DETERMINATION OF VIRAL TROPISM BY GENOTYPING AND PHENOTYPING ASSAYS IN BRAZILIAN HIV-1-INFECTED PATIENTS

The clinical application of CCR5 antagonists involves first determining the coreceptor usage by the infecting viral strain. Bioinformatics programs that predict coreceptor usage could provide an alternative method to screen candidates for treatment with CCR5 antagonists, particularly in countries with limited financial resources. Thus, the present study aims to identify the best approach using bioinformatics tools for determining HIV-1 coreceptor usage in clinical practice. Proviral DNA sequences and Trofile results from 99 HIV-1-infected subjects under clinical monitoring were analyzed in this study. Based on the Trofile results, the viral variants present were 81.1% R5, 21.4% R5X4 and 1.8% X4. Determination of tropism using a Geno2pheno_[coreceptor] analysis with a false positive rate of 10% gave the most suitable performance in this sampling: the R5 and X4 strains were found at frequencies of 78.5% and 28.4%, respectively, and there was 78.6% concordance between the phenotypic and genotypic results. Further studies are needed to clarify how genetic diversity amongst virus strains affects bioinformatics-driven approaches for determining tropism. Although this strategy could be useful for screening patients in developing countries, some limitations remain that restrict the wider application of coreceptor usage tests in clinical practice.     

Short communication: Phenotypic protease inhibitor resistance and cross-resistance in the clinic from 2006 to 2008 and mutational prevalences in HIV from patients with discordant tipranavir and darunavir susceptibility phenotypes

To test tipranavir (TPV) or darunavir (DRV) as treatment options for patients with phenotypic resistance to protease inhibitors (PIs), including lopinavir, saquinavir, atazanavir, and fosamprenavir, the PhenoSense GT database was analyzed for susceptibility to DRV or TPV among PI-resistant isolates. The Monogram Biosciences HIV database (South San Francisco, CA) containing 7775 clinical isolates (2006-2008) not susceptible to at least one first-generation PI was analyzed. Phenotypic responses [resistant (R), partially susceptible (PS), or susceptible (S)] were defined by upper and lower clinical cut-offs to each PI. Genotypes were screened for amino acid substitutions associated with TPV-R/DRV-S and TPV-S/DRV-R phenotypes. In all, 4.9% (378) of isolates were resistant to all six PIs and 31.0% (2407) were resistant to none. Among isolates resistant to all four first-generation PIs, DRV resistance increased from 21.2% to 41.9% from 2006 to 2008, respectively, and resistance to TPV remained steady (53.9 to 57.3%, respectively). Higher prevalence substitutions in DRV-S/TPV-R isolates versus DRV-R/TPV-S isolates, respectively, were 82L/T (44.4% vs. 0%) and 83D (5.8% vs. 0%). Higher prevalence substitutions in DRV-R/TPV-S virus were 50V (0.0% vs. 28.9%), 54L (1.0% vs. 36.1%), and 76V (0.4% vs. 15.5%). Mutations to help predict discordant susceptibility to DRV and TPV in isolates with reduced susceptibility to other PIs were identified. DRV resistance mutations associated with improved virologic response to TPV were more prevalent in DRV-R/TPV-S isolates. TPV resistance mutations were more prevalent in TPV-R and DRV-S isolates. These results confirm the impact of genotype on phenotype, illustrating how HIV genotype and phenotype data assist regimen optimization.     

Evidence of low vitamin D intakes in the Australian population points to a need for data-driven nutrition policy for improving population vitamin D status

Background

Nearly one in four Australian adults is vitamin D deficient (serum 25-hydroxyvitamin D concentrations [25(OH)D] < 50 nmol L^–1) and current vitamin D intakes in the Australian population are unknown. Internationally, vitamin D intakes are commonly below recommendations, although estimates generally rely on food composition data that do not include 25(OH)D. We aimed to estimate usual vitamin D intakes in the Australian population.

Methods

Nationally representative food consumption data were collected for Australians aged ≥ 2 years (n = 12,153) as part of the cross-sectional 2011–2013 Australian Health Survey (AHS). New analytical vitamin D food composition data for vitamin D₃, 25(OH)D₃, vitamin D₂ and 25(OH)D₂ were mapped to foods and beverages that were commonly consumed by AHS participants. Usual vitamin D intakes (µg day^–1) by sex and age group were estimated using the National Cancer Institute method.

Results

Assuming a 25(OH)D bioactivity factor of 1, mean daily intakes of vitamin D ranged between 1.84 and 3.25 µg day^–1. Compared to the estimated average requirement of 10 µg day^–1 recommended by the Institute of Medicine, more than 95% of people had inadequate vitamin D intakes. We estimated that no participant exceeded the Institute of Medicine's Upper Level of Intake (63–100 µg day^–1, depending on age group).

Conclusions

Usual vitamin D intakes in Australia are low. This evidence, paired with the high prevalence of vitamin D deficiency in Australia, suggests that data-driven nutrition policy is required to safely increase dietary intakes of vitamin D and improve vitamin D status at the population level.