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Background:HIV-infected adults have increased fracture risk. Objectives:To generate pilot data comparing bone density, structure, and strength between HIV-infected adults with and without a prior fracture. Methods:Adults with and without a prior fracture after their HIV diagnosis were matched 1:1 based on age, sex, race, and smoking history. Participants underwent dual-energy X-ray absorptiometry (DXA), trabecular bone score (TBS), hip structural analyses (HSA), vertebral fracture assessment (VFA), high-resolution peripheral quantitative tomography (HR-pQCT) and measurement of bone turnover markers. Results were compared between cases and controls, with differences expressed as percentages of control group values. Results:23 pairs were included. On DXA, cases had lower areal bone mineral density (aBMD) at the total hip (median difference in T-score −0.25,p = 0.04), but not the lumbar spine (median difference in T-score 0.10,p = 0.68). Cases had greater abnormalities in HSA and most HR-pQCT and HSA measures, by up to 15%. VFA revealed two subclinical fractures among cases but none among controls. TBS, CTX, and P1NP levels were similar between groups, with differences of 1.9% (p = 0.90), 9.7% (p = 0.55), and 10.0% (p = 0.24), respectively. For each parameter, we report the median and interquartile range for the absolute and relative difference between cases and controls, the correlation between cases and controls, and our recruitment rates, to inform the design of future studies. Conclusions:These pilot data suggest potential differences in bone structure, estimated bone strength, and asymptomatic vertebral fractures among HIV-infected adults with and without fracture, warranting further study as markers of fracture risk in HIV. [ABSTRACT FROM AUTHOR]

Systemic inflammation and immune activation may persist in HIV-infected persons on suppressive combination antiretroviral therapy (cART) and contribute to adverse health outcomes. We compared markers of immune activation, inflammation, and abnormal glucose and lipid metabolism in HIV-infected adults according to herpes simplex virus type 2 (HSV-2) serostatus in a 6-month observational cohort study in Toronto, Canada. HIV-infected adults on suppressive (viral load <50 copies/ml) cART were categorized as HSV-2 seropositive or seronegative using the HerpeSelect ELISA, and underwent study visits at baseline, 3 months, and 6 months. The primary outcome was the median percentage of activated (CD38+HLADR+) CD8 T cells. Secondary outcome measures included additional immune (activated CD4, regulatory T cells) and inflammatory (hsCRP, D-dimer, IL-1b, IL-6, MCP-1, TNF, sICAM-1, sVCAM-1, Ang1/Ang2 ratio) markers. Metabolic outcomes included the proportion with impaired fasting glucose/impaired glucose tolerance/diabetes, insulin sensitivity (calculated using the Matsuda index), insulin resistance (homeostasis model assessment of insulin resistance), and fasting lipids. The impact of HSV-2 on each outcome was estimated using generalized estimating equation regression models. Of 84 participants, 38 (45%) were HSV-2 seropositive. HSV signs and symptoms were uncommon. Aside from D-dimer, which was more often detectable in HSV-2 seropositives (adjusted odds ratio=3.58, 95% CI=1.27, 10.07), HSV-2 serostatus was not associated with differences in any other immune, inflammatory cytokine, acute phase reactant, endothelial activation, or metabolic markers examined in univariable or multivariable models. During the study, CD8 and CD4 T cell activation declined by 0.16% and 0.08% per month, respectively, while regulatory T cells increased by 0.05% per month. HSV-2 serostatus was not consistently associated with immune activation, inflammatory, or lipid and glucose metabolic markers in this cohort of HIV-infected adults on suppressive cART. [ABSTRACT FROM AUTHOR]

Older HIV-positive patients may experience reduced benefit and increased toxicities from combination anti-retroviral therapies (cART) due to late diagnosis, weakened immune systems, and other age-related physiological changes. This study investigates the effect of age on time to virologic suppression and CD4 cell count response to cART. Data were collected from a tertiary care immunodeficiency clinic in Toronto. HIV-positive patients with cART initiation after 1/1/1998 were included. Log logistic accelerated failure time models were used to estimate the effect of age on time to virologic suppression. Mixed linear models were used to evaluate CD4 cell response to treatment. A total of 502 patients were studied; 445 were less than 50 years old and 57 were age 50 or over. Of these 73% were male. Thirty-one percent started treatment with boosted protease inhibitors and 43% with non-nucleoside reverse transcriptase inhibitors. In a log logistic model adjusting for gender, immigration status, AIDS-defining illness, years since HIV diagnosis, baseline CD4 count and viral load, cART type, calendar year of cART initiation, and hepatitis C diagnosis, older age was not associated with time to virologic suppression (n =418, time ratio = 0.94, p = 0.20). In a multivariable mixed linear regression model adjusting for the same covariates, age was not associated with CD4 cell count response (n = 418, ß = 0.34, p = 0.96). Time to virologic suppression and im-munologic response were not significantly different among older and younger patients. Further studies should investigate adherence, comorbidities, and regimen changes in addition to the current covariates. [ABSTRACT FROM AUTHOR]