Current Antiretroviral Treatment Among People With Human Immunodeficiency Virus in the United States: Findings from the Centers for AIDS Research Network of Integrated Clinic Systems Cohort

Ma, Jimmy; Nance, Robin M.; Delaney, Joseph A.; Whitney, Bridget M; Bamford, Laura; Gravett, Ronnie M; Moore, Richard D.; Napravnik, Sonia; Mayer, Kenneth H.; Jacobson, Jeffrey M.; Christopoulos, Katerina; Burkholder, Greer A.; Keruly, Jeanne C.; Eron, Joseph J.; Martin, Jeffrey N.; Saag, Michael S.; Crane, Heidi M.; Kitahata, Mari M.

doi:10.1093/cid/ciac086

Cited by 4 publications

(2 citation statements)

References 10 publications

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“…The time period of this study (2011-2021) is representative of the era with updated recommendations for HIV treatment, including immediate initiation of ART following HIV diagnosis [22]. Furthermore, within CNICS, almost all PWH are prescribed ART (>96% in 2019-2020) [62]. Therefore, we suspect this HR may indicate PWH not taking ART having more recently diagnosed HIV, and less time living with HIV to impact the development of frailty.…”

Section: Discussionmentioning

confidence: 99%

Development of Frail RISC-HIV: a Risk Score for Predicting Frailty Risk in the Short-term for Care of People with HIV

Ruderman¹,

Nance²,

Drumright³

et al. 2023

Aids

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Objective: Frailty is common among people with HIV (PWH), so we developed frail risk in the short-term for care (RISC)-HIV, a frailty prediction risk score for HIV clinical decision-making. Design: We followed PWH for up to 2 years to identify short-term predictors of becoming frail. Methods: We predicted frailty risk among PWH at seven HIV clinics across the United States. A modified self-reported Fried Phenotype captured frailty, including fatigue, weight loss, inactivity, and poor mobility. PWH without frailty were separated into training and validation sets and followed until becoming frail or 2 years. Bayesian Model Averaging (BMA) and five-fold-cross-validation Lasso regression selected predictors of frailty. Predictors were selected by BMA if they had a greater than 45% probability of being in the best model and by Lasso if they minimized mean squared error. We included age, sex, and variables selected by both BMA and Lasso in Frail RISC-HIV by associating incident frailty with each selected variable in Cox models. Frail RISC-HIV performance was assessed in the validation set by Harrell's C and lift plots. Results: Among 3170 PWH (training set), 7% developed frailty, whereas among 1510 PWH (validation set), 12% developed frailty. BMA and Lasso selected baseline frailty score, prescribed antidepressants, prescribed antiretroviral therapy, depressive symptomology, and current marijuana and illicit opioid use. Discrimination was acceptable in the validation set, with Harrell's C of 0.76 (95% confidence interval: 0.73–0.79) and sensitivity of 80% and specificity of 61% at a 5% frailty risk cutoff. Conclusions: Frail RISC-HIV is a simple, easily implemented tool to assist in classifying PWH at risk for frailty in clinics.

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Section: Discussionmentioning

confidence: 99%

Development of Frail RISC-HIV: a Risk Score for Predicting Frailty Risk in the Short-term for Care of People with HIV

Ruderman¹,

Nance²,

Drumright³

et al. 2023

Aids

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“…For example, a study recently presented at CROI demonstrated the changes in ART among PWH in the United States over time. 26 It showed the very rapid transition from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate over the past 3 years. Figure 4 demonstrates the rapid change in single-tablet regimens.…”

Section: Lesson 3: Timely Datamentioning

confidence: 99%

HIV, Aging, and Comorbidities Research in Clinical Cohorts: 3 Lessons Learned Using Examples From the CNICS Cohort

Crane

Drumright

2022

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background: Owing to ongoing improvements in antiretroviral therapy, people with HIV (PWH) are achieving near-normal lifespans with many surviving into middle and old age. Despite this success, PWH have a higher than expected risk of developing non-AIDS comorbidities, multimorbidity, and functional decline at ages younger than those without HIV. Methods: As part of the Inter-CFAR (Center for AIDS Research) Symposium, HIV and Aging in the era of Antiretroviral Therapy and COVID-19 , we presented a research update from HIV clinical cohorts and specifically described 3 lessons learned from the Centers for AIDS Research Network of Integrated Clinical Systems cohort that are important for HIV and aging research moving forward. Results: Adjudicated outcomes are particularly beneficial for less common comorbidities such as myocardial infarction. Multiple ascertainment approaches increase sensitivity over using diagnoses alone (89% vs. 44%). Adjudication eliminates false-positive events and allows myocardial infarction types to be identified. Comorbidity research has often relied on composite outcomes, such as all cardiovascular diseases, often to increase power. Mechanistic differences across outcomes demonstrate the importance of moving away from many composite outcomes. Timely data are needed to ensure findings are relevant to improve care or outcomes for the population of PWH who are currently aging. Conclusions: A better understanding of the causes, mechanisms, prevention and treatment of functional decline, comorbidities, and multimorbidities is a crucial research focus as PWH are aging. Clinical cohorts with timely, comprehensive harmonized clinical data and carefully adjudicated outcomes are ideally positioned to improve understanding of these questions.

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Novel Pyrazole Derivatives Bearing Carbonitrile and Substituted Thiazole Moiety for Selective COX‐2 Inhibition

Arzuk,

Karakuş,

Ergüç

et al. 2024

ChemistrySelect

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In this study, a series of derivatives of pyrazole hybrid structures containing carbonitrile and substituted thiazole moiety were designed to search for selective COX‐2 inhibition. The designed target structures were synthesized with easy, practical, and efficient procedures. COX‐1/2 inhibition and cytotoxic effects of the synthesized compounds were evaluated in NIH/3T3 and MDA‐MD‐231 cell lines for inhibition concentration and selectivity index. The results showed that the compounds have an inhibitory effect with higher selectivity towards COX‐2 overall in both cell lines and moderate antiproliferative activity by targeting the breast cancer cell line MDA‐MB‐231. Among the 19 compounds synthesized (19 a–t), especially compound 19 m was found to be highly effective with COX‐2 inhibition of 5.63 μM in the NIH/3T3 cell line and 4.12 μM in the MDA‐MB‐231 cell line. Moreover, molecular docking studies showed that the compounds indeed exhibited higher affinity for the COX‐2 active site. The theoretical ADMET properties of the presented compounds were calculated, and the results showed that the compounds may have a more favorable pharmacokinetic effect profile than the selective COX‐2 inhibitor Celecoxib, thus promising COX‐2 inhibitor drug candidates for the future.

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Current Antiretroviral Treatment Among People With Human Immunodeficiency Virus in the United States: Findings from the Centers for AIDS Research Network of Integrated Clinic Systems Cohort

Cited by 4 publications

References 10 publications

Development of Frail RISC-HIV: a Risk Score for Predicting Frailty Risk in the Short-term for Care of People with HIV

Development of Frail RISC-HIV: a Risk Score for Predicting Frailty Risk in the Short-term for Care of People with HIV

HIV, Aging, and Comorbidities Research in Clinical Cohorts: 3 Lessons Learned Using Examples From the CNICS Cohort

Novel Pyrazole Derivatives Bearing Carbonitrile and Substituted Thiazole Moiety for Selective COX‐2 Inhibition

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