Clinical Evaluation of an Affordable Qualitative Viral Failure Assay for HIV Using Dried Blood Spots in Uganda

Background

WHO recommends regular viral load (VL) monitoring of patients on antiretroviral therapy (ART) for timely detection of virological failure, prevention of acquired HIV drug resistance (HIVDR) and avoiding unnecessary switching to second-line ART. However, the cost and complexity of routine VL testing remains prohibitive in most resource limited settings (RLS). We evaluated a simple, low–cost, qualitative viral–failure assay (VFA) on dried blood spots (DBS) in three clinical settings in Uganda.

Methods

We conducted a cross–sectional diagnostic accuracy study in three HIV/AIDS treatment centres at the Joint Clinical Research Centre in Uganda. The VFA employs semi-quantitative detection of HIV–1 RNA amplified from the LTR gene. We used paired dry blood spot (DBS) and plasma with the COBASAmpliPrep/COBASTaqMan, Roche version 2 (VL_ref) as the reference assay. We used the VFA at two thresholds of viral load, (>5,000 or >1,000 copies/ml).

Results

496 paired VFA and VL_ref results were available for comparative analysis. Overall, VFA demonstrated 78.4% sensitivity, (95% CI: 69.7%–87.1%), 93% specificity (95% CI: 89.7%–96.4%), 89.3% accuracy (95% CI: 85%–92%) and an agreement kappa = 0.72 as compared to the VL_ref. The predictive values of positivity and negativity among patients on ART for >12 months were 72.7% and 99.3%, respectively.

Conclusions

VFA allowed 89% of correct classification of VF. Only 11% of the patients were misclassified with the potential of unnecessary or late switch to second–line ART. Our findings present an opportunity to roll out simple and affordable VL monitoring for HIV–1 treatment in RLS.     

Data-Mining Discovery of Pattern and Process in Ecological Systems

ABSTRACT Most ecologists use statistical methods as their main analytical tools when analyzing data to identify relationships between a response and a set of predictors; thus, they treat all analyses as hypothesis tests or exercises in parameter estimation. However, little or no prior knowledge about a system can lead to creation of a statistical model or models that do not accurately describe major sources of variation in the response variable. We suggest that under such circumstances data mining is more appropriate for analysis. In this paper we 1) present the distinctions between data-mining (usually exploratory) analyses and parametric statistical (confirmatory) analyses, 2) illustrate 3 strengths of data-mining tools for generating hypotheses from data, and 3) suggest useful ways in which data mining and statistical analyses can be integrated into a thorough analysis of data to facilitate rapid creation of accurate models and to guide further research.     

Phylogeny of the tribe Sciophilini (Diptera: Mycetophilidae: Sciophilinae)

The monophyly and phylogenetic relationships within the species rich Sciophilini (Diptera: Mycetophilidae) were analysed, based on 96 adult morphological characters. The cladistic analysis included 80 Sciophilini exemplar species (representing all but 1 of the 36 genera placed previously in the Sciophilini) and 11 outgroup taxa of other mycetophilid tribes. The monophyly of Sciophilini was supported in the parsimony analysis by four synapomorphies. The tribe now contains 34 genera: Acnemia Winnertz, Acomoptera Vockeroth, Adicroneura Vockeroth, Afrocnemia Matile, Allocotocera Mik, Anaclileia Meunier, Aneura Marshall, Austrosciophila Tonnoir, Azana Walker, Baeopterogyna Vockeroth, Cluzobra Edwards, Drepanocercus Vockeroth, Duretophragma Borkent gen.n. , Eudicrana Loew, Leptomorphus Curtis, Loicia Vockeroth, Megalopelma Enderlein, Monoclona Mik, Morganiella Tonnoir & Edwards, Neoallocotocera Tonnoir, Neoaphelomera Miller, Neotrizygia Tonnoir & Edwards, Neuratelia Rondani, Paramorganiella Tonnoir, Paratinia Mik, Paratrizygia Tonnoir, Parvicellula Marshall, Phthinia Winnertz, Polylepta Winnertz, Sciophila Meigen, Stenophragma Skuse, Tasmanina Tonnoir, Taxicnemis Tonnoir & Edwards, and Trizygia Skuse. Four genera placed previously in Sciophilini (Coelophthinia Edwards, Impleta Plassmann, Speolepta Edwards and Syntemna Winnertz) are transferred to the Gnoristini. Neoneurotelia Shinji and Neoparatinia Shinji are considered nomina dubia . Diagnoses are given for all genera in the tribe. Duretophragma gen.n. is described for the following species (all of which are comb.n. ): Duretophragma andina (Duret), Duretophragma argentina (Duret), Duretophragma glabanum (Johannsen), Duretophragma fusca (Edwards), Duretophragma humeralis (Edwards), Duretophragma intermedia (Edwards), Duretophragma longifurcata (Freeman) (type species), Duretophragma morigenea (Edwards), Duretophragma naumanni (Duret), Duretophragma nigricauda (Edwards), Duretophragma obscura (Duret), Duretophragma ochracea (Freeman), Duretophragma pleuralis (Edwards) and Duretophragma similis (Johannsen). Other new generic combinations include: Trizygia albidens (Oliveira & Amorim) comb.n. , Trizygia alvesi (Oliveira & Amorim) comb.n. , Trizygia balbi (Oliveira & Amorim) comb.n. , Trizygia camargoi (Oliveira & Amorim) comb.n. and Afrocnemia stellamicans (Chandler) comb.n .     

Nocturne for an unknown pollinator: first description of a night‐flowering orchid (Bulbophyllum nocturnum)

Bulbophyllum nocturnum , a species of section Epicrianthes from New Britain, is described and illustrated. It is the first known example of an orchid species in which the flowers open after dark and close in the morning. The poorly understood pollination biology of section Epicrianthes, a clade with highly unusual flowers, is discussed. Attention is drawn to the close resemblance between the petal appendages of some species and the fruiting bodies of certain Myxogastria. © 2011 The Linnean Society of London, Botanical Journal of the Linnean Society, 2011, 167 , 344–350.     

The male genital tract and aedeagal components of the Diptera with a discussion of their phylogenetic significance

The male genital tract of Diptera is surveyed, based on whole dissections, with emphasis on nematocerous infraorders and especially the Culicomorpha. The genital tracts of all available nematocerous families are described and illustrated, including, for the first time, those of the families Thaumaleidae, Dixidae, Hesperinidae, and Pachyneuridae, and, as an outgroup, the mecopteran family Nannochoristidae (Mecoptera). On the basis of outgroup comparison, the Diptera + Mecoptera + Siphonaptera share the synapomorphies of accessory gland continuous with the vas deferens and U-shaped vasa deferentia. Further synapomorphies of the male genital tract provide evidence of the monophyly of the Mecoptera + Siphonaptera, Boreidae + Siphonaptera, and the Blephariceridae + Psychodidae + Trichoceridae + Anisopodidae + Brachycera. The Bibionomorpha, Culicomorpha, and Ptychopteromorpha share the synapomorphy of paired, two- to three-chambered accessory gland complexes, with secondary losses in Corethrellidae + Culicidae. It is concluded that there is no convincing evidence for the monophyly of the Chironomoidea. A sperm pump with an ejaculatory apodeme and the absence of a spermatophore are considered to be part of the ground plan of Diptera, but, because of uncertainty as to the identity of the basal lineage within Diptera and the homology of the sperm pump outside of Diptera, the polarity of these features cannot be presently interpreted.  © 2007 The Linnean Society of London, Zoological Journal of the Linnean Society , 2007, 150 , 711–742.     

Use of Anti-Retroviral Therapy in Tuberculosis Patients on Second-Line Anti-TB Regimens: A Systematic Review

Introduction

Use of antiretroviral therapy (ART) during treatment of drug susceptible tuberculosis (TB) improves survival. However, data from HIV infected individuals with drug resistant TB are lacking. Second line TB drugs when combined with ART may increase drug interactions and lead to higher rates of toxicity and greater noncompliance. This systematic review sought to determine the benefit of ART in the setting of second line drug therapy for drug resistant TB.

Methods

We included individual patient data from studies that evaluated treatment of drug-resistant tuberculosis in HIV-1 infected individuals published between January 1980 and December of 2009. We evaluated the effect of ART on treatment outcomes, time to smear and culture conversion, and adverse events.

Results

Ten observational studies, including data from 217 subjects, were analyzed. Patients using ART during TB treatment had increased likelihood of cure (hazard ratio (HR) 3.4, 95% CI 1.6–7.4) and decreased likelihood of death (HR 0.4, 95% CI 0.3–0.6) during treatment for drug resistant TB. These associations remained significant in patients with a CD4 less than 200 cells/mm³ and less than 50 cells/mm³, and when correcting for drug resistance pattern.

Limitations

We identified only observational studies from which individual patient data could be drawn. Limitations in study design, and heterogeneity in a number of the outcomes of interest had the potential to introduce bias.

Discussion

While there are insufficient data to determine if ART use increases adverse drug interactions when used with second line TB drugs, ART use during treatment of drug resistant TB appears to improve cure rates and decrease risk of death. All individuals with HIV appear to benefit from ART use during treatment for TB.     

Evaluation of three sampling methods to monitor outcomes of antiretroviral treatment programmes in low- and middle-income countries

Background

Retention of patients on antiretroviral therapy (ART) over time is a proxy for quality of care and an outcome indicator to monitor ART programs. Using existing databases (Antiretroviral in Lower Income Countries of the International Databases to Evaluate AIDS and Médecins Sans Frontières), we evaluated three sampling approaches to simplify the generation of outcome indicators.

Methods and Findings

We used individual patient data from 27 ART sites and included 27,201 ART-naive adults (≥15 years) who initiated ART in 2005. For each site, we generated two outcome indicators at 12 months, retention on ART and proportion of patients lost to follow-up (LFU), first using all patient data and then within a smaller group of patients selected using three sampling methods (random, systematic and consecutive sampling). For each method and each site, 500 samples were generated, and the average result was compared with the unsampled value. The 95% sampling distribution (SD) was expressed as the 2.5^th and 97.5^th percentile values from the 500 samples. Overall, retention on ART was 76.5% (range 58.9–88.6) and the proportion of patients LFU, 13.5% (range 0.8–31.9). Estimates of retention from sampling (n = 5696) were 76.5% (SD 75.4–77.7) for random, 76.5% (75.3–77.5) for systematic and 76.0% (74.1–78.2) for the consecutive method. Estimates for the proportion of patients LFU were 13.5% (12.6–14.5), 13.5% (12.6–14.3) and 14.0% (12.5–15.5), respectively. With consecutive sampling, 50% of sites had SD within ±5% of the unsampled site value.

Conclusions

Our results suggest that random, systematic or consecutive sampling methods are feasible for monitoring ART indicators at national level. However, sampling may not produce precise estimates in some sites.