Discordance between Etravirine Phenotype and Genotype-Based Predicted Phenotype for Subtype C HIV-1 from First-Line Antiretroviral Therapy Failures in South Africa

ABSTRACT Etravirine (ETR) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) used in treatment-experienced individuals. Genotypic resistance test-interpretation systems can predict ETR resistance; however, genotype-based algorithms are derived primarily from HIV-1 subtype B and may not accurately predict resistance in non-B subtypes. The frequency of ETR resistance among recombinant subtype C HIV-1 and the accuracy of genotypic interpretation systems were investigated. HIV-1LAI containing full-length RT from HIV-1 subtype C-positive individuals experiencing virologic failure (>10,000 copies/ml and >1 NNRTI resistance-associated mutation) were phenotyped for ETR susceptibility. Fold change (FC) was calculated against a composite 50% effective concentration (EC50) from treatment-naive individuals and three classifications were assigned: (i) <2.9-FC, susceptible; (ii) ≥2.9- to 10-FC, partially resistant; and (iii) >10-FC, fully resistant. The Stanford HIVdb-v8.4 was used for genotype predictions merging the susceptible/potential low-level and low-level/intermediate groups for 3 × 3 comparison. Fifty-four of a hundred samples had reduced ETR susceptibility (≥2.9-FC). The FC correlated with HIVdb-v8.4 (Spearman’s rho = 0.62; P < 0.0001); however, 44% of samples were partially (1 resistance classification difference) and 4% completely discordant (2 resistance classification differences). Of the 34 samples with an FC of >10, 26 were HIVdb-v8.4 classified as low-intermediate resistant. Mutations L100I, Y181C, or M230L were present in 27/34 (79%) of samples with an FC of >10 but only in 2/46 (4%) of samples with an FC of <2.9. No other mutations were associated with ETR resistance. Viruses containing the mutation K65R were associated with reduced ETR susceptibility, but 65R reversions did not increase ETR susceptibility. Therefore, genotypic interpretation systems were found to misclassify ETR susceptibility in HIV-1 subtype C samples. Modifications to genotypic algorithms are needed to improve the prediction of ETR resistance for the HIV-1 subtype C.

Adult ADHD in the South African workplace: the usefulness of a self-report screening measure and preliminary prevalence estimates

In the South African context, resource constraints often preclude the comprehensive assessment of large numbers of people for the likelihood of Adult Attention-Deficit/Hyperactivity Disorder (ADHD). Primary screening through a self-report measure may be useful to stream at-risk individuals towards diagnostic assessment services, as well as being useful in population and workplace based research. The present study set out, first, to investigate the usefulness of a self-report ADHD scale to identify at-risk individuals, and, second, to provide preliminary prevalence estimates for Adult ADHD, guided by Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) criteria, in a South African workplace sample. Workers in full-time skilled employment ( N = 1,917), aged 18–44, completed a self-report Adult ADHD scale, and participated in an interview with a psychologist. Their scale data, using three different scoring and interpretation systems, were subjected to statistical analysis. Favourable internal reliability and positive predictive validity were found. Different interpretation systems provided different prevalence estimations: using DSM-5 criteria, a total prevalence estimate of 3.3 % was calculated (attention deficit subtype = 0.9%, hyperactivity-impulsivity subtype = 1.0%, and combined subtype = 1.4%). The positive predictive validity found with this sample suggests that this scale can be used constructively in research or screening contexts to identify at-risk individuals. Furthermore, preliminary prevalence estimates for Adult ADHD, guided by DSM-5 criteria, are now available for a South African workplace sample.

sierra-local: A lightweight standalone application for secure HIV-1 drug resistance prediction

Genotypic resistance interpretation systems for the prediction and interpretation of HIV-1 antiretroviral resistance are an important part of the clinical management of HIV-1 infection. Current interpretation systems are generally hosted on remote webservers that enable clinical laboratories to generate resistance predictions easily and quickly from patient HIV-1 sequences encoding the primary targets of modern antiretroviral therapy. However they also potentially compromise a health provider’s ethical, professional, and legal obligations to data security, patient information confidentiality, and data provenance. Furthermore, reliance on web-based algorithms makes the clinical management of HIV-1 dependent on a network connection. Here, we describe the development and validation of sierra-local, an open-source implementation of the Stanford HIVdb genotypic resistance interpretation system for local execution, which aims to resolve the ethical, legal, and infrastructure issues associated with remote computing. This package reproduces the HIV-1 resistance scoring by the web-based Stanford HIVdb algorithm with a high degree of concordance (99.997%) and a higher level of performance than current methods of accessing HIVdb programmatically.

A Review on Intelligent Monitoring and Activity Interpretation

This survey paper provides a tour of the various monitoring and activity interpretation frameworks found in the literature. The needs of monitoring and interpretation systems are presented in relation to the area where they have been developed or applied. Their evolution is studied to better understand the characteristics of current systems. After this, the main features of monitoring and activity interpretation systems are defined.

UNDERSTANDING LINEAR AND NONLINEAR ASPECTS OF PRODUCT CONCEPT DEVELOPMENT FROM THE ORGANISATIONAL INTERPRETATION PERSPECTIVE

The product concept is crucial in new product development (NPD) because it represents an NPD project’s goal. In this context, most prior studies have regarded product concept development as a linear process but some recent studies have revealed that it also has nonlinear characteristics. The objective of this paper is to explore why this inconsistency has arisen and to develop a model and theory that illustrate both aspects of product concept development. To achieve this, we adopt the perspective of organisational interpretation systems (Daft and Weick (1984). Toward a model of organisations as interpretation systems. Academy of Management Review, 9(2), 289–295) and explore eight product development cases. Consequently, we develop a three-stage model and find that the linearity or nonlinearity of product concept development is determined by each NPD team’s assumption about the environment. We also consider product innovativeness and function equivocality, and establish that these are related to the NPD teams’ assumptions about the environment.