The Relationships between Total Body, Lumbar Spine and Femoral Neck Bone Mineral Density T-Scores for Diagnosis of Low Bone Mass in HIVInfected Patients

Background: The total bone mineral density T-score cutoff for low bone mass underestimates the frequency shown by femoral neck and lumbar T-score cutoffs. Objective: To determine whether a total body DXA T-score cutoff can be found that will produce results similar those obtained by local measurements of the femoral neck and lumbar spine. Methodology: Participants were all HIV-infected; 1730 males and 840 females. T-score correlations of the three sites were obtained. ROC analyses were performed to obtain the T-score cutoffs for the total body that would produce results that best matched those of the femoral neck and lumbar spine. Low bone mass was defined as a T-score <-1, which includes both osteopenia and osteoporosis categories as defined by the World Health Organization (WHO). The efficacy of the derived T-score cutoffs were determined by cross tabulation of the modified total body classifications against the femoral neck and lumbar spine classification, and rated by the kappa coefficient of agreement and percent of agreement (concordance). Results: Spearman rank correlations varied from 0.570 to 0.752 between total body, lumbar spine and femoral neck T-scores. Area under the ROC curve varied from 0.777 to 0.874 for the different paired sites. The T-score cutoffs for the total body were selected from the ROC curves at a point where the sum of the sensitivity and specificity is a maximum. Cross tabulation of the binary categories. i.e., normal or abnormal, of the total body using the derived T-score cutoffs against those of the femoral neck and lumbar spine registered a reduction of false negatives, but it was associated with a consistent increase in the number of false positives. The resultant kappa coefficients of agreement varied from 0.429 to 0.564; a moderate rating when perfect agreement is 1.0. Conclusion: The modification of the total body T-score cutoffs for the disclosure of low bone mass at the femoral neck and lumbar spine is not sufficiently accurate for clinical application, in particular fracture risk prediction

Predictors of transitions in frailty severity and mortality among people aging with HIV.

BACKGROUND: People aging with HIV show variable health trajectories. Our objective was to identify longitudinal predictors of frailty severity and mortality among a group aging with HIV. METHODS: Exploratory analyses employing a multistate transition model, with data from the prospective Modena HIV Metabolic Clinic Cohort Study, based in Northern Italy, begun in 2004. Participants were followed over four years from their first available visit. We included all 963 participants (mean age 46.8±7.1; 29% female; 89% undetectable HIV viral load; median current CD4 count 549, IQR 405–720; nadir CD4 count 180, 81–280) with four-year data. Frailty was quantified using a 31-item frailty index. Outcomes were frailty index score or mortality at four-year follow-up. Candidate predictor variables were baseline frailty index score, demographic (age, sex), HIV-disease related (undetectable HIV viral load, current CD4+ T-cell count, nadir CD4 count, duration of HIV infection, and duration of antiretroviral therapy [ARV] exposure), and behavioral factors (smoking, injection drug use (IDU), and hepatitis C virus co-infection). RESULTS: Four-year mortality was 3.0% (n = 29). In multivariable analyses, independent predictors of frailty index at follow-up were baseline frailty index (RR 1.06, 95% CI 1.05–1.07), female sex (RR 0.93, 95% CI 0.87–0.98), nadir CD4 cell count (RR 0.96, 95% CI 0.93–0.99), duration of HIV infection (RR 1.06, 95% CI 1.01–1.12), duration of ARV exposure (RR 1.08, 95% CI 1.02–1.14), and smoking pack-years (1.03, 1.01–1.05). Independent predictors of mortality were baseline frailty index (OR 1.19, 1.02–1.38), current CD4 count (0.34, 0.20–0.60), and IDU (2.89, 1.30–6.42). CONCLUSIONS: Demographic, HIV-disease related, and social and behavioral factors appear to confer risk for changes in frailty severity and mortality among people aging with HIV

Cognitive health in persons with human immunodeficiency virus: the impact of early treatment, comorbidities, and aging

With the advent of virally suppressive antiretroviral therapy (ART), life expectancy for persons with human immunodeficiency virus (HIV) with access to ART now approaches that of the general population. As persons with HIV age, noninfectious comorbidities occur more frequently compared with persons without HIV. Such comorbidities are likely to affect cognitive health, which may also be affected by lifestyle factors that may differ in persons with HIV. At the National Institutes of Health–supported meeting on Biotypes of Central Nervous System (CNS) Complications in persons with HIV, a session was devoted to early HIV treatment, noninfectious comorbidities, and aging as each pertains to cognitive health. Areas of consideration included acute and early HIV infection (presentation by Phillip Chan), drugs of abuse (Scott Letendre), stroke and cerebrovascular disease (Felicia Chow), mental health (John Joska), and aging (Julian Falutz). These presentations were followed by a discussion session led by Woody Lin, Jose A. Muñoz-Moreno, Paola Cinque, and Jeff Taylor. Alan Winston and Bruce Brew chaired the meeting with Jasmini Alagaratnam and Htein Linn Aung acting as rapporteurs. Here we present the main topics covered in the presentations, and the associated discussions highlighting knowledge gaps and future directions

Approach to Dyslipidemia, Lipodystrophy, and Cardiovascular Risk in Patients with HIV Infection

There is a significant prevalence (20%–80% depending on the population and the study) of lipid disorders and other cardiovascular risk factors in people living with HIV infection. This review focuses on HIV and HIV treatment–associated metabolic and cardiovascular concerns, including dyslipidemias, lipodystrophy syndromes, endothelial dysfunctions, and associated metabolic events such as insulin resistance. Emerging hypotheses of the underlying pathophysiology of these issues, with impact on selection of specific antiretroviral treatment (ART) strategies, therapy, and preventive approaches to decreasing cardiovascular risk and other problems associated with these syndromes are discussed. Screening for cardiovascular risk as part of the decision of starting antiretroviral therapy, and during care of patients with HIV regardless of ART therapy status, is suggested with particular areas of focus. Statins, other hyperlipidemic therapies, treatment for specific problems arising due to lipodystrophy, and implications on ART selection to avoid drug interactions and adverse effects are also discussed

Recombinant Human Growth Hormone and Rosiglitazone for Abdominal Fat Accumulation in HIV- Infected Patients with Insulin Resistance: A Randomized, Double-Blind, Placebo-Controlled, Factorial Trial

Background: Recombinant human growth hormone (rhGH) reduces visceral adipose tissue (VAT) volume in HIV-infected patients but can worsen glucose homeostasis and lipoatrophy. We aimed to determine if adding rosiglitazone to rhGH would abrogate the adverse effects of rhGH on insulin sensitivity (SI) and subcutaneous adipose tissue (SAT) volume. Methodology/Principal Findings: Randomized, double-blind, placebo-controlled, multicenter trial using a 262 factorial design in which HIV-infected subjects with abdominal obesity and insulin resistance were randomized to rhGH 3 mg daily, rosiglitazone 4 mg twice daily, combination rhGH + rosiglitazone, or double placebo (control) for 12 weeks. The primary endpoint was change in SI by frequently sampled intravenous glucose tolerance test from entry to week 12. Body composition was assessed by whole body magnetic resonance imaging (MRI) and dual Xray absorptiometry (DEXA). Seventy-seven subjects were randomized of whom 72 initiated study drugs. Change in SI from entry to week 12 differed across the 4 arms by 1-way ANCOVA (P = 0.02); by pair-wise comparisons, only rhGH (decreasing SI; P = 0.03) differed significantly from control. Changes from entry to week 12 in fasting glucose and glucose area under the curve on 2- hour oral glucose tolerance test differed across arms (1-way ANCOVA P = 0.004), increasing in the rhGH arm relative to control. VAT decreased significantly in the rhGH arms (217.5% in rhGH/rosiglitazone and 222.7% in rhGH) but not in the rosiglitazone alone (22.5%) or control arms (21.9%). SAT did not change significantly in any arm. DEXA results were consistent with the MRI data. There was no significant rhGH x rosiglitazone interaction for any body composition parameter. Conclusions/Significance: The addition of rosiglitazone abrogated the adverse effects of rhGH on insulin sensitivity and glucose tolerance while not significantly modifying the lowering effect of rhGH on VAT

Insulin-like growth factors and related proteins in plasma and cerebrospinal fluids of HIV-positive individuals

BACKGROUND: Clinically significant dysregulation of the insulin-like growth factor (IGF) family proteins occurs in HIV-infected individuals, but the details including whether the deficiencies in IGFs contribute to CNS dysfunction are unknown. METHODS: We measured the levels of IGF1, IGF2, IGFBP1, IGFBP2, and IGF2 receptor (IGF2R) in matching plasma and cerebrospinal fluid (CSF) samples of 107 HIV+ individuals from CNS HIV Antiretroviral Therapy Effects Research (CHARTER) and analyzed their associations with demographic and disease characteristics, as well as levels of several soluble inflammatory mediators (TNFα, IL-6, IL-10, IL-17, IP-10, MCP-1, and progranulin). We also determined whether IGF1 or IGF2 deficiency is associated with HIV-associated neurocognitive disorder (HAND) and whether the levels of soluble IGF2R (an IGF scavenging receptor, which we also have found to be a cofactor for HIV infection in vitro) correlate with HIV viral load (VL). RESULTS: There was a positive correlation between the levels of IGF-binding proteins (IGFBPs) and those of inflammatory mediators: between plasma IGFBP1 and IL-17 (β coefficient 0.28, P = 0.009), plasma IGFBP2 and IL-6 (β coefficient 0.209, P = 0.021), CSF IGFBP1 and TNFα (β coefficient 0.394, P < 0.001), and CSF IGFBP2 and TNF-α (β coefficient 0.14, P < 0.001). As IGFBPs limit IGF availability, these results suggest that inflammation is a significant factor that modulates IGF protein expression/availability in the setting of HIV infection. However, there was no significant association between HAND and the reduced levels of plasma IGF1, IGF2, or CSF IGF1, suggesting a limited power of our study. Interestingly, plasma IGF1 was significantly reduced in subjects on non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART) compared to protease inhibitor-based therapy (174.1 ± 59.8 vs. 202.8 ± 47.3 ng/ml, P = 0.008), suggesting a scenario in which ART regimen-related toxicity can contribute to HAND. Plasma IGF2R levels were positively correlated with plasma VL (β coefficient 0.37, P = 0.021) and inversely correlated with current CD4+ T cell counts (β coefficient −0.04, P = 0.021), supporting our previous findings in vitro. CONCLUSIONS: Together, these results strongly implicate (1) an inverse relationship between inflammation and IGF growth factor availability and the contribution of IGF deficiencies to HAND and (2) the role of IGF2R in HIV infection and as a surrogate biomarker for HIV VL. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-015-0288-6) contains supplementary material, which is available to authorized users

Managing the Older Adult Patient with HIV

This concise, clinically focused pocket guide offers a complete overview of HIV in the older patient and reviews the latest guidelines, treatment options, clinical trials, and management of HIV within this subgroup. The easily accessible text offers infectious disease specialists and other health care professionals with an excellent quick reference tool, with full color tables and figures enhancing the text further. HIV is a chronic disease that affects the immune system, leading to AIDS. As treatments have progressed and patients with HIV are living longer a new aspect has to be taken in to consideration when treating HIV and other conditions. Comorbidities are rife within older adults with HIV, as many of the treatments for HIV cause long-term side effects, such as heart conditions and cancer. Special consideration must be taken to ensure no toxic drug-drug interactions between treatments