Hospital Readmissions Among Persons With Human Immunodeficiency Virus in the United States and Canada, 2005-2018: A Collaboration of Cohort Studies.

BACKGROUND: Hospital readmission trends for persons with human immunodeficiency virus (PWH) in North America in the context of policy changes, improved antiretroviral therapy (ART), and aging are not well-known. We examined readmissions during 2005-2018 among adult PWH in NA-ACCORD. METHODS: Linear risk regression estimated calendar trends in 30-day readmissions, adjusted for demographics, CD4 count, AIDS history, virologic suppression (<400 copies/mL), and cohort. RESULTS: We examined 20 189 hospitalizations among 8823 PWH (73% cisgender men, 38% White, 38% Black). PWH hospitalized in 2018 versus 2005 had higher median age (54 vs 44 years), CD4 count (469 vs 274 cells/µL), and virologic suppression (83% vs 49%). Unadjusted 30-day readmissions decreased from 20.1% (95% confidence interval [CI], 17.9%-22.3%) in 2005 to 16.3% (95% CI, 14.1%-18.5%) in 2018. Absolute annual trends were -0.34% (95% CI, -.48% to -.19%) in unadjusted and -0.19% (95% CI, -.35% to -.02%) in adjusted analyses. By index hospitalization reason, there were significant adjusted decreases only for cardiovascular and psychiatric hospitalizations. Readmission reason was most frequently in the same diagnostic category as the index hospitalization. CONCLUSIONS: Readmissions decreased over 2005-2018 but remained higher than the general population's. Significant decreases after adjusting for CD4 count and virologic suppression suggest that factors alongside improved ART contributed to lower readmissions. Efforts are needed to further prevent readmissions in PWH.

Glucan rich nutrition does not increase gut translocation of beta-glucan.

BACKGROUND: (1-3)-b-D-glucan (BDG) is a fungal cell wall component and, in the absence of invasive fungal infection, a novel biomarker for microbial translocation of endogenous fungal products from the gastrointestinal tract into systemic circulation. However, its value as a marker of fungal translocation is limited by a concern that plant BDG-rich food influences blood BDG levels. METHODS: We conducted a pilot clinical trial to evaluate the impact of a standardised oral BDG challenge on blood BDG levels in participants with and without elevated microbial translocation. We enrolled 14 participants including 8 with HIV infection, 2 with advanced liver cirrhosis, and 4 healthy controls. After obtaining a baseline blood sample, participants received a standardised milkshake containing high levels of BDG followed by serial blood samples up to 8 hours after intake. RESULTS: The standardised oral BDG challenge approach did not change the blood BDG levels over time in all participants. We found consistently elevated blood BDG levels in one participant with advanced liver cirrhosis and a single person with HIV with a low CD4 count of 201 cells/mm3 . CONCLUSION: Our findings indicate that BDG blood levels were not influenced by plant origin BDG-rich nutrition in PWH, people with advanced liver cirrhosis, or healthy controls. Future studies are needed to analyse gut mycobiota populations in individuals with elevated blood BDG levels.

Successful optimization of antiretroviral regimens in treatment-experienced people living with HIV undergoing liver transplantation.

Modern antiretroviral therapy (ART) extends life expectancy for people living with HIV (PLWH). However, most older PLWH (≥50 years) "aged" with HIV and were exposed to historical HIV care practices and older, more toxic ART. In PLWH with exposure to older and multiple ART regimens, the drug interactions between ART frequently used in treatment-experienced persons and commonly used immunosuppressants remain a significant challenge. However, the advent of newer ART classes (eg, integrase non-strand transfer inhibitors) and more advanced HIV genetic resistance testing may allow optimization of ART regimens with minimal drug interactions. Here, we present a case series of three PLWH whose complicated ART interacted (or was at risk for interacting) with their post-liver transplant immunosuppression. After a review of their proviral DNA resistance testing, they successfully transitioned onto safer integrase non-strand transfer inhibitor-containing ART regimens without viral blips or evidence of organ rejection.

Sexual Partner Concurrency Among Partners Reported by MSM with Recent HIV Infection.

We examined concurrency among sexual partners reported by men who have sex with men (MSM) with recent (acute or early) HIV infection in San Diego, California (2002-2015). Partners overlapping in time in the past 3 months were considered concurrent. Logistic generalized linear mixed models were used to identify factors associated with concurrency at the partner-level. 56% (388/699) of partners were concurrent to ≥1 other partner. The odds of concurrency were higher among partners >10 years younger than the participant (vs. within 10 years of age) [adjusted odds ratio (AOR) = 2.22, 95% confidence interval (CI) 1.09-4.52], longer term partners (AOR per month = 1.02, 95% CI 1.01-1.03), and partners met online (AOR = 1.56, 95% CI 0.98-2.48). Concurrency is common among partners of recently HIV-infected MSM. Tailored HIV prevention strategies for MSM with older partners, longer term partners, and partners met online may help minimize the potential impact of concurrency on HIV transmission.

Are we prepped for preexposure prophylaxis (PrEP)? Provider opinions on the real-world use of PrEP in the United States and Canada.

BACKGROUND: Preexposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine (Truvada) has demonstrated efficacy in placebo-controlled clinical trials involving men who have sex with men, high-risk heterosexuals, serodiscordant couples, and intravenous drug users. To assist in the real-world provision of PrEP, the Centers for Disease Control and Prevention (CDC) has released guidance documents for PrEP use. METHODS: Adult infectious disease physicians were surveyed about their opinions and current practices of PrEP through the Emerging Infections Network (EIN). Geographic information systems analysis was used to map out provider responses across the United States. RESULTS: Of 1175 EIN members across the country, 573 (48.8%) responded to the survey. A majority of clinicians supported PrEP but only 9% had actually provided it. Despite CDC guidance, PrEP practices were variable and clinicians reported many barriers to its real-world provision. CONCLUSIONS: The majority of adult infectious disease physicians across the United States and Canada support PrEP but have vast differences of opinion and practice, despite the existence of CDC guidance documents. The success of real-world PrEP will likely require multifaceted programs addressing barriers to its provision and will be assisted with the development of comprehensive guidelines for real-world PrEP.

Engagement of Sexual Violence Survivors in Research: Trauma-Informed Research in the THRIVE Study.

Given the potential for retraumatization among survivors of sexual violence engaged in research, we aimed to provide pertinent knowledge and exemplification of the integration of trauma-informed practice to research with survivors. Grounded in trauma-informed care, we discuss the need for trauma-informed research, drawing upon experiences and data from a longitudinal case-control study on sexual violence. Through trauma-informed research settings, we can improve research experiences for survivors of sexual violence, as demonstrated by positive experiences of participants in The THRIVE Study. By meeting the needs of survivors, researchers can increase participation while maximizing the research quality and advancement of research.

Cost savings associated with testing of antibodies, antigens, and nucleic acids for diagnosis of acute HIV infection.

Efforts to identify all persons infected with HIV in the United States are driven by the hope that early diagnosis will lower risk behaviors and decrease HIV transmission. Identification of HIV-infected people earlier in the course of their infection with HIV antigen/antibody (Ag/Ab) combination assays (4th-generation HIV assays) should help achieve this goal. We compared HIV RNA nucleic acid test (NAT) results to the results of a 4th-generation Ag/Ab assay (Architect HIV Ag/Ab Combo [HIV Combo] assay; Abbott Diagnostics) in 2,744 HIV antibody-negative samples. Fourteen people with acute HIV infection (HIV antibody negative/NAT positive) were identified; the HIV Combo assay detected nine of these individuals and was falsely negative in the remaining five. All five persons missed by the HIV Combo assay were in the stage of exponential increase in plasma virus associated with acute HIV infection (3, 7, 20, 35, 48). In contrast, most acutely infected persons detected by the HIV Combo assay demonstrated either a plateauing or decreasing plasma viral load. The HIV Combo assay also classified as positive five other samples which were negative by NAT. Taken together, the HIV Combo assay had a sensitivity of 73.7% and a specificity of 99.8%. Using published data, we estimated secondary transmission events had HIV infection in these five individuals remained undiagnosed. Screening of our population with NAT cost more than screening with the HIV Combo assay but achieved new diagnoses that we predict resulted in health care savings that far exceed screening costs. These findings support the use of more sensitive assays, like NAT, in HIV screening of populations with a high prevalence of acute HIV infection.

Racial and ethnic disparities in coronavirus disease 2019 disease incidence independent of comorbidities, among people with HIV in the United States.

OBJECTIVES: To define the incidence of clinically detected coronavirus disease 2019 (COVID-19) in people with HIV (PWH) in the United States and evaluate how racial and ethnic disparities, comorbidities, and HIV-related factors contribute to risk of COVID-19. DESIGN: Observational study within the CFAR Network of Integrated Clinical Systems cohort in seven cities during 2020. METHODS: We calculated cumulative incidence rates of COVID-19 diagnosis among PWH in routine care by key characteristics including race/ethnicity, current and lowest CD4+ cell count, and geographic area. We evaluated risk factors for COVID-19 among PWH using relative risk regression models adjusted with disease risk scores. RESULTS: Among 16 056 PWH in care, of whom 44.5% were black, 12.5% were Hispanic, with a median age of 52 years (IQR 40-59), 18% had a current CD4+ cell count less than 350 cells/µl, including 7% less than 200; 95.5% were on antiretroviral therapy (ART), and 85.6% were virologically suppressed. Overall in 2020, 649 PWH were diagnosed with COVID-19 for a rate of 4.94 cases per 100 person-years. The cumulative incidence of COVID-19 was 2.4-fold and 1.7-fold higher in Hispanic and black PWH respectively, than non-Hispanic white PWH. In adjusted analyses, factors associated with COVID-19 included female sex, Hispanic or black identity, lowest historical CD4+ cell count less than 350 cells/µl (proxy for CD4+ nadir), current low CD4+ : CD8+ ratio, diabetes, and obesity. CONCLUSION: Our results suggest that the presence of structural racial inequities above and beyond medical comorbidities increased the risk of COVID-19 among PWH. PWH with immune exhaustion as evidenced by lowest historical CD4+ cell count or current low CD4+ : CD8+ ratio had greater risk of COVID-19.

Bone Mineral Density Screening Among People With HIV: A Population-Based Analysis in the United States.

HIV infection is associated with premature bone loss. The potential impact of recently updated osteoporosis screening guidelines is unknown. In a population-based cohort, we found low adherence and sex differences among eligible people with HIV.

The biobehavioral impacts of sexual violence: Findings from an acute repeat survivor of vaginal rape.

BACKGROUND: Individuals who have experienced repeat sexual violence victimization face adverse mental and physical health outcomes, including immune and stress response functioning. We aim to further understand repeat sexual violence victimization to develop responsive and appropriate treatment for survivors of sexual violence. METHODS: We present the immunological and contextual findings of a participant (N = 1) who experienced repeat sexual violence victimization during her enrollment in The THRIVE Study, a prospective case-control study of women aged 14-45 years, who have experienced recent consensual vaginal penetration ("controls") or forced vaginal penetration ("cases"). Participants complete a survey, HIV/sexually transmitted infection, and pregnancy testing, blood sampling for C-reactive protein and adrenocorticotrophic hormone, collection of cervicovaginal fluid for immunological biomarkers, and self-collection of saliva samples for cortisol measurements, across study visits (Baseline, 1, and 3 months). RESULTS: The case study participant, aged 18 years upon enrollment, experienced sexual trauma before four of five study visits. Trends in the mental health indicators demonstrate reciprocal fluctuations in adverse mental health and resilience in accordance with revictimization and circumstantial changes. Suppressed immune biomarkers appear to correlate with increased adverse mental health, while mental health recovery trends with immunological recovery. The participant presents with dysregulated hypothalamic-pituitary-adrenal axis diurnal profile. CONCLUSIONS: This profile illustrates the intra-individual biobehavioral impact of experience with revictimization over the course of 6 months, capturing experiences that are rarely studied either longitudinally or with the depth of the current research. The findings underscore the value of monitoring cervicovaginal immune functioning and hypothalamic-pituitary-adrenal axis dysregulation in coordination with changes in mental health over the course of repeated sexual trauma.

What lessons it might teach us? Community engagement in HIV research.

PURPOSE OF REVIEW: Partnerships between academia and the community led to historic advances in HIV and paved the way for ongoing community engagement in research. Three decades later, we review the state of community engagement in HIV research, discuss best practices as supported by literature, explore innovations, and identify ongoing gaps in knowledge. RECENT FINDINGS: The community of people living with and at risk for HIV remains actively involved in the performance of HIV research. However, the extent of participation is highly variable despite long standing and established principles and guidelines of good participatory practices (GPP) and community-based participatory research (CBPR). Current literature reveals that known barriers to successful community engagement continue to exist such as power differences, and poor scientific or cultural competency literacy. Several high-quality studies share their experiences overcoming these barriers and demonstrate the potential of CBPR through reporting of qualitative and quantitative outcomes. SUMMARY: Greater time and attention should be placed on the development of community engagement in HIV research. A large body of literature, including innovative cross-cutting approaches, exists to guide and inform best practices and mitigate common barriers. However, we recognize that true growth and expansion of CBPR within HIV and in other fields will require a greater breadth of research reporting qualitative and quantitative outcomes.

The Role of Stress and Genital Immunity in Sexual Trauma and HIV Susceptibility Among Adolescent Girls and Adult Women (The THRIVE Study): Protocol for a Longitudinal Case-Control Study.

BACKGROUND: The relationship between sexual violence and HIV risk has been extensively documented through social and behavioral research; however, the underlying biological mechanisms are poorly understood. OBJECTIVE: The purpose of the THRIVE (Trauma and HIV Risk: Investigating Stress and the Immune Disruption of the Vaginal Environment) Study is to examine the impact of sexual trauma due to sexual violence on HIV susceptibility through dysregulation of soluble inflammatory and anti-inflammatory and anti-HIV biomarkers in the female genital tract and dysregulation of the hypothalamic-pituitary-adrenal axis among adolescent girls and adult women. METHODS: The THRIVE Study is a longitudinal case-control study conducted in San Diego, CA, among a racially diverse sample. Cases are adolescent girls (aged 14-19 years) or adult women (aged 20-45 years) who have experienced forced vaginal penetration by a phallus perpetrated by a man within the past 15 days. Controls are adolescent girls or adult women who have engaged in consensual vaginal sex with a man within the past 15 days. At baseline and 1- and 3-month follow-up study visits, participants undergo a urine-based pregnancy test; venipuncture blood draw for HIV, C-reactive protein, adrenocorticotropic hormone, and progesterone testing; a 45-min interviewer-administered computer survey; and cervicovaginal lavage to measure proinflammatory and anti-inflammatory and anti-HIV soluble immune biomarkers. After each study visit, participants self-collect saliva specimens (upon waking, 30 min after waking, and 45 min after waking) at home for 3 consecutive days, which are later assayed for cortisol and dehydroepiandrosterone sulfate. Participants receive compensation at each study visit and for the return of saliva specimens, and a list of local medical and support services. Study procedures use trauma-informed care methods, given the sensitive nature of the study and enrollment of women in the acute phase after sexual trauma. All research staff and investigators adhere to ethical principles and guidelines in the conduct of research activities. Data will be analyzed for descriptive and inferential analyses. RESULTS: The recruitment of participants is ongoing. The publication of the first results is expected by late 2021. CONCLUSIONS: The THRIVE Study will provide foundational knowledge on how sexual trauma due to sexual violence increases susceptibility to HIV acquisition via alterations in cervicovaginal immune regulation and the psychobiology of the stress responses. These findings will inform future research on mechanistic models of in vitro and in vivo injury and cervicovaginal wound healing processes, which may lead to the development of nonvaccine biomedical HIV prevention products for girls and women. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18190.

Association of Pain and Pain Medication Use with Multiple Characteristics of Older People Living with HIV.

People living with HIV (PLWH) experience chronic pain that may impact function. Gaps in knowledge exist for factors that impact pain and pain medication use in older (age 50+) PLWH. Data for this study were obtained from the Aging with Dignity, Health, Optimism and Community (ADHOC) cohort, an observational study of older PLWH from 10 clinics across the United States. Participants self-reported socioeconomic, psychosocial, and health factors via an online questionnaire. Of 1,051 participants, 66% reported pain. In a multivariable regression model, multimorbidity and tobacco use were associated with a greater likelihood of experiencing pain, whereas being male, black, and having higher cognitive function were associated with a lower likelihood of experiencing pain. Of the 696 participants who reported pain, 46% reported using pain medication. In a multivariable regression model, pain medication use was associated with multimorbidity and with lower income. Recognition of the factors associated with pain and pain medication use in this vulnerable population may lead to strategies that mitigate negative health outcomes.

Substantial decline in heavily treated therapy-experienced persons with HIV with limited antiretroviral treatment options.

OBJECTIVE: Historically, a high burden of resistance to antiretroviral therapy (ART) in heavily treatment-experienced (HTE) persons with HIV (PWH) resulted in limited treatment options (LTOs). We evaluated the prevalence, risk factors, and virologic control of HTE PWH with LTO throughout the modern ART era. DESIGN: We examined all ART-experienced PWH in care between 2000 and 2017 in the Centers for AIDS Research Network of Integrated Clinical Systems cohort. METHODS: We computed the annual prevalence of HTE PWH with LTO defined as having two or less available classes with two or less active drugs per class based on genotypic data and cumulative antiretroviral resistance. We used multivariable Cox proportional hazards models to examine risk of LTO by 3-year study entry periods adjusting for demographic and clinical characteristics. RESULTS: Among 27 133 ART-experienced PWH, 916 were classified as having LTO. The prevalence of PWH with LTO was 5.2-7.5% in 2000-2006, decreased to 1.8% in 2007, and remained less than 1% after 2012. Persons entering the study in 2009-2011 had an 80% lower risk of LTO compared with those entering in 2006-2008 (adjusted hazard ratio 0.20; 95% confidence interval: 0.09-0.42). We found a significant increase in undetectable HIV viral loads among PWH ever classified as having LTO from less than 30% in 2001 to more than 80% in 2011, comparable with persons who never had LTO. CONCLUSION: Results of this large multicenter study show a dramatic decline in the prevalence of PWH with LTO to less than 1% with the availability of more potent drugs and a marked increase in virologic suppression in the current ART era.

The Current State of HIV and Aging: Findings Presented at the 10th International Workshop on HIV and Aging.

With increasing effectiveness of antiretroviral therapy, people with HIV (PWH) are living longer and the prevalence of older PWH continues to increase. Accordingly, PWH are experiencing an increased burden of age-related comorbidities. With this shifting demographics, clinicians and researchers face additional challenges in how to identify, address, and manage the complex intersections of HIV- and aging-related conditions. Established in 2009, the International Workshop on HIV and Aging brings together clinicians and researchers in cross-disciplinary fields along with community advocates and PWH to address the multidisciplinary nature of HIV and aging. This article summarizes plenary talks from the 10th Annual International Workshop on HIV and Aging, which took place in New York City on October 10 and 11, 2019. Presentation topics included the following: the burdens of HIV-associated comorbidities, aging phenotypes, community engagement, and loneliness; these issues are especially important for older PWH, considering the current COVID-19 pandemic. We also discuss broad questions and potential directions for future research necessary to better understand the interaction between HIV and aging.

The As and Bs of HIV and Hepatitis Co-Infection.

Hepatitis A and B co-infection among people living with HIV are public health challenges that account for an increasing degree of morbidity and mortality. Understanding the changing epidemiology, clinical manifestations, and new approaches to treatment and prevention continues to be important in the care of people living with HIV. We conducted a review of the literature that included studies on hepatitis A and HIV co-infection and hepatitis B and HIV co-infection, focusing on epidemiology, clinical manifestations, treatment, and prevention. Important updates include the changing epidemiology of hepatitis A outbreaks among the homeless and individuals who use substances, and novel approaches to hepatitis B vaccination and hepatitis B cure strategies.