80 copies/mL at both determinations had no negative influence on the PPV (83.3%; 90/108).The current WHO-definition misclassifies patients who harbor resistant virus at VL below 1000 c/mL as "nonfailing." Lowering the threshold to VL ≥80 copies/mL identifies a significantly higher number of patients with treatment-resistant virus and should be considered.

Still Far From 90-90-90: Virologic Outcomes of Children on Antiretroviral Therapy in Nurse-led Clinics in Rural Lesotho.

This survey assessed virologic outcomes of children on antiretroviral therapy and potential predictors in 10 nurse-led clinics in Lesotho. Viral suppression was achieved in 72% of the 191 children. No predictors for virologic outcome were found, underlining the need for routine viral load testing in resource-limited settings to achieve 90-90-90.

Clinical and socio-demographic predictors for virologic failure in rural Southern Africa: preliminary findings from CART-1.

INTRODUCTION: In 2013, the World Health Organization (WHO) recommended scaling up of routine viral load (VL) monitoring for patients on antiretroviral therapy (ART) in resource-limited settings [1]. During the transition phase from no VL-testing at all to routine VL-monitoring, targeted VL for groups at particular risk of virologic failure (VF) may be an option [2]. We present socio-demographic and clinical risk factors for VF in a cohort in rural Lesotho with no access to VL prior to the study. MATERIALS AND METHODS: Data derive from a cross-sectional study providing multi-disease screening as well as VL testing to adult patients (≥16 years old) on first-line ART ≥6 months [3]. VF was defined as VL≥1000 copies/mL. Assessed potential predictors of VF were: (1) socio-demographic (sex, age, wealth-quintile, education, employment status, disclosure of HIV status to environment, travel-time to facility); (2) treatment history (history of treatment interruption >2 days, previous drug substitution within first-line ART, time on ART, ART-base and -backbone); (3) adherence (pill count) and (4) clinical (clinical or immunological failure as defined by WHO guidelines [1], presence of papular pruritic eruption (PPE)). All variables with association to VF in univariate analysis were included in a multivariate logistic regression reporting adjusted Odds ratios (aOR). RESULTS: Data from 1,488 patients were analyzed. Overall VF-prevalence was 6.9% (95% CI 5.7-8.3). In univariate analysis, the following were associated with VF: age <30, lower wealth-quintile, no primary education, history of treatment interruption, nevirapine-base, zidovudine-backbone, history of drug substitution, travel-time to clinic ≥2 hours, disclosure of HIV status to <5 persons, clinical failure, presence of PPE and immunological failure. In multivariate analysis, 6 out of the above 12 variables were independent predictors: age <30 years (aOR: 2.4; 95% CI 1.1-5.3, p=0.029), history of treatment interruption (2.5; 1.3-4.7, p=0.005), PPE (6.9; 2.5-18.9, p<0.001), immunological failure (11.5; 5.7-23.2, p<0.001), history of drug substitution (1.9; 1.0-3.7, p=0.043), disclosure of HIV status to <5 persons (1.8; 1.1-3.1, p=0.03). CONCLUSION: In this cohort in rural Lesotho, several socio-demographic and clinical predictors were associated with VF. Particularly age <30 years, history of treatment interruption, PPE and immunological failure were strongly associated with VF. These patients may be prioritized for targeted VL-testing.