Concurrent advanced HIV disease and viral load suppression in a high-burden setting: Findings from the 2015-6 ZIMPHIA survey.

BACKGROUND: As Zimbabwe approaches epidemic control of HIV, programs now prioritize viral load over CD4 monitoring, making it difficult to identify persons living with HIV (PLHIV) suffering from advanced disease (AD). We present an analysis of cross-sectional ZIMPHIA data, highlighting PLHIV with AD and concurrent viral load suppression (VLS). METHODS: ZIMPHIA collected blood specimens for HIV testing from 22,501 consenting adults (ages 15 years and older); 3,466 PLHIV had CD4 and VL results. Household HIV testing used the national serial algorithm, and those testing positive then received point-of-care CD4 enumeration with subsequent VL testing. We used logistic regression analysis to explore factors associated with concurrent AD and VLS (<1000 copies/mL). All analyses were weighted to account for complex survey design. RESULTS: Of the 3,466 PLHIV in the survey with CD4 and VL results, 17% were found to have AD (CD4<200cells/mm3). Of all AD patients, 30% had VLS. Concurrent AD and VLS was associated with male sex (aOR 2.45 95%CI 1.61-3.72), older age (35-49 years [aOR 2.46 95%CI 1.03-5.91] and 50+ years [aOR 4.82 95%CI 2.02-11.46] vs 15-24 years), and ART duration (<6 months [aOR 0.46 95%CI 0.29-0.76] and 6-24 months [aOR 2.07 95%CI 1.35-3.17] vs more than 2 years). The relationship between sex and AD is driven by age with significant associations among men aged 25-34, (aOR 3.37 95%CI 1.35-8.41), 35-49 (aOR 5.13 95%CI 2.16-12.18), and 50+ (aOR 12.56 95%CI 4.82-32.72) versus men aged 15-24. CONCLUSIONS: The percentage of PLHIV with AD and VLS illustrates the conundrum of decreased support for CD4 monitoring, as these patients may not receive appropriate clinical services for advanced HIV disease. In high-prevalence settings such as Zimbabwe, CD4 monitoring support warrants further consideration to differentiate care appropriately for the most vulnerable PLHIV. Males may need to be prioritized, given their over-representation in this sub-population.

The effect of nanoscale surface curvature on the oligomerization of surface-bound proteins.

The influence of surface topography on protein conformation and association is used routinely in biological cells to orchestrate and coordinate biomolecular events. In the laboratory, controlling the surface curvature at the nanoscale offers new possibilities for manipulating protein-protein interactions and protein function at surfaces. We have studied the effect of surface curvature on the association of two proteins, α-lactalbumin (α-LA) and ß-lactoglobulin (ß-LG), which perform their function at the oil-water interface in milk emulsions. To control the surface curvature at the nanoscale, we have used a combination of polystyrene (PS) nanoparticles (NPs) and ultrathin PS films to fabricate chemically pure, hydrophobic surfaces that are highly curved and are stable in aqueous buffer. We have used single-molecule force spectroscopy to measure the contour lengths Lc for α-LA and ß-LG adsorbed on highly curved PS surfaces (NP diameters of 27 and 50 nm, capped with a 10 nm thick PS film), and we have compared these values in situ with those measured for the same proteins adsorbed onto flat PS surfaces in the same samples. The Lc distributions for ß-LG adsorbed onto a flat PS surface contain monomer and dimer peaks at 60 and 120 nm, respectively, while α-LA contains a large monomer peak near 50 nm and a dimer peak at 100 nm, with a tail extending out to 200 nm, corresponding to higher order oligomers, e.g. trimers and tetramers. When ß-LG or α-LA is adsorbed onto the most highly curved surfaces, both monomer peaks are shifted to much smaller values of Lc. Furthermore, for ß-LG, the dimer peak is strongly suppressed on the highly curved surface, whereas for α-LA the trimer and tetramer tail is suppressed with no significant change in the dimer peak. For both proteins, the number of higher order oligomers is significantly reduced as the curvature of the underlying surface is increased. These results suggest that the surface curvature provides a new method of manipulating protein-protein interactions and controlling the association of adsorbed proteins, with applications to the development of novel biosensors.

Variability of mineral intakes from drinking water: a possible explanation for the controversy over the relationship of water quality to cardiovascular disease.

The assumption that people using the same water supply have similar intakes of minerals from drinking water is examined. Duplicate samples of all water drunk during a 24 hour period, including that boiled for beverage preparation, were collected by 109 adult subjects. The results showed that there may be more than a tenfold variation in the amount of water people drink daily. In addition it was found that the mineral concentrations in the 24 hour samples can vary markedly from those in water collected from the source or supply or from household taps which are the usual sampling points for epidemiological studies. The convention of using total hardness as an indicator of mineral intakes from hard and soft water is questioned.

Estimations of daily mineral intakes from drinking water.

Duplicate samples of all tap water drank over 24 h, including that used for beverage preparation, were collected from 109 adult subjects. There were more than ten-fold variations in daily water intakes. The mineral concentrations in the 24-h samples from households on the same public water supply showed considerable variation, the differences sometimes being greater than those found in water samples from different sources. These findings raise considerable doubt about the accuracy of accepted methods for the estimation of mineral intakes from drinking water. Although the mineral concentrations in water samples were generally very low some subjects received 10 per cent or more of their recommended dietary intake of Cu and Zn from this source. The implications of the findings are discussed.

Heptachlor residue accumulation and depletion in broiler chickens.

Broiler chickens were fed heptachlor in concentrations of 0, 0.01, 0.03, 0.1, and 0.3 mg/kg of the ration for the first 8 weeks of life. There were no adverse effects on health or performance. Residue concentrations in adipose tissue increased rapidly for 1 to 2 weeks and then tended to plateau at concentrations about five times greater than those in the rations. Birds exposed only during the 7th week of life stored 25% as much residue as did the chickens exposed in the 1st week, but the former also ate only 63% as much feed. Fat extracted from liver and muscle contained more residue than did fat extracted from adipose tissue. The ratio of the concentration of heptachlor to its epoxide metabolite was higher in muscle fat than in heptic or abdominal fat. Residue concentrations depleted by about half in the first 4 weeks after cessation of exposure.