Co-Operative Additive Effects between HLA Alleles in Control of HIV-1

Background: HLA class I genotype is a major determinant of the outcome of HIV infection, and the impact of certain alleles on HIV disease outcome is well studied. Recent studies have demonstrated that certain HLA class I alleles that are in linkage disequilibrium, such as HLA-A*74 and HLA-B*57, appear to function co-operatively to result in greater immune control of HIV than mediated by either single allele alone. We here investigate the extent to which HLA alleles - irrespective of linkage disequilibrium - function co-operatively. Methodology/Principal Findings: We here refined a computational approach to the analysis of >2000 subjects infected with C-clade HIV first to discern the individual effect of each allele on disease control, and second to identify pairs of alleles that mediate ‘co-operative additive’ effects, either to improve disease suppression or to contribute to immunological failure. We identified six pairs of HLA class I alleles that have a co-operative additive effect in mediating HIV disease control and four hazardous pairs of alleles that, occurring together, are predictive of worse disease outcomes (q<0.05 in each case). We developed a novel ‘sharing score’ to quantify the breadth of CD8+ T cell responses made by pairs of HLA alleles across the HIV proteome, and used this to demonstrate that successful viraemic suppression correlates with breadth of unique CD8+ T cell responses (p = 0.03). Conclusions/Significance: These results identify co-operative effects between HLA Class I alleles in the control of HIV-1 in an extended Southern African cohort, and underline complementarity and breadth of the CD8+ T cell targeting as one potential mechanism for this effect

A lowered salt intake does not compromise iodine status in Cape Town, South Africa, where salt iodization is mandatory

Objective Universal salt iodization is an effective strategy to optimize population-level iodine. At the same time as salt-lowering initiatives are encouraged globally, there is concern about compromised iodine intakes. This study investigated whether salt intakes at recommended levels resulted in a suboptimal iodine status in a country where salt is the vehicle for iodine fortification. Methods Three 24-h urine samples were collected for the assessment of urinary sodium and one sample was taken for urinary iodine concentrations (UICs) in a convenience sample of 262 adult men and women in Cape Town, South Africa. Median UIC was compared across categories of sodium excretion equivalent to salt intakes lower than 5, 5 to 9, and greater than or equal to 9 g/d. Results The median UIC was 120 μg/L (interquartile range 75.3–196.3), indicating iodine sufficiency. Less one-fourth (23.2%) of subjects had urinary sodium excretion values within the desirable range (salt \u3c5 g/d), 50.7% had high values (5–9 g/d), and 22.8% had very high values (≥9 g/d). No association between urinary iodine and mean 3 × 24-h urinary sodium concentration was found (r = 0.087, P = 0.198) and UIC status did not differ according to urinary sodium categories (P = 0.804). Conclusion In a country with mandatory universal salt iodization, consumers with salt intakes within the recommended range (\u3c5 g/d) are iodine replete, and median UIC does not differ across categories of salt intake. This indicates that much of the dietary salt is provided from non-iodinated sources, presumably added to processed foods

Change in knowledge in a coronary heart disease risk factor intervention study in three communities

We investigated health and diet knowledge as it relates to coronary heart disease (CHD) in three rural areas which participated in a community-oriented CHD risk factor intervention study. Knowledge of risk factors (risk knowledge) was fairly satisfactory at baseline, but diet knowledge was poor. Males, the young, and individuals with a lower level of education had less knowledge. Intervention consisted of a 3-year small mass media programme in one community (low-intensity intervention, LII), additional interpersonal intervention to high-risk individuals in the second (high-intensity intervention, HII), and no intervention in the control community (C). In the cohorts, with the baseline survey and the follow-up study 4 years apart, knowledge improved by 8.1% points in males (7.5% in females) in the HII community and by 7.1% (6.5%) in the LII community, compared to 5.5% (4.8%) in the C community (Pcommunity intervention CHD risk factor knowledge knowledge change