High turnaround times and low viral resuppression rates after reinforced adherence counselling following a confirmed virological failure diagnostic algorithm in HIV‐infected patients on first‐line antiretroviral therapy from Tanzania

Objective Early identification of confirmed virological failure is paramount to avoid accumulation of drug resistance in patients on antiretroviral therapy (ART). Scale‐up of HIV‐RNA monitoring in Africa and timely switch to second‐line regimens are challenged. Methods A WHO adapted confirmed virological treatment screening algorithm (HIV‐RNA screening, enhanced adherence counselling, confirmatory HIV‐RNA testing) was evaluated in HIV‐infected patients on first‐line ART from Tanzania. The main endpoints included viral resuppression and virological failure rates, retention and turnaround time of the screening algorithm until second‐line ART initiation. Secondary endpoints included risk factors for virological treatment failure and patterns of genotypic drug resistance. Results HIV‐RNA >1000 copies/ml at first screening was detected in 58/356 (16.3%) patients (median time‐on‐treatment 6.3 years, 25% immunological treatment failure). Adjusted risk factors for virological failure were age <30 years (RR 5.2 [95% CI: 2.5–10.8]), years on ART ≥3 years (RR 3.0 [1.0–8.9]), CD4‐counts <200 cells/µl (RR 9.3 [4.0–21.8]) and poor self‐reported treatment adherence (RR 2.0 [1.2–3.4]). Resuppression of HIV‐RNA <1000 copies/ml was observed in 5/50 (10%) cases after enhanced adherence counselling. Confirmatory testing within 3 months was performed in only 46.6% and switch to second‐line ART within 6 months in 60.4% of patients. Major NNRTI‐mutation were detected in all of 30 patients, NRTI mutations in 96.7% and ≥3 thymidine‐analogue mutations in 40%. No remaining NRTI options were predicted in 57% and limited susceptibility in 23% of patients. Conclusion We observed low levels of viral resuppression following adherence counselling, associated with high levels of accumulated drug resistance. High visit burden and turnaround times for confirmed virological failure diagnosis further delayed switching to second‐line treatment which could be improved using novel point‐of‐care viral load monitoring systems

Dynamic MAIT cell response with progressively enhanced innateness during acute HIV-1 infection.

Mucosa-associated invariant T (MAIT) cell loss in chronic HIV-1 infection is a significant insult to antimicrobial immune defenses. Here we investigate the response of MAIT cells during acute HIV-1 infection utilizing the RV217 cohort with paired longitudinal pre- and post-infection samples. MAIT cells are activated and expand in blood and mucosa coincident with peak HIV-1 viremia, in a manner associated with emerging microbial translocation. This is followed by a phase with elevated function as viral replication is controlled to a set-point level, and later by their functional decline at the onset of chronic infection. Interestingly, enhanced innate-like pathways and characteristics develop progressively in MAIT cells during infection, in parallel with TCR repertoire alterations. These findings delineate the dynamic MAIT cell response to acute HIV-1 infection, and show how the MAIT compartment initially responds and expands with enhanced function, followed by progressive reprogramming away from TCR-dependent antibacterial responses towards innate-like functionality

Comparison of 4- and 5-beam acoustic Doppler current profiler configurations for measurement of turbulent kinetic energy

Acoustic Doppler current profilers (ADCPs) are commonly used to assess mean currents and turbulence at energetic sites. Since 2014, five-beam ADCP configurations have become more common, but conventional analysis of turbulence properties is still based on the four-beam Janus configuration. We use measurements from a single site to investigate improved estimates of turbulent kinetic energy (TKE) that are made possible by the addition of a fifth vertical beam. We conclude that four-beam estimates of TKE are suitable in most cases, and exhibit lower variance than five-beam estimates, but are more prone to contamination by wave activity

Wuchereria bancrofti infection is linked to systemic activation of CD4 and CD8 T cells

Background Susceptibility to HIV has been linked to systemic CD4+ T cell activation in cohorts of seronegative individuals with high HIV-exposure risk. We recently described an increased risk of HIV transmission in individuals infected with Wuchereria bancrofti, the causative agent for lymphatic filariasis, in a prospective cohort study. However, the reason for this phenomenon needs further investigation. Methodology/Principal findings Two-hundred and thirty-five HIV negative adults were tested using Trop Bio ELISA for detection of W. bancrofti infection and Kato Katz urine filtration and stool based RT-PCR for detection of soil transmitted helminths and schistosomiasis. FACS analysis of the fresh peripheral whole blood was used to measure T cell activation markers (HLA-DR, CD38), differentiation markers (CD45, CD27), markers for regulatory T cells (FoxP3, CD25) and the HIV entry receptor CCR5. Frequencies of activated HLA-DRpos CD4 T cells were significantly increased in subjects with W. bancrofti infection (n = 33 median: 10.71%) compared to subjects without any helminth infection (n = 42, median 6.97%, p = 0.011) or those with other helminths (Schistosoma haematobium, S. mansoni, Trichuris trichiura, Ascaris lumbricoides, hookworm) (n = 151, median 7.38%, p = 0.009). Similarly, a significant increase in HLA-DR(pos)CD38(pos) CD4 T cells and effector memory cells CD4 T cells (CD45RO(pos)CD27(neg)) was observed in filarial infected participants. Multivariable analyses further confirmed a link between W. bancrofti infection and systemic activation of CD4 T cells independent of age, fever, gender or other helminth infections. Conclusions/Significance W. bancrofti infection is linked to systemic CD4 T cell activation, which may contribute to the increased susceptibility of W. bancrofti infected individuals to HIV infection

Low specificity of determine HIV1/2 RDT using whole blood in south west Tanzania

Objective: To evaluate the diagnostic performance of two rapid detection tests (RDTs) for HIV 1/2 in plasma and in whole blood samples. Methods: More than 15,000 study subjects above the age of two years participated in two rounds of a cohort study to determine the prevalence of HIV. HIV testing was performed using the Determine HIV 1/2 test (Abbott) in the first (2006/2007) and the HIV 1/2 STAT-PAK Dipstick Assay (Chembio) in the second round (2007/2008) of the survey. Positive results were classified into faint and strong bands depending on the visual appearance of the test strip and confirmed by ELISA and Western blot. Results: The sensitivity and specificity of the Determine RDT were 100% (95% confidence interval = 86.8 to 100%) and 96.8% (95.9 to 97.6%) in whole blood and 100% (99.7 to 100%) and 97.9% (97.6 to 98.1%) in plasma respectively. Specificity was highly dependent on the tested sample type: when using whole blood, 67.1% of positive results were false positive, as opposed to 17.4% in plasma. Test strips with only faint positive bands were more often false positive than strips showing strong bands and were more common in whole blood than in plasma. Evaluation of the STAT-PAK RDT in plasma during the second year resulted in a sensitivity of 99.7% (99.1 to 99.9%) and a specificity of 99.3% (99.1 to 99.4%) with 6.9% of the positive results being false. Conclusions: Our study shows that the Determine HIV 1/2 strip test with its high sensitivity is an excellent tool to screen for HIV infection, but that – at least in our setting – it can not be recommended as a confirmatory test in VCT campaigns where whole blood is used

Expansion of Inefficient HIV-Specific CD8 T Cells during Acute Infection

ABSTRACT Attrition within the CD4 + T cell compartment, high viremia, and a cytokine storm characterize the early days after HIV infection. When the first emerging HIV-specific CD8 + T cell responses gain control over viral replication it is incomplete, and clearance of HIV infection is not achieved even in the rare cases of individuals who spontaneously control viral replication to nearly immeasurably low levels. Thus, despite their partial ability to control viremia, HIV-specific CD8 + T cell responses are insufficient to clear HIV infection. Studying individuals in the first few days of acute HIV infection, we detected the emergence of a unique population of CD38 + CD27 − CD8 + T cells characterized by the low expression of the CD8 receptor (CD8 dim ). Interestingly, while high frequencies of HIV-specific CD8 + T cell responses occur within the CD38 + CD27 − CD8 dim T cell population, the minority populations of CD8 bright T cells are significantly more effective in inhibiting HIV replication. Furthermore, the frequency of CD8 dim T cells directly correlates with viral load and clinical predictors of more rapid disease progression. We found that a canonical burst of proliferative cytokines coincides with the emergence of CD8 dim T cells, and the size of this population inversely correlates with the acute loss of CD4 + T cells. These data indicate, for the first time, that early CD4 + T cell loss coincides with the expansion of a functionally impaired HIV-specific CD8 dim T cell population less efficient in controlling HIV viremia. IMPORTANCE A distinct population of activated CD8 + T cells appears during acute HIV infection with diminished capacity to inhibit HIV replication and is predictive of viral set point, offering the first immunologic evidence of CD8 + T cell dysfunction during acute infection

Comparison of ADCP observations and 3D model simulations of turbulence at a tidal energy site

Field measurement of turbulence in strong tidal currents is difficult and expensive, but the tidal energy industry needs to accurately quantify turbulence for adequate resource characterisation and device design. Models that can predict such turbulence could reduce measurement costs. We compare a Regional Ocean Modelling System (ROMS) simulation with acoustic Doppler current profiler (ADCP) measurements from a highly-energetic tidal site. This comparison shows the extent to which turbulence can be quantified by ROMS, using the conventional k−ε turbulence closure model. Both model and observations covered the same time period, encompassing two spring-neap cycles. Turbulent kinetic energy (TKE) density was calculated from measurements using the variance method; turbulent dissipation, ε, was calculated using the structure function method. Measurements show that wave action dominates turbulent fluctuations in the upper half of the water column; comparing results for deeper water, however, shows very strong agreement. A best fit between ROMS and ADCP results for mean velocity yields R2=0.98; for TKE, R2 is 0.84 when strongly wave-dominated times are excluded. Dissipation agrees less well: although time series of ε are well-correlated at similar depths, ROMS estimates a greater magnitude of dissipation than is measured, by a factor of up to 4.8

Improved salt iodation methods for small-scale salt producers in low-resource settings in Tanzania

Background: Universal salt iodation will prevent iodine deficiency disorders (IDD). Globally, salt-iodation technologies mostly target large and medium-scale salt-producers. Since most producers in low-income countries are small-scale, we examined and improved the performance of hand and knapsack-sprayers used locally in Tanzania. Methods: We studied three salt facilities on the Bagamoyo coast, investigating procedures for preparing potassium-iodate solution, salt spraying and mixing. Different concentrations of solution were prepared and tested using different iodation methods, with the aim of attaining correct and homogeneous iodine levels under real-life conditions. Levels achieved by manual mixing were compared to those achieved by machine mixing. Results: The overall median iodation level in samples of salt iodated using previously existing methods was 10.6 ppm (range 1.1 – 110.0 ppm), with much higher levels in the top than the bottom layers of the salt bags, p < 0.0001. Experimentation using knapsack-sprayers and manual mixing led to the reliable achievement of levels (60.9 ppm ± 7.4) that fell within the recommended range of 40 – 80 ppm. The improved methods yielded homogenous iodine concentrations in all layers of salt-bags (p = 0.58) with 96% of the samples (n = 45) falling within 40 – 80 ppm compared to only 9% (n = 45) before the experiment and training (p < 0.0001). For knapsack-spraying, a machine mixer improved the iodine levels and homogeneity slightly compared to manual mixing (p = 0.05). Conclusion: Supervised, standardized salt iodation procedures adapted to local circumstances can yield homogeneous iodine levels within the required range, overcoming a major obstacle to universal salt iodation

Low sensitivity of a urine LAM-ELISA in the diagnosis of pulmonary tuberculosis

<p>Abstract</p> <p>Background</p> <p>The development and evaluation of rapid and accurate new diagnostic tools is essential to improve tuberculosis (TB) control in developing countries. In a previous study, the first release of a urine LAM-ELISA by Chemogen (Portland, USA) has been evaluated with a promising sensitivity and specificity for the diagnosis of pulmonary TB. In the present study, the now commercially available assay has been clinically assessed regarding its diagnostic value alone and in combination with clinical co-factors.</p> <p>Methods</p> <p>The test was applied to two urine samples from 291 consecutively enrolled Tanzanian patients with suspected pulmonary tuberculosis. The participants were subsequently assigned to classification groups according to microbiological, clinical and radiological findings at recruitment and during a maximum follow up period of 56 days.</p> <p>Results</p> <p>Only 35 out of 69 pulmonary TB cases -confirmed by smear microscopy and/or solid culture and/or liquid culture- showed at least one positive LAM-ELISA result (sensitivity 50.7%). The sensitivity was noticeably higher in females (66.7%) and in HIV positive participants (62.0%). The specificity amounted to 87.8% and was determined in participants with negative results in all microbiological tests and with sustained recovery under antibiotic treatment at day 56. Correlation with urinalysis revealed that proteinuria was significantly and positively associated with LAM-positivity (<it>P </it>= 0.026).</p> <p>Conclusion</p> <p>This commercially available generation of LAM-ELISA does not appear to be useful as an independent diagnostic test for pulmonary tuberculosis. The question whether the assay is suitable as a supplemental device in the diagnosis of HIV-associated TB, requires further investigations.</p