Dataset Information

Structural Bone Deficits in HIV/HCV-Coinfected, HCV-Monoinfected, and HIV-Monoinfected Women.

ABSTRACT:

Background

Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is associated with reduced bone mineral density (BMD) and increased fracture rates, particularly in women. The structural underpinnings for skeletal fragility in coinfected women have not been characterized. We used tibial peripheral quantitative computed tomography to evaluate skeletal parameters in women, by HIV/HCV status.

Methods

We conducted a cross-sectional study among 50 HIV/HCV-coinfected, 51 HCV-monoinfected, and 50 HIV-monoinfected women. Tibial volumetric BMD and cortical dimensions were determined with peripheral quantitative computed tomography. Race-specific z scores for age were generated using 263 female reference participants without HIV infection or liver disease.

Results

Coinfected participants had lower mean z scores for trabecular volumetric BMD (-0.85), cortical volumetric BMD (-0.67), cortical area (-0.61), and cortical thickness (-0.77) than reference participants (all P < .001). The smaller cortical dimensions were due to greater mean z scores for endosteal circumference (+0.67; P < .001) and comparable z scores for periosteal circumference (+0.04; P = .87). Trabecular volumetric BMD was lower in coinfected than in HCV- or HIV-monoinfected participants. HCV-infected women with stage 3-4 liver fibrosis had lower mean z scores for trabecular volumetric BMD, cortical thickness, and total hip BMD those with stage 0-2 fibrosis.

Conclusions

Compared with healthy reference patients, HIV/HCV-coinfected women had decreased tibial trabecular volumetric BMD, diminished cortical dimensions, and significant endocortical bone loss.

SUBMITTER: Lo Re V

PROVIDER: S-EPMC4548465 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Publications

Structural Bone Deficits in HIV/HCV-Coinfected, HCV-Monoinfected, and HIV-Monoinfected Women.

Lo Re Vincent V Lynn Kenneth K Stumm Emily R ER Long Jin J Nezamzadeh Melissa S MS Baker Joshua F JF Hoofnagle Andrew N AN Kapalko Angela J AJ Mounzer Karam K Zemel Babette S BS Tebas Pablo P Kostman Jay R JR Leonard Mary B MB

The Journal of infectious diseases 20150309 6

<h4>Background</h4>Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is associated with reduced bone mineral density (BMD) and increased fracture rates, particularly in women. The structural underpinnings for skeletal fragility in coinfected women have not been characterized. We used tibial peripheral quantitative computed tomography to evaluate skeletal parameters in women, by HIV/HCV status.<h4>Methods</h4>We conducted a cross-sectional study among 50 HIV/HCV-coin ...[more]

PMID: 25754980

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Project description:Pre-existing low-frequency resistance-associated variants (RAVs) may jeopardize successful sustained virological responses (SVR) to HCV treatment with direct-acting antivirals (DAAs). However, the potential impact of low-frequency (∼0.1%) mutations, concatenated mutations (haplotypes), and their association with genotypes (Gts) on the treatment outcome has not yet been elucidated, most probably owing to the difficulty in detecting pre-existing minor haplotypes with sufficient length and accuracy. Herein, we characterize a methodological framework based on Illumina MiSeq next-generation sequencing (NGS) coupled with bioinformatics of quasispecies reconstruction (QSR) to realize highly accurate variant calling and genotype-haplotype detection. The core-to-NS3 protease coding sequences in 10 HCV monoinfected patients, 5 of whom had a history of blood transfusion, and 11 HCV/HIV coinfected patients with hemophilia, were studied. Simulation experiments showed that, for minor variants constituting more than 1%, our framework achieved a positive predictive value (PPV) of 100% and sensitivities of 91.7-100% for genotyping and 80.6% for RAV screening. Genotyping analysis indicated the prevalence of dominant Gt1a infection in coinfected patients (6/11 vs 0/10, p = 0.01). For clinical samples, minor genotype overlapping infection was prevalent in HCV/HIV coinfected hemophiliacs (10/11) and patients who experienced whole-blood transfusion (4/5) but none in patients without exposure to blood (0/5). As for RAV screening, the Q80K/R and S122K/R variants were particularly prevalent among minor RAVs observed, detected in 12/21 and 6/21 cases, respectively. Q80K was detected only in coinfected patients, whereas Q80R was predominantly detected in monoinfected patients (1/11 vs 7/10, p < 0.01). Multivariate interdependence analysis revealed the previously unrecognized prevalence of Gt1b-Q80K, in HCV/HIV coinfected hemophiliacs [Odds ratio = 13.4 (3.48-51.9), p < 0.01]. Our study revealed the distinct characteristics of viral quasispecies between the subgroups specified above and the feasibility of NGS and QSR-based genetic deconvolution of pre-existing minor Gts, RAVs, and their interrelationships.

Dataset Information

Structural Bone Deficits in HIV/HCV-Coinfected, HCV-Monoinfected, and HIV-Monoinfected Women.

Background

Methods

Results

Conclusions

Publications

Structural Bone Deficits in HIV/HCV-Coinfected, HCV-Monoinfected, and HIV-Monoinfected Women.

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