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Background: Osteoporosis is common among HIV-infected persons and contributes to risk of fragility fracture. While ART initiation is associated with decreases in bone mineral density and increases in bone turnover, the impact of HIV on bone metabolism is unclear.Methods: We identified men at the Chicago site of the Multicenter AIDS Cohort Study who HIV seroconverted while under observation. Concentrations of 25-OH vitamin D, bone turnover markers [procollagen type 1 N terminal propeptide (P1NP), osteocalcin (OC), C-telopeptide (CTX)] and sclerostin were measured from stored serum obtained at pre-HIV infection, pre-ART and post-ART initiation timepoints. Mixed models, with each biomarker as an outcome, were fitted. Timepoint, age, CD4 count (cells/mm 3 ), HIV-viral suppression, season and an age by timepoint interaction term were considered as fixed effects.Results: Data from 52 participants revealed that median duration between HIV seroconversion and ART initiation was 8.7 years (IQR 3.7-11.6). Median CD4 and plasma HIV-RNA concentrations were 445 (IQR 298.5-689) and 20 184 copies/mL (IQR 6237-64 340), respectively, at the pre-ART timepoint. Multivariate analyses demonstrated pre-HIV infection levels of OC that were higher than pre-ART levels (6.8 versus 5.7 ng/mL, P  =   0.04); and pre-ART levels of sclerostin that were higher than post-ART levels (0.033 versus 0.02 ng/mL, P  <0.001). No changes in P1NP, CTX and 25-OH vitamin D levels were detected.Conclusions: HIV seroconversion was associated with decreased OC levels while ART initiation was associated with decreases in sclerostin, a negative regulator of bone formation. Our results suggest that both HIV infection and ART have an impact on bone metabolism in white men. [ABSTRACT FROM AUTHOR]

Objectives: There are few data on the real-world experience of FDA-approved oral hepatitis C virus (HCV) direct-acting antiviral (DAA) drug combinations in HIV/HCV-coinfected patients. We evaluated the safety and efficacy of DAA therapies in a cohort of HIV/HCV patients in a large urban clinic in Chicago.Methods: HIV/HCV-coinfected adults (≥18 years) enrolled in the Northwestern University Viral Hepatitis Registry between January 2013 and June 2015 were analysed. Treated patients received one of the following DAA combinations: sofosbuvir/ledipasvir, sofosbuvir/ribavirin, sofosbuvir/simeprevir or paritaprevir/ritonavir/ombitasvir/dasabuvir ± ribavirin. The primary outcome was sustained virological response at 12 weeks after DAA completion (SVR12).Results: Seventy-seven HIV/HCV patients were evaluated for DAA therapy. Most patients were male (62/77, 81%) and infected with HCV genotype 1 (67/77, 87%). Some 32/77 (42%) were cirrhotic and 29/77 (38%) had received prior treatment with an IFN-containing regimen. DAA therapy was more likely to be started in Caucasians than persons of other ethnicities (P = 0.01). The overall SVR12 rate was 92% in 52 patients who completed therapy and had follow-up by the end of the study: sofosbuvir/simeprevir, 32/33 (97%); sofosbuvir/ribavirin, 4/7 (57%); sofosbuvir/ledipasvir, 11/11 (100%); and paritaprevir/ritonavir/ombitasvir/dasabuvir, 1/1 (100%). Four patients relapsed after therapy with sofosbuvir/simeprevir (n = 1) or sofosbuvir/ribavirin (n = 3). Adverse events were uncommon and did not result in DAA treatment interruption or discontinuation.Conclusions: The HCV DAA combinations of sofosbuvir/ledipasvir and sofosbuvir/simeprevir were highly effective and well tolerated in this diverse population of HIV/HCV-coinfected patients, many of whom had advanced liver disease. HIV coinfection should not be considered a barrier to successful HCV treatment with DAAs. [ABSTRACT FROM AUTHOR]

Background There is limited evidence that among HIV-infected patients haemoglobin A1c (HbA1c) values may not accurately reflect glycaemia. We assessed HbA1c discordance (observed HbA1c − expected HbA1c) and associated factors among HIV-infected participants in the Multicenter AIDS Cohort Study (MACS). Methods Fasting glucose (FG) and HbA1c were measured at each semi-annual MACS visit since 1999. All HIV-infected and HIV-uninfected men for whom at least one FG and HbA1c pair measurement was available were evaluated. Univariate median regression determined the association between HbA1c and FG by HIV serostatus. The relationship between HbA1c and FG in HIV-uninfected men was used to determine the expected HbA1c. Generalized estimating equations determined factors associated with the Hb1Ac discordance among HIV-infected men. Clinically significant discordance was defined as observed HbA1c − expected HbA1c ≤−0.5%. Results Over 13 years, 1500 HIV-uninfected and 1357 HIV-infected men were included, with a median of 11 visits for each participant. At an FG of 125 mg/dL, the median HbA1c among HIV-infected men was 0.21% lower than among HIV-uninfected men and the magnitude of this effect increased with FG >126 mg/dL. Sixty-three percent of HIV-infected men had at least one visit with clinically significant HbA1c discordance, which was independently associated with: low CD4 cell count (<500 cells/mm3); a regimen containing a protease inhibitor, a non-nucleoside reverse transcriptase inhibitor or zidovudine; high mean corpuscular volume; and abnormal corpuscular haemoglobin. Conclusion HbA1c underestimates glycaemia in HIV-infected patients and its use in patients with risk factors for HbA1c discordance may lead to under-diagnosis and to under-treatment of established diabetes mellitus. [ABSTRACT FROM PUBLISHER]

Background Identifying factors associated with mortality for HIV-infected patients with persistent viraemia despite antiretroviral (ARV) therapy may inform diagnostic and treatment strategies. Methods We analysed data from viraemic triple-ARV-class-experienced HIV Outpatient Study patients seen during 1 January 1999 to 31 December 2012 who, despite treatment that included ARVs from three major drug classes [nucleoside analogue reverse transcriptase inhibitors, non-nucleoside analogue reverse transcriptase inhibitors and protease inhibitors (PIs)], had plasma HIV RNA levels [viral load (VL)] >1000 copies/mL [‘triple ARV class failure’ (TCF)]. The baseline was defined as the date of meeting the TCF criteria during 1999–2008. We identified factors associated with mortality using Cox regression. Results Of 597 patients who met the TCF criteria (median follow-up after baseline 4.9 years), 115 (19.3%) died. Baseline factors associated with mortality were age per 10 years [hazard ratio (HR) 1.61, 95% CI 1.28–2.02], risk of HIV from use of injection drugs (HR 1.81, 95% CI 1.10–2.98), CD4+ T cell count <200 cells/mm3 (HR 3.68, 95% CI 2.41–5.62), VL ≥5.0 log10 copies/mL (HR 2.91, 95% CI 1.88–4.49) and receiving a first combination ARV therapy regimen that was PI-based (HR 2.44, 95% CI 1.47–4.06); receiving a novel ARV agent during follow-up (HR 0.45, 95% CI 0.22–0.93) was protective. Genotypic resistance testing results were available for 274 (45.9%) of the TCF patients, of whom 47 (17.2%) died. In this group, factors associated with death were increasing age (HR 1.94, 95% CI 1.36–2.78, per 10 year increment), risk of HIV from use of injection drugs (HR 2.71, 95% CI 1.37–5.39), baseline VL ≥5.0 log10 copies/mL (HR 5.35, 95% CI 2.82–10.1) and receiving PI-based first combination ARV therapy regimen (HR 3.20, 95% CI 1.25–8.17). No HIV mutations or combinations of mutations were significantly associated with survival. Conclusions Factors significantly associated with mortality risk among TCF patients who received ongoing ARV therapy included traditional clinical predictors but not the presence, type or number of HIV genetic mutations. The use of novel ARV drugs by these ARV therapy-experienced patients was associated with an improved survival. [ABSTRACT FROM PUBLISHER]