Browsing by Author "Koethe, John R."

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    Contribution of Behavioral Health Factors to Non-AIDS-Related Comorbidities: an Updated Review
    (SpringerLink, 2020-08) Chichetto, Natalie E.; Polanka, Brittanny M.; So-Armah, Kaku A.; Sung, Minhee; Stewart, Jesse C.; Koethe, John R.; Edelman, E. Jennifer; Tindle, Hilary A.; Freiberg, Matthew S.; Psychology, School of Science
    Purpose of review: We summarize recent literature on the contribution of substance use and depression to non-AIDS-related comorbidities. Discussion of recent randomized clinical trials and implementation research to curtail risk attributed to each behavioral health issue is provided. Recent findings: Smoking, unhealthy alcohol use, opioid use, and depression are common among PWH and individually contribute to increased risk for non-AIDS-related comorbidities. The concurrence of these conditions is notable, yet understudied, and provides opportunity for linked-screening and potential treatment of more than one behavioral health factor. Current results from randomized clinical trials are inconsistent. Investigating interventions to reduce the impact of these behavioral health conditions with a focus on implementation into clinical care is important. Non-AIDS-defining cancers, cardiovascular disease, liver disease, and diabetes are leading causes of morbidity in people with HIV. Behavioral health factors including substance use and mental health issues, often co-occurring, likely contribute to the excess risk of non-AIDS-related comorbidities.
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    Greater Weight Gain in Treatment-naive Persons Starting Dolutegravir-based Antiretroviral Therapy
    (Oxford, 2019-05) Bourgi, Kassem; Rebeiro, Peter F.; Turner, Megan; Castilho, Jessica L.; Hulgan, Todd; Raffanti, Stephen P.; Koethe, John R.; Sterling, Timothy R.; Medicine, School of Medicine
    Background Recent studies have reported weight gain in virologically suppressed persons living with human immunodeficiency virus (PLWH) switched from older antiretroviral therapy (ART) to newer integrase strand transfer inhibitor (INSTI)–based regimens. In this study, we investigated whether weight gain differs among treatment-naive PLWH starting INSTI-based regimens compared to other ART regimens. Methods Adult, treatment-naive PLWH in the Vanderbilt Comprehensive Care Clinic cohort initiating INSTI-, protease inhibitor (PI)–, and nonnucleoside reverse transcriptase inhibitor (NNRTI)–based ART between January 2007 and June 2016 were included. We used multivariable linear mixed-effects models to generate marginal predictions of weights over time, adjusting for baseline clinical and demographic characteristics. We used restricted cubic splines to relax linearity assumptions and bootstrapping to generate 95% confidence intervals. Results Among 1152 ART-naive PLWH, 351 initiated INSTI-based regimens (135 dolutegravir, 153 elvitegravir, and 63 raltegravir), 86% were male, and 49% were white. At ART initiation, median age was 35 years, body mass index was 25.1 kg/m2, and CD4+ T-cell count was 318 cells/μL. Virologic suppression at 18 months was similar between different ART classes. At all examined study time points, weight gain was highest among PLWH starting dolutegravir. At 18 months, PLWH on dolutegravir gained 6.0 kg, compared to 2.6 kg for NNRTIs (P < .05), and 0.5 kg for elvitegravir (P < .05). PLWH starting dolutegravir also gained more weight at 18 months compared to raltegravir (3.4 kg) and PIs (4.1 kg), though these differences were not statistically significant. Conclusions Treatment-naive PLWH starting dolutegravir-based regimens gained significantly more weight at 18 months than those starting NNRTI-based and elvitegravir-based regimens.
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    Relationships between adiposity distribution and metabolic health in preconception women in South Africa
    (Wiley, 2022-01-03) Prioreschi, Alessandra; Koethe, John R.; Aronoff, David M.; Goldstein, Jeffrey A.; Norris, Shane A.; Medicine, School of Medicine
    Objective: Adipose tissue is a central regulator of metabolic health and a contributor to systemic inflammation. Patterns of adiposity deposition are important to understand for optimizing health. This study aimed to asses relationships between adiposity deposition and metabolic and inflammatory biomarkers in South African women prior to conception. Methods: Non-pregnant, healthy women (n = 298) were recruited for this cross-sectional study via home visits. Body composition was measured by Dual X-ray Absorptiometry. Inflammation markers C-reactive protein (CRP), alpha1-acid glycoprotein (AGP), hemoglobin A1c (HbA1c), and blood pressure were scored according to risk. A summative metabolic health risk score was created for women with obesity. Generalized regression models assessed relationships between adiposity deposition and outcomes with adjustment for potential confounders. Results: Obesity was present in 22% of women (mean age = 20.93 years). Fat mass index was associated with inflammation and metabolic health risk (β = 0.58; p < 0.01). Visceral fat, trunk:limb ratio, android:gynoid ratio, body mass index, weight, and waist circumference were positively associated with CRP, AGP, and metabolic health risk (p < 0.01). Weight was associated with Hba1c (β < 0.01; p < 0.05). Participants with obesity and low metabolic health risk had lower fat mass index and visceral fat than participants with obesity and higher metabolic health risk. Conclusions: Black South African women accumulated excess adipose tissue in abdominal regions. While fat mass and body mass were associated with inflammation and metabolic health risk, women with obesity and with lower fat mass index and lower visceral adipose tissue were metabolically protected. Identification of women at risk for metabolic disease preconception could help ensure future healthy pregnancies and prevent transference of risk to offspring.
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    Risk of Incident Diabetes Mellitus, Weight Gain, and Their Relationships With Integrase Inhibitor-Based Initial Antiretroviral Therapy Among Persons With Human Immunodeficiency Virus in the United States and Canada
    (Oxford University Press, 2021) Rebeiro, Peter F.; Jenkins, Cathy A.; Bian, Aihua; Lake, Jordan E.; Bourgi, Kassem; Moore, Richard D.; Horberg, Michael A.; Matthews, W. Christopher; Silverberg, Michael J.; Thorne, Jennifer; Mayor, Angel M.; Lima, Viviane D.; Palella, Frank J., Jr.; Saag, Michael S.; Althoff, Keri N.; Gill, M. John; Wong, Cherise; Klein, Marina B.; Crane, Heidi M.; Marconi, Vincent C.; Shepherd, Bryan E.; Sterling, Timothy R.; Koethe, John R.; Medicine, School of Medicine
    Background: Integrase strand transfer inhibitor (INSTI)-based combination antiretroviral therapy (cART) is associated with greater weight gain among persons with human immunodeficiency virus (HIV), though metabolic consequences, such as diabetes mellitus (DM), are unclear. We examined the impact of initial cART regimen and weight on incident DM in a large North American HIV cohort (NA-ACCORD). Methods: cART-naive adults (≥18 years) initiating INSTI-, protease inhibitor (PI)-, or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens from January 2007 through December 2017 who had weight measured 12 (±6) months after treatment initiation contributed time until clinical DM, virologic failure, cART regimen switch, administrative close, death, or loss to follow-up. Multivariable Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident DM by cART class. Mediation analyses, with 12-month weight as mediator, similarly adjusted for all covariates. Results: Among 22 884 eligible individuals, 47% started NNRTI-, 30% PI-, and 23% INSTI-based cART with median follow-up of 3.0, 2.3, and 1.6 years, respectively. Overall, 722 (3%) developed DM. Persons starting INSTIs vs NNRTIs had incident DM risk (HR, 1.17 [95% CI, .92-1.48]), similar to PI vs NNRTI initiators (HR, 1.27 [95% CI, 1.07-1.51]). This effect was most pronounced for raltegravir (HR, 1.42 [95% CI, 1.06-1.91]) vs NNRTI initiators. The INSTI-DM association was attenuated (HR, 1.03 [95% CI, .71-1.49] vs NNRTIs) when accounting for 12-month weight. Conclusions: Initiating first cART regimens with INSTIs or PIs vs NNRTIs may confer greater risk of DM, likely mediated through weight gain.
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    The impact of HIV and ART exposure during pregnancy on fetal growth: a prospective study in a South African cohort
    (BMC, 2023-06-03) Mtintsilana, Asanda; Norris, Shane A.; Dlamini, Siphiwe N.; Nyati, Lukhanyo H.; Aronoff, David M.; Koethe, John R.; Goldstein, Jeffrey A.; Prioreschi, Alessandra; Medicine, School of Medicine
    Background: In utero exposure to human immunodeficiency virus (HIV) and antiretroviral (ART) is associated with adverse birth outcomes, which are often attributed to alterations in placental morphology. This study used structural equation models (SEMs) to examine the impact of HIV and ART exposure on fetal growth outcomes and whether these associations are mediated by placental morphology in urban-dwelling Black South African women. Methods: This prospective cohort study included pregnant women living with HIV (WLWH, n = 122) and not living with HIV (WNLWH, n = 250) that underwent repeated ultrasonography during pregnancy, and at delivery, to determine fetal growth parameters in Soweto, South Africa. The size and the velocity of fetal growth measures (i.e., head and abdominal circumference, biparietal diameter, and femur length) were calculated using the Superimposition by Translation and Rotation. Placenta digital photographs taken at delivery were used to estimate morphometric parameters and trimmed placental weight was measured. All WLWH were receiving ART for the prevention of vertical transmission of HIV. Results: A trend towards a lower placental weight and significantly shorter umbilical cord length was reported in WLWH compared to their counterparts. After sex stratification, umbilical cord length was significantly shorter in males born to WLWH than in male fetuses born to WNLWH (27.3 (21.6-32.8) vs. 31.4 (25.0-37.0) cm, p = 0.015). In contrast, female fetuses born to WLWH had lower placental weight, birth weight (2.9 (2.3-3.1) vs. 3.0 (2.7-3.2) kg), and head circumference (33 (32-34) vs. 34 (33-35) cm) than their counterparts (all p ≤ 0.05). The SEM models showed an inverse association between HIV and head circumference size and velocity in female fetuses. In contrast, HIV and ART exposure was positively associated with femur length growth (both size and velocity) and abdominal circumference velocity in male fetuses. None of these associations appeared to be mediated via placental morphology. Conclusion: Our findings suggest that HIV and ART exposure directly affects head circumference growth in females and abdominal circumference velocity in male fetuses; but may improve femur length growth in male fetuses only.