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Introduction: Tenofovir disoproxil fumarate (TDF) has been associated with greater incidences of bone complications, which might be modified by some concomitantly administered antiretrovirals, possibly by their effect on tenofovir concentrations. We compared bone adverse outcomes among treatment-naïve HIV-infected US veterans initiating efavirenz (EFV)-containing TDF/emtricitabine (FTC) regimens versus those initiating non-EFV-containing TDF/FTC regimens.Methods: Using national Veterans Health Administration clinical and administrative data sets, we identified a cohort of treatment-naïve HIV-infected veterans without bone disease who initiated therapy with TDF/FTC plus EFV, rilpivirine, elvitegravir/cobicistat, or ritonavir-boosted protease inhibitors in 2003-2015. The primary composite adverse bone outcome was the unadjusted incidence rate (IR) of osteoporosis, osteopenia, or fragility fracture (any hip, wrist, or spine fracture). To account for selection bias and confounding, we used inverse probability of treatment-weighted Cox proportional hazards regression models to calculate adjusted hazard ratios (HRs) for each outcome associated with EFV + TDF/FTC versus each non-EFV-containing TDF/FTC regimen.Results: Of 33,048 HIV-positive veterans, 7161 initiated a TDF/FTC-containing regimen (mean age, 50 years; baseline CD4 < 200 cells/mm3, 33.3%; HIV-1 RNA > 100,000 copies/ml, 22.3%; mean follow-up, 13.0 months). Of these, 4137 initiated EFV- and 3024 non-EFV-containing regimens. Veterans initiating EFV- versus non-EFV-containing TDF/FTC regimens had a lower IR of the composite bone outcome (29.3 vs. 41.4 per 1000 patient-years), with significant risk reductions for this outcome [HR, 0.69; 95% confidence interval (CI), 0.58-0.83] and fragility fracture (HR, 0.59; 95% CI, 0.44-0.78).Conclusion: EFV + TDF/FTC is associated with a lower risk of adverse bone outcomes compared with other TDF-containing regimens in the VHA.Funding: Bristol-Myers Squibb. [ABSTRACT FROM AUTHOR]

Purpose of the Study: Postmenopausal osteoporosis can impact quality-of-life even prefracture. To determine whether osteoporosis should be a greater concern in women Veterans versus non-Veterans, we compared fracture rates and bone mineral density (BMD) for Veterans and non-Veterans using Women's Health Initiative data. Design and Methods: In this cohort study, participants were women aged 50-79 years. Outcomes were hip, central body, and limb fractures occurring during up to 19 years of follow-up and hip, spine, and whole body BMD collected three times over a 6-year period in a participant subsample. Covariates comprised risk factors for fracture, including fall history and other components of the World Health Organization Fracture Risk Assessment Tool (FRAX). Cox Proportional Hazards models were used to examine fracture rates for Veterans compared with non-Veterans. Results: Of 161,808 women, 145,521 self-identified as Veteran (n = 3,719) or non-Veteran (n = 141,802). Baseline FRAX scores showed that Veterans had higher 10-year probabilities for any major fracture (13.3 vs 10.2; p < .01) and hip fracture (4.1 vs 2.2; p < .01) compared with non-Veterans. The age-adjusted rate of hip fracture per 1,000 person-years for Veterans was 3.3 versus 2.4 for non-Veterans (p < .01). After adjustment, the hazards ratio for hip fracture was 1.24 (95% confidence interval 1.03-1.49) for Veterans versus non-Veterans. Hazards ratios at other anatomic sites did not differ by Veteran status. Mean BMD at baseline and at Years 3 and 6 also did not differ by Veteran status at any site. Implications: Women Veterans had an increased hip fracture rate not explained by differences in well-recognized fracture risk factors. [ABSTRACT FROM AUTHOR]

Background: This study estimated the risk of infection-related hospitalizations and death in patients with and without multiple sclerosis (MS). Methods: We identified adults with MS in the US Department of Veterans Affairs (VA) system between 1999 and 2010. Each veteran with MS was matched, on age and sex, with up to four veterans without MS. Multivariable Cox proportional hazards regression models were performed to assess the influence of MS on the development of serious and fatal infections. Results: The cohort included 7743 veterans with MS and 30,972 veterans without MS. Mean (SD) age was 53.8 (13.3) years, and 80.8% were male. The incidence per 1000 person-years of overall serious infections was 19.2 (95% confidence interval [CI], 17.6-20.8) for those with MS and 10.3 (95% CI, 9.8-10.9) for those without MS. Fatal infection incidence rates were 1.2 (95% CI, 0.8-1.7) for patients with MS and 0.5 (95% CI, 0.3-0.6) for patients without MS. Regression models showed that veterans with MS were at greater risk for overall serious (hazard ratio [HR] = 1.52, P < .01) and fatal (HR = 1.85, P = .03) infections and serious respiratory (HR = 1.31, P = .01), urinary tract (HR = 4.44, P < .01), and sepsis-related infections (HR = 2.56, P < .01). Conclusions: This study provides evidence that VA patients with MS are more likely than those without MS to be hospitalized and die of infection. [ABSTRACT FROM AUTHOR]

Background Patients with chronic hepatitis C (HCV) frequently discontinued dual therapy with pegylated interferon alfa (Peg-IFN) plus ribavirin (RBV) before reaching the recommended duration of 48 or 24 weeks for genotypes (G) 1/4 or 2/3, respectively. We quantified rates of discontinuation despite efficacy (non-LOE) versus lack of efficacy (LOE) versus discontinuation for unknown reasons in a national database of United States veterans. Methods We identified a population-based cohort of U.S. veterans with encounters from 2004 through 2009 who had lab-confirmed HCV infection and initiated therapy with Peg-IFN plus RBV in Veterans Health Administration medical centers. Pharmacy data were used to determine therapy duration, defined as the sum of Peg-IFN days supplied. Patients "discontinued" if they failed to receive at least 44 (G1/4) or 20 weeks (G2/3) of therapy. We classified discontinuations as due to non-LOE, LOE, or unknown reasons using a classification rule based on treatment duration and laboratory confirmed response. Results Of 321,238 diagnosed HCV patients during the evaluation period, 9.7% initiated therapy and 6.4% met all other inclusion criteria. 54.9% of patients discontinued early; of these, 41.2% discontinued due to non-LOE reasons, 12.5% discontinued for LOE reasons, and 46.3% discontinued for unknown reasons. Among non-LOE discontinuers, most (60.1%) discontinued in the first 4 weeks of therapy, which constitutes 13.6% of all treated patients. Conclusions We observed a high proportion of early discontinuations with dual-therapy regimens in a national cohort of HCV-infected veterans. If this trend persists in the triple-therapy era, then efforts must be undertaken to improve adherence. [ABSTRACT FROM AUTHOR]