Cardiovascular Disease Risk Factor Control in People With and Without HIV.

BACKGROUND: Management of hypertension, dyslipidemia, diabetes and other modifiable factors may mitigate the cardiovascular disease (CVD) risk in people with human immunodeficiency virus (HIV, PWH) compared with people without HIV (PWoH). METHODS: This was a retrospective cohort study of 8285 PWH and 170 517 PWoH from an integrated health system. Risk factor control was measured using a novel disease management index (DMI) accounting for amount/duration above treatment goals (0% to 100% [perfect control]), including 2 DMIs for hypertension (diastolic and systolic blood pressure), 3 for dyslipidemia (low-density lipoprotein, total cholesterol, triglycerides), and 1 for diabetes (HbA1c). CVD risk by HIV status was evaluated overall and in subgroups defined by DMIs, smoking, alcohol use, and overweight/obesity in adjusted Cox proportional hazards models. RESULTS: PWH and PWoH had similar DMIs (80%-100%) except for triglycerides (worse for PWH) and HbA1c (better for PWH). In adjusted models, PWH had an elevated risk of CVD compared with PWoH (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.07-1.31). This association was attenuated in subgroups with controlled dyslipidemia and diabetes but remained elevated for PWH with controlled hypertension or higher total cholesterol. The strongest HIV status association with CVD was seen in the subgroup with frequent unhealthy alcohol use (HR, 2.13; 95% CI, 1.04-4.34). CONCLUSIONS: Control of dyslipidemia and diabetes, but not hypertension, attenuated the HIV status association with CVD. The strong association of HIV and CVD with frequent unhealthy alcohol use suggests enhanced screening and treatment of alcohol problems in PWH is warranted.

The forecasted prevalence of comorbidities and multimorbidity in people with HIV in the United States through the year 2030: A modeling study.

BACKGROUND: Estimating the medical complexity of people aging with HIV can inform clinical programs and policy to meet future healthcare needs. The objective of our study was to forecast the prevalence of comorbidities and multimorbidity among people with HIV (PWH) using antiretroviral therapy (ART) in the United States (US) through 2030. METHODS AND FINDINGS: Using the PEARL model-an agent-based simulation of PWH who have initiated ART in the US-the prevalence of anxiety, depression, stage ≥3 chronic kidney disease (CKD), dyslipidemia, diabetes, hypertension, cancer, end-stage liver disease (ESLD), myocardial infarction (MI), and multimorbidity (≥2 mental or physical comorbidities, other than HIV) were forecasted through 2030. Simulations were informed by the US CDC HIV surveillance data of new HIV diagnosis and the longitudinal North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) data on risk of comorbidities from 2009 to 2017. The simulated population represented 15 subgroups of PWH including Hispanic, non-Hispanic White (White), and non-Hispanic Black/African American (Black/AA) men who have sex with men (MSM), men and women with history of injection drug use and heterosexual men and women. Simulations were replicated for 200 runs and forecasted outcomes are presented as median values (95% uncertainty ranges are presented in the Supporting information). In 2020, PEARL forecasted a median population of 670,000 individuals receiving ART in the US, of whom 9% men and 4% women with history of injection drug use, 60% MSM, 8% heterosexual men, and 19% heterosexual women. Additionally, 44% were Black/AA, 32% White, and 23% Hispanic. Along with a gradual rise in population size of PWH receiving ART-reaching 908,000 individuals by 2030-PEARL forecasted a surge in prevalence of most comorbidities to 2030. Depression and/or anxiety was high and increased from 60% in 2020 to 64% in 2030. Hypertension decreased while dyslipidemia, diabetes, CKD, and MI increased. There was little change in prevalence of cancer and ESLD. The forecasted multimorbidity among PWH receiving ART increased from 63% in 2020 to 70% in 2030. There was heterogeneity in trends across subgroups. Among Black women with history of injection drug use in 2030 (oldest demographic subgroup with median age of 66 year), dyslipidemia, CKD, hypertension, diabetes, anxiety, and depression were most prevalent, with 92% experiencing multimorbidity. Among Black MSM in 2030 (youngest demographic subgroup with median age of 42 year), depression and CKD were highly prevalent, with 57% experiencing multimorbidity. These results are limited by the assumption that trends in new HIV diagnoses, mortality, and comorbidity risk observed in 2009 to 2017 will persist through 2030; influences occurring outside this period are not accounted for in the forecasts. CONCLUSIONS: The PEARL forecasts suggest a continued rise in comorbidity and multimorbidity prevalence to 2030, marked by heterogeneities across race/ethnicity, gender, and HIV acquisition risk subgroups. HIV clinicians must stay current on the ever-changing comorbidities-specific guidelines to provide guideline-recommended care. HIV clinical directors should ensure linkages to subspecialty care within the clinic or by referral. HIV policy decision-makers must allocate resources and support extended clinical capacity to meet the healthcare needs of people aging with HIV.

Clinically recognized sleep disorders in people living with HIV.

OBJECTIVE: Despite recognition that people with HIV (PWH) are more vulnerable to sleep issues, there is limited understanding of clinically recognized sleep disorders in this population. Our objective was to evaluate the full spectrum of sleep disorder types diagnosed among PWH in care. METHODS: We conducted a retrospective cohort study of PWH, and a comparator group of people without HIV (PWoH), in a large healthcare system. The incidence of clinically diagnosed sleep disorders was calculated using Poisson regression for three outcomes: any type of sleep disorder, insomnia, and sleep apnea. Incidence was compared between PWH and PWoH by computing the adjusted incidence rate ratio (aIRR), accounting for sleep disorder risk factors. Comparisons to PWoH were made for all PWH combined, then with PWH stratified by HIV management status (well-managed HIV defined as being on antiretroviral therapy, HIV RNA <200 copies/mL, and CD4 count ≥500 cells/µL). RESULTS: The study included 9076 PWH and 205 178 PWoH (mean age 46 years, 90% men). Compared with PWoH, sleep disorder incidence was greater among PWH overall [aIRR = 1.19, 95% confidence interval (CI): 1.12-1.26], particularly for insomnia (aIRR = 1.56, 95% CI: 1.45-1.67). Sleep apnea incidence was lower among PWH (aIRR = 0.90, 95% CI: 0.84-0.97). In HIV management subgroups, PWH without well-managed HIV had lower sleep apnea incidence (vs. PWoH: aIRR = 0.79, 95% CI: 0.70-0.89) but PWH with well-managed HIV did not (vs. PWoH: aIRR = 0.97, 95% CI: 0.89-1.06). CONCLUSIONS: PWH have high sleep disorder incidence, and insomnia is the most common clinical diagnosis. Lower sleep apnea incidence among PWH may reflect underdiagnosis in those with sub-optimally treated HIV and will be important to investigate further.

Electrophysiological correlates of (mis)judging social information.

Social information can be used to optimize decision-making. However, the simultaneous presentation of multiple sources of advice can lead to a distinction bias in judging the validity of the information. While the involvement of event-related potential (ERP) components in social information processing has been studied, how they are modulated by (mis)judging an advisor's information validity remains unknown. In two experiments participants performed a decision-making task with highly accurate or inaccurate cues. Each experiment consisted of an initial, learning, and test phase. During the learning phase, three advice cues were simultaneously presented and the validity of them had to be assessed. The effect of different cue constellations on ERPs was investigated. In the subsequent test phase, the willingness to follow or oppose an advice cue was tested. Results demonstrated the distinction bias with participants over or underestimating the accuracy of the most uncertain cues. The P2 amplitude was significantly increased during cue presentation when advisors were in disagreement as compared to when all were in agreement, regardless of cue validity. Further, a larger P3 amplitude during outcome presentation was found when advisors were in disagreement and increased with more informative cues. As such, the most uncertain cues were related to the smallest P3 amplitude. The findings hint at the possible role of P3 in judging and learning the predictability of social cues. This study provides novel insights into the role of P2 and P3 components during the judgment of social information validity.

A Latent Class Analysis of Substance Use and Longitudinal HIV RNA Patterns Among PWH in DC Cohort.

People with HIV (PWH) with substance use disorders (SUD) have worse health outcomes than PWH without SUD. Our objective was to characterize substance use patterns and their impact on longitudinal HIV RNA trajectories among those enrolled in an observational study of PWH in care in Washington, DC. Substance use by type (alcohol, cannabis, opioid, stimulant, hallucinogen, inhalant, sedative) was used to identify shared patterns of substance use using Latent Class Analysis (LCA). A multinomial logistic regression model evaluated the association between the resulting substance use classes and the membership probability in longitudinal HIV RNA trajectory groups. There were 30.1% of participants with at least one substance reported. LCA resulted in a three-class model: (1) Low-Level Substance Use, (2) Opioid Use, and (3) Polysubstance. The Opioid and Polysubstance Use classes were more likely to have a mental health diagnosis (45.4% and 53.5%; p < 0.0001). Members in the Opioid Use class were older (median age of 54.9 years (IQR 50.3-59.2) than both the Polysubstance and Low-Level Substance Use Classes (p < 0.0001). There were 3 HIV RNA trajectory groups: (1) Undetectable, (2) Suppressed, and (3) Unsuppressed HIV RNA over 18 months of follow-up. The probability of being in the unsuppressed HIV RNA group trajectory when a member of the Opioid Use or Polysubstance Use classes was 2.5 times and 1.5 times greater than the Low-Level Substance Use class, respectively. The Opioid Use and Polysubstance Use classes, with higher-risk drug use, should be approached with more targeted HIV-related care to improve outcomes.

Mixed Methods Analysis of Telehealth Experience, Satisfaction, and Quality of Care During the COVID Pandemic Among Persons with HIV in Washington, DC.

The purpose of this study is to describe telehealth experiences and quality of HIV care provided to an urban population of people with HIV (PWH) in Washington, DC. We used self-reported survey data from a cohort of PWH in the DC Cohort longitudinal study linked to medical records (October 26, 2020-December 31, 2021). Analyses followed a mixed-methods approach, including prevalence estimates and multivariable logistic regression of telehealth use by demographic and HIV characteristics. We measured primary motivation, modes of engagement, and telehealth satisfaction. Qualitative responses to open-ended questions were coded using collaborative coding. A framework developed by the National Quality Forum (NQF) was applied to the results. Among 978 participants, 69% reported using telehealth for HIV care during the pandemic. High school graduates were less likely to use telehealth compared to those with college education (aOR 0.69, 95% CI 0.48, 0.98). PWH with > 1 co-morbid condition were more likely to use telehealth compared to those without (aOR 1.42, 95% CI 1.02, 1.95). The majority reported satisfaction with telehealth (81%). Qualitative analysis of telehealth satisfaction found that most responses were related to access to care and technology, effectiveness, and patient experience. PWH using telehealth during the pandemic were satisfied with their experience though use differed demographically. Telehealth was used effectively to overcome barriers to care engagement, including transportation, costs, and time. As we transition away from the emergency pandemic responses, it will be important to determine how this technology can be used in the future in an equitable manner to further strengthen HIV care engagement.

Prevalence and risk factors for post-COVID conditions of COVID-19 among persons with HIV in Washington, DC.

Post-COVID conditions (long COVID) are defined as COVID symptoms persisting 28 days post-initial infection. The limited research available on the prevalence and experiences of post-COVID conditions among persons with HIV (PWH) indicates potential increased risk for post-COVID conditions. The purpose of this study was to characterize prevalence, symptom clustering, impact, and potential risk factors of post-COVID conditions among PWH. Data come from the COVID-19 survey, conducted as a sub-study of the DC Cohort Longitudinal HIV Study, an ongoing study of over 12,000 PWH living in Washington, DC. Survey data were matched to electronic medical record data. Prevalence estimates and multivariable logistic regression analyses were calculated comparing those with and without post-COVID conditions. The prevalence of post-COVID conditions among PWH was 46% with no significant differences among demographic or HIV measures. Those with history of asthma were more likely to report post-COVID conditions symptoms. Among those with post-COVID conditions, 81% reported three or more initial COVID symptoms. Retired/disabled PWH were more likely to report post-COVID conditions compared to employed (aOR = 2.37, 95% CI = 1.06, 5.33). Post-COVID conditions significantly limited activities of daily living. Programs are needed to address the long-term impact of post-COVID conditions on activities of daily living among PWH.

Evaluating Clinic-Based Interventions to Reduce Racial Differences in Mortality Among People With Human Immunodeficiency Virus in the United States.

BACKGROUND: Mortality remains elevated among Black versus White adults receiving human immunodeficiency virus (HIV) care in the United States. We evaluated the effects of hypothetical clinic-based interventions on this mortality gap. METHODS: We computed 3-year mortality under observed treatment patterns among >40 000 Black and >30 000 White adults entering HIV care in the United States from 1996 to 2019. We then used inverse probability weights to impose hypothetical interventions, including immediate treatment and guideline-based follow-up. We considered 2 scenarios: "universal" delivery of interventions to all patients and "focused" delivery of interventions to Black patients while White patients continued to follow observed treatment patterns. RESULTS: Under observed treatment patterns, 3-year mortality was 8% among White patients and 9% among Black patients, for a difference of 1 percentage point (95% confidence interval [CI], .5-1.4). The difference was reduced to 0.5% under universal immediate treatment (95% CI, -.4% to 1.3%) and to 0.2% under universal immediate treatment combined with guideline-based follow-up (95% CI, -1.0% to 1.4%). Under the focused delivery of both interventions to Black patients, the Black-White difference in 3-year mortality was -1.4% (95% CI, -2.3% to -.4%). CONCLUSIONS: Clinical interventions, particularly those focused on enhancing the care of Black patients, could have significantly reduced the mortality gap between Black and White patients entering HIV care from 1996 to 2019.

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.

Effect of Adopting the New Race-Free 2021 Chronic Kidney Disease Epidemiology Collaboration Estimated Glomerular Filtration Rate Creatinine Equation on Racial Differences in Kidney Disease Progression Among People With Human Immunodeficiency Virus: An Observational Study.

BACKGROUND: The impact of adopting a race-free estimated glomerular filtration rate (eGFR) creatinine (eGFRcr) equation on racial differences in chronic kidney disease (CKD) progression among people with human immunodeficiency virus (PWH) is unknown. METHODS: We defined eGFR stages using the original race-adjusted Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFRcr equation and the new race-free CKD-EPI eGFRcr equation. We then estimated 5-year probabilities of transitioning from baseline kidney function to more advanced eGFR stages and examined the association of race (black vs white) with rates of CKD progression using Markov models. RESULTS: With the race-adjusted eGFRcr equation, black participants (n = 31 298) had a lower risk of progressing from eGFR stage 1 to 2 (hazard ratio [HR], 0.77; 95% confidence interval [CI], .73-.82), an equal risk of progressing from stage 2 to 3 (1.00; .92-.07) and a 3-fold risk of progressing from stage 3 to 4 or 5 (3.06; 2.60-3.62), compared with white participants (n = 27 542). When we used the race-free eGFRcr equation, 16% of black participants were reclassified into a more severe eGFR stage at baseline. The reclassified black individuals had a higher prevalence of CKD risk factors than black PWH who were not reclassified. With the race-free eGFRcr equation, black participants had a higher risk of disease progression across all eGFR stages than white participants. CONCLUSIONS: The original eGFRcr equation systematically masked a subgroup of black PWH who are at high-risk of CKD progression. The new race-free eGFRcr equation unmasks these individuals and may allow for earlier detection and management of CKD.

Human Immunodeficiency Virus Status, Tenofovir Exposure, and the Risk of Poor Coronavirus Disease 19 Outcomes: Real-World Analysis From 6 United States Cohorts Before Vaccine Rollout.

BACKGROUND: People with human immunodeficiency virus (HIV) (PWH) may be at increased risk for severe coronavirus disease 2019 (COVID-19) outcomes. We examined HIV status and COVID-19 severity, and whether tenofovir, used by PWH for HIV treatment and people without HIV (PWoH) for HIV prevention, was associated with protection. METHODS: Within 6 cohorts of PWH and PWoH in the United States, we compared the 90-day risk of any hospitalization, COVID-19 hospitalization, and mechanical ventilation or death by HIV status and by prior exposure to tenofovir, among those with severe acute respiratory syndrome coronavirus 2 infection between 1 March and 30 November 2020. Adjusted risk ratios (aRRs) were estimated by targeted maximum likelihood estimation, with adjustment for demographics, cohort, smoking, body mass index, Charlson comorbidity index, calendar period of first infection, and CD4 cell counts and HIV RNA levels (in PWH only). RESULTS: Among PWH (n = 1785), 15% were hospitalized for COVID-19 and 5% received mechanical ventilation or died, compared with 6% and 2%, respectively, for PWoH (n = 189 351). Outcome prevalence was lower for PWH and PWoH with prior tenofovir use. In adjusted analyses, PWH were at increased risk compared with PWoH for any hospitalization (aRR, 1.31 [95% confidence interval, 1.20-1.44]), COVID-19 hospitalizations (1.29 [1.15-1.45]), and mechanical ventilation or death (1.51 [1.19-1.92]). Prior tenofovir use was associated with reduced hospitalizations among PWH (aRR, 0.85 [95% confidence interval, .73-.99]) and PWoH (0.71 [.62-.81]). CONCLUSIONS: Before COVID-19 vaccine availability, PWH were at greater risk for severe outcomes than PWoH. Tenofovir was associated with a significant reduction in clinical events for both PWH and PWoH.

Optimizing Treatment for Human Immunodeficiency Virus to Improve Clinical Outcomes Using Precision Medicine.

In first-line antiretroviral therapy (ART) for human immunodeficiency virus (HIV) treatment, some subgroups of patients may respond better to an efavirenz-based regimen than an integrase strand transfer inhibitor (InSTI)-based regimen, or vice versa, due to patient characteristics modifying treatment effects. Using data based on nearly 16,000 patients from the North American AIDS Cohort Collaboration on Research and Design from 2009-2016, statistical methods for precision medicine were employed to estimate an optimal treatment rule that minimizes the 5-year risk of the composite outcome of acquired immune deficiency syndrome (AIDS)-defining illnesses, serious non-AIDS events, and all-cause mortality. The treatment rules considered were functions that recommend either an efavirenz- or InSTI-based regimen conditional on baseline patient characteristics such as demographic information, laboratory results, and health history. The estimated 5-year risk under the estimated optimal treatment rule was 10.0% (95% confidence interval (CI): 8.6, 11.3), corresponding to an absolute risk reduction of 2.3% (95% CI: 0.9, 3.8) when compared with recommending an efavirenz-based regimen for all patients and 2.6% (95% CI: 1.0, 4.2) when compared with recommending an InSTI-based regimen for all. Tailoring ART to individual patient characteristics may reduce 5-year risk of the composite outcome compared with assigning all patients the same drug regimen.

Improvements in Virologic Control Among PWH Over Time: Narrowing the Gap Between Those With and Without STIs.

Using the incidence of bacterial sexually transmitted infection (STI) as a surrogate for condomless sexual behavior, we assessed the association between STI and uncontrolled HIV replication among in-care persons with HIV (PWH) enrolled in a longitudinal HIV cohort study in the District of Columbia (the DC Cohort). Although STI occurrence initially correlated with higher HIV viral load (VL), this difference became more attenuated over time (2012-2016). This was true overall and among those with the greatest number of STIs [age 18-34, men who have sex with men (MSM)]. This likely reflects gains in population-wide virologic control through improved antiretroviral therapy and access to care, which helps mitigate the risk of HIV transmission.

HIV care continuum outcomes among recently diagnosed people with HIV (PWH) in Washington, DC.

The Ending the HIV Epidemic initiative aims to decrease new HIV infections and promote test-and-treat strategies. Our aims were to establish a baseline of HIV outcomes among newly diagnosed PWH in Washington, DC (DC), a 'hotspot' for the HIV epidemic. We also examined sociodemographic and clinical factors associated with retention in care (RIC), antiretroviral therapy (ART) initiation and viral suppression (VS) among newly diagnosed PWH in the DC Cohort from 2011-2016. Among 455 newly diagnosed participants, 92% were RIC at 12 months, ART was initiated in 65% at 3 months and 91% at 12 months, VS in at least 17% at 3 months and 82% at 12 months and 55% of those with VS at 12 months had sustained VS for an additional 12 months. AIDS diagnosis was associated with RIC (aOR 2.99; 1.13-2.28), ART initiation by 3 months (aOR 2.58; 1.61-4.12) and VS by 12 months (aOR4.87; 1.69-14.03). This analysis contributes to our understanding of the HIV treatment dynamics of persons with recently diagnosed HIV infection in a city with a severe HIV epidemic.

Psychosocial impacts of the COVID-19 pandemic from a cross-sectional Survey of people living with HIV in Washington, DC.

BACKGROUND: COVID-19 has not only taken a staggering toll in terms of cases and lives lost, but also in its psychosocial effects. We assessed the psychosocial impacts of the COVID-19 pandemic in a large cohort of people with HIV (PWH) in Washington DC and evaluated the association of various demographic and clinical characteristics with psychosocial impacts. METHODS: From October 2020 to December 2021, DC Cohort participants were invited to complete a survey capturing psychosocial outcomes influenced by the COVID-19 pandemic. Some demographic variables were also collected in the survey, and survey results were matched to additional demographic data and laboratory data from the DC Cohort database. Data analyses included descriptive statistics and multivariable logistic regression models to evaluate the association between demographic and clinical characteristics and psychosocial impacts, assessed individually and in overarching categories (financial/employment, mental health, decreased social connection, and substance use). RESULTS: Of 891 participants, the median age was 46 years old, 65% were male, and 76% were of non-Hispanic Black race/ethnicity. The most commonly reported psychosocial impact categories were mental health (78% of sample) and financial/employment (56% of sample). In our sample, older age was protective against all adverse psychosocial impacts. Additionally, those who were more educated reported fewer financial impacts but more mental health impacts, decreased social connection, and increased substance use. Males reported increased substance use compared with females. CONCLUSIONS: The COVID-19 pandemic has had substantial psychosocial impacts on PWH, and resiliency may have helped shield older adults from some of these effects. As the pandemic continues, measures to aid groups vulnerable to these psychosocial impacts are critical to help ensure continued success towards healthy living with HIV.

Association of Race and Ethnicity With Initial Prescription of Antiretroviral Therapy Among People With HIV in the US.

Importance: Integrase strand transfer inhibitor (INSTI)-containing antiretroviral therapy (ART) is currently the guideline-recommended first-line treatment for HIV. Delayed prescription of INSTI-containing ART may amplify differences and inequities in health outcomes. Objectives: To estimate racial and ethnic differences in the prescription of INSTI-containing ART among adults newly entering HIV care in the US and to examine variation in these differences over time in relation to changes in treatment guidelines. Design, Setting, and Participants: Retrospective observational study of 42 841 adults entering HIV care from October 12, 2007, when the first INSTI was approved by the US Food and Drug Administration, to April 30, 2019, at more than 200 clinical sites contributing to the North American AIDS Cohort Collaboration on Research and Design. Exposures: Combined race and ethnicity as reported in patient medical records. Main Outcomes and Measures: Probability of initial prescription of ART within 1 month of care entry and probability of being prescribed INSTI-containing ART. Differences among non-Hispanic Black and Hispanic patients compared with non-Hispanic White patients were estimated by calendar year and time period in relation to changes in national guidelines on the timing of treatment initiation and recommended initial treatment regimens. Results: Of 41 263 patients with information on race and ethnicity, 19 378 (47%) as non-Hispanic Black, 6798 (16%) identified as Hispanic, and 13 539 (33%) as non-Hispanic White; 36 394 patients (85%) were male, and the median age was 42 years (IQR, 30 to 51). From 2007-2015, when guidelines recommended treatment initiation based on CD4+ cell count, the probability of ART initiation within 1 month of care entry was 45% among White patients, 45% among Black patients (difference, 0% [95% CI, -1% to 1%]), and 51% among Hispanic patients (difference, 5% [95% CI, 4% to 7%]). From 2016-2019, when guidelines strongly recommended treating all patients regardless of CD4+ cell count, this probability increased to 66% among White patients, 68% among Black patients (difference, 2% [95% CI, -1% to 5%]), and 71% among Hispanic patients (difference, 5% [95% CI, 1% to 9%]). INSTIs were prescribed to 22% of White patients and only 17% of Black patients (difference, -5% [95% CI, -7% to -4%]) and 17% of Hispanic patients (difference, -5% [95% CI, -7% to -3%]) from 2009-2014, when INSTIs were approved as initial therapy but were not yet guideline recommended. Significant differences persisted for Black patients (difference, -6% [95% CI, -8% to -4%]) but not for Hispanic patients (difference, -1% [95% CI, -4% to 2%]) compared with White patients from 2014-2017, when INSTI-containing ART was a guideline-recommended option for initial therapy; differences by race and ethnicity were not statistically significant from 2017-2019, when INSTI-containing ART was the single recommended initial therapy for most people with HIV. Conclusions and Relevance: Among adults entering HIV care within a large US research consortium from 2007-2019, the 1-month probability of ART prescription was not significantly different across most races and ethnicities, although Black and Hispanic patients were significantly less likely than White patients to receive INSTI-containing ART in earlier time periods but not after INSTIs became guideline-recommended initial therapy for most people with HIV. Additional research is needed to understand the underlying racial and ethnic differences and whether the differences in prescribing were associated with clinical outcomes.

Five-Year Mortality for Adults Entering Human Immunodeficiency Virus Care Under Universal Early Treatment Compared With the General US Population.

BACKGROUND: Mortality among adults with human immunodeficiency virus (HIV) remains elevated over those in the US general population, even in the years after entry into HIV care. We explore whether the elevation in 5-year mortality would have persisted if all adults with HIV had initiated antiretroviral therapy within 3 months of entering care. METHODS: Among 82 766 adults entering HIV care at North American AIDS Cohort Collaboration clinical sites in the United States, we computed mortality over 5 years since entry into HIV care under observed treatment patterns. We then used inverse probability weights to estimate mortality under universal early treatment. To compare mortality with those for similar individuals in the general population, we used National Center for Health Statistics data to construct a cohort representing the subset of the US population matched to study participants on key characteristics. RESULTS: For the entire study period (1999-2017), the 5-year mortality among adults with HIV was 7.9% (95% confidence interval [CI]: 7.6%-8.2%) higher than expected based on the US general population. Under universal early treatment, the elevation in mortality for people with HIV would have been 7.2% (95% CI: 5.8%-8.6%). In the most recent calendar period examined (2011-2017), the elevation in mortality for people with HIV was 2.6% (95% CI: 2.0%-3.3%) under observed treatment patterns and 2.1% (.0%-4.2%) under universal early treatment. CONCLUSIONS: Expanding early treatment may modestly reduce, but not eliminate, the elevation in mortality for people with HIV.

Discrimination and Calibration of the Veterans Aging Cohort Study Index 2.0 for Predicting Mortality Among People With Human Immunodeficiency Virus in North America.

BACKGROUND: The updated Veterans Aging Cohort Study (VACS) Index 2.0 combines general and human immunodeficiency virus (HIV)-specific biomarkers to generate a continuous score that accurately discriminates risk of mortality in diverse cohorts of persons with HIV (PWH), but a score alone is difficult to interpret. Using data from the North American AIDS Cohort Collaboration (NA-ACCORD), we translate VACS Index 2.0 scores into validated probability estimates of mortality. METHODS: Because complete mortality ascertainment is essential for accurate calibration, we restricted analyses to cohorts with mortality from the National Death Index or equivalent sources. VACS Index 2.0 components were ascertained from October 1999 to April 2018. Mortality was observed up to March 2019. Calibration curves compared predicted (estimated by fitting a gamma model to the score) to observed mortality overall and within subgroups: cohort (VACS/NA-ACCORD subset), sex, age <50 or ≥50 years, race/ethnicity, HIV-1 RNA ≤500 or >500 copies/mL, CD4 count <350 or ≥350 cells/µL, and years 1999-2009 or 2010-2018. Because mortality rates have decreased over time, the final model was limited to 2010-2018. RESULTS: Among 37230 PWH in VACS and 8061 PWH in the NA-ACCORD subset, median age was 53 and 44 years; 3% and 19% were women; and 48% and 39% were black. Discrimination in NA-ACCORD (C-statistic = 0.842 [95% confidence interval {CI}, .830-.854]) was better than in VACS (C-statistic = 0.813 [95% CI, .809-.817]). Predicted and observed mortality largely overlapped in VACS and the NA-ACCORD subset, overall and within subgroups. CONCLUSIONS: Based on this validation, VACS Index 2.0 can reliably estimate probability of all-cause mortality, at various follow-up times, among PWH in North America.

Antibiotics prior to age 2 years have limited association with preschool growth trajectory.

BACKGROUND: Prior studies of early antibiotic use and growth have shown mixed results, primarily on cross-sectional outcomes. This study examined the effect of oral antibiotics before age 24 months on growth trajectory at age 2-5 years. METHODS: We captured oral antibiotic prescriptions and anthropometrics from electronic health records through PCORnet, for children with ≥1 height and weight at 0-12 months of age, ≥1 at 12-30 months, and ≥2 between 25 and 72 months. Prescriptions were grouped into episodes by time and by antimicrobial spectrum. Longitudinal rate regression was used to assess differences in growth rate from 25 to 72 months of age. Models were adjusted for sex, race/ethnicity, steroid use, diagnosed asthma, complex chronic conditions, and infections. RESULTS: 430,376 children from 29 health U.S. systems were included, with 58% receiving antibiotics before 24 months. Exposure to any antibiotic was associated with an average 0.7% (95% CI 0.5, 0.9, p < 0.0001) greater rate of weight gain, corresponding to 0.05 kg additional weight. The estimated effect was slightly greater for narrow-spectrum (0.8% [0.6, 1.1]) than broad-spectrum (0.6% [0.3, 0.8], p < 0.0001) drugs. There was a small dose response relationship between the number of antibiotic episodes and weight gain. CONCLUSION: Oral antibiotic use prior to 24 months of age was associated with very small changes in average growth rate at ages 2-5 years. The small effect size is unlikely to affect individual prescribing decisions, though it may reflect a biologic effect that can combine with others.

Risk of HCC With Hepatitis B Viremia Among HIV/HBV-Coinfected Persons in North America.

BACKGROUND AND AIMS: Chronic HBV is the predominant cause of HCC worldwide. Although HBV coinfection is common in HIV, the determinants of HCC in HIV/HBV coinfection are poorly characterized. We examined the predictors of HCC in a multicohort study of individuals coinfected with HIV/HBV. APPROACH AND RESULTS: We included persons coinfected with HIV/HBV within 22 cohorts of the North American AIDS Cohort Collaboration on Research and Design (1995-2016). First occurrence of HCC was verified by medical record review and/or cancer registry. We used multivariable Cox regression to determine adjusted HRs (aHRs [95% CIs]) of factors assessed at cohort entry (age, sex, race, body mass index), ever during observation (heavy alcohol use, HCV), or time-updated (HIV RNA, CD4+ percentage, diabetes mellitus, HBV DNA). Among 8,354 individuals coinfected with HIV/HBV (median age, 43 years; 93% male; 52.4% non-White), 115 HCC cases were diagnosed over 65,392 person-years (incidence rate, 1.8 [95% CI, 1.5-2.1] events/1,000 person-years). Risk factors for HCC included age 40-49 years (aHR, 1.97 [1.22-3.17]), age ≥50 years (aHR, 2.55 [1.49-4.35]), HCV coinfection (aHR, 1.61 [1.07-2.40]), and heavy alcohol use (aHR, 1.52 [1.04-2.23]), while time-updated HIV RNA >500 copies/mL (aHR, 0.90 [0.56-1.43]) and time-updated CD4+ percentage <14% (aHR, 1.03 [0.56-1.90]) were not. The risk of HCC was increased with time-updated HBV DNA >200 IU/mL (aHR, 2.22 [1.42-3.47]) and was higher with each 1.0 log10 IU/mL increase in time-updated HBV DNA (aHR, 1.18 [1.05-1.34]). HBV suppression with HBV-active antiretroviral therapy (ART) for ≥1 year significantly reduced HCC risk (aHR, 0.42 [0.24-0.73]). CONCLUSION: Individuals coinfected with HIV/HBV on ART with detectable HBV viremia remain at risk for HCC. To gain maximal benefit from ART for HCC prevention, sustained HBV suppression is necessary.