Building an Infectious Disease Diversity, Equity, and Antiracism (ID2EA) Curriculum: A Single Center's Experience and Reflections.

In response to longstanding healthcare inequities unmasked by the Coronavirus Disease 2019 pandemic, the infectious diseases (ID) section at the Yale School of Medicine designed and implemented a pilot curriculum integrating Infectious Disease Diversity, Equity, and Antiracism (ID2EA) into ID educational training and measured program outcomes. We herein describe a mixed-methods assessment of section members on whether the ID2EA curriculum affected their beliefs and behaviors regarding racism and healthcare inequities. Participants rated the curriculum as useful (92% averaging across sessions) and effective in achieving stated learning objectives (89% averaging across sessions), including fostering understanding of how inequities and racism are linked to health disparities and identifying strategies to effectively deal with racism and inequities. Despite limitations in response rates and assessment of longer-term behavioral change, this work demonstrates that training in diversity, equity, and antiracism can be successfully integrated into ID physicians' educational activities and affect physicians' perspectives on these topics.

Long-term quantitative assessment of anti-SARS-CoV-2 spike protein immunogenicity (QUASI) after COVID-19 vaccination in older people living with HIV (PWH).

BACKGROUND: The durability of immune responses to COVID-19 vaccines among older people living with HIV (PWH) is clinically important. METHODS: We aimed to assess vaccine-induced humoral immunity and durability in older PWH (≥ 55 years, n = 26) over 6 months (post-initial BNT162b2 series). A secondary and exploratory objective was to assess T-cell response and BNT162b2 booster reactogenicity, respectively. Our Visit 1 (3 weeks post-initial BNT162b2 dose) SARS-CoV-2 humoral immunity results are previously reported; these subjects were recruited for Visit 2 [2 weeks (+ 1 week window) post-second vaccination] and Visit 3 [6 months (± 2 week window) post-initial vaccination] in a single-center longitudinal observational study. Twelve participants had paired Visit 2/3 SARS-CoV-2 Anti-Spike IgG data. At Visit 3, SARS-CoV-2 Anti-Spike IgG testing occurred, and 5 subjects underwent T-cell immune response evaluation. Thereafter, subjects were offered BNT162b2 booster (concurrent day outside our study) per US FDA/CDC guidance; reactogenicity was assessed. The primary study outcome was presence of detectable Visit 3 SARS-CoV-2 Anti-Spike-1-RBD IgG levels. Secondary and exploratory outcomes were T-cell immune response and BNT162b2 booster reactogenicity, respectively. Wilcoxon signed-rank tests analyzed median SARS-CoV-2 Anti-Spike IgG 6-month trends. RESULTS: At Visit 3, 26 subjects underwent primary analysis with demographics noted: Median age 61 years; male n = 16 (62%), female n = 10 (38%); Black n = 13 (50%), White n = 13 (50%). Most subjects (n = 20, 77%) had suppressed HIV viremia on antiretroviral therapy, majority (n = 24, 92%) with CD4 > 200 cells/µL. At Visit 3, 26/26 (100%) had detectable Anti-Spike-1-RBD (≥ 0.8 U/mL). Among 12 subjects presenting to Visit 2/3, median SARS-CoV-2 Anti-Spike 1-RBD was 2087 U/mL at Visit 2, falling to 581.5 U/mL at Visit 3 (p = 0.0923), with a median 3.305-fold decrease over 6 months. Among subjects (n = 5) with 6-month T-cell responses measured, all had detectable cytokine-secreting anti-spike CD4 responses; 3 had detectable CD4 + Activation induced marker (AIM) + cells. Two had detectable cytokine-secreting CD8 responses, but all had positive CD8 + AIM + cells. CONCLUSIONS: Among older PWH, SARS-CoV-2 Anti-Spike IgG and virus-specific T-cell responses are present 6 months post-primary BNT162b2 vaccination, and although waning, suggest retention of some degree of long-term protective immunity.

Qualitative assessment of anti-SARS-CoV-2 spike protein immunogenicity (QUASI) after COVID-19 vaccination in older people living with HIV.

OBJECTIVES: Effective and safe COVID-19 vaccines have been developed and have resulted in decreased incidence and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and can decrease secondary transmission. However, there are concerns about dampened immune responses to COVID-19 vaccination among immunocompromised patients, including people living with HIV (PLWH), which may blunt the vaccine's efficacy and durability of protection. This study aimed to assess the qualitative SARS-CoV-2 vaccine immunogenicity among PLWH after vaccination. METHODS: We conducted targeted COVID-19 vaccination (all received BNT162b2 vaccine) of PLWH (aged ≥ 55 years per state guidelines) at Yale New Haven Health System and established a longitudinal survey to assess their qualitative antibody responses at 3 weeks after the first vaccination (and prior to receipt of the second dose of the COVID-19 vaccine) (visit 1) and at 2-3 weeks after the second vaccination (visit 2) but excluded patients with prior COVID-19 infection. Our goal was to assess vaccine-induced immunity in the population we studied. Qualitative immunogenicity testing was performed using Healgen COVID-19 anti-Spike IgG/IgM rapid testing. Poisson regression with robust standard errors was used to determine factors associated with a positive IgG response. RESULTS: At visit 1, 45 of 78 subjects (57.7%) tested positive for SARS-CoV-2 anti-Spike IgG after the first dose of COVID-19 vaccine. Thirty-nine subjects returned for visit 2. Of these, 38 had positive IgG (97.5%), including 20 of 21 subjects (95.2%) with an initial negative anti-Spike IgG. Our bivariate analysis suggested that participants on an antiretroviral regimen containing integrase strand transfer inhibitors [relative risk (RR) = 1.81, 95% confidence interval (CI): 0.92-3.56, p = 0.085] were more likely to seroconvert after the first dose of the COVID-19 vaccine, while those with a CD4 count < 500 cells/µL (RR = 0.59, 95% CI: 0.33-1.05, p = 0.071), and those diagnosed with cancer or another immunosuppressive condition (RR = 0.49, 95% CI: 0.18-1.28, p = 0.15) may have been less likely to seroconvert after the first dose of the COVID-19 vaccine. The direction of these associations was similar in the multivariate model, although none of these findings reached statistical significance (RRintegrase inhibitor  = 1.71, 95% CI: 0.90-3.25, p = 0.10; RRCD4 count  = 0.68, 95% CI: 0.39-1.19, p = 0.18; RRcancer or another immunosuppressive condition  = 0.50, 95% CI: 0.19-1.33, p = 0.16). With regard to immunogenicity, we were able to record very high rates of new seroconversion following the second dose of the COVID-19 vaccine. CONCLUSIONS: Our study suggests that completing a two-dose series of BNT162b2 vaccine is critical for PLWH given suboptimal seroconversion rates after the first dose and subsequent improved seroconversion rates after the second dose.

Confronting Another Pandemic: Lessons from HIV can Inform Our COVID-19 Response.

The novel coronavirus 2019 illness (COVID-19) has completely transformed and uprooted lives across the globe. While different diseases, there are critical observations and lessons to be learned from the ongoing HIV epidemic to inform our response to COVID-19. We reflect on how this relates to (1) testing, including contact tracing; (2) health system redesign; (3) telehealth; (4) health disparities; (5) political denial, with inadequate and uncoordinated governmental response; (6) occupational exposure; and (7) complex reactions among healthcare providers. Decades of experiences with HIV provide an important framework for moving forward as we combat COVID-19.

Turning the tide against tuberculosis.

Despite affecting men, women, and children for millennia, tuberculosis (TB) is the most neglected disease. In contrast, the global response to HIV has reached a defining moment. By uniting efforts, promptly integrating major scientific findings for both treatment and prevention, and scaling up services, the once inconceivable end to the HIV epidemic may no longer be an illusion. "The world has made defeating AIDS a top priority. This is a blessing. But TB remains ignored" - Nelson Mandela. While there is no doubt that revolutionary diagnostics and new and repurposed drugs have provided some hope in the fight against TB, it is evident that scientific advances on their own are inadequate to achieve the World Health Organization's ambitious goal to end TB by 2035. In this article, the consequences of a myopic and conventional biomedical approach to TB, which has ultimately permeated to the level of individual patient care, are highlighted.

Cost-Effectiveness of Community-Based TB/HIV Screening and Linkage to Care in Rural South Africa.

South Africa has one of the highest burdens of TB worldwide, driven by the country's widespread prevalence of HIV, and further complicated by drug resistance. Active case finding within the community, particularly in rural areas where healthcare access is limited, can significantly improve diagnosis and treatment coverage in high-incidence settings. We evaluated the potential health and economic consequences of implementing community-based TB/HIV screening and linkage to care. Using a dynamic model of TB and HIV transmission over a time horizon of 10 years, we compared status quo TB/HIV control to community-based TB/HIV screening at frequencies of once every two years, one year, and six months. We also considered the impact of extending IPT from 36 months for TST positive and 12 months for TST negative or unknown patients (36/12) to lifetime use for all HIV-infected patients. We conducted a probabilistic sensitivity analysis to assess the effect of parameter uncertainty on the cost-effectiveness results. We identified four strategies that saved the most life years for a given outlay: status quo TB/HIV control with 36/12 months of IPT and TB/HIV screening strategies at frequencies of once every two years, one year, and six months with lifetime IPT. All of these strategies were very cost-effective at a threshold of $6,618 per life year saved (the per capita GDP of South Africa). Community-based TB/HIV screening with linkage to care is therefore very cost-effective in rural South Africa.

An inter-professional 'advocacy and activism in global health': module for the training of physician-advocates.

Medical students typically learn about the role of physicians as health advocates through a component of the health professionalism curriculum. Recently, there has been a call for increased exposure to health advocacy in undergraduate medical education so that students can develop the interest, knowledge, skills, and attitudes that they will utilize throughout their careers as physician-advocates. We developed a four-session Advocacy and Activism training module that consisted of formal didactic teaching, training in basic skills, debate and discussion, and the development and presentation of advocacy projects. There were several uniquely innovative aspects of this module, including its structure, content, and inter-professional approach that included students of medicine, nursing, and public health. However, this approach also resulted in some important and unexpected limitations. We were encouraged by the quality of student participation during the module, as well as specific feedback regarding the format and content. The module was a low-cost, easy-to-implement, and academically rigorous model that can be implemented by interested students and faculty at other schools. We plan to continue to develop this program in the future, and we believe that other medical institutions should consider a similar model for introducing students to their future role as health advocates.

Preparing for highly active antiretroviral therapy rollout in rural South Africa: an assessment using the information, motivation, and behavioral skills model.

Following a controversial history and before South Africa started the world's largest highly active antiretroviral therapy (HAART) rollout, little was known about community-level information, motivation, and behavioral skills (IMB) regarding HAART in high-HIV-prevalence rural communities. The IMB model has been shown to predict behaviors that are associated with desirable HAART outcomes. We conducted an anonymous, cross-sectional "HAART-Felt Prospects" survey among HIV-serostatus-unknown young adults in Tugela Ferry, KwaZulu-Natal. We aimed to identify behavioral aspects of HAART preparedness that could be targeted by local interventions to enhance HAART outcomes. Data analysis included: percent correct, thematic means based on a four-point Likert-scale, and composite quotients. Subjects (N=176) were Zulu (99%), young (mean 19 years), and severely impoverished (55%). Relatively high levels of information were reported: overall correct score was 46%, secondary-transmission-of-resistance information was highest (81%), and only 15% reported traditional or government-advocated folk remedies cure or treat HIV/AIDS. Motivation quotient was "consistent" with favorable HAART behaviors; attitudes toward medication-taking behaviors (3.48) and condom use during HAART (3.43) ranked the highest. Desire for HIV testing (71%) was associated with HIV treatment optimism [adjusted odds ratio (AOR)=4.0, p=0.0004] and previous experience with good treatment outcome [AOR=3.2, p=0.01]. Acceptance of HAART (93%) was associated with HIV optimism [AOR=18.0, p=0.001] and not believing government-advocated folk remedies cure or treat HIV/AIDS [AOR=10.0, p=0.04]. Behavioral skills quotient was "neutral" for favorable HAART behaviors; side effects self-efficacy was the highest (3.16); and medication-taking self-efficacy the lowest (2.51). Only 47% believed disclosing HIV-serostatus would be easy. Despite controversy surrounding HAART initiation, these results suggest that local South African at-risk youth were relatively well-poised for HAART rollout. This conclusion is supported by subsequent successful HAART rollout locally. Community-based assessments are urgently needed as HAART rollouts continue. Adaptation of this IMB-based survey may better inform efforts to enhance HAART-program implementation in resource-limited settings globally.

Development and assessment of an innovative culturally sensitive educational videotape to improve adherence to highly active antiretroviral therapy in Soweto, South Africa.

The increasing availability of antiretroviral medication (ARV) therapy in the face of limited chronic medication-taking experience among resource-poor South Africans has raised concerns about adequate adherence to these medications. We hypothesized that a culturally sensitive audiovisual patient education program would be of substantial and measurable benefit in increasing patient understanding of the concepts of ARV resistance risk and medication-taking skills. To identify potential barriers to adherence and successful strategies to promote adherence, 6 focus groups with health care providers and HIV-positive adherence counselors were held, resulting in the production of a 17-minute culturally sensitive educational videotape. Basic drug-taking concepts and practical advice on how to improve adherence were presented in the videotape. Thirty-four HIV-positive patients (including 11 ARV-naive patients and 23 ARV-experienced patients) were shown the educational videotape, and their knowledge about medication taking was evaluated by a 24-point pre- and postvideotape questionnaire. On average, the 34 patients gained 2.2 knowledge points (P = 0.021). ARV-naive patients had an average improvement of 3.0 points (P = 0.0028), with most significant gains in the areas of understanding medication-taking strategies and side effects. These preliminary findings indicate that a culturally sensitive educational videotape can improve medication-taking knowledge in South Africa and that further study of the potential efficacy of using media technology to improve individuals' adherence to ARV therapy is warranted.

A pilot study of once-daily antiretroviral therapy integrated with tuberculosis directly observed therapy in a resource-limited setting.

To determine the feasibility and effectiveness of integrating highly active antiretroviral therapy (HAART) into existing tuberculosis directly observed therapy (TB/DOT) programs, we performed a pilot study in an urban TB clinic in South Africa. Patients with smear-positive pulmonary TB were offered HIV counseling and testing. Twenty HIV-positive patients received once-daily didanosine (400 mg) plus lamivudine (300 mg) plus efavirenz (600 mg) administered concomitantly with standard TB therapy Monday to Friday and self-administered on weekends. After completing TB therapy, patients were referred to an HIV clinic for continued treatment. At baseline, patients had a mean CD4 count of 230 cells/mm(3) (range: 24-499 cells/mm(3)) and a mean viral load of 5.75 log(10) (range: 3.81-7.53 log(10)). Seventeen completed combined standard TB and HIV therapy; 16 of 20 (80%) patients enrolled and 15 of 17 (88%) patients completing standard TB therapy achieved a viral load <50 copies/mL and mean CD4 count increase of 148 cells/mm(3). TB was cured in 17 of 20 (85%) enrolled patients and 17 of 19 (89%) patients with drug-sensitive TB. Treatment was well tolerated, with minimal gastrointestinal, hepatic, skin, or neurologic toxicity. The project was well accepted and integrated into the daily TB clinic functions. This pilot study demonstrates that TB/DOT programs can be feasible and effective sites for HIV identification and the introduction and monitoring of a once-daily HAART regimen in resource-limited settings.