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Background: Racial inequities exist in retention in human immunodeficiency virus (HIV) care and multilevel analyses are needed to contextualize and address these differences. Leveraging data from a multisite clinical cohort of people with HIV (PWH), we assessed the relationships between patient race and residential characteristics with missed HIV care visits., Methods: Medical record and patient-reported outcome (PRO; including mental health and substance-use measures) data were drawn from 7 participating Center for AIDS Research Network of Integrated Clinical Systems (CNICS) sites including N = 20 807 PWH from January 2010 through December 2015. Generalized estimating equations were used to account for nesting within individuals and within census tracts in multivariable models assessing the relationship between race and missed HIV care visits, controlling for individual demographic and health characteristics and census tract characteristics., Results: Black PWH resided in more disadvantaged census tracts, on average. Black PWH residing in census tracts with higher proportion of Black residents were more likely to miss an HIV care visit. Non-Black PWH were less likely to miss a visit regardless of where they lived. These relationships were attenuated when PRO data were included., Conclusions: Residential racial segregation and disadvantage may create inequities between Black PWH and non-Black PWH in retention in HIV care. Multilevel approaches are needed to retain PWH in HIV care, accounting for community, healthcare setting, and individual needs and resources., Competing Interests: Potential conflicts of interest. P. F. R. reports consulting fees paid to the author from Gilead and Janssen. J. K. reports a leadership or fiduciary role on the American Board of Internal Medicine, Infectious Disease Specialty Board (payment to author; ended 2020). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: The Second Universal Definition of Myocardial Infarction (MI) divides MIs into different types. Type 1 MIs result spontaneously from instability of atherosclerotic plaque, whereas type 2 MIs occur in the setting of a mismatch between oxygen demand and supply, as with severe hypotension. Type 2 MIs are uncommon in the general population, but their frequency in human immunodeficiency virus (HIV)-infected individuals is unknown., Objectives: To characterize MIs, including type; identify causes of type 2 MIs; and compare demographic and clinical characteristics among HIV-infected individuals with type 1 vs type 2 MIs., Design, Setting, and Participants: This longitudinal study identified potential MIs among patients with HIV receiving clinical care at 6 US sites from January 1, 1996, to March 1, 2014, using diagnoses and cardiac biomarkers recorded in the centralized data repository. Sites assembled deidentified packets, including physician notes and electrocardiograms, procedures, and clinical laboratory tests. Two physician experts adjudicated each event, categorizing each definite or probable MI as type 1 or type 2 and identifying the causes of type 2 MI., Main Outcomes and Measures: The number and proportion of type 1 vs type 2 MIs, demographic and clinical characteristics among those with type 1 vs type 2 MIs, and the causes of type 2 MIs., Results: Among 571 patients (median age, 49 years [interquartile range, 43-55 years]; 430 men and 141 women) with definite or probable MIs, 288 MIs (50.4%) were type 2 and 283 (49.6%) were type 1. In analyses of type 1 MIs, 79 patients who underwent cardiac interventions, such as coronary artery bypass graft surgery, were also included, totaling 362 patients. Sepsis or bacteremia (100 [34.7%]) and recent use of cocaine or other illicit drugs (39 [13.5%]) were the most common causes of type 2 MIs. A higher proportion of patients with type 2 MIs were younger than 40 years (47 of 288 [16.3%] vs 32 of 362 [8.8%]) and had lower current CD4 cell counts (median, 230 vs 383 cells/µL), lipid levels (mean [SD] total cholesterol level, 167 [63] vs 190 [54] mg/dL, and mean (SD) Framingham risk scores (8% [7%] vs 10% [8%]) than those with type 1 MIs or who underwent cardiac interventions., Conclusions and Relevance: Approximately half of all MIs among HIV-infected individuals were type 2 MIs caused by heterogeneous clinical conditions, including sepsis or bacteremia and recent use of cocaine or other illicit drugs. Demographic characteristics and cardiovascular risk factors among those with type 1 and type 2 MIs differed, suggesting the need to specifically consider type among HIV-infected individuals to further understand MI outcomes and to guide prevention and treatment.

Latinos represent a growing proportion of HIV cases in North Carolina (NC). Understanding how immigrants are involved in local HIV transmission is important to guide interventions. We used phylogenetics to characterize Latino involvement in local HIV transmission chains. Transmission clusters were identified from maximum-likelihood phylogenies constructed with HIV pol sequences from 177 Latinos and 1,496 non-Latinos receiving care in NC. Highly supported clusters involving one or more Latinos were characterized. Migration data were obtained from interviews and chart review. Factors associated with cluster membership were identified using log-binomial regression. Most Latinos were male (76%), immigrants (83%), and had HIV-1B (99%). Immigrants were more likely to report heterosexual risk (67% vs. 23%) than U.S.-born Latinos (p < 0.01). We identified 32 clusters that included one or more Latinos; these involved 53 Latinos (30%) and 41 non-Latinos. Immigrant and U.S.-born Latinos were equally likely to be in clusters, but immigrants were more likely to be in clusters with another Latino (78% vs. 29%; p = 0.02). Cluster composition by ethnicity and risk behavior varied by cluster size; larger clusters contained fewer immigrants and more men who have sex with men (MSM). Factors associated with immigrant membership in local transmission clusters included age <30 years [RR 2.34 (95% CI 1.47-3.73)], Mexican origin [RR 2.55 (95% CI 1.29-6.88)], and residing in the United States longer before diagnosis [RR 1.53 (95% CI 1.09-2.15), per 10 years]. While some Latinos immigrate with HIV infection, many immigrants are involved in transmission networks after arrival, particularly MSM. HIV testing and prevention interventions must consider this heterogeneity and may be better targeted by integrating phylogenetic analyses.

Objective: To assess opportunities for transmitted drug resistance (TDR), we examined sexual risk behaviours, HIV viraemia and antiretroviral resistance among patients in care., Design: A retrospective, cross-sectional analysis of clinical cohort data., Methods: For 244 UNC Center for AIDS Research HIV Clinical Cohort participants, demographic and behavioural data were obtained during in-person interviews between 2000 and 2011. Genotypic resistance tests were interpreted using WHO surveillance drug resistance mutations (SDRMs). Log-linear binomial regression was used to evaluate associations with TDR risk, defined as unprotected sex in the prior 6 months, HIV RNA at least 400 copies/ml and at least one SDRM., Results: Participants included 91 (37%) women and 153 men, of whom 92 (60%) were MSM. Median age was 43 years; 70% were Black (n = 171). Most (97%) were antiretroviral-experienced; 44% had exposure to more than four regimens. Among 204 individuals on antiretrovirals, 42% reported suboptimal adherence and 29% were viraemic. Over half of participants had at least one SDRM (n = 131); 26 (11%) had triple-class resistance. Overall, 70% were sexually active, and 55% used condoms inconsistently. Thirty (12%) reported unprotected sex during periods of drug-resistant viraemia. Higher TDR risk was associated with prior homelessness [adjusted prevalence ratio (aPR) 2.20, 95% confidence interval (CI) 1.16-4.18], active substance use (aPR 3.12, 95% CI 1.47-6.62) and nonsignificantly with MSM (aPR 1.75, 95% CI 0.93-3.28)., Conclusion: A small but significant proportion of clinic patients with drug-resistant HIV engage in sexual behaviours that place others at risk for TDR. Targeted efforts in secondary prevention could have an impact on TDR incidence, over time.

The associations of acute HIV infection (AHI) and other predictors with transmitted drug resistance (TDR) prevalence were assessed in a cohort of HIV-infected, antiretroviral-naïve patients. AHI was defined as being seronegative with detectable HIV RNA. Binomial regression was used to estimate prevalence ratios and 95% confidence intervals for associations with TDR. Among 43 AHI patients, TDR prevalence was 20.9%, whereas prevalence was 8.6% among 677 chronically infected patients. AHI was associated with 1.9 times the prevalence of TDR (95% confidence intervals: 1.0 to 3.6) in multivariable analysis. AHI patients may represent a vanguard group that portends increasing TDR in the future.

Background: Although combination antiretroviral therapy continues to evolve, with potentially more effective options emerging each year, the ability of therapy to prevent multiple regimen failure and mortality in clinical practice remains poorly defined., Methods: Sixteen cohorts representing over 60 sites contributed data on all individuals who initiated combination antiretroviral therapy. We identified those individuals who experienced virologic failure (defined as a human immunodeficiency virus [HIV] RNA level >1000 copies/mL), received modified therapy, and subsequently had a second episode of virologic failure. Multivariate Cox regression was used to assess factors associated with time to second regimen failure and the time to death after the onset of second regimen failure., Results: Of the 42,790 individuals who received therapy, 7159 experienced a second virologic failure. The risk of second virologic failure decreased from 1996 (56 cases per 100 person-years) through 2005 (16 cases per 100 person-years; P < .001). The cumulative mortality after onset of second virologic failure was 26% at 5 years and decreased over time. A history of AIDS, a lower CD4(+) T cell count, and a higher plasma HIV RNA level were each independently associated with mortality. Similar trends were observed when analysis was limited to the subset of previously treatment-naive patients, Conclusions: Although the rates of multiple regimen failure have decreased dramatically over the past decade, mortality rates for those who have experienced failure of at least 2 regimens have remained high. Plasma HIV RNA levels, CD4(+) T cell counts at time of treatment failure, and a history of AIDS remain independent risk factors for death, which emphasizes that these factors remain important targets for those in need of more-aggressive therapeutic interventions.

Plasma HIV RNA copy number is a strong prognostic marker of progression to AIDS in antiretroviral-naive persons. Recent research suggests women have lower HIV RNA levels than comparable men. Because clinical care recommendations currently include HIV RNA thresholds as a guide to initiating antiretroviral therapy (ART), the authors undertook the present quantitative meta-analysis to explore the relation between gender and plasma HIV RNA levels. A gender difference in HIV RNA levels was observed in the CD4-unadjusted and -adjusted analyses. The summary estimate including only CD4-adjusted results with the lowest heterogeneity indicated that on average, women have 41% lower plasma HIV RNA levels than men (-.23 log; 95% confidence interval [CI], -.16 to -.31 log ). Because numerous studies have found similar HIV disease progression rates in men and women, adjusted for CD4 but not HIV RNA, the present meta-analysis supports the use of lower HIV RNA thresholds in women than in men to guide initiation of ART. Given the patient characteristics in the original studies used in this meta-analysis, the results are most likely to apply to therapy-naive persons with CD4 lymphocyte counts >200 cells/mm, a subgroup for whom HIV RNA levels may strongly influence the decision to initiate therapy.

We developed, implemented, and evaluated a myocardial infarction (MI) adjudication protocol for cohort research of human immunodeficiency virus. Potential events were identified through the centralized Centers for AIDS Research Network of Integrated Clinical Systems data repository using MI diagnoses and/or cardiac enzyme laboratory results (1995-2012). Sites assembled de-identified packets, including physician notes and results from electrocardiograms, procedures, and laboratory tests. Information pertaining to the specific antiretroviral medications used was redacted for blinded review. Two experts reviewed each packet, and a third review was conducted if discrepancies occurred. Reviewers categorized probable/definite MIs as primary or secondary and identified secondary causes of MIs. The positive predictive value and sensitivity for each identification/ascertainment method were calculated. Of the 1,119 potential events that were adjudicated, 294 (26%) were definite/probable MIs. Almost as many secondary (48%) as primary (52%) MIs occurred, often as the result of sepsis or cocaine use. Of the patients with adjudicated definite/probable MIs, 78% had elevated troponin concentrations (positive predictive value = 57%, 95% confidence interval: 52, 62); however, only 44% had clinical diagnoses of MI (positive predictive value = 45%, 95% confidence interval: 39, 51). We found that central adjudication is crucial and that clinical diagnoses alone are insufficient for ascertainment of MI. Over half of the events ultimately determined to be MIs were not identified by clinical diagnoses. Adjudication protocols used in traditional cardiovascular disease cohorts facilitate cross-cohort comparisons but do not address issues such as identifying secondary MIs that may be common in persons with human immunodeficiency virus.

Objectives Adipose tissue affects several aspects of the cellular immune system, but prior epidemiological studies have differed on whether a higher body mass index ( BMI) promotes CD4 T-cell recovery on antiretroviral therapy ( ART). The objective of this analysis was to assess the relationship between BMI at ART initiation and early changes in CD4 T-cell count. Methods We used the North American AIDS Cohort Collaboration on Research and Design ( NA- ACCORD) data set to analyse the relationship between pre-treatment BMI and 12-month CD4 T-cell recovery among adults who started ART between 1998 and 2010 and maintained HIV-1 RNA levels < 400 copies/mL for at least 6 months. Multivariable regression models were adjusted for age, race, sex, baseline CD4 count and HIV RNA level, year of ART initiation, ART regimen and clinical site. Results A total of 8381 participants from 13 cohorts contributed data; 85% were male, 52% were nonwhite, 32% were overweight ( BMI 25-29.9 kg/m2) and 15% were obese ( BMI > 30 kg/m2). Pretreatment BMI was associated with 12-month CD4 T-cell change ( P < 0.001), but the relationship was nonlinear ( P < 0.001). Compared with a reference of 22 kg/m2, a BMI of 30 kg/m2 was associated with a 36 cells/μL [95% confidence interval ( CI) 14, 59 cells/μL] greater CD4 T-cell count recovery among women and a 19 cells/μL (95% CI 9, 30 cells/μL) greater recovery among men at 12 months. At a BMI > 30 kg/m2, the observed benefit was attenuated among men to a greater degree than among women, although this difference was not statistically significant. Conclusions A BMI of approximately 30 kg/m2 at ART initiation was associated with greater CD4 T-cell recovery at 12 months compared with higher or lower BMI values, suggesting that body composition may affect peripheral CD4 T-cell recovery. [ABSTRACT FROM AUTHOR]

Background Highly active antiretroviral therapy (HAART) has increased longevity. Currently, women comprise >50% of HIV-infected individuals worldwide. It is not known if there are differences between the sexes in the immunological and virological responses to HAART across the age strata. Methods Immunological reconstitution and virological response in the first 6 months of a first HAART regimen in two observational clinical HIV-infected cohorts were compared by both sex and age (≥50 vs. <50 years old). Results A total of 246 individuals (28% women) were included in the study; 63 cases (≥50 years old) and 183 controls (<50 years old). Over two-thirds of patients had HIV RNA levels <400 HIV-1 RNA copies/mL and CD4 count increases ≥50 cells/μL at 6 months from therapy initiation. There were no differences in immunological reconstitution across age and sex strata ( P=0.81) and no differences in virological suppression, even after adjusting for type of HAART ( P=0.68) or restricting the analysis to women only ( P=0.81). These results suggest that younger and older women and men may have similar short-term initial HAART outcomes. Conclusions Further evaluation of longer term clinical response to initial HAART regimen based on sex and age is indicated, especially with more efficacious and simplified antiretroviral regimens and the associated decrease in mortality. [ABSTRACT FROM AUTHOR]

During the initial year of HIV diagnosis, while patients are often overwhelmed adjusting to this life changing diagnosis, they must develop self-care behaviors for attending regular medical care visits and antiretroviral therapy (ART) adherence to achieve and sustain viral suppression (VS). Maintaining “HIV adherence” and integrating it into one's daily life is required to sustain VS over time. The HIV care continuum or “treatment cascade,” an epidemiological snapshot of the national epidemic in the United States (US), indicates that a minority of persons living with HIV (PLWH) have achieved VS. Little evidence exists regarding the effects of interventions focusing on PLWH newly initiating outpatient HIV care. An intervention that focuses on both retention in care and ART adherence skills delivered during the pivotal first year of HIV care is lacking. To address this, we developed a theory-based intervention evaluated in the Integrating Engagement and Adherence Goals upon Entry (iENGAGE) study, a National Institute of Allergy and Infectious Diseases (NIAID) funded randomized behavioral intervention trial. Here we present the study objectives, design and rationale, as well as the intervention components, targeting rapid and sustained VS through retention in HIV care and ART adherence during participants' first year of HIV care. The primary outcome of the study is 48-week VS (<200 c/mL). The secondary outcomes are retention in care, including HIV visit adherence and visit constancy, as well as ART adherence. [ABSTRACT FROM AUTHOR]