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1.  Trabecular and cortical microarchitecture in postmenopausal HIV-infected women 
Calcified tissue international  2013;92(6):557-565.
Objective
To assess the effects of HIV infection and antiretroviral therapy (ART) on trabecular and cortical microarchitecture in postmenopausal minority women.
Methods
A subgroup of 106 (46 HIV-infected, 60 uninfected) postmenopausal Hispanic and African American women from an established cohort had areal bone mineral density (aBMD) measured by dual-energy x-ray absorptiometry, and trabecular and cortical volumetric BMD (vBMD) and microarchitecture measured by high-resolution peripheral quantitative computed tomography (HRpQCT) at the radius and tibia.
Results
HIV-infected women were slightly younger (58±1 versus 61±1 yrs, p=0.08), and had lower body mass index (BMI, 28±1 versus 32±1 kg/m2, p<0.01). BMI-adjusted aBMD Z scores were lower in HIV-infected women at the lumbar spine, total hip and ultradistal radius. Serum N-telopeptide and C-telopeptide levels were also higher in HIV-infected women. Trabecular and cortical vBMD were similar at the radius, but cortical area (105.5±2.4 versus 120.6±2.0mm2, p<0.01) and thickness (956±33 versus 1075±28 m, p<0.01) at the tibia were approximately 11–12% lower in HIV-infected women. Differences remained significant after adjusting for age, BMI and race/ethnicity. In contrast, cortical porosity was similar in both groups.
Conclusion
Although HIV-infected postmenopausal women had lower aBMD at the spine, total hip and ultradistal radius and higher levels of bone resorption markers, the only differences detected by HRpQCT were lower cortical thickness and area at the tibia.
doi:10.1007/s00223-013-9716-8
PMCID: PMC3656136  PMID: 23460340
HIV; microarchitecture; cortical structure; osteoporosis; postmenopausal women
2.  Relationship of vitamin D, HIV, HIV treatment and lipid levels in the Women’s Interagency HIV study (WIHS) of HIV-infected and un-infected women in the US 
Relationships between vitamin D, lipids, HIV infection, and HIV treatment (±ART) were investigated with Women’s Interagency HIV Study data (n=1758 middle-aged women) using multivariable regression. 63 % had vitamin D deficiency. Median 25-OH vitamin D was highest in HIV-infected +ART-treated women (17 ng/mL, p<0.001), but the same in HIV-uninfected or HIV-infected without ART (14 ng/mL). Vitamin D levels were lower if ART included efavirenz (15 vs 19 ng/mL, p<0.001). The most common lipid abnormality was high triglycerides (≥200 mg/dL) in HIV-infected +ART, (13%, vs 7% of HIV-infected without ART and 5% of HIV-uninfected (p<0.001) with a positive relationship between 25-OH-D and triglycerides (95% confidence interval 0.32 to 1.69, p<.01). No relationships between 25-OH-D and cholesterol were detected. Vitamin D deficiency is common irrespective of HIV status but influenced by HIV treatment. Similarly, vitamin D levels were positively related to triglycerides only in ART treated HIV infected, and unrelated to cholesterol.
doi:10.1177/2325957413506748
PMCID: PMC4016117  PMID: 24668135
Vitamin D; lipids; HIV infected; HIV uninfected; 25-OH vitamin D; cholesterol; LDL-cholesterol; triglycerides; lipids; WIHS
3.  Incident fractures in HIV-infected individuals: a systematic review and meta-analysis 
AIDS (London, England)  2013;27(12):1949-1957.
Objective(s)
Some but not all studies indicate that individuals with HIV infection are at an increased risk of fracture. We systematically reviewed the literature to investigate whether incidence of fracture (both overall and fragility) differs between individuals with and without HIV.
Design
A systematic review and meta-analysis.
Methods
Medline, Scopus and the Cochrane Library databases for all studies ever published up to 28 September 2012 and electronically available conference abstracts from CROI, ASBMR, IAS and AIDS were searched. All studies reporting incidence of all fracture and fragility fracture in HIV-infected adults were included. A random effects model was used to calculate pooled estimates of incidence rate ratios (IRRs) for studies that presented data for HIV-infected and controls. For all studies, incidence rates of fracture and predictors of fracture among HIV-infected individuals were summarized.
Results
Thirteen eligible studies were analysed, of which seven included controls. Nine studies reported all incident fractures and 10 presented incident fragility fractures. The pooled IRR was 1.58 [95% confidence interval (CI) 1.25–2.00] for all fracture and 1.35 (95% CI 1.10–1.65) for fragility fracture. Smoking, white race and older age were consistent predictors for fragility fractures.
Conclusion
Our results indicate that HIV infection is associated with a modest increase in incident fracture. Future research should focus on clarifying risk factors, designing appropriate interventions and the long-term implications of this increased risk for an ageing HIV-infected population.
doi:10.1097/QAD.0b013e328361d241
PMCID: PMC4030545  PMID: 24126140
bone; fracture; fracture incidence; fragility fracture; HIV
4.  Physiologic Frailty and Fragility Fracture in HIV-Infected Male Veterans 
Frailty, as measured by the Veterans Aging Cohort Study Index, is an important predictor of fragility fracture in the context of established fracture risk factors. Anemia and increasing age drive this association in a male veteran population.
Background. The Veterans Aging Cohort Study (VACS) Index is associated with all-cause mortality in individuals infected with human immunodeficiency virus (HIV). It is also associated with markers of inflammation and may thus reflect physiologic frailty. This analysis explores the association between physiologic frailty, as assessed by the VACS Index, and fragility fracture.
Methods. HIV-infected men from VACS were included. We identified hip, vertebral, and upper arm fractures using ICD-9-CM codes. We used Cox regression models to assess fragility fracture risk factors including the VACS Index, its components (age, hepatitis C status, FIB-4 score, estimated glomerular filtration rate, hemoglobin, HIV RNA, CD4 count), and previously identified risk factors for fragility fractures.
Results. We included 40 115 HIV-infected male Veterans. They experienced 588 first fragility fractures over 6.0 ± 3.9 years. The VACS Index score (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.11–1.19), white race (HR, 1.92; 95% CI, 1.63–2.28), body mass index (HR, 0.94; 95% CI, .92–.96), alcohol-related diagnoses (HR, 1.65; 95% CI, 1.26–2.17), cerebrovascular disease (HR, 1.95; 95% CI, 1.14–3.33), proton pump inhibitor use (HR, 1.87; 95% CI, 1.54–2.27), and protease inhibitor use (HR, 1.25; 95% CI, 1.04–1.50) were associated with fracture risk. Components of the VACS Index score most strongly associated with fracture risk were age (HR, 1.40; 95% CI, 1.27–1.54), log HIV RNA (HR, 0.91; 95% CI, .88–.94), and hemoglobin level (HR, 0.82; 95% CI, .78–.86).
Conclusions. Frailty, as measured by the VACS Index, is an important predictor of fragility fractures among HIV-infected male Veterans.
doi:10.1093/cid/cit056
PMCID: PMC3634308  PMID: 23378285
HIV; frailty; fragility fractures; Veterans
5.  Vitamin D, Bone, and HIV Infection 
Topics in antiviral medicine  2012;20(5):168-172.
Vitamin D deficiency has been associated with increased risk for falls and fractures, diabetes and obesity, cardiovascular disease, some malignancies, and tuberculosis. Observational data have suggested benefit of higher vitamin D levels in many of these settings. However, data from randomized trials supporting the benefit of vitamin D supplementation are generally lacking, apart from data showing benefit in preventing falls and fractures in the elderly. HIV-infected persons have a high prevalence of vitamin D deficiency and insufficiency, and some antiretroviral drugs are known to interfere with vitamin D metabolism. However, as in the general population, there are currently few data from clinical trials to identify benefits of vitamin D screening and supplementation in the HIV-infected population. A rational approach is to screen at-risk patients (eg, those aged 50 years and older and those with osteoporosis, prior fracture, or high risk for falls); supplementation may be considered in specific subgroups of patients.
PMCID: PMC4019218  PMID: 23363695
6.  Lower peak bone mass and abnormal trabecular and cortical microarchitecture in young men infected with HIV early in life 
AIDS (London, England)  2014;28(3):345-353.
Introduction
HIV infection and antiretroviral therapy (ART) early in life may interfere with acquisition of peak bone mass, thereby increasing fracture risk in adulthood.
Methods
We conducted a cross-sectional study of dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) in 30 HIV-infected African–American or Hispanic Tanner stage 5 men aged 20–25 on ART (15 perinatally infected and 15 infected during adolescence) and 15 HIV-uninfected controls.
Results
HIV-infected men were similar in age and BMI, but were more likely to be African–American (P = 0.01) than uninfected men. DXA-derived areal bone mineral density (aBMD) Z-scores were 0.4–1.2 lower in HIV-infected men at the spine, hip, and radius (all P < 0.05). At the radius and tibia, total and trabecular volumetric BMD (vBMD), and cortical and trabecular thickness were between 6 and 19% lower in HIV-infected than uninfected men (P <0.05). HIV-infected men had dramatic deficiencies in plate-related parameters by individual trabeculae segmentation (ITS) analyses and 14–17% lower bone stiffness by finite element analysis revealed. Differences in most HR-pQCT parameters remained significant after adjustment for race/ethnicity. No DXA or HR-pQCT parameters differed between men infected perinatally or during adolescence.
Conclusion
At an age by which young men have typically acquired peak bone mass, HIV-infected men on ART have lower BMD, markedly abnormal trabecular plate and cortical microarchitecture, and decreased whole bone stiffness, whether infected perinatally or during adolescence. Reduced bone strength in young adults infected with HIV early in life may place them at higher risk for fractures as they age.
doi:10.1097/QAD.0000000000000070
PMCID: PMC4019223  PMID: 24072196
bone microarchitecture; bone mineral density; bone strength; high-resolution peripheral quantitative computed tomography; peak bone mass; perinatal HIV infection
7.  Association of Regional Body Composition with Bone Mineral Density in HIV-infected and Uninfected Women: Women's Interagency HIV Study 
Objective
To understand how regional body composition affects bone mineral density (BMD) in HIV-infected and uninfected women.
Methods
Dual energy X-ray absorptiometry was used to measure regional lean and fat mass and BMD at lumbar spine (LS), total hip (TH), and femoral neck (FN) in 318 HIV-infected and 122 HIV-uninfected Women's Interagency HIV Study participants at baseline and 2 and 5 years later. Total lean and fat mass were measured using bioimpedance analysis. Multivariate marginal linear regression models assessed the association of HIV status and body composition on BMD change.
Results
Compared to HIV-uninfected women, HIV-infected women were older (44 vs. 37 yrs), more likely to be HCV-infected (32% vs. 14%), and post-menopausal (26% vs. 3%), and had lower baseline total fat mass, trunk fat and leg fat. In multivariate models, increased total lean mass was independently associated with increased BMD at LS, TH and FN and total fat mass was associated with increased BMD at TH and FN (all p<0.05). When total fat was replaced in multivariate models with trunk fat and leg fat, increased trunk fat (and not leg fat) was associated with increased TH and FN BMD (p<0.001).
Conclusions
Total fat and lean mass are strong, independent predictors of TH and FN BMD, and lean mass was associated with greater LS BMD. Regardless of HIV status, greater trunk fat (and not leg fat) was associated with increased TH and FN BMD, suggesting that weight bearing fat may be a more important predictor of BMD in the hip.
doi:10.1097/QAI.0b013e31826cba6c
PMCID: PMC3494812  PMID: 22895436
Body composition; fat redistribution; bone mineral density; HIV; women
8.  Klebsiella pneumoniae K1 Liver Abscess and Septic Endophthalmitis in a U.S. Resident 
Journal of Clinical Microbiology  2013;51(3):1049-1051.
Klebsiella pneumoniae K1 is a major agent of hepatic abscess with metastatic disease in East Asia, with sporadic reports originating elsewhere. We report a case of abscess complicated by septic endophthalmitis caused by a wzyAKpK1-positive Klebsiella strain in a U.S. resident, raising concern for global emergence.
doi:10.1128/JCM.02853-12
PMCID: PMC3592058  PMID: 23303492
9.  High Performance Liquid Chromatography-Mass Spectrometry (LC-MS) assay for polymyxin B1 and B2 in human plasma 
Therapeutic Drug Monitoring  2012;34(4):398-405.
Background
Polymyxin B is an old antibiotic with increasing clinical relevance in the treatment of multi-drug resistant Gram-negative bacterial infections. However, current dosing regimens are largely empiric as clinical pharmacological characterization of the drug has been hindered by the lack of assays to measure polymyxin B in human plasma.
Methods
A high performance liquid chromatography-mass spectrometry (LC-MS) assay was developed to quantify polymyxin B1 and B2 in human plasma using pure calibrators. After purification with a solid-phase extraction column, polymyxin B1 and B2 were separated on a C18 column by gradient chromatography with an overall runtime of 12 minutes. Polymyxin B1 and B2 were ionized by positive electron spray ionization and the resulting ions specific to polymyxin B1 and B2 were monitored (selected ion recording).
Results
The dominant ions produced were [M + 2H]2+ at m/z 602.6 and 595.5 for polymyxin B1 and polymyxin B2, respectively. The assay was linear between concentrations of 100 and 2500 ng/ml, with inter-day precision of 5.9% and 3.4% at 100 ng/mL and 5.3% and 4.0% at 2000 ng/ml for polymyxin B1 and polymyxin B2, respectively. Accuracy was 80.2% and 82.2% at 100 ng/mL and 99.9% and 109.6% at 2000 ng/ml for polymyxin B1 and polymyxin B2, respectively. No interference from other drugs commonly administered with polymyxin B was detected. The performance of the assay is affected by gross hemolysis and hyperlipemia. The method was successfully applied to patient samples. Interestingly, in a single patient the ratio of B1 and B2 did not change over a period of 12 hours after administration of the drug.
Conclusions
A simple method for the simultaneous measurement of polymyxin B1 and polymyxin B2 in human plasma is described, which has the potential to optimize clinical use of this valuable antibiotic by permitting pharmacokinetic studies and therapeutic drug monitoring.
doi:10.1097/FTD.0b013e31825c827a
PMCID: PMC3394890  PMID: 22735673
Polymyxin B; liquid chromatography-mass spectrometry; pharmacokinetics; therapeutic drug monitoring; multidrug-resistant gram-negative bacterial infections
10.  Fractures after antiretroviral initiation 
AIDS (London, England)  2012;26(17):2175-2184.
Background
Bone mineral density declines by 2–6% within 1–2 years after initiation of antiretroviral therapy (ART); however, it is uncertain whether this results in an immediate or cumulative increase in fracture rates.
Methods
We evaluated the incidence and predictors of fracture in 4640 HIV-positive participants from 26 randomized ART studies followed in the AIDS Clinical Trials Group (ACTG) Longitudinal-Linked Randomized Trial study for a median of 5 years. Fragility and nonfragility fractures were recorded prospectively at semiannual visits. Incidence was calculated as fractures/total person-years. Cox proportional hazards models evaluated effects of traditional fracture risks, HIV disease characteristics, and ART exposure on fracture incidence.
Results
Median (interquartile range) age was 39 (33, 45) years; 83% were men, 48% white, and median nadir CD4 cell count was 187 (65, 308) cells/μl. Overall, 116 fractures were reported in 106 participants with median time-to-first fracture of 2.3 years. Fracture incidence was 0.40 of 100 person-years among all participants and 0.38 of 100 person-years among 3398 participants who were ART naive at enrollment into ACTG parent studies. Among ART-naive participants, fracture rates were higher within the first 2 years after ART initiation (0.53/100 person-years) than subsequent years (0.30/100 person-years). In a multivariate analysis of ART-naive participants, increased hazard of fracture was associated with current smoking and glucocorticoid use but not with exposure to specific antiretrovirals.
Conclusion
Fracture rates were higher within the first 2 years after ART initiation, relative to subsequent years. However, continuation of ART was not associated with increasing fracture rates in these relatively young HIV-positive individuals.
doi:10.1097/QAD.0b013e328359a8ca
PMCID: PMC3652631  PMID: 22951635
antiretroviral initiation; bone loss; fracture; fracture incidence; HIV
11.  The Association of HIV Status with Bacterial Vaginosis and Vitamin D in the United States 
Journal of Women's Health  2011;20(10):1497-1503.
Abstract
Objective
To estimate the association between vitamin D deficiency and bacterial vaginosis (BV) among nonpregnant HIV-infected and uninfected women.
Methods
In a substudy of the Women's Interagency HIV Study, including women from Chicago and New York, the association between BV and vitamin D deficiency, demographics, and disease characteristics was tested using generalized estimating equations. Deficiency was defined as <20 ng/mL 25 (OH) vitamin D and insufficiency as >20 and ≤30 ng/mL. BV was defined by the Amsel criteria.
Results
Among 602 observations of nonpregnant women (480 HIV infected and 122 uninfected), BV was found in 19%. Vitamin D deficiency was found in 59.4%, and insufficiency was found in 24.4%. In multivariable analysis, black race was the most significant predictor of BV (adjusted odds ratio [AOR] 5.90, (95% confidence interval [CI] 2.52-13.8). Vitamin D deficiency was independently associated with BV among HIV-infected women (AOR 3.12, 95% CI 1.16-8.38) but not among HIV-uninfected women. There was a negative linear correlation between vitamin D concentration and prevalence of BV in HIV-infected women (r=−0.15, p=0.001).
Conclusions
Vitamin D deficiency was very common in this cohort and significantly associated with BV among HIV-infected women. These preliminary findings suggest that further epidemiologic and mechanistic exploration of the relationship between vitamin D and BV in HIV-infected women is warranted.
doi:10.1089/jwh.2010.2685
PMCID: PMC3233211  PMID: 21875343
12.  Associations of Education Level and Bone Density Tests among Cognitively Intact Elderly White Women in Managed Medicare 
Objectives. To examine associations between having bone density tests and level of education among white elderly women in managed Medicare. Method. Data from the ninth through twelfth cohort (2006–2009) of the Medicare Health Outcome Survey (HOS) of managed Medicare plans were analyzed; 239331 white elderly women were included. Respondents were grouped by education level and the percentages of respondents who had lifetime bone density testing done among each group were analyzed. Results. 62.7% of respondents with less than a high school education reported previously taking a bone density test. This was lower than the 73.8% for respondents who completed high school and the 81.0% for respondents with more than a high school education. When potential confounding factors such as age, body mass index, marital status, smoking history, year of HOS survey, and region were factored in, the odds ratios of having a bone density test when compared to respondents with less than a high school education were 1.61 and 2.39, respectively, for those with just a high school education and more than a high school education (P < 0.001). Conclusion. Higher education was independently associated with greater use of bone density test in these elderly white women.
doi:10.1155/2012/179150
PMCID: PMC3463901  PMID: 23056041
13.  Effects of Darunavir/Ritonavir-Based Therapy on Metabolic and Anthropometric Parameters in Women and Men Over 48 Weeks 
AIDS Patient Care and STDs  2011;25(6):333-340.
Abstract
Gender-based differences in lipids have been noted in antiretroviral clinical trials. We present the metabolic and anthropometric data from the GRACE (Gender, Race And Clinical Experience) study by gender. Treatment-experienced adults received darunavir/ritonavir (DRV/r) 600/100 mg twice daily, plus a background regimen, over 48 weeks. Fasting blood samples were obtained for lipid, glucose, and insulin measurements at baseline and at weeks 24 and 48/early discontinuation. Anthropometric measurements were taken at baseline and at weeks 12, 24, and 48/discontinuation. The Assessment of Body Change and Distress questionnaire was administered at baseline and regular intervals. Descriptive statistics as well as comparisons using a Wilcoxon rank-sum test are reported. Four hundred twenty-nine patients (women, n=287; men, n=142) enrolled in GRACE; 94 women (32.8%) and 33 men (23.2%) discontinued the trial. Median changes in triglycerides from baseline to week 48 were higher in men (25 mg/dL versus 8 mg/dL; p=0.006); the mean change in triglycerides was higher in men than in women in all racial subgroups. Other lipid and glucose level changes were similar between genders. Anthropometric parameters increased for both genders, with larger increases in women. Patients' perceptions of body changes concurred with physical measurements. The proportion of women who were “satisfied” or “very satisfied” with their bodies increased from 45.2% to 57.8% from baseline to week 48 (p=0.005), while the proportion of men who were “satisfied” or “very satisfied” with their bodies increased from 56.3% to 61.5% from baseline to week 48 (p=0.317). DRV/r-based therapy was associated with small to moderate changes in metabolic parameters, and few between-gender differences were observed. Levels of self-reported, body-related distress improved for women and men over 48 weeks.
doi:10.1089/apc.2010.0386
PMCID: PMC3143406  PMID: 21612545
14.  Fracture incidence in HIV-infected women: results from the Women’s Interagency HIV Study 
AIDS (London, England)  2010;24(17):2679-2686.
Background
The clinical importance of the association of HIV infection and antiretroviral therapy (ART) with low bone mineral density (BMD) in premenopausal women is uncertain because BMD stabilizes on established ART and fracture data are limited.
Methods
We measured time to first new fracture at any site with median follow-up of 5.4 years in 2391 (1728 HIV-infected, 663 HIV-uninfected) participants in the Women’s Interagency HIV Study (WIHS). Self-report of fracture was recorded at semiannual visits. Proportional hazard models assessed predictors of incident fracture.
Results
At baseline, HIV-infected women were older (40 ± 9 vs. 36 ± 10 years, P <0.0001), more likely to report postmenopausal status and be hepatitis C virus-infected, and weighed less than HIV-uninfected women. Among HIV-infected women, mean CD4+ cell count was 482 cells/μl; 66% were taking ART. Unadjusted incidence of fracture did not differ between HIV-infected and uninfected women (1.8 vs. 1.4/100 person-years, respectively, P = 0.18). In multivariate models, white (vs. African-American) race, hepatitis C virus infection, and higher serum creatinine, but not HIV serostatus, were statistically significant predictors of incident fracture. Among HIV-infected women, older age, white race, current cigarette use, and history of AIDS-defining illness were associated with incidence of new fracture.
Conclusion
Among predominantly premenopausal women, there was little difference in fracture incidence rates by HIV status, rather traditional risk factors were important predictors. Further research is necessary to characterize fracture risk in HIV-infected women during and after the menopausal transition.
doi:10.1097/QAD.0b013e32833f6294
PMCID: PMC3108019  PMID: 20859192
fracture; fragility fracture; HIV-infected women; premenopausal
15.  Bone mass and mineral metabolism in HIV+ postmenopausal women 
The objective of this cross-sectional study was to estimate the prevalence of and risk factors for osteoporosis in HIV+ postmenopausal women. Bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) and biochemical indices of mineral metabolism were measured in 31 Hispanic and African American HIV+ postmenopausal women. BMD was compared with 186 historical controls, matched for age, ethnicity and postmenopausal status. Mean BMD was significantly lower at the lumbar spine and total hip in the HIV+ group, as compared with controls. Prevalence of osteoporosis was higher in the HIV+ group than controls at the lumbar spine (42% vs 23%, p=0.03) and total hip (10% vs 1%, p=0.003). Among HIV+ women, time since menopause and weight were significant predictors of BMD, while duration or class of antiretroviral therapy (ART), AIDS diagnosis, nadir CD4, steroid use, and vitamin D deficiency were not. Prevalence of osteoporosis is substantially higher in HIV+ Hispanic and African-American postmenopausal women than in controls. Established osteoporosis risk factors were more important in predicting BMD than factors associated with HIV infection and ART. Long-term management of the growing female HIV population should include the evaluation for and management of osteoporosis.
doi:10.1007/s00198-005-1845-0
PMCID: PMC3108020  PMID: 15754081
Bone metabolism; HIV; Osteoporosis; Postmenopausal women
16.  Bone Disease in HIV Infection: A Practical Review and Recommendations for HIV Care Providers 
Low bone mineral density (BMD) is prevalent in human immunodeficiency virus (HIV)–infected subjects. Initiation of antiretroviral therapy is associated with a 2%–6% decrease in BMD over the first 2 years, a decrease that is similar in magnitude to that sustained during the first 2 years of menopause. Recent studies have also described increased fracture rates in the HIV-infected population. The causes of low BMD in individuals with HIV infection appear to be multifactorial and likely represent a complex interaction between HIV infection, traditional osteoporosis risk factors, and antiretroviral-related factors. In this review, we make the point that HIV infection should be considered as a risk factor for bone disease. We recommend screening patients with fragility fractures, all HIV-infected post-menopausal women, and all HIV-infected men ≥50 years of age. We also discuss the importance of considering secondary causes of osteoporosis. Finally, we discuss treatment of the more severe cases of bone disease, while outlining the caveats and gaps in our knowledge.
doi:10.1086/656412
PMCID: PMC3105903  PMID: 20839968
17.  Increased Risk of Fragility Fractures among HIV Infected Compared to Uninfected Male Veterans 
PLoS ONE  2011;6(2):e17217.
Background
HIV infection has been associated with an increased risk of fragility fracture. We explored whether or not this increased risk persisted in HIV infected and uninfected men when controlling for traditional fragility fracture risk factors.
Methodology/Principal Findings
Cox regression models were used to assess the association of HIV infection with the risk for incident hip, vertebral, or upper arm fracture in male Veterans enrolled in the Veterans Aging Cohort Study Virtual Cohort (VACS-VC). We calculated adjusted hazard ratios comparing HIV status and controlling for demographics and other established risk factors. The sample consisted of 119,318 men, 33% of whom were HIV infected (34% aged 50 years or older at baseline, and 55% black or Hispanic). Median body mass index (BMI) was lower in HIV infected compared with uninfected men (25 vs. 28 kg/m2; p<0.0001). Unadjusted risk for fracture was higher among HIV infected compared with uninfected men [HR: 1.32 (95% CI: 1.20, 1.47)]. After adjusting for demographics, comorbid disease, smoking and alcohol abuse, HIV infection remained associated with an increased fracture risk [HR: 1.24 (95% CI: 1.11, 1.39)]. However, adjusting for BMI attenuated this association [HR: 1.10 (95% CI: 0.97, 1.25)]. The only HIV-specific factor associated with fragility fracture was current protease inhibitor use [HR: 1.41 (95% CI: 1.16, 1.70)].
Conclusions/Significance
HIV infection is associated with fragility fracture risk. This risk is attenuated by BMI.
doi:10.1371/journal.pone.0017217
PMCID: PMC3040233  PMID: 21359191
18.  Short term bone loss in HIV infected premenopausal women 
Background
Low bone mineral density (BMD) has been reported in HIV + women, but less is known about the longitudinal evolution of BMD and fracture incidence.
Methods
In 100 HIV+ and 68 HIV− premenopausal women in the Women’s Interagency HIV Study (WIHS), BMD was measured by dual energy x-ray absorptiometry at the femoral neck (FN) and lumbar spine (LS) at index visit and after a median of 2.5 years.
Results
In HIV+ women, BMD at index visit was normal but 5% lower at the LS and FN than in HIV− women. Annual percent decrease in BMD did not differ between HIV+ and HIV− women at the LS (−0.8±0.2% vs −0.4±0.2%, p=0.20) or FN (−0.8±0.3% vs −0.6±0.3%, p=0.56), and remained similar after adjustment for age, weight, and BMD at index visit. Among HIV+ women, bone loss was associated with vitamin D deficiency and opiate use but not with use or class of antiretrovirals. Incidence of self-reported fracture was 0.74/100 person-years in HIV+ women, and similar in HIV− women.
Conclusions
In premenopausal HIV+ women, index BMD was lower than comparable HIV− women; however, rates of bone loss at the LS and FN were similar over 2.5 years of observation, irrespective of ART.
doi:10.1097/QAI.0b013e3181bf6471
PMCID: PMC2813405  PMID: 19890216
19.  A Comparison of Two Approaches to Text Processing: Facilitating Chart Reviews of Radiology Reports in Electronic Medical Records 
Chart review is central to health services research. Text processing, which analyzes free-text fields through automated methods, can facilitate this process. We compared precision and accuracy of NegEx and SQLServer 2008 Free-Text Search in identifying acute fractures in radiology reports.
The term “fracture” was included in 23,595 radiology reports from the Veterans Aging Cohort Study. Four hundred reports were randomly selected and manually reviewed for acute fractures to establish a gold standard. Reports were then processed by SQLServer and NegEx. Results were compared to the gold standard to determine accuracy, precision, recall, and F-statistic.
NegEx and the gold standard identified acute fractures in 13 reports. SQLServer identified 2 in a report-based analysis (precision: 1.00; accuracy: 0.97; recall: 0.15; F-statistic: 0.26), and 12 in a sentence-by-sentence analysis (precision: 1.00; recall: 0.92; accuracy: 0.92; F-statistic: 0.96).
Text-processing tools utilizing basic database or programming skills are comparable, precise, and accurate in identifying reports for review.
PMCID: PMC2966352  PMID: 21063542
20.  Five cases of bacteraemia due to Gordonia species 
Journal of Medical Microbiology  2009;58(Pt 10):1376-1378.
Gordonia species are aerobic Gram-positive bacilli and a rare cause of human disease. To our knowledge, there are only two cases of human infection with Gordonia sputi reported in the literature. We report five cases of bacteraemia due to Gordonia species at our institution since 2005, including four caused by G. sputi. Three of these cases were likely related to chronic indwelling central venous catheters.
doi:10.1099/jmm.0.010272-0
PMCID: PMC3192486  PMID: 19528153
21.  Low bone-mineral density in patients with HIV: pathogenesis and clinical significance 
Purpose of review
Low bone-mineral density is a recently recognized metabolic complication of HIV infection and its treatment. While the clinical impact of low bone-mineral density remains uncertain, the prolongation of survival attributable to more effective antiretroviral therapy has contributed to an aging population of HIV-infected patients who may be prone to developing fragility fractures.
Recent findings
While most of the available data are on young men, recent publications have increased our understanding of the epidemiology of low bone-mineral density and bone loss in HIV-positive women. Most studies suggest that initiation of certain combinations of antiretroviral agents may be associated with moderate bone loss initially, but bone-mineral density usually stabilizes or improves with longer follow-up. Most studies suggest that, despite lower bone-mineral density, fragility fractures are relatively uncommon in HIV-positive patients, perhaps because of their relative youth.
Summary
The pathogenesis of low bone-mineral density in HIV-positive patients is complex and multifactorial, and its clinical impact remains unclear. Further research is needed to clarify the approach to optimal screening and treatment of osteoporosis in the setting of HIV infection.
doi:10.1097/MED.0b013e3280109b6c
PMCID: PMC2868191  PMID: 20467568
HIV; low bone-mineral density; metabolic complications; osteoporosis

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