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After more than 36,500 health care workers at the University of California received at least one dose of vaccine, 71% of 379 workers with positive SARS-CoV-2 tests had positive results within 2 weeks after the first dose. Of 37 workers with positive results after the second dose, 7 had positive results 15 or more days after the dose.

The treatment of metabolic disease is becoming an increasingly important component of the long-term management of patients with well controlled HIV on antiretroviral therapy (ART). Metabolic diseases probably develop at the intersection of traditional risk factors (such as obesity, tobacco use, and genetic predisposition) and HIV-specific and ART-specific contributors (including chronic inflammation and immune activation). This Review discusses present knowledge on adipose tissue dysfunction, insulin–glucose homoeostasis, lipid disturbances, and cardiovascular disease risk in people with HIV on ART. Although new antiretroviral drugs are believed to induce fewer short-term metabolic perturbations than do older drugs, the long-term effects of these drugs are not fully understood. Additionally, patients remain at increased risk of cardiovascular disease and other metabolic comorbidities. Research and treatment should focus on selection of ART that is both virologically effective and has minimum metabolic effects, minimisation of traditional risk factors for metabolic disease, and development of novel therapies to treat metabolic disease in patients with HIV, including use of anti-inflammatory and immunomodulatory drugs.

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.

Background The COVID-19 pandemic resulted in the rapid implementation of telemedicine for HIV care at federally qualified health centers (FQHCs) in the United States. We sought to understand use of telemedicine (telephone and video) at two FQHCs in Los Angeles, and the client attitudes towards and experiences with telemedicine as part of future HIV care. Methods We conducted surveys with 271 people living with HIV (PLHIV), with questions covering sociodemographic factors, telemedicine attitudes and experiences, technological literacy, and access to technological resources and privacy. Survey data were analyzed utilizing summary statistics, chi-square analyses, and Fisher’s exact test to understand associations between sociodemographic factors and telemedicine attitudes and experiences. Results Sixty percent of the sample had used any telemedicine and, of these, 93% utilized only telephone visits. Almost all respondents (95%, n  = 257) had access to a functioning smartphone and self-rated their technological literacy as high. Most had consistent access to privacy (88%, n  = 239), and those without privacy noted this as a barrier to the use of telemedicine. The main benefits of telemedicine (compared to in person) were savings of time and money, convenience, and ability to complete appointments as scheduled. Just over half of PLHIV said they would feel more comfortable discussing sensitive topics (e.g., substance use, relationship issues) in person than over telephone (60%, n  = 164) or video (55%, n  = 151). Despite limited experience with video telemedicine, half of all participants desired a mix of telephone and video visits as part of their future HIV care. Conclusions During a mature phase of the COVID-19 pandemic, PLHIV in our study showed high satisfaction with telemedicine, largely conducted as telephone visits, and high interest in telemedicine visits as a component of their future HIV care. Future studies should explore barriers to implementing video telemedicine in FQHCs and determine telemedicine’s impact on clinical outcomes, including engagement and viral suppression.

To mitigate the loss of lives during the COVID-19 pandemic, emergency use authorization was given to several anti-SARS-CoV-2 monoclonal antibody (mAb) therapies for the treatment of mild-to-moderate COVID-19 in patients with a high risk of progressing to severe disease. Monoclonal antibodies used to treat SARS-CoV-2 target the spike protein of the virus and block its ability to enter and infect target cells. Monoclonal antibody therapy can thus accelerate the decline in viral load and lower hospitalization rates among high-risk patients with variants susceptible to mAb therapy. However, viral resistance has been observed, in some cases leading to a transient viral rebound that can be as large as 3–4 orders of magnitude. As mAbs represent a proven treatment choice for SARS-CoV-2 and other viral infections, evaluation of treatment-emergent mAb resistance can help uncover underlying pathobiology of SARS-CoV-2 infection and may also help in the development of the next generation of mAb therapies. Although resistance can be expected, the large rebounds observed are much more difficult to explain. We hypothesize replenishment of target cells is necessary to generate the high transient viral rebound. Thus, we formulated two models with different mechanisms for target cell replenishment (homeostatic proliferation and return from an innate immune response antiviral state) and fit them to data from persons with SARS-CoV-2 treated with a mAb. We showed that both models can explain the emergence of resistant virus associated with high transient viral rebounds. We found that variations in the target cell supply rate and adaptive immunity parameters have a strong impact on the magnitude or observability of the viral rebound associated with the emergence of resistant virus. Both variations in target cell supply rate and adaptive immunity parameters may explain why only some individuals develop observable transient resistant viral rebound. Our study highlights the conditions that can lead to resistance and subsequent viral rebound in mAb treatments during acute infection.

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.

Current cell-based assays for determining the functional properties of high-density lipoproteins (HDL) have limitations. We report here the development of a new, robust fluorometric cell-free biochemical assay that measures HDL lipid peroxidation (HDLox) based on the oxidation of the fluorochrome Amplex Red. HDLox correlated with previously validated cell-based (r = 0.47, p<0.001) and cell-free assays (r = 0.46, p<0.001). HDLox distinguished dysfunctional HDL in established animal models of atherosclerosis and Human Immunodeficiency Virus (HIV) patients. Using an immunoaffinity method for capturing HDL, we demonstrate the utility of this novel assay for measuring HDLox in a high throughput format. Furthermore, HDLox correlated significantly with measures of cardiovascular diseases including carotid intima media thickness (r = 0.35, p<0.01) and subendocardial viability ratio (r = -0.21, p = 0.05) and physiological parameters such as metabolic and anthropometric parameters (p<0.05). In conclusion, we report the development of a new fluorometric method that offers a reproducible and rapid means for determining HDL function/quality that is suitable for high throughput implementation.

Inflammation associated with increased risk of comorbidities persists in people living with HIV (PWH) on combination antiretroviral therapy (ART). A recent placebo-controlled trial of low-dose methotrexate (MTX) in PWH found that numbers of total CD4 and CD8 T cells decreased in the low-dose MTX arm. In this report we analyzed T cell phenotypes and additional plasma inflammatory indices in samples from the trial. We found that cycling (Ki67+) T cells lacking Bcl-2 were reduced by MTX but plasma inflammatory cytokines were largely unaffected. In a series of in vitro experiments to further investigate the mechanisms of MTX activity, we found that MTX did not inhibit effector cytokine production but inhibited T cell proliferation downstream of mTOR activation, mitochondrial function, and cell cycle entry. This inhibitory effect was reversible with folinic acid, suggesting low-dose MTX exerts anti-inflammatory effects in vivo in PWH largely by blocking T cell proliferation via dihydrofolate reductase inhibition, yet daily administration of folic acid did not rescue this effect in trial participants. Our findings identify the main mechanism of action of this widely used anti-inflammatory medicine in PWH and may provide insight into how MTX works in the setting of other inflammatory conditions.

Combination antiretroviral therapy (ART) for the treatment of human immunodeficiency virus (HIV) infection is one of the most important advances in medicine in the past quarter century. The availability of several single-tablet multidrug treatment regimens that effectively control the replication of HIV type 1 (HIV-1) has dramatically improved the prognosis of people living with HIV who are able to adhere to daily oral therapy. Now two pivotal international, phase 3, randomized trials — Antiretroviral Therapy as Long Acting Suppression (ATLAS) and First Long-Acting Injectable Regimen (FLAIR), the results of which are reported in the Journal 1,2 — show 48-week outcomes among . . .

Hypertension is among the most commonly diagnosed non-communicable diseases in Africa, and studies have demonstrated a high prevalence of hypertension among individuals with HIV. Despite high prevalence, there has been limited attention on the clinical outcomes of hypertension treatment in this population. We sought to characterize rates of and factors associated with blood pressure control over one year among individuals on antiretroviral therapy (ART) and antihypertensive medications. We performed a prospective observational cohort study at an HIV clinic in Malawi. We defined uncontrolled hypertension as a systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg at two or more follow-up visits during the year, while controlled hypertension was defined as <140 mm Hg systolic and <90 mm Hg diastolic at all visits, or at all but one visit. We calculated an antihypertensive non-adherence score based on self-report of missed doses at each visit (higher score = worse adherence) and used rank sum and chi-square tests to compare sociodemographic and clinical factors (including adherence) associated with blood pressure control over the year. At study entry, 158 participants (23.5%) were on antihypertensive medication; participants had a median age of 51.0 years, were 66.5% female, and had a median of 6.9 years on ART. 19.0% (n = 30) achieved blood pressure control over the year of follow-up. Self-reported non-adherence to hypertension medications was the only factor significantly associated with uncontrolled blood pressure. The average non-adherence score for those with controlled blood pressure was 0.22, and for those with uncontrolled blood pressure was 0.61 (p = 0.009). Adults living with HIV and hypertension in our cohort had low rates of blood pressure control over one year associated with self-reported non-adherence to antihypertensive medications. Given the high prevalence and incidence of hypertension, interventions to improve blood pressure control are needed to prevent associated long-term cardio- and cerebrovascular morbidity and mortality.