Acceptability of Long-Acting Injectable Antiretroviral Therapy Among People with HIV Receiving Care at Three Ryan White Funded Clinics in the United States.

Understanding the acceptability of long-acting injectable antiretroviral therapy (LAI-ART) among people with HIV (PWH), especially priority populations, is essential for effective implementation. We conducted semi-structured interviews with patients in three Ryan White-funded HIV clinics in San Francisco, Chicago, and Atlanta. We employed maximal variation sampling across age, gender, race, ethnicity, and time living with HIV and oversampled for individuals with suboptimal clinical engagement. An 8-step hybrid deductive and inductive thematic analysis approach guided data analysis. Between August 2020 and July 2021, we conducted 72 interviews. Median age was 46 years; 28% were ciswomen, 7% transwomen, 44% Black/African-American and 35% Latinx, 43% endorsed a psychiatric diagnosis, 35% were experiencing homelessness/unstable housing, and 10% had recent substance use. Approximately 24% were sub-optimally engaged in care. We observed a spectrum of LAI-ART acceptability, ranging from enthusiasm to hesitancy to rejection. We also characterized four emergent orientations towards LAI-ART: innovator, pragmatist, deliberator, and skeptic. Overall, the majority of participants expressed favorable initial reactions towards LAI-ART. Most approached LAI-ART pragmatically, but acceptability was not static, often increasing over the course of the interview. Participants considered their HIV providers as essential for affirming personal relevance. HIV stigma, privacy concerns, and medical mistrust had varied impacts, sometimes facilitating and other times hindering personal relevance. These findings held across priority populations, specifically young adults, cis/trans women, racial/ethnic minorities, and individuals with suboptimal clinical engagement. Further research is needed to explore the transition from hypothetical acceptance to uptake and to confirm the actual benefits and drawbacks of this treatment.

RESUMEN: La aceptabilidad de la terapia antirretroviral inyectable de acción prolongada (LAI-ART, por su sigla en inglés) entre personas con VIH es esencial para una implementación efectiva. Durante el periodo de agosto de 2020 a julio de 2021, realizamos 72 entrevistas semiestructuradas con personas con VIH en clínicas públicas ubicadas en San Francisco, Chicago y Atlanta. Un análisis temático, tanto deductivo como inductivo, guio nuestra investigación. Observamos un espectro de aceptabilidad de LAI-ART que va desde el entusiasmo hasta la indecisión y el rechazo. También caracterizamos cuatro orientaciones actitudinales emergentes hacia LAI-ART: innovadora, pragmática, deliberativa y escéptica. Los participantes también señalaron la importancia de sus proveedores de VIH para validar su relevancia personal. El estigma asociado al VIH, preocupaciones sobre la privacidad y desconfianza en el sistema médico tuvieron diversos impactos, a veces facilitando y otras veces obstaculizando la relevancia personal. Entre las poblaciones prioritarias del estudio, los resultados fueron consistentes.

Centring the health of women across the HIV research continuum.

Despite tremendous advances in HIV research, women and gender diverse people-particularly women from racial and ethnic groups under-represented in research, transgender women, and young women-remain disproportionately affected by HIV. Women and gender diverse people face unique challenges and have been under-represented in HIV research. The National Institutes of Health (NIH) is tasked to apply fundamental knowledge about the nature and behaviour of living systems to enhance health, lengthen life, and reduce disability. Rigorous exploration of-and interventions for-the individual, social, biological, structural, and environmental factors that influence HIV prevention, transmission, treatment, and cure is crucial to advance research for women, girls, and gender diverse people across the lifespan. In this Position Paper, we introduce a framework for an intersectional, equity-informed, data-driven approach to research on HIV and women and highlight selected issues for women and gender diverse people, including HIV prevention, HIV cure, ageing with HIV, substance use and misuse, violence, pregnancy, and breastfeeding or chestfeeding. This framework underlines a new HIV and Women Signature Programme from the NIH Office of AIDS Research and Office of Research on Women's Health that advances the NIH vision for women's health, in which all women receive evidence-based HIV prevention, treatment, and care across their lifespan tailored to their unique needs, circumstances, and goals. The time is now to centre the health of women, girls, and gender diverse people across the HIV research continuum.

Long-Acting Injectable Antiretrovirals for HIV Treatment: A Multi-Site Qualitative Study of Clinic-Level Barriers to Implementation in the United States.

Long-acting injectable antiretroviral therapy (LAI ART) has the potential to address adherence obstacles associated with daily oral ART, leading to enhanced treatment uptake, adherence, and viral suppression among people living with HIV (PLWH). Yet, its potential may be limited due to ongoing disparities in availability and accessibility. We need a better understanding of the organizational context surrounding the implementation of LAI ART, and to inform its widespread rollout, we conducted 38 in-depth interviews with medical and social service providers who offer HIV care at private and hospital-based clinics across six US cities. Our findings highlight real-world implementation barriers outside of clinical trial settings. Providers described ongoing and anticipated barriers across three stages of LAI ART implementation: (1) Patient enrollment (challenges registering patients and limited insurance coverage), (2) medication delivery (insufficient personnel and resources), and (3) leadership and management (lack of interprofessional coordination and a lack of programming guidelines). Providers described how these barriers would have a disproportionate impact on under-resourced clinics, potentially exacerbating existing disparities in LAI ART access and adherence. Our findings suggest strategies that clinic leadership, policymakers, and other stakeholders can pursue to promote rapid and equitable LAI ART implementation in clinics across the United States. Resource and staffing investments could support clinics to begin, sustain, and scale up LAI ART delivery; additionally, the establishment of guidelines and tools could facilitate wider adoption of LAI ART across clinical settings. These efforts are crucial to promote resourced, standardized, and equitable implementation of LAI ART and maximize its potential to help end the HIV epidemic.

Retinopathy Associated With Ritonavir Treatment for HIV Infection: A Case Series Reappraisal in the COVID-19 Era.

Purpose: To report 3 cases of retinopathy secondary to ritonavir use in the treatment of HIV. Methods: A retrospective review of patient records was performed for data including ophthalmic examination findings, demographic and HIV clinical characteristics, and progression of maculopathy disease. The review identified 3 patients with a history of HIV treated with antiretroviral therapy including ritonavir who had been evaluated for bilateral vision loss in both eyes. Results: A fundus examination of each patient revealed characteristic macular atrophy, and optical coherence tomography demonstrated corresponding central outer retinal atrophy. Uveitis workup results were unremarkable. Given the characteristics of macular atrophy, history of ritonavir use, and the absence of intraocular inflammation, all 3 patients were diagnosed with bilateral ritonavir-associated retinopathy. Each patients' vision continued to deteriorate, even after the cessation of ritonavir. Conclusions: Ritonavir toxicity should be considered in the differential diagnosis of retinopathy among patients with an exposure history.

Pivoting from in-person to phone survey assessment of alcohol and substance use: effects on representativeness in a United States prospective cohort of women living with and without HIV.

Background: Many clinical and population-based research studies pivoted from in-person assessments to phone-based surveys due to the COVID-19 pandemic. The impact of these transitions on survey response remains understudied, especially for people living with HIV. Given that there are gender-specific trends in alcohol and substance use, it is particularly important to capture these data for women.Objective: Identify factors associated with responding to an alcohol and substance use phone survey administered during the COVID-19 pandemic in the Women's Interagency HIV Study, a multicenter US prospective cohort of women living with and without HIV.Methods: We used multivariable logistic regression to assess for associations of pre-pandemic (April-September 2019) sociodemographic factors, HIV status, housing status, depressive symptoms, alcohol use, and substance use with response to an early-pandemic (August-September 2020) phone survey.Results: Of 1,847 women who attended an in-person visit in 2019, 78% responded to a phone survey during the pandemic. The odds of responding were lower for women of Hispanic ethnicity (aOR 0.47 95% CI 0.33-0.66, ref=Black/African American) and those who reported substance use (aOR 0.63 95% CI 0.41-0.98). By contrast, the odds were higher for White women (aOR 1.64 95% CI 1.02-2.70, ref=Black/African American) and those with stable housing (aOR 1.74 95% CI 1.24-2.43).Conclusions: Pivoting from an in-person to phone-administered alcohol and substance use survey may lead to underrepresentation of key subpopulations of women who are often neglected in substance use and HIV research. As remote survey methods become more common, investigators need to ensure that the study population is representative of the target population.

Subclinical Atherosclerosis Across the Menopausal Transition in Women With and Without HIV.

The menopausal transition is a pivotal time of cardiovascular risk, but knowledge is limited in HIV. We studied longitudinal carotid artery intima-media thickness (CIMT) in the Women's Interagency HIV Study (2004-2019; 979 women/3247 person-visits; 72% with HIV). Among women with HIV only, those who transitioned had greater age-related CIMT progression compared to those remaining premenopausal (difference in slope = 1.64 µm/year, P = .002); and CIMT increased over time in the pretransition (3.47 µm/year, P = .002) and during the menopausal transition (9.41 µm/year, P < .0001), but not posttransition (2.9 µm/year, P = .19). In women with HIV, menopause may accelerate subclinical atherosclerosis as measured by CIMT.

Plasma Biomarkers of Alzheimer Disease in Women With and Without HIV.

Importance: Blood-based biomarkers associated with increased risk of Alzheimer disease (AD) are understudied in people living with and without HIV, particularly women. Objective: To determine whether baseline or 1-year changes in plasma amyloid-ß40 (Aß40), Aß42, ratio of Aß42 to Aß40, total tau (t-tau), phosphorylated tau 231 (p-tau231), glial fibrillary acidic protein (GFAP), and/or neurofilament light chain (NFL) are associated with neuropsychological performance (NP) among women living with HIV (WLWH) and women living without HIV (WLWOH). Design, Setting, and Participants: This longitudinal, prospective, cohort study with 1-year repeated clinical measures (NP only measured once) and biospecimen collection occurred between 2017 and 2019. Participants were women aged 40 years or older from 10 clinical research sites in cities across the US that were part of the Women's Interagency HIV Study. Data analysis was conducted from April to December 2022. Exposure: Laboratory-confirmed HIV status and AD biomarkers. Main Outcomes and Measures: Sociodemographically adjusted NP T-scores (attention and working memory, executive function, processing speed, memory, learning, verbal fluency, motor function, and global performance) were the primary outcomes. Baseline and 1-year fasting plasma Aß40, Aß42, t-tau, p-tau231, GFAP, and NFL levels were measured and analyzed using multivariable linear regression. Results: The study consisted of 307 participants (294 aged ≥50 years [96%]; 164 African American or Black women [53%]; 214 women with a high school education or higher [70%]; 238 women who were current or former smokers [78%]; and 236 women [77%] who were overweight or obese [body mass index >25]) including 209 WLWH and 98 WLWOH. Compared with WLWOH at baseline, WLWH performed worse on learning (mean [SD] T-score 47.8 [11.3] vs 51.4 [10.5]), memory (mean [SD] T-score 48.3 [11.6] vs 52.4 [10.2]), verbal fluency (mean [SD] T-score 48.3 [9.8] vs 50.7 [8.5]), and global (mean [SD] T-score 49.2 [6.8] vs 51.1 [5.9]) NP assessments. Baseline median Aß40, GFAP, and NFL levels were higher among WLWH vs WLWOH. There were no differences in 1-year biomarker change by HIV serostatus. Lower learning, memory, and motor NP were associated with 1-year Aß40 increase; lower learning and motor with Aß42 increase; lower motor with p-tau231 increase; and lower processing speed, verbal fluency and motor with NFL increase in the entire sample. Among WLWH, a 1-year increase in Aß40 from baseline to follow-up was associated with worse learning, memory, and global NP; a 1-year increase in t-tau with worse executive function; and a 1-year increase in NFL with worse processing speed. Among WLWOH, a 1-year increase in Aß40 and Aß42 were associated with poorer memory performance and NFL was associated with poorer motor performance. Conclusions and Relevance: These findings suggest that increases in certain plasma AD biomarkers are associated with NP in WLWH and WLWOH and may be associated with later onset of AD, and measuring these biomarkers could be a pivotal advancement in monitoring aging brain health and development of AD among women with and without HIV.

Aging-Related Comorbidity Burden Among Women and Men With or At-Risk for HIV in the US, 2008-2019.

Importance: Despite aging-related comorbidities representing a growing threat to quality-of-life and mortality among persons with HIV (PWH), clinical guidance for comorbidity screening and prevention is lacking. Understanding comorbidity distribution and severity by sex and gender is essential to informing guidelines for promoting healthy aging in adults with HIV. Objective: To assess the association of human immunodeficiency virus on the burden of aging-related comorbidities among US adults in the modern treatment era. Design, Setting, and Participants: This cross-sectional analysis included data from US multisite observational cohort studies of women (Women's Interagency HIV Study) and men (Multicenter AIDS Cohort Study) with HIV and sociodemographically comparable HIV-seronegative individuals. Participants were prospectively followed from 2008 for men and 2009 for women (when more than 80% of participants with HIV reported antiretroviral therapy use) through last observation up until March 2019, at which point outcomes were assessed. Data were analyzed from July 2020 to April 2021. Exposures: HIV, age, sex. Main Outcomes and Measures: Comorbidity burden (the number of total comorbidities out of 10 assessed) per participant; secondary outcomes included individual comorbidity prevalence. Linear regression assessed the association of HIV status, age, and sex with comorbidity burden. Results: A total of 5929 individuals were included (median [IQR] age, 54 [46-61] years; 3238 women [55%]; 2787 Black [47%], 1153 Hispanic or other [19%], 1989 White [34%]). Overall, unadjusted mean comorbidity burden was higher among women vs men (3.4 [2.1] vs 3.2 [1.8]; P = .02). Comorbidity prevalence differed by sex for hypertension (2188 of 3238 women [68%] vs 2026 of 2691 men [75%]), psychiatric illness (1771 women [55%] vs 1565 men [58%]), dyslipidemia (1312 women [41%] vs 1728 men [64%]), liver (1093 women [34%] vs 1032 men [38%]), bone disease (1364 women [42%] vs 512 men [19%]), lung disease (1245 women [38%] vs 259 men [10%]), diabetes (763 women [24%] vs 470 men [17%]), cardiovascular (493 women [15%] vs 407 men [15%]), kidney (444 women [14%] vs 404 men [15%]) disease, and cancer (219 women [7%] vs 321 men [12%]). In an unadjusted model, the estimated mean difference in comorbidity burden among women vs men was significantly greater in every age strata among PWH: age under 40 years, 0.33 (95% CI, 0.03-0.63); ages 40 to 49 years, 0.37 (95% CI, 0.12-0.61); ages 50 to 59 years, 0.38 (95% CI, 0.20-0.56); ages 60 to 69 years, 0.66 (95% CI, 0.42-0.90); ages 70 years and older, 0.62 (95% CI, 0.07-1.17). However, the difference between sexes varied by age strata among persons without HIV: age under 40 years, 0.52 (95% CI, 0.13 to 0.92); ages 40 to 49 years, -0.07 (95% CI, -0.45 to 0.31); ages 50 to 59 years, 0.88 (95% CI, 0.62 to 1.14); ages 60 to 69 years, 1.39 (95% CI, 1.06 to 1.72); ages 70 years and older, 0.33 (95% CI, -0.53 to 1.19) (P for interaction = .001). In the covariate-adjusted model, findings were slightly attenuated but retained statistical significance. Conclusions and Relevance: In this cross-sectional study, the overall burden of aging-related comorbidities was higher in women vs men, particularly among PWH, and the distribution of comorbidity prevalence differed by sex. Comorbidity screening and prevention strategies tailored by HIV serostatus and sex or gender may be needed.

Association of marijuana, tobacco and alcohol use with estimated glomerular filtration rate in women living with HIV and women without HIV.

OBJECTIVE: Marijuana, tobacco and alcohol use are prevalent among people with HIV and may adversely affect kidney function in this population. We determined the association of use of these substances with estimated glomerular filtration rate (eGFR) among women with HIV (WWH) and women without HIV. DESIGN: We undertook a repeated measures study of 1043 WWH and 469 women without HIV within the United States Women's Interagency HIV Study, a multicenter, prospective cohort of HIV-seropositive and HIV-seronegative women. METHODS: We quantified substance exposures using semi-annual questionnaires. Using pooled eGFR data from 2009 to 2019, we used linear regression models with multivariable generalized estimating equations to ascertain associations between current and cumulative substance use exposures with eGFR, adjusting for sociodemographics, chronic kidney disease risk factors and HIV-related factors. RESULTS: Marijuana use of 1-14 days/month versus 0 days/month was associated with 3.34 ml/min per 1.73 m 2 [95% confidence interval (CI) -6.63, -0.06] lower eGFR and marijuana use of >0.02-1.6 marijuana-years versus 0-0.2 marijuana-years was associated with 3.61 ml/min per 1.73 m 2 (95% CI -5.97, -1.24) lower eGFR. Tobacco use was not independently associated with eGFR. Alcohol use of seven or more drinks/week versus no drinks/week was associated with 5.41 ml/min per 1.73 m 2 (95% CI 2.34, 8.48) higher eGFR and alcohol use of >0.7-4.27 drink-years and >4.27 drink-years versus 0-0.7 drink-years were associated with 2.85 ml/min per 1.73 m 2 (95% CI 0.55, 5.15) and 2.26 ml/min per 1.73 m 2 (95% CI 0.33, 4.20) higher eGFR, respectively. CONCLUSION: Among a large cohort of WWH and women without HIV, marijuana use was associated with a lower eGFR while alcohol use was associated with a higher eGFR.

Cumulative Human Immunodeficiency Virus (HIV)-1 Viremia Is Associated With Increased Risk of Multimorbidity Among US Women With HIV, 1997-2019.

Background: To evaluate the effect of cumulative human immunodeficiency virus (HIV)-1 viremia on aging-related multimorbidity among women with HIV (WWH), we analyzed data collected prospectively among women who achieved viral suppression after antiretroviral therapy (ART) initiation (1997-2019). Methods: We included WWH with ≥2 plasma HIV-1 viral loads (VL) <200 copies/mL within a 2-year period (baseline) following self-reported ART use. Primary outcome was multimorbidity (≥2 nonacquired immune deficiency syndrome comorbidities [NACM] of 5 total assessed). The trapezoidal rule calculated viremia copy-years (VCY) as area-under-the-VL-curve. Cox proportional hazard models estimated the association of time-updated cumulative VCY with incident multimorbidity and with incidence of each NACM, adjusting for important covariates (eg, age, CD4 count, etc). Results: Eight hundred six WWH contributed 6368 women-years, with median 12 (Q1-Q3, 7-23) VL per participant. At baseline, median age was 39 years, 56% were Black, and median CD4 was 534 cells/mm3. Median time-updated cumulative VCY was 5.4 (Q1-Q3, 4.7-6.9) log10 copy-years/mL. Of 211 (26%) WWH who developed multimorbidity, 162 (77%) had incident hypertension, 133 (63%) had dyslipidemia, 60 (28%) had diabetes, 52 (25%) had cardiovascular disease, and 32 (15%) had kidney disease. Compared with WWH who had time-updated cumulative VCY <5 log10, the adjusted hazard ratio of multimorbidity was 1.99 (95% confidence interval [CI], 1.29-3.08) and 3.78 (95% CI, 2.17-6.58) for those with VCY 5-6.9 and ≥7 log10 copy-years/mL, respectively (P < .0001). Higher time-updated cumulative VCY increased the risk of each NACM. Conclusions: Among ART-treated WWH, greater cumulative viremia increased the risk of multimorbidity and of developing each NACM, and hence this may be a prognostically useful biomarker for NACM risk assessment in this population.

The Effect of Menopausal Status, Age, and Human Immunodeficiency Virus (HIV) on Non-AIDS Comorbidity Burden Among US Women.

Menopause may impact the earlier onset of aging-related comorbidities among women with versus without human immunodeficiency virus (HIV). We found that menopausal status, age, and HIV were independently associated with higher comorbidity burden, and that HIV impacted burden most in the pre-/perimenopausal phases.

The association between comorbidities and coronavirus disease 2019 hospitalization among people with HIV differs by age.

OBJECTIVES: To determine whether factors associated with coronavirus disease 2019 (COVID-19) hospitalization among people with HIV (PWH) differ by age stratum. DESIGN: Retrospective cohort study. METHODS: All adult PWH with a positive SARS-CoV-2 PCR in a public safety-net health system between 1 March 2020 and 28 February 2021 and a Veterans Affairs Medical Center between 1 1 March 2020 and 15 November 2020 in Atlanta, Georgia were included. We performed multivariable logistic regression to determine demographic and clinical factors associated with COVID-19 hospitalization overall and stratified by age less than 50 and at least 50 years. RESULTS: Three hundred and sixty-five PWH (mean age 49 years, 74% cisgender male, 82% black) were included. Ninety-six percent were on antiretroviral therapy (ART), 87% had CD4 + T-cell count at least 200 cells/µl, and 89% had HIV-1 RNA less than 200 copies/ml. Overall, age [adjusted odds ratio (aOR) 95% confidence interval (CI) 1.07 (1.04-1.10)], later date of SARS-CoV-2 infection [aOR 0.997 (0.995-1.00)], heart disease [aOR 2.27 (1.06-4.85)], and history of hepatitis C virus (HCV) [aOR 2.59 (1.13-5.89)] were associated with COVID-19 hospitalization. Age-adjusted comorbidity burden was associated with 30% increased risk of hospitalization [aOR 1.30 (1.11-1.54)]. Among 168 PWH less than 50 years old, older age [aOR 1.09 (1.01-1.18)] and no ART use [aOR 40.26 (4.12-393.62)] were associated with hospitalization; age-adjusted comorbidity burden was not ( P  = 0.25). Among 197 PWH at least 50, older age [aOR 1.10 (1.04-1.16)], heart disease [aOR 2.45 (1.04-5.77)], history of HCV [aOR 3.52 (1.29-9.60)], and age-adjusted comorbidity burden [aOR 1.36 (1.12-1.66)] were associated with hospitalization. CONCLUSION: Comorbidity burden is more strongly associated with COVID-19 hospitalization among older, rather than younger, PWH. These findings may have important implications for risk-stratifying COVID-19 therapies and booster recommendations in PWH.

Early Experience Implementing Long-Acting Injectable Cabotegravir/Rilpivirine for Human Immunodeficiency Virus-1 Treatment at a Ryan White-Funded Clinic in the US South.

Background: Long-acting injectable (LAI) antiretroviral therapy (ART) has the potential to improve medication adherence, reduce human immunodeficiency virus (HIV) stigma, and promote equity in care outcomes among people with HIV (PWH). We describe our early experience implementing LAI-cabotegravir/rilpivirine (CAB/RPV) for maintenance HIV-1 treatment. Methods: We launched a pilot LAI-ART program at a large Ryan White-funded clinic in the Southeast, which accept provider-initiated referrals from April 14, 2021 to December 1, 2021. Our interdisciplinary program team (Clinician-Pharmacy-Nursing) verified clinical eligibility and pursued medication access for eligible patients. We describe (1) demographic and clinical variables of PWH referred and enrolled and (2) early outcomes among those accessing LAI-CAB/RPV. Results: Among 58 referrals, characteristics were median age 39 (Q1-Q3, 30.25-50) years, 74% male, and 81% Black, and payor source distribution was 26% Private, 21% Medicare, 19% Medicaid, and 34% AIDS Drugs Assistance Program. Forty-five patients (78%) met clinical eligibility for LAI-CAB/RPV; ineligibility concerns included evidence of confirmed or possible RPV resistance (n = 8), HIV nonsuppression (n = 3), possible RPV hypersensitivity (n = 1), and pregnancy (n = 1). Among 45 eligible PWH, 39 (87%) enrolled and 15 (38%) initiated LAI-CAB/RPV after a median of 47 (Q1-Q3, 31-95) days since enrollment. Conclusions: Implementing LAI-ART at a Southern US Ryan White-funded clinic has been challenged by the following: substantial human resource capital to attain drug, administer injections, and support enrolled patients; delayed therapy initiation due to insurance denials; patient ineligibility primarily due to possible RPV resistance; and inability to provide drug regardless of payor source. These barriers may perpetuate disparities in ART access and outcomes among PWH and should be urgently addressed so that LAI-ART can be offered equitably.

Bone, Brain, Heart study protocol: A resilient nested, tripartite prospective cohort study of the role of estrogen depletion on HIV pathology.

PURPOSE: We describe the rationale for and design of an innovative, nested, tripartite prospective observational cohort study examining whether relative estrogen insufficiency-induced inflammation amplifies HIV-induced inflammation to cause end organ damage and worsen age-related co-morbidities affecting the neuro-hypothalamic-pituitary-adrenal axis (Brain), skeletal (Bone), and cardiovascular (Heart/vessels) organ systems (BBH Study). METHODS: The BBH parent study is the Multicenter AIDS Cohort/Women's Interagency HIV Study Combined Cohort Study (MWCCS) with participants drawn from the Atlanta MWCCS site. BBH will enroll a single cohort of n = 120 women living with HIV and n = 60 HIV-negative women, equally distributed by menopausal status. The innovative multipart nested study design of BBH, which draws on data collected by the parent study, efficiently leverages resources for maximum research impact and requires extensive oversight and management in addition to careful implementation. The presence of strong infrastructure minimized BBH study disruptions due to changes in the parent study and the COVID-19 pandemic. CONCLUSION: BBH is poised to provide insight into sex and HIV associations with the neuro-hypothalamic-pituitary-adrenal axis, skeletal, and cardiovascular systems despite several major, unexpected challenges.

Nested and multipart prospective observational studies, flaming fiasco or efficiently economical?: The Brain, Bone, Heart case study.

BACKGROUND: Collecting new data from cross-sectional/survey and cohort observational study designs can be expensive and time-consuming. Nested (hierarchically cocooned within an existing parent study) and/or Multipart (≥ 2 integrally interlinked projects) study designs can expand the scope of a prospective observational research program beyond what might otherwise be possible with available funding and personnel. The Brain, Bone, Heart (BBH) study provides an exemplary case to describe the real-world advantages, challenges, considerations, and insights from these complex designs. MAIN: BBH is a Nested, Multipart study conducted by the Specialized Center for Research Excellence (SCORE) on Sex Differences at Emory University. BBH is designed to examine whether estrogen insufficiency-induced inflammation compounds HIV-induced inflammation, leading to end-organ damage and aging-related co-morbidities affecting the neuro-hypothalamic-pituitary-adrenal axis (brain), musculoskeletal (bone), and cardiovascular (heart) organ systems. Using BBH as a real-world case study, we describe the advantages and challenges of Nested and Multipart prospective cohort study design in practice. While excessive dependence on its parent study can pose challenges in a Nested study, there are significant advantages to the study design as well. These include the ability to leverage a parent study's resources and personnel; more comprehensive data collection and data sharing options; a broadened community of researchers for collaboration; dedicated longitudinal research participants; and, access to historical data. Multipart, interlinked studies that share a common cohort of participants and pool of resources have the advantage of dedicated key personnel and the challenge of increased organizational complexity. Important considerations for each study design include the stability and administration of the parent study (Nested) and the cohesiveness of linkage elements and staff organizational capacity (Multipart). CONCLUSION: Using the experience of BBH as an example, Nested and/or Multipart study designs have both distinct advantages and potential vulnerabilities that warrant consideration and require strong biostatistics and data management leadership to optimize programmatic success and impact.

Cardiovascular Implications of Immune Disorders in Women.

Immune responses differ between men and women, with women at higher risk of developing chronic autoimmune diseases and having more robust immune responses to many viruses, including HIV and hepatitis C virus. Although immune dysregulation plays a prominent role in chronic systemic inflammation, a key driver in the development of atherosclerotic cardiovascular disease (ASCVD), standard ASCVD risk prediction scores underestimate risk in populations with immune disorders, particularly women. This review focuses on the ASCVD implications of immune dysregulation due to disorders with varying global prevalence by sex: autoimmune disorders (female predominant), HIV (male-female equivalent), and hepatitis C virus (male predominant). Factors contributing to ASCVD in women with immune disorders, including traditional risk factors, dysregulated innate and adaptive immunity, sex hormones, and treatment modalities, are discussed. Finally, the need to develop new ASCVD risk stratification tools that incorporate variables specific to populations with chronic immune disorders, particularly in women, is emphasized.

Patient Experiences with Telemedicine for HIV Care During the First COVID-19 Wave in Atlanta, Georgia.

We explored experiences with telemedicine among persons with HIV (PWH) during the first wave of the coronavirus disease 2019 (COVID-19) pandemic. A convenience sample of adults (>18 years) receiving care in an urban clinic in Atlanta were invited to participate. Patients completed a structured survey that assessed the usefulness, quality, satisfaction, and concerns with telemedicine services (telephone calls) received during the first wave of the COVID-19 pandemic (March-May 2020). Demographic, plasma HIV-1 RNA, and CD4+ T cell count data were obtained through medical chart abstraction. Bootstrapped t-tests and chi-square tests were used to examine differences in patient experiences by age, sex, and race. Of 406 PWH contacted, 101 completed the survey (median age 55 years, 84% men, 77% Black, 98% virally suppressed, median CD4 count 572 cells/µL). The main HIV care disruptions experienced were delays in follow-up visits (40%), difficulty getting viral load measured (35%), and difficulty accessing antiretroviral therapy (21%). Participant ratings for quality (median score 6.5/7), usefulness (median score 6.0/7), and satisfaction (median score 6.3/7) with telemedicine were high. However, 28% of patients expressed concerns about providers' ability to examine them and about the lack of laboratory tests. More women had concerns about providers' ability to examine them (92% vs. 50%, p = .005) and about the safety of their personal information (69% vs. 23%, p = .002) compared with men. No age or race differences were observed. Although PWH are generally satisfied with telephone-based telemedicine, concerns with its use were notable, particularly among women. Future HIV telemedicine models should address these.

Sex Differences in Non-AIDS Comorbidities Among People With Human Immunodeficiency Virus.

Women are grossly underrepresented in human immunodeficiency virus (HIV) clinical and translational research. This is concerning given that people with HIV (PWH) are living longer, and thus accumulating aging-related non-AIDS comorbidities (NACMs); emerging evidence suggests that women are at higher risk of NACM development and progression compared with men. It is widely recognized that women vs men have greater immune activation in response to many viruses, including HIV-1; this likely influences sex-differential NACM development related to differences in HIV-associated chronic inflammation. Furthermore, many sociobehavioral factors that contribute to aging-related NACMs are known to differ by sex. The objectives of this review were to (1) synthesize sex-stratified data on 4 NACMs among PWH: bone disease, cardiovascular disease, metabolic dysfunction, and neurocognitive impairment; (2) evaluate the characteristics of key studies assessing sex differences in NACMs; and (3) introduce potential biological and psychosocial mechanisms contributing to emerging trends in sex-differential NACM risk and outcomes among PWH.