Frailty and Pre-Frailty in a Contemporary Cohort of HIV-Infected Adults.

OBJECTIVES: To determine the prevalence of pre-frailty among HIV-infected persons and associations with pre-frailty and frailty in this population. DESIGN, SETTING AND PARTICIPANTS: From a contemporary, prospective observational cohort of HIV-infected persons (SUN Study), we determined, using a cross-sectional analytic study design, the proportions of non-frail, pre-frail, and frail persons by the respective presence of 0, 1-2, and ≥ 3 of 5 established frailty criteria: unintentional weight loss, exhaustion, physical-inactivity, weak-grip and slow-walk. We evaluated associations with pre-frailty/frailty using multivariate analysis. RESULTS: Of 322 participants assessed (79% men, 58% white non-Hispanic, median age 47 years, 95% on combination antiretroviral therapy [cART], median CD4 + cell count 641 cells/mm3 and 93% HIV RNA < 400 copies/mL), 57% were non-frail, 38% pre-frail, and 5% frail. Age increased from non-frailty through frailty. Notably, however, half of pre-frail and frail participants were < 50 years, and of those, 42% and 100%, respectively, were long-term unemployed (versus 16% of non-frail counterparts). In multivariate analysis, pre-frail/frail participants were more likely to have Hepatitis C seropositivity (adjusted odds ratio [aOR] 3.24, 95% CI: 1.35-7.78), a history of AIDS-defining-illness (aOR 3.51, 95% CI: 1.82-6.76), greater depressive symptoms (aOR 1.16, 95% CI:1.09-1.23), higher D-dimer levels (aOR 2.94, 95% CI:1.10-7.87), and were less likely to be white non-Hispanic (aOR 0.35, 95% CI: 0.20-0.61). CONCLUSIONS: Pre-frailty and frailty are prevalent in the cART era and are associated with unemployment even among persons < 50 years. Pre-frailty appears to be an intermediate state in the spectrum from non-frailty through frailty and our characterization of pre-frailty/frailty suggests complex multifactorial associations.

Are neighborhood conditions associated with HIV management?

OBJECTIVES: HIV infection has become a manageable chronic disease as a result of treatment advances. Secondary prevention efforts have proved inadequate to reduce the estimated incidence of new HIV infections. Epidemiological data suggest that geographical clustering of new HIV infections is a common phenomenon, particularly in urban areas among populations of low socioeconomic status. This study aimed to assess the relationship between neighbourhood conditions and HIV management and engagement in high-risk behaviours. METHODS: During routine out-patient HIV clinic visits, 762 individuals from the St Louis metropolitan area completed behavioural assessments in 2008. Biomedical markers were abstracted from their medical records. Multi-level analyses were conducted based on individuals' census tracts. RESULTS: The majority of the sample were male and African American. In the adjusted models, individuals residing in neighbourhoods with higher poverty rates were more likely to have lower CD4 cell counts and be current smokers. In neighbourhoods with higher rates of unemployment, individuals were less likely to have a current antiretroviral prescription. In more racially segregated neighbourhoods, individuals reported more depressive symptoms. CONCLUSIONS: Despite the advances in HIV disease management, neighbourhood characteristics contribute to disparities in HIV care. Interventions that address neighbourhood conditions as barriers to HIV management may provide improved health outcomes.

Sub-optimal CD4 recovery on long-term suppressive highly active antiretroviral therapy is associated with favourable outcome.

OBJECTIVES: To examine risk factors for sub-optimal CD4 recovery on suppressive highly active antiretroviral therapy (HAART) and assess long-term clinical and immunological outcomes. METHODS: Retrospective analysis of 286 HIV-positive patients from a university clinic who initiated HAART with CD4 count <350 cells/microL between January 1996 and July 2006 and achieved > or =52 weeks of viral suppression (VS). Sub-optimal and optimal CD4 count recovery were defined by gains of <150 and > or =150 cells/microL during the first year of VS, respectively. Risk factors were analysed by multivariate logistic regression and markers of immune maturation and activation were evaluated prospectively for a sub-group of patients with prolonged (>5 years) VS. RESULTS: One hundred and two (36%) patients had sub-optimal CD4 recovery. Male gender, lower pre-HAART viral load, HAART toxicity and use of opportunistic infection (OI) prophylaxis were independent risk factors on multivariate analysis (P<0.05). Outcomes of duration of VS on HAART (4 years), new OI events (1%) and mortality (5%) were similar between groups. Markers of immune maturation and activation were higher among patients with sub-optimal CD4 recovery (P<0.05). CONCLUSIONS: Among HIV-positive patients with long-term VS, sub-optimal CD4 recovery was common but morbidity and mortality remained low. In addition, persistent CD4 T-cell activation appeared to blunt long-term CD4 gains.

Gastric carcinoid: germline and somatic mutation of the neurofibromatosis type 1 gene.

Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominantly inherited conditions. A range of complications has been described, including gastrointestinal manifestations. Gastric carcinoid tumours are associated with multiple endocrine neoplasia, atrophic gastritis and pernicious anaemia but have not been reported in NF1 in the absence of other predisposing factors. We report the occurrence and investigation of a gastric carcinoid tumour in a 23-year-old woman with previously uncomplicated NF1. Analysis of the tumour tissue revealed loss of heterozygosity at the NF1 gene locus but a normal karyotype and an absence of microsatellite instability. A germline NF1 gene nonsense mutation in exon 37 was detected by denaturing high-performance liquid chromatography and DNA sequence analysis. This is the first reported occurrence of a gastric carcinoid tumour in a patient with NF1 in the absence of other predisposing factors such as pernicious anaemia. The analyses indicate that the carcinoid arose through NF1 gene inactivation but in the absence of an inherited NF1 gene microdeletion. This case adds to the range of gastrointestinal tumours that may be encountered in patients with NF1, particularly in those who present with upper gastrointestinal haemorrhage.