Virological Failure and Acquired Genotypic Resistance Associated With Contemporary Antiretroviral Treatment Regimens.

BACKGROUND: There are few descriptions of virologic failure (VF) and acquired drug resistance (HIVDR) in large cohorts initiating contemporary antiretroviral therapy (ART). METHODS: We studied all persons with HIV (PWH) in a California clinic population initiating ART between 2010 and 2017. VF was defined as not attaining virologic suppression, discontinuing ART, or virologic rebound prompting change in ART. RESULTS: During the study, 2315 PWH began ART. Six companion drugs were used in 93.3% of regimens: efavirenz, elvitegravir/c, dolutegravir, b-darunavir, rilpivirine, and raltegravir. During a median follow-up of 36 months, 214 (9.2%) PWH experienced VF (2.8 per 100 person-years) and 62 (2.7%) experienced HIVDR (0.8 per 100 person-years). In multivariable analyses, younger age, lower CD4 count, higher virus load, and b-atazanavir were associated with increased VF risk; lower CD4 count, higher virus load, and nevirapine were associated with increased HIVDR risk. Compared with efavirenz, dolutegravir, raltegravir, and b-darunavir were associated with reduced HIVDR risk. Risks of VF and HIVDR were not significantly associated with ART initiation year. Of the 62 PWH with HIVDR, 42 received an non-nucleoside RT inhibitor (NNRTI), 15 an integrase-strand transfer inhibitor (INSTI), and 5 a protease inhibitor (PI). Among those with HIVDR on an NNRTI or first-generation INSTI, 59% acquired dual class resistance and 29% developed tenofovir resistance; those receiving a PI or dolutegravir developed just M184V. CONCLUSIONS: Despite the frequent use of contemporary ART regimens, VF and HIVDR continue to occur. Further efforts are required to improve long-term ART virological responses to prevent the consequences of ongoing HIV-1 replication including virus transmission and HIVDR.

Semantic Memory in the Clinical Progression of Alzheimer Disease.

BACKGROUND AND OBJECTIVE: Semantic memory measures may be useful in tracking and predicting progression of Alzheimer disease. We investigated relationships among semantic memory tasks and their 1-year predictive value in women with Alzheimer disease. METHODS: We conducted secondary analyses of a randomized clinical trial of raloxifene in 42 women with late-onset mild-to-moderate Alzheimer disease. We assessed semantic memory with tests of oral confrontation naming, category fluency, semantic recognition and semantic naming, and semantic density in written narrative discourse. We measured global cognition (Alzheimer Disease Assessment Scale, cognitive subscale), dementia severity (Clinical Dementia Rating sum of boxes), and daily function (Activities of Daily Living Inventory) at baseline and 1 year. RESULTS: At baseline and 1 year, most semantic memory scores correlated highly or moderately with each other and with global cognition, dementia severity, and daily function. Semantic memory task performance at 1 year had worsened one-third to one-half standard deviation. Factor analysis of baseline test scores distinguished processes in semantic and lexical retrieval (semantic recognition, semantic naming, confrontation naming) from processes in lexical search (semantic density, category fluency). The semantic-lexical retrieval factor predicted global cognition at 1 year. Considered separately, baseline confrontation naming and category fluency predicted dementia severity, while semantic recognition and a composite of semantic recognition and semantic naming predicted global cognition. No individual semantic memory test predicted daily function. CONCLUSIONS: Semantic-lexical retrieval and lexical search may represent distinct aspects of semantic memory. Semantic memory processes are sensitive to cognitive decline and dementia severity in Alzheimer disease.

Risk Factors and Temporal Trends of Hospital-Acquired Infections (HAIs) Among HIV Positive Patients in Urban New York City Hospitals: 2006 to 2014.

BACKGROUND: HIV-infected patients may be at a greater risk of Hospital-Acquired Infections (HAIs) but risks factors for HAIs have not been well described in this population. OBJECTIVE: The aim of this study was to examine the incidence, temporal trends and risk factors of HAIs among adult HIV positive patients. METHODS: This was a retrospective cohort study carried out in an academic health system in New York City which included four hospitals over a 9-year period from 2006 to 2014. Simple and multiple logistic regression models were built to determine risk factors associated with site-specific HAIs such as Urinary Tract Infections (UTIs), Pneumonia (PNUs) and Bloodstream Infections (BSIs). FINDINGS: There were 10,575 HIV positive discharges and 1,328 had HAIs: 697 UTIs, 555 BSIs and 192 PNUs. The incidence rate of HAIs decreased from 19.8 to 15.1 new infections per 1000 persondays between 2006 and 2014 (p value<0.001). In addition to the expected risk factors of urinary catheter use for UTI and central venous line use for BSI, symptomatic HIV and renal failure were significant risk factors for both UTIs (95% CI OR: (1.24, 2.27) and (1.46, 2.11) respectively) and BSIs (95% CIs OR: (2.28, 4.18) and (1.81, 2.71) respectively). CONCLUSION: HIV-infected patients had similar risk factors for HAIs as HIV-uninfected patients. Further research is required to address how patients' CD4 counts and viral loads affect their susceptibility to HAIs.