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Background: The SARS-CoV-2 pandemic has resulted in an increase in telemedicine utilization for routine HIV care. However, there is limited information on perceptions of and experiences with telemedicine from United States (U.S.) federally qualified health centers (FQHCs) offering HIV care. We sought to understand telemedicine experiences of stakeholders with various roles: people living with HIV (PLHIV), clinical (clinicians and case managers), programmatic (clinic administrators), and policy (policymakers). Methods: Qualitative interviews about benefits and challenges of telemedicine (telephone and video) for HIV care were conducted with 31 PLHIV and 23 other stakeholders (clinicians, case managers, clinic administrators, and policymakers). Interviews were transcribed, translated to English if conducted in Spanish, coded, and analyzed for major themes. Results: Almost all PLHIV felt capable of engaging in telephone visits, with some expressing interest in learning how to use video visits as well. Nearly all PLHIV wanted to continue telemedicine as part of their routine HIV care, and this was also endorsed by clinical, programmatic and policy stakeholders. Interviewees agreed that telemedicine for HIV care has benefits for PLHIV, especially savings of time and transportation costs, which also reduced stress. Clinical, programmatic, and policy stakeholders expressed concerns around patients' technological literacy and resources, as well as their access to privacy, and some felt that PLHIV strongly preferred in-person visits. These stakeholders also commonly reported clinic-level implementation challenges, including integrating telephone and video telemedicine into workflows and difficulty with video visit platforms. Conclusions: Telemedicine for HIV care, largely delivered via telephone (audio-only), was highly acceptable and feasible for both PLHIV, clinicians, and other stakeholders. Addressing barriers for stakeholders in incorporating video visits will be important for the successful implementation of telemedicine with video as part of routine HIV care at FQHCs. [ABSTRACT FROM AUTHOR]

Background Among people with HIV (PWH), sex differences in presentations of atherosclerotic cardiovascular disease (ASCVD) may be influenced by differences in coronary plaque parameters, immune/inflammatory biomarkers, or relationships therein. Methods REPRIEVE, a primary ASCVD prevention trial, enrolled antiretroviral therapy (ART)–treated PWH. At entry, a subset of US participants underwent coronary computed tomography angiography (CTA) and immune phenotyping (n = 755 CTA; n = 725 CTA + immune). We characterized sex differences in coronary plaque and immune/inflammatory biomarkers and compared immune-plaque relationships by sex. Unless noted otherwise, analyses adjust for ASCVD risk score. Results The primary analysis cohort included 631 males and 124 females. ASCVD risk was higher among males (median: 4.9% vs 2.1%), while obesity rates were higher among females (48% vs 21%). Prevalence of any plaque and of plaque with either ≥1 visible noncalcified portion or vulnerable features (NC/V-P) was lower among females overall and controlling for relevant risk factors (RR [95% CI] for any plaque:.67 [.50,.92]; RR for NC/V-P:.71 [.51, 1.00] [adjusted for ASCVD risk score and body mass index]). Females showed higher levels of IL-6, hs-CRP, and D-dimer and lower levels of Lp-PLA2 (P <.001 for all). Higher levels of Lp-PLA2, MCP-1, and oxLDL were associated with higher plaque (P <.02) and NC/V-P prevalence, with no differences by sex. Among females but not males, D-dimer was associated with higher prevalence of NC/V-P (interaction P =.055). Conclusions Among US PWH, females had a lower prevalence of plaque and NC/V-P, as well as differences in key immune/inflammatory biomarkers. Immune-plaque relationships differed by sex for D-dimer but not other tested parameters. Clinical Trial Registration. ClinicalTrials.gov; identifier: NCT0234429 (date of initial registration: 22 January 2015). [ABSTRACT FROM AUTHOR]

Working in an unprecedented time frame, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership developed and launched 9 master protocols between 14 April 2020 and 31 May 2021 to allow for the coordinated and efficient evaluation of multiple investigational therapeutic agents for COVID-19. The ACTIV master protocols were designed with a portfolio approach to serve the following patient populations with COVID-19: mild to moderately ill outpatients, moderately ill inpatients, and critically ill inpatients. To facilitate the execution of these studies and minimize start-up time, ACTIV selected several existing networks to launch the master protocols. The master protocols were also designed to test several agent classes prioritized by ACTIV that covered the spectrum of the disease pathophysiology. Each protocol, either adaptive or pragmatic, was designed to efficiently select those treatments that provide benefit to patients while rapidly eliminating those that were either ineffective or unsafe. The ACTIV Therapeutics-Clinical Working Group members describe the process by which these master protocols were designed, developed, and launched. Lessons learned that may be useful in meeting the challenges of a future pandemic are also described. [ABSTRACT FROM AUTHOR]

Lipohypertrophy in HIV-infected patients is associated with metabolic abnormalities. Raltegravir (RAL) is not known to induce fat changes or severe metabolic perturbations. HIV-infected women with central adiposity and HIV-1 RNA less than 50 copies per milliliter on non-nucleoside reverse transcriptase inhibitor (NNRTI)- or protease inhibitor (PI)-based antiretroviral therapy (ART) continued their nucleoside reverse transcriptase inhibitor (NRTI) backbone and were randomized to switch to open label RAL immediately or after 24 weeks. The primary end point was 24-week between-group change in computed tomography (CT)-quantified visceral adipose tissue (AT) volume. Fasting lipids, glucose, C-reactive protein (CRP), anthropometric measurements, and patient-reported quality of life assessments were also measured. Thirty-six subjects provided 80% power to detect a 10% between-group difference in visceral AT over 24 weeks. Thirty-seven of 39 enrolled subjects completed week 24. At entry, subjects were 75% black or Hispanic, and on 62% PI-based and 38% NNRTI-based regimens. The median age was 43 years, CD4 count 558 cells per microliter, and body mass index (BMI) 32 kg/m2. After 24 weeks, no statistically significant changes in visceral or subcutaneous AT, anthropometrics, BMI, glucose, or CRP were observed. In subjects receiving RAL, significant improvements in total and LDL cholesterol ( p=0.04), self-reported belly size ( p=0.02) and composite body size ( p=0.02) were observed. Body size changes correlated well with percent visceral AT change. No RAL-related adverse events occurred. Compared to continued PI or NNRTI, switch to RAL was associated with statistically significant 24-week improvements in total and LDL cholesterol but not AT volumes. Additional insights into AT and metabolic changes in women on RAL will be provided by 48-week follow-up of the immediate-switch arm. [ABSTRACT FROM AUTHOR]

The article discusses the use of postexposure prophylaxis against human immunodeficiency virus (HIV) infection in the U.S. as of October 2009. It says that a 24-year-old man reported that he had receptive anal intercourse with an anonymous male partner 36 hours before he went into an outpatient clinic. According to the author, the history of the use of postexposure prophylaxis as a treatment for this chronic infection can be traced back to the early parts of the 1990s, which was the time when antiviral treatment was limited. Details of assessing the need for postexposure prophylaxis and the prevalence of HIV infection in the country are also discussed.

Postexposure prophylaxis after sexual exposure to human immunodeficiency virus (HIV) is recommended by state and national agencies. A cross-sectional survey of 117 Los Angeles County sites found that 17 sites (14.5%) offer postexposure prophylaxis. Ten sites (8.5%) offer postexposure prophylaxis to patients who are uninsured. General availability of postexposure prophylaxis should be a public health priority. [ABSTRACT FROM AUTHOR]

There has been a significant and dramatic change in the management of HIV infection since the introduction of potent antiretroviral therapy in 1996. There has also been a significant decrease in morbidity and mortality among persons living with HIV infection resulting from improved access to care, prophylaxis against opportunistic infections, and antiretroviral therapy. A working group of clinical scientists was chosen by the HIV Medicine Association of the Infectious Diseases Society of America to develop guidelines addressing the primary care of persons infected with HIV. The purpose of these guidelines is to assist health care providers in the primary care management of persons infected with HIV, including a description of baseline laboratory screening and adherence issues.

Examines the use of amprenavir in treating HIV-positive adults in the United States. Characterization of amprenavir; Effectiveness of the combination of amprenavir drug; Comparison of the effectiveness between amprenavir, zidovudine and lamivudine.

Background: Cytokines and chemokines play a critical role in the response to infection and vaccination. We aimed to assess the longitudinal association of COVID-19 vaccination with cytokine and chemokine concentrations and trajectories among people with SARS-CoV-2 infection., Methods: In this longitudinal, prospective cohort study, blood samples were used from participants enrolled in a multi-centre randomised trial assessing the efficacy of convalescent plasma therapy for ambulatory COVID-19. The trial was conducted in 23 outpatient sites in the USA. In this study, participants (aged ≥18 years) were restricted to those with COVID-19 before vaccination or with breakthrough infections who had blood samples and symptom data collected at screening (pre-transfusion), day 14, and day 90 visits. Associations between COVID-19 vaccination status and concentrations of 21 cytokines and chemokines (measured using multiplexed sandwich immunoassays) were examined using multivariate linear mixed-effects regression models, adjusted for age, sex, BMI, hypertension, diabetes, trial group, and COVID-19 waves (pre-alpha or alpha and delta)., Findings: Between June 29, 2020, and Sept 30, 2021, 882 participants recently infected with SARS-CoV-2 were enrolled, of whom 506 (57%) were female and 376 (43%) were male. 688 (78%) of 882 participants were unvaccinated, 55 (6%) were partly vaccinated, and 139 (16%) were fully vaccinated at baseline. After adjusting for confounders, geometric mean concentrations of interleukin (IL)-2RA, IL-7, IL-8, IL-15, IL-29 (interferon-λ), inducible protein-10, monocyte chemoattractant protein-1, and tumour necrosis factor-α were significantly lower among the fully vaccinated group than in the unvaccinated group at screening. On day 90, fully vaccinated participants had approximately 20% lower geometric mean concentrations of IL-7, IL-8, and vascular endothelial growth factor-A than unvaccinated participants. Cytokine and chemokine concentrations decreased over time in the fully and partly vaccinated groups and unvaccinated group. Log 10 cytokine and chemokine concentrations decreased faster among participants in the unvaccinated group than in other groups, but their geometric mean concentrations were generally higher than fully vaccinated participants at 90 days. Days since full vaccination and type of vaccine received were not correlated with cytokine and chemokine concentrations., Interpretation: Initially and during recovery from symptomatic COVID-19, fully vaccinated participants had lower concentrations of inflammatory markers than unvaccinated participants suggesting vaccination is associated with short-term and long-term reduction in inflammation, which could in part explain the reduced disease severity and mortality in vaccinated individuals., Funding: US Department of Defense, National Institutes of Health, Bloomberg Philanthropies, State of Maryland, Mental Wellness Foundation, Moriah Fund, Octapharma, HealthNetwork Foundation, and the Shear Family Foundation., Competing Interests: Declaration of interests KAG reports consultancy work for the Aspen Institute, Teach for America, serving as a non-paid member of a scientific advisory board for Pfizer, and writing COVID-19 management guidelines for UpToDate. AGA reports consultancy work for Implementation Group, Hirslanden Klinik, and Elsevier. ERC reports receiving unrestricted research grants from Gilead and Merck paid to the Regents of the University of California and participating in an advisory board to Theratechnologies for an unrelated topic. JSC reports consultancy work for Merck and Company in 2021. TJG reports employment by Fenwal, a Fresenius Kabi Company. LLH reports research funding to Johns Hopkins Center of American Indian Health from AstraZeneca, US Centers for Disease Control and Prevention, Merck, NIH, and Pfizer. MAH reports contracts from Gilead Sciences, Insmed, and AN2 Therapeutics to the University of Cincinnati. GSM reports research grant support from Teva, Alk-Abello, Genentech, Novartis, GlaxoSmithKline, and Sanofi-Regeneron, serving as an immediate past president of the American Academy of Allergy Asthma and Immunology, and is co-chair of the Continuous Assessment Program Examination for the American Board of Allergy and Immunology. BP reports participating in part of the COVID-19 trials and pulmonary arterial hypertension trials. JHP reports research funding from MindRhythm. JSR is a consultant and advisor with Sanofi Genzyme, and a board of directors member with the American Society for Apheresis. SK reports helping to produce educational materials related to HIV with Integritas Communications and Vindico Medical Education. AC reports serving on the scientific advisory board of SAB Biotherapeutics. EMB reports personal fees and non-financial support from Terumo BCT, Abbott Laboratories, Tegus, and UptoDate, is a member of the US Food and Drug Administration Blood Products Advisory Committee, and served on a convalescent plasma guideline panel. DH reports personal fees from Neurelis, Neurotrope, and medicolegal consulting. DJS is a founder and board member with stock options (macrolide for malaria) for AliquantumRx and reports consulting for Hemex Health and royalties for malaria diagnostic test control standards to Alere. SLH reports serving on the data monitoring committee for Pfizer. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Polyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain., Methods: In this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status. Participants were enrolled within 8 days after symptom onset and received a transfusion within 1 day after randomization. The primary outcome was Covid-19-related hospitalization within 28 days after transfusion., Results: Participants were enrolled from June 3, 2020, through October 1, 2021. A total of 1225 participants underwent randomization, and 1181 received a transfusion. In the prespecified modified intention-to-treat analysis that included only participants who received a transfusion, the primary outcome occurred in 17 of 592 participants (2.9%) who received convalescent plasma and 37 of 589 participants (6.3%) who received control plasma (absolute risk reduction, 3.4 percentage points; 95% confidence interval, 1.0 to 5.8; P = 0.005), which corresponded to a relative risk reduction of 54%. Evidence of efficacy in vaccinated participants cannot be inferred from these data because 53 of the 54 participants with Covid-19 who were hospitalized were unvaccinated and 1 participant was partially vaccinated. A total of 16 grade 3 or 4 adverse events (7 in the convalescent-plasma group and 9 in the control-plasma group) occurred in participants who were not hospitalized., Conclusions: In participants with Covid-19, most of whom were unvaccinated, the administration of convalescent plasma within 9 days after the onset of symptoms reduced the risk of disease progression leading to hospitalization. (Funded by the Department of Defense and others; CSSC-004 ClinicalTrials.gov number, NCT04373460.)., (Copyright © 2022 Massachusetts Medical Society.)

As early and effective antiretroviral therapy has become more widespread, HIV has transitioned from a progressive, fatal disease to a chronic, manageable disease marked by elevated risk of chronic comorbid diseases, including cardiovascular diseases (CVDs). Rates of myocardial infarction, heart failure, stroke, and other CVD manifestations, including pulmonary hypertension and sudden cardiac death, are significantly higher for people living with HIV than for uninfected control subjects, even in the setting of HIV viral suppression with effective antiretroviral therapy. These elevated risks generally persist after demographic and clinical risk factors are accounted for and may be partly attributed to chronic inflammation and immune dysregulation. Data on long-term CVD outcomes in HIV are limited by the relatively recent epidemiological transition of HIV to a chronic disease. Therefore, our understanding of CVD pathogenesis, prevention, and treatment in HIV relies on large observational studies, randomized controlled trials of HIV therapies that are underpowered to detect CVD end points, and small interventional studies examining surrogate CVD end points. The purpose of this document is to provide a thorough review of the existing evidence on HIV-associated CVD, in particular atherosclerotic CVD (including myocardial infarction and stroke) and heart failure, as well as pragmatic recommendations on how to approach CVD prevention and treatment in HIV in the absence of large-scale randomized controlled trial data. This statement is intended for clinicians caring for people with HIV, individuals living with HIV, and clinical and translational researchers interested in HIV-associated CVD.

Objective- We evaluated the biological effects of low-dose methotrexate on 3 novel brachial artery grayscale ultrasound measures that may indicate subclinical arterial injury. Approach and Results- Exploratory analysis from a clinical trial of people with HIV infection at increased cardiovascular disease risk who were randomly assigned to low-dose methotrexate (target dose 15 mg/wk) or placebo. Brachial artery ultrasound grayscale median, gray level difference statistic texture-contrast (GLDS-CON), and gray level texture entropy were measured at baseline and after 24 weeks of intervention. Findings from the intention-to-treat (N=148) and adequately-dosed (N=118) populations were consistent, so the adequately-dosed population results are presented. Participants were a median (Q1, Q3) age of 54 (50, 60) years. After 24 weeks, the low-dose methotrexate intervention was associated with a 25.4% (-18.1, 58.6; P=0.007) increase in GLDS-CON compared with 1.3% (-29.1, 44.7; P=0.97) with placebo ( P=0.05) and a 0.10 u (-0.06, 0.23; P=0.026) increase in entropy compared with 0.02 u (-0.11, 0.14; P=0.54) with placebo ( P=0.14). At week 24, changes in CD4+ T cells correlated inversely with changes in GLDS-CON (ρ=-0.20; P=0.031), and entropy (ρ=-0.21; P=0.023). Changes in D-dimer levels, but no other inflammatory biomarkers, also correlated inversely with changes in GLDS-CON (ρ=-0.23; P=0.014) and entropy (ρ=-0.26; P=0.005). Conclusions- Brachial artery GLDS-CON and entropy increased after 24 weeks of low-dose methotrexate, though the latter was not significantly different from placebo. Grayscale changes were associated with decreases in CD4+ T-cell and D-dimer concentrations and may indicate favorable arterial structure changes.

As antiretroviral therapy (ART) expands in resource-limited settings, understanding the impact of ART on pregnancy outcomes is critical. We analyzed women who became pregnant on ART while enrolled in a clinical trial (HPTN 052, ACTG A5208, and ACTG A5175); the majority of women were from Africa, with a median age of 29 years. Eligible women were on ART at conception and had a documented date of a last menstrual period and a pregnancy outcome. The primary outcome was non-live birth (stillbirth; spontaneous abortion; elective termination; or ectopic pregnancy) versus live birth. Preterm birth (<37 weeks completed gestation) was a secondary outcome. We used Cox proportional hazards regression models with time-varying covariates. 359 women became pregnant, of whom 253 (70%) met inclusion criteria: 127 (50%) were on NNRTI-based ART, 118 (47%) on PI-based ART, and 8 (3%) on 3-NRTIs at conception. There were 160 (63%) live births (76 term and 84 preterm), 11 (4%) stillbirths, 51 (20%) spontaneous abortions, 28 (11%) elective terminations, and 3 (1%) ectopic pregnancies. In multivariable analysis adjusted for region, parent study, and pre-pregnancy ART class, only older age was associated with increased hazard of preterm birth [HR: 2.49 for age 25-30 years; 95% CI: 1.18-5.26; p = 0.017]. Women conceiving on ART had high rates of preterm birth and other adverse pregnancy outcomes. Despite the benefits of ART, studies designed to investigate the effects of preconception ART on pregnancy outcomes are needed., Competing Interests: The authors have declared that no competing interests exist.

The Gender, Race, and Clinical Experience (GRACE) study was designed to assess sex-based differences in darunavir/ ritonavir-based therapy and to enroll a female population representative of the racial demographics of women with human immunodeficiency virus (HIV)/AIDS in the United States. Here, we report week 48 results, stratified by race. GRACE was a multicenter, open-label, phase 3b study. Patients received 600 mg of darunavir and 100 mg of ritonavir twice daily plus an investigator-selected optimized background regimen. Virologic response (HIV-1 RNA < 50 copies/ mL) and safety were assessed over 48 weeks. Post hoc multivariate analyses were performed to investigate factors associated with response. Of 429 patients enrolled, 61.5% were black, 22.4% were Hispanic, and 15.2% were white. Black patients had more advanced disease at baseline, and more black patients discontinued (32.6%) than Hispanic (24%) or white (26.2%) patients. In the intent-to-treat population, similar response rates were seen in Hispanic (61.5%) and white patients (60.0%); lower response rates were observed in black patients (48.5%). Similar trends were observed in the nonvirologic failure censored population. The multivariate analysis revealed that being of a nonblack race was significantly associated with improved response (P = .009). Overall, darunavir/ritonavir-based therapy was well tolerated, regardless of race. Diarrhea, nausea, and rash were the most commonly reported grade 2 to 4 adverse events (at least possibly related to darunavir/ritonavir). Darunavir/ritonavir treatment is safe and effective in treatment-experienced patients, irrespective of sex or race. Despite the controlled trial environment, more black patients discontinued and experienced virologic failure than Hispanic or white patients.