"Do We Stay or Do We Go?" The Impact of Anti-LGBTQ+ Legislation on the HIV Workforce in the South.

The human immunodeficiency virus (HIV) workforce continues to face a crisis, particularly in the southern United States. Adding to known issues of administrative burden and less competitive compensation, recent anti- lesbian, gay, bisexual, transgender and queer (LGBTQ+) legislation threatens the already strained HIV workforce. HIV care providers advocate for all aspects of their patient's lives, including those needing gender-affirming care. The recent legislative targets against transgender patients, which involves many people with HIV, will clearly add to the burden on individual HIV care providers and therefore the HIV workforce. Recruitment and retention efforts in states impacted by these laws will become increasingly difficult without advocacy for the patients we serve. The HIV workforce must work together with LGBTQ+ populations to address these recent laws and promote the well-being of all our patients and colleagues.

Interprofessional Education: An Innovative Approach to Increase the Human Immunodeficiency Virus Workforce.

Ending the human immunodeficiency virus (HIV) epidemic relies on a robust clinical workforce. The Southeast AIDS Education and Training Center's interprofessional education program is a novel approach to increasing the interest and ability of early health professional learners to provide high-quality, comprehensive, person-first care for people with HIV. Key Points: Interprofessional education (IPE) focusing on multidisciplinary care for people with HIV can serve as a novel way to increase the HIV workforce. This brief report describes the IPE program of the Southeast AIDS Education and Training Center.

Cryptococcal Meningitis and Clinical Outcomes in Persons With Human Immunodeficiency Virus: A Global View.

BACKGROUND: Cryptococcal meningitis (CM) is a major cause of morbidity and mortality in persons with human immunodeficiency virus (HIV; PWH). Little is known about CM outcomes and availability of diagnostic and treatment modalities globally. METHODS: In this retrospective cohort study, we investigated CM incidence and all-cause mortality in PWH in the International Epidemiology Databases to Evaluate AIDS cohort from 1996 to 2017. We estimated incidence using quasi-Poisson models adjusted for sex, age, calendar year, CD4 cell count (CD4), and antiretroviral therapy (ART) status. Mortality after CM diagnosis was examined using multivariable Cox models. A site survey from 2017 assessed availability of CM diagnostic and treatment modalities. RESULTS: Among 518 852 PWH, there were 3857 cases of CM with an estimated incidence of 1.54 per 1000 person-years. Mortality over a median of 2.6 years of post-CM diagnosis follow-up was 31.6%, with 29% lost to follow-up. In total, 2478 (64%) were diagnosed with CM after ART start with a median of 253 days from ART start to CM diagnosis. Older age (hazard [HR], 1.31 for 50 vs 35 years), lower CD4 (HR, 1.15 for 200 vs 350 cells/mm3), and earlier year of CM diagnosis (HR, 0.51 for 2015 vs 2000) were associated with higher mortality. Of 89 sites, 34% reported access to amphotericin B; 12% had access to flucytosine. CONCLUSIONS: Mortality after CM diagnosis was high. A substantial portion of CM cases occurred after ART start, though incidence and mortality may be higher than reported due to ascertainment bias. Many sites lacked access to recommended CM treatment.

Principles for Ending Human Immunodeficiency Virus as an Epidemic in the United States: A Policy Paper of the Infectious Diseases Society of America and the HIV Medical Association.

While we have the tools to achieve this goal, the persistent barriers to healthcare services experienced by too many individuals will need to be addressed to make significant progress and improve the health and quality of life of all people with human immunodeficiency virus (HIV). The necessary structural changes require actions by federal, state, and local policymakers and range from ensuring universal access to healthcare services to optimizing care delivery to ensuring a robust and diverse infectious diseases and HIV workforce. In this article, we outlines 10 key principles for policy reforms that, if advanced, would make ending the HIV epidemic in the United States possible and could have much more far-reaching effects in improving the health of our nation.

Ending the HIV Epidemic: We Have the Tools, Do We Have the Will?

This Viewpoint identifies several barriers to ending the HIV epidemic and urges increasing expertise in HIV medicine in underserved areas like the South challenging legislation designed to keep students ignorant.

Detecting Drug-Drug Interactions in COVID-19 Patients.

COVID-19 patients with multiple comorbid illnesses are more likely to be using polypharmacy to treat their COVID-19 disease and comorbid conditions. Previous literature identified several DDIs in COVID-19 patients; however, various DDIs are unrecognized. This study aims to discover novel DDIs by conducting comprehensive research on the FDA Adverse Event Reporting System (FAERS) data from January 2020 to March 2021. We applied seven algorithms to discover DDIs. In addition, the Liverpool database containing DDI confirmed by clinical trials was used as a gold standard to determine novel DDIs in COVID-19 patients. The seven models detected 2,516 drug-drug pairs having adverse events (AEs), 49 out of which were confirmed by the Liverpool database. The remaining 2,467 drug pairs tested to be significant by the seven models can be candidate DDIs for clinical trial hypotheses. Thus, the FAERS database, along with informatics approaches, provides a novel way to select candidate drug-drug pairs to be examined in COVID-19 patients.

Late-onset opportunistic infections while receiving anti-retroviral therapy in Latin America: burden and risk factors.

OBJECTIVES: The aim of this study was to describe the incidence, clinical characteristics, and risk factors of late-onset opportunistic infections (LOI) in people who live with HIV (PWLHA) within the Caribbean, Central and South America network for HIV epidemiology. METHODS: We performed a retrospective cohort study including treatment-naive PWLHA enrolled at seven sites (Argentina, Brazil, Chile, Peru, Mexico, and two sites in Honduras). Follow-up began at 6 months after treatment started. Outcomes were LOI, loss to follow-up, and death. We used a Cox proportional hazards model and a competing risks model to evaluate risk factors. RESULTS: A total of 10,583 patients were included. Median follow up was at 5.4 years. LOI occurred in 895 (8.4%) patients. Median time to opportunistic infection was 2.1 years. The most common infections were tuberculosis (39%), esophageal candidiasis (10%), and Pneumocystis jirovecii (P. jirovecii) pneumonia (10%). Death occurred in 576 (5.4%) patients, and 3021 (28.5%) patients were lost to follow-up. A protease inhibitor-based regimen (hazard ratio 1.25), AIDS-defining events during the first 6 months of antiretroviral-treatment (hazard ratio 2.12), starting antiretroviral-treatment in earlier years (hazard ratio 1.52 for 2005 vs 2010), and treatment switch (hazard ratio 1.31) were associated with a higher risk of LOI. CONCLUSION: LOI occurred in nearly one in 10 patients. People with risk factors could benefit from closer follow-up.

Multisystem Inflammatory Syndrome in an Adult With COVID-19.

Multisystem inflammatory syndrome (MIS) in children is a severe illness characterized by fever, laboratory evidence of inflammation, and multisystem organ dysfunction resulting from severe acute respiratory syndrome coronavirus 2 infection in a patient younger than 21 years. We present the case of a 39-year-old man with evidence of prior COVID-19 who seemed to meet all non-age-related criteria for MIS in children as well as criteria for the working definition of MIS in adults, and who improved after treatment with aspirin, corticosteroids, and intravenous immunoglobulin. Clinicians should be aware of this new inflammatory illness, not only in children but potentially also in adults with antecedent or concurrent COVID-19.

Outcomes After Second-Line Antiretroviral Therapy in Children Living With HIV in Latin America.

BACKGROUND: Little is known about the long-term outcomes of children living with HIV in Latin America. Few studies have examined antiretroviral therapy (ART) regimen switches in the years after the introduction of ART in this population. This study aimed to assess clinical outcomes among children who started second-line ART in the Caribbean, Central and South America network for HIV epidemiology. METHODS: Children (<18 years old) with HIV who switched to second-line ART at sites within Caribbean, Central and South America network for HIV epidemiology were included. The cumulative incidence and relative hazards of virologic failure while on second-line ART, loss to follow-up, additional major ART regimen changes, and all-cause mortality were evaluated using competing risks methods and Cox models. RESULTS: A total of 672 children starting second-line ART were included. Three years after starting second-line ART, the cumulative incidence of death was 0.10 [95% confidence interval (CI) 0.08 to 0.13], loss to follow-up was 0.14 (95% CI: 0.11 to 0.17), and major regimen change was 0.19 (95% CI: 0.15 to 0.22). Of those changing regimens, 35% were due to failure and 11% due to toxicities/side effects. Among the 312 children with viral load data, the cumulative incidence of virologic failure at 3 years was 0.62 (95% CI: 0.56 to 0.68); time to virologic failure and regimen change were uncorrelated (rank correlation -0.001; 95% CI -0.18 to 0.17). CONCLUSIONS: Poor outcomes after starting second-line ART in Latin America were common. The high incidence of virologic failure and its poor correlation with changing regimens was particularly worrisome. Additional efforts are needed to ensure children receive optimal ART regimens.

Infectious Diseases and Advocacy: This Is our Lane.

The disparate effects of severe acute respiratory syndrome coronavirus 2 virus on communities of color, paired with disjointed federal and local responses to the pandemic and the ongoing examples of structural racism's effects on health, highlight the need for physician advocacy on behalf of patients. The job of infectious disease physicians has always involved caring for the "whole patient," but the need for advocacy around issues related to racism, housing, food insecurity, substance use disorders, and mental health has increased. Advocacy at all levels-local, regional, and national-can make a difference and be a profoundly rewarding part of the career of an infectious disease/HIV physician.

The Struggling Infectious Diseases Fellow: Remediation Challenges and Opportunities.

Remediation of struggling learners is a challenge faced by all educators. In recognition of this reality, and in light of contemporary challenges facing infectious diseases (ID) fellowship program directors, the Infectious Diseases Society of America Training Program Directors' Committee focused the 2018 National Fellowship Program Directors' Meeting at IDWeek on "Remediation of the Struggling Fellow." Small group discussions addressed 7 core topics, including feedback and evaluations, performance management and remediation, knowledge deficits, fellow well-being, efficiency and time management, teaching skills, and career development. This manuscript synthesizes those discussions around a competency-based framework to provide program directors and other educators with a roadmap for addressing common contemporary remediation challenges.

Temporal changes in ART initiation in adults with high CD4 counts in Latin America: a cohort study.

INTRODUCTION: In 2013, the World Health Organization (WHO) recommended initiating combination ART (cART) in all adults with HIV and CD4+ lymphocyte counts (CD4) <500 cells/mm3 . In 2015, this was updated to recommend cART initiation in all patients with HIV, regardless of CD4 count. Implementation of these guidelines in real-world settings has not been evaluated in Latin America. To assess changes in time to cART initiation during routine care, we estimated trends in time from enrolment in care to cART initiation in HIV-positive adults with high CD4 counts in the Caribbean, Central and South America network for HIV Epidemiology (CCASAnet) during 2003 to 2017. METHODS: All cART-naive individuals ≥18 years of age from 2003 to 2017 with CD4 ≥350 cells/mm3 and without AIDS at enrolment at five CCASAnet sites (Brazil, Chile, Honduras, Mexico and Peru) were included. Patients without information regarding AIDS-defining events were excluded. We estimated unadjusted median time from enrolment to cART initiation by calendar year using Kaplan-Meier methods and calculated adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for trends in cART initiation using Cox models and restricted cubic splines for continuous variables, accounting for age, sex, CD4 at enrolment, route of HIV transmission and clinic site. RESULTS: Of the 3171 patients included, 1,650 (52%) had CD4 ≥500 cells/mm3 at enrolment. Median time to cART initiation after 2013 was 6.21 weeks (interquartile range (IQR): 1.89, 23.21), and 4.71 weeks (IQR: 1.43, 9.57) after 2015. Among 763 (24%) patients who never initiated cART, 33 (4.3%) were reported as deceased, 481 (63%) were lost to follow-up, and 249 (33%) were administratively censored before initiation. Adjusted probability of cART initiation greatly increased in recent years, in particular after 2013 and 2015 (2013 vs. 2003: HR = 7.14; 95% CI: 5.84 to 8.73, and 2015 vs. 2003: HR = 12.60; 95% CI: 10.37 to 15.32). CONCLUSIONS: Time to cART initiation decreased substantially, roughly following changes in WHO guidelines in this real-world setting in Latin America. However, a very high proportion of patients never started cART, compromising retention in care and survival, as shown by their higher proportion of LTFU and death, which reinforce the notion that earlier treatment implementation strategies are needed.

A Unique Case of Burkholderia cepacia Prosthetic Mitral Valve Endocarditis and Literature Review.

Burkholderia cepacia prosthetic valve endocarditis (PVE) is extremely rare, with few cases in the literature. A report of a patient with PVE is described, followed by a literature review on B. cepacia PVE. A 38 year old man with poor dentition and a history of intravenous drug use (IVDU) and mitral valve replacement was found to have a mitral valve vegetation. Five sets of blood cultures on different days grew B. cepacia. Individual sets of blood cultures on different dates also isolated S. viridans (outside hospital culture), methicillin-resistant S. epidermidis (hospital day 1), and Bacillus spp. (hospital day 6). He was successfully treated with ceftazidime and levofloxacin as dual therapy for B. cepacia PVE, in addition to vancomycin for gram positive coverage. This case report and review highlights the possibility of B. cepacia PVE in immunocompetent patients with poor dentition, with the potential for a successful outcome following combination antimicrobial therapy.

Antimicrobial exposure and the risk of delirium in critically ill patients.

BACKGROUND: Prior retrospective cross-sectional work has associated antimicrobials with a non-specific phrase: encephalopathy without seizures. The purpose of this study is to determine whether different classes of antimicrobials have differential associations with the daily risk of delirium after critical illness is adjusted for. METHODS: Our study was a nested cohort that enrolled non-neurological critically ill adults from a medical or surgical intensive care unit (ICU) with daily follow-up to 30 days. Our independent variable was exposure to previous-day antimicrobial class: beta-lactams (subclasses: penicillins, first- to third-generation cephalosporins, fourth-generation cephalosporins, and carbapenems), macrolides, fluoroquinolones, and other. We adjusted for baseline covariates (age, comorbidities, cognition scores, sepsis, and mechanical ventilation), previous-day covariates (delirium, doses of analgesics/sedatives, and antipsychotic use), and same-day covariates (illness severity). Our primary outcome of delirium was measured by using the Confusion Assessment Method for the ICU. A daily delirium logistic regression model was used with an ICU time-restricted sensitivity analysis including daily adjustment for sepsis and mechanical ventilation. RESULTS: Of 418 ICU patients, delirium occurred in 308 (74%) with a median of 3 days (interquartile range 2-6) among those affected and 318 (76%) were exposed to antimicrobials. When covariates and ICU type were adjusted for, only first- to third-generation cephalosporins were associated with delirium (logistic regression model odds ratio (OR) = 2.2, 95% confidence interval (CI) 1.28-3.79, P = 0.004; sensitivity analysis OR = 2.13, 95% CI 1.10-4.10, P = 0.024). CONCLUSIONS: First-, second-, and third-generation cephalosporins doubled the odds of delirium after baseline co-morbidities, ICU type, the course of critical care, and other competing antimicrobial and psychotropic medication risks were adjusted for. We did not find an association between delirium and cefepime, penicillins, carbapenems, fluoroquinolones, or macrolides.

Survival after cancer diagnosis in a cohort of HIV-positive individuals in Latin America.

BACKGROUND: This study aimed to evaluate trends and predictors of survival after cancer diagnosis in persons living with HIV in the Caribbean, Central, and South America network for HIV epidemiology cohort. METHODS: Demographic, cancer, and HIV-related data from HIV-positive adults diagnosed with cancer ≤ 1 year before or any time after HIV diagnosis from January 1, 2000-June 30, 2015 were retrospectively collected. Cancer cases were classified as AIDS-defining cancers (ADC) and non-AIDS-defining cancers (NADC). The association of mortality with cancer- and HIV-related factors was assessed using Kaplan-Meier curves and Cox proportional hazards models stratified by clinic site and cancer type. RESULTS: Among 15,869 patients, 783 had an eligible cancer diagnosis; 82% were male and median age at cancer diagnosis was 39 years (interquartile range [IQR]: 32-47). Patients were from Brazil (36.5%), Argentina (19.9%), Chile (19.7%), Mexico (19.3%), and Honduras (4.6%). A total of 564 ADC and 219 NADC were diagnosed. Patients with NADC had similar survival probabilities as those with ADC at one year (81% vs. 79%) but lower survival at five years (60% vs. 69%). In the adjusted analysis, risk of mortality increased with detectable viral load (adjusted hazard ratio [aHR] = 1.63, p = 0.02), age (aHR = 1.02 per year, p = 0.002) and time between HIV and cancer diagnoses (aHR = 1.03 per year, p = 0.01). CONCLUSION: ADC remain the most frequent cancers in the region. Overall mortality was related to detectable viral load and age. Longer-term survival was lower after diagnosis of NADC than for ADC, which may be due to factors unrelated to HIV.

Health Literacy and Demographic Disparities in HIV Care Continuum Outcomes.

Studies evaluating the association between human immunodeficiency virus (HIV) infection continuum of care outcomes [antiretroviral (ART) adherence, retention in care, viral suppression] and health literacy have yielded conflicting results. Moreover, studies from the southern United States, a region of the country disproportionately affected by the HIV epidemic and low health literacy, are lacking. We conducted an observational cohort study among 575 people living with HIV (PLWH) at the Vanderbilt Comprehensive Care Clinic (Nashville, Tennessee). Health literacy was measured using the brief health literacy screen, a short tool which can be administered verbally by trained clinical personnel. Low health literacy was associated with a lack of viral suppression, but not with poor ART adherence or poor retention. Age and racial disparities in continuum of care outcomes persisted after accounting for health literacy, suggesting that factors in addition to health literacy must be addressed in order to improve outcomes for PLWH.

Trends in HIV Continuum of Care Outcomes over Ten Years of Follow-Up at a Large HIV Primary Medical Home in the Southeastern United States.

Longitudinal studies of retention in care (RIC) and viral suppression (VS) in the southeastern United States (US), a region disproportionately affected by HIV infection, are lacking. HIV-infected adults with ≥1 medical visit at the Vanderbilt Comprehensive Care Clinic (Nashville, Tennessee) from 2004 to 2013 were included. RIC was ≥2 (a) laboratory dates [CD4+ counts or HIV-1 viral loads (VLs)] or (b) provider encounters and/or laboratory dates in the year of interest, ≥90 days apart. VS was a VL of <200 copies/ml at last measurement in the year of interest. Modified Poisson regression estimated relative risk (RR) of RIC and VS, adjusting for age, race, sex, HIV transmission risk, and socioeconomic status (SES). Among 4,641 persons, 76.8% achieved RIC and 70.2% achieved VS. RIC and VS increased from 2004 to 2013 (p < .001 each). For lack of RIC, younger patients (RR = 1.2 and RR = 1.1, 18-24 and 25-34 vs. 35-44 year-olds, respectively), Blacks (RR = 1.3 vs. Whites), and injection drug users (IDUs) (RR = 1.2 vs. heterosexual contact [Hetero]) fared worse (p < .05 each); those with male-to-male sexual contact fared better (RR = 0.8 vs. Hetero, p < .05). For lack of VS, younger patients (RR = 1.3 and RR = 1.2, 18-24 and 25-34 vs. 35-44 year olds, respectively), Blacks (RR 1.3 vs. Whites), Females (RR = 1.1 vs. Males), IDUs (RR 1.3 vs. Hetero), and those with low SES (RR = 1.1 vs. not low SES) fared worse (p < .05, each). RIC and VS increased over time, suggesting that efforts to improve outcomes have been effective. However, disparities persist and resources should focus on groups most at risk.

Time to HAART Initiation after Diagnosis and Treatment of Opportunistic Infections in Patients with AIDS in Latin America.

BACKGROUND: Since 2009, earlier initiation of highly active antiretroviral therapy (HAART) after an opportunistic infection (OI) has been recommended based on lower risks of death and AIDS-related progression found in clinical trials. Delay in HAART initiation after OIs may be an important barrier for successful outcomes in patients with advanced disease. Timing of HAART initiation after an OI in "real life" settings in Latin America has not been evaluated. METHODS: Patients in the Caribbean, Central and South America network for HIV Epidemiology (CCASAnet) ≥18 years of age at enrolment, from 2001-2012 who had an OI before HAART initiation were included. Patients were divided in an early HAART (EH) group (those initiating within 4 weeks of an OI) and a delayed HAART (DH) group (those initiating more than 4 weeks after an OI). All patients with an AIDS-defining OI were included. In patients with more than one OI the first event reported was considered. Calendar trends in the proportion of patients in the EH group (before and after 2009) were estimated by site and for the whole cohort. Factors associated with EH were estimated using multivariable logistic regression models. RESULTS: A total of 1457 patients had an OI before HAART initiation and were included in the analysis: 213 from Argentina, 686 from Brazil, 283 from Chile, 119 from Honduras and 156 from Mexico. Most prevalent OI were Tuberculosis (31%), followed by Pneumocystis pneumonia (24%), Invasive Candidiasis (16%) and Toxoplasmosis (9%). Median time from OI to HAART initiation decreased significantly from 5.7 (interquartile range [IQR] 2.8-12.1) weeks before 2009 to 4.3 (IQR 2.0-7.1) after 2009 (p<0.01). Factors associated with starting HAART within 4 weeks of OI diagnosis were lower CD4 count at enrolment (p-<0.001), having a non-tuberculosis OI (p<0.001), study site (p<0.001), and more recent years of OI diagnosis (p<0.001). DISCUSSION: The time from diagnosis of an OI to HAART initiation has decreased in Latin America coinciding with the publication of evidence of its benefit. We found important heterogeneity between sites which may reflect differences in clinical practices, local guidelines, and access to HAART. The impact of the timing of HAART initiation after OI on patient survival in this "real life" context needs further evaluation.

Temporal Trends in Age at HIV Diagnosis in Cohorts in the United States, the Caribbean, and Central and South America.

In the United States (USA), the age of those newly diagnosed with HIV is changing, particularly among men who have sex with men (MSM). A retrospective analysis included HIV-infected adults from seven sites in the Caribbean, Central and South America network (CCASAnet) and the Vanderbilt Comprehensive Care Clinic (VCCC-Nashville, Tennessee, USA). We estimated the proportion of patients <25 years at HIV diagnosis by calendar year among the general population and MSM. 19,466 (CCASAnet) and 3,746 (VCCC) patients were included. The proportion <25 years at diagnosis in VCCC increased over time for both the general population and MSM (p < 0.001). Only in the Chilean site for the general population and the Brazilian site for MSM were similar trends seen. Subjects <25 years of age at diagnosis were less likely to be immunocompromised at enrollment at both the VCCC and CCASAnet. Recent trends in the USA of greater numbers of newly diagnosed young patients were not consistently observed in Latin America and the Caribbean. Prevention efforts tailored to young adults should be increased.

Barriers to using text message appointment reminders in an HIV clinic.

INTRODUCTION: Failure to attend medical appointments among persons living with human immunodeficiency virus (HIV) has been associated with poor health outcomes. Text message appointment reminders are a novel tool to potentially improve appointment attendance, but the feasibility of this tool among persons living with HIV in the United States is unknown. SUBJECTS AND METHODS: We conducted a randomized, controlled trial of text message reminders in a large HIV clinic. Patients who declined enrollment were asked for reasons for declining. For all patients randomized, demographic and clinical data were collected from medical records. RESULTS: Of 94 patients screened for the study, 42 (45%) did not elect to participate; the most common reason for declining participation was the lack of either a cell phone or text messaging service. Cost, comfort with text messaging, and privacy were other major barriers to study enrollment. Among the 25 subjects randomized to receive text messages, 6 (24%) had their phones disconnected prior to the appointment reminder date. Ultimately, there were no differences in clinic attendance rates between the group that received text reminders versus the group that did not (72% versus 81%, p=0.42) in an intention-to-treat analysis. CONCLUSIONS: Although text message reminders may be successful in certain groups of patients, barriers must be addressed before they are used as a universal approach to improve clinic attendance.