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BackgroundPeople with HIV (PWH) with access to antiretroviral therapy (ART) experience excess morbidity and mortality compared with uninfected patients, particularly those with persistent viremia and without CD4+ cell recovery. We compared outcomes for medical intensive care unit (MICU) survivors with unsuppressed (>500 copies/ml) and suppressed (≤500 copies/ml) HIV-1 RNA and HIV-uninfected survivors, adjusting for CD4+ cell count.SettingWe studied 4537 PWH [unsuppressed = 38%; suppressed = 62%; 72% Veterans Affairs-based (VA) and 10 531 (64% VA) uninfected Veterans who survived MICU admission after entering the Veterans Aging Cohort Study (VACS) between fiscal years 2001 and 2015.MethodsPrimary outcomes were all-cause 30-day and 6-month readmission and mortality, adjusted for demographics, CD4+ cell category (≥350 (reference); 200-349; 50-199;

BackgroundDespite treatment with virologically suppressive antiretroviral therapy (ART), neurocognitive impairment may persist or develop de novo in aging HIV-infected individuals. We evaluated advancing age as a predictor of neurocognitive impairment in a large cohort of previously ART-naive individuals on long-term ART.DesignThe AIDS Clinical Trials Group Longitudinal Linked Randomized Trials was a prospective cohort study of HIV-infected individuals originally enrolled in randomized ART trials. This analysis examined neurocognitive outcomes at least 2 years after ART initiation.MethodsAll participants underwent annual neurocognitive testing consisting of Trail making A and B, the wechsler adult intelligence scale-revised Digit Symbol and Hopkins Verbal Learning Tests. Uni and multivariable repeated measures regression models evaluated factors associated with neurocognitive performance. Predictors at parent study entry (ART naive) included entry demographics, smoking, injection drug use, hepatitis B surface antigen, hepatitis C virus serostatus, history of stroke, ART regimen type, pre-ART nadir CD4 cell count, and plasma viral load and as well as time-updated plasma viral load and CD4 cell count.ResultsThe cohort comprised 3313 individuals with median pre-ART age of 38 years, 20% women; 36% Black, non-Hispanic; 22% Hispanic. Virologic suppression was maintained at 91% of follow-up visits. Neurocognitive performance improved with years of ART. After adjusting for the expected effects of age using norms from HIV-negative individuals, the odds of neurocognitive impairment at follow-up visits among the HIV infected increased by nearly 20% for each decade of advancing age.ConclusionDespite continued virologic suppression and neurocognitive improvement in the cohort as a whole, older individuals were more likely to have neurocognitive impairment than younger individuals.

BackgroundDefining the association of non-AIDS-defining events with inflammation and immune activation among human immunodeficiency virus (HIV)-infected persons with antiretroviral therapy (ART)-associated virological suppression is critical to identifying interventions to decrease the occurrence of these events.MethodsWe conducted a case-control study of HIV-infected subjects who had achieved virological suppression within 1 year after ART initiation. Cases were patients who experienced non-AIDS-defining events, defined as myocardial infarction, stroke, non-AIDS-defining cancer, non-AIDS-defining serious bacterial infection, or death. Controls were matched to cases on the basis of age, sex, pre-ART CD4(+) T-cell count, and ART regimen. Peripheral blood mononuclear cells and plasma specimens obtained at the visit before ART initiation (hereafter, baseline), the visit approximately 1 year after ART initiation (hereafter, year 1), and the visit immediately preceding the non-AIDS-defining event (hereafter, pre-event) were analyzed for activated CD4(+) and CD8(+) T cells, plasma interleukin 6 (IL-6) level, soluble tumor necrosis factor receptor I (sTNFR-I) level, sTNFR-II level, soluble CD14 level, kynurenine-to-tryptophan (KT) ratio, and D-dimer level. Conditional logistic regression analysis was used to study the association between biomarkers and outcomes, with adjustment for potential confounders.ResultsHigher IL-6 level, sTNFR-I level, sTNFR-II level, KT ratio, and D-dimer level at year 1 were associated with the occurrence of a non-AIDS-defining event. Significant associations were also seen between non-AIDS-defining events and values of these biomarkers in specimens obtained at baseline and the pre-event time points. Effects remained significant after control for confounders. T-cell activation was not significantly related to outcomes.ConclusionsInterventional trials to decrease the incidence of non-AIDS-defining events among HIV-infected persons with virological suppression should consider targeting the pathways represented by these soluble markers. Clinical Trials Registration. NCT00001137.

The first cure of HIV-1 infection was achieved through complex, multimodal therapy including myeloablative chemotherapy, total body irradiation, anti-thymocyte globulin, and allogeneic stem cell transplantation with a CCR5 delta32 homozygous donor. The contributions of each component of this therapy to HIV-1 eradication are unclear. To assess the impact of cytotoxic chemotherapy alone on HIV-1 persistence, we longitudinally evaluated low-level plasma viremia and HIV-1 DNA in PBMC from patients in the ACTG A5001/ALLRT cohort on suppressive antiretroviral therapy (ART) who underwent chemotherapy for HIV-1 related lymphoma without interrupting ART. Plasma HIV-1 RNA, total HIV-1 DNA and 2-LTR circles (2-LTRs) in PBMC were measured using sensitive qPCR assays. In the 9 patients who received moderately intensive chemotherapy for HIV-1 related lymphoma with uninterrupted ART, low-level plasma HIV-1 RNA did not change significantly with chemotherapy: median HIV-1 RNA was 1 copy/mL (interquartile range: 1.0 to 20) pre-chemotherapy versus 4 copies/mL (interquartile range: 1.0 to 7.0) post-chemotherapy. HIV-1 DNA levels also did not change significantly, with median pre-chemotherapy HIV-1 DNA of 355 copies/106 CD4+ cells versus 228 copies/106 CD4+ cells post-chemotherapy. 2-LTRs were detectable in 2 of 9 patients pre-chemotherapy and in 3 of 9 patients post-chemotherapy. In summary, moderately intensive chemotherapy for HIV-1 related lymphoma in the context of continuous ART did not have a prolonged impact on HIV-1 persistence. Clinical trials registration unique identifier: NCT00001137.

Background: People aging with and without HIV (PWH and PWoH) want to avoid neurocognitive dysfunction, especially delirium. Continued use of alcohol in conjunction with neurocognitively active medications (NCAMs) may be a largely underappreciated cause, especially for PWH who experience polypharmacy a decade earlier than PWoH. We compare absolute and relative risk of delirium among PWH and PWoH by age, level of alcohol use, and exposure to NCAMs. Methods: Using the VACS cohort, we compare absolute and relative risk of inpatient delirium among PWH and PWoH by age, level of alcohol use, and exposure to NCAMs between 2007 and 2019. We matched each case based on age, race/ethnicity, sex, HIV, baseline year, and observation time with up to 5 controls. The case/control date was defined as date of admission for cases and the date corresponding to the same length of time on study for controls. Level of alcohol use was defined using Alcohol Use Disorder Identification Test–Consumption (AUDIT‐C). Medication exposure was measured from 45 to 3 days prior to index date; medications were classified as anticholinergic NCAM, non‐anticholinergic NCAM, or non NCAM and counts generated. We used logistic regression to determine odds ratios (ORs) for delirium associated with medication counts stratified by HIV status and adjusted for demographics, severity of illness, and related diagnoses. Results: PWH experienced a higher incidence of delirium (5.6, [95% CI 5.3–5.9/1000 PY]) than PWoH (5.0, [95% CI 4.8–5.1/1000 PY]). In multivariable analysis, anticholinergic and non‐anticholinergic NCAM counts and level of alcohol use demonstrated strong independent dose–response associations with delirium. Conclusions: Decreasing alcohol use and limiting the use of neurocognitively active medications may help decrease excess rates of delirium, especially among PWH. [ABSTRACT FROM AUTHOR]

Background: Polypharmacy is associated with dyspnea in cross-sectional studies, but associations have not been determined in longitudinal analyses. Statins are commonly prescribed but their contribution to dyspnea is unknown. We determined whether polypharmacy was associated with dyspnea trajectory over time in adults with advanced illness enrolled in a statin discontinuation trial, overall, and in models stratified by statin discontinuation. Methods: Using data from a parallel-group unblinded pragmatic clinical trial (patients on statins ≥3 months with life expectancy of 1 month to 1 year, enrolled in the parent study between June 3, 2011, and May 2, 2013, n = 308/381 [81%]), we restricted analyses to patients with available baseline medication count and ≥1 dyspnea score. Polypharmacy was assessed by self-reported chronic medication count. Dyspnea trajectory group, our primary outcome, was determined over 24 weeks using the Edmonton Symptom Assessment System. Results: The mean age of the patients was 73.8 years (standard deviation [SD]: ±11.0) and the mean medication count was 11.6 (SD: ±5.0). We identified 3 dyspnea trajectory groups: none (n = 108), mild (n = 130), and moderate–severe (n = 70). Statins were discontinued in 51.8%, 48.5%, and 42.9% of patients, respectively. In multivariable models adjusting for age, sex, diagnosis, and statin discontinuation, each additional medication was associated with 8% (odds ratio [OR] = 1.08 [1.01-1.14]) and 16% (OR = 1.16 [1.08-1.25]) increased risk for mild and moderate–severe dyspnea, respectively. In stratified models, polypharmacy was associated with dyspnea in the statin continuation group only (mild OR = 1.12 [1.01-1.24], moderate–severe OR = 1.24 [1.11-1.39]) versus statin discontinuation (mild OR = 1.03 [0.95-1.12], and moderate–severe OR = 1.09 [0.98-1.22]). Conclusion: Polypharmacy was strongly associated with dyspnea. Prospective interventions to decrease polypharmacy may impact dyspnea symptoms, especially for statins. [ABSTRACT FROM AUTHOR]