Incidence of non-AIDS defining comorbidities among young adults with perinatally acquired HIV in North America.

OBJECTIVE: The aim of this study is to describe the incidence of diabetes mellitus type 2 (T2DM), hypercholesterolemia, hypertriglyceridemia, hypertension, and chronic kidney disease (CKD) from 2000 to 2019 among North American adults with perinatally acquired HIV (PHIV) aged 18-30 years. DESIGN: Description of outcomes based on electronic health records for a cohort of 375 young adults with PHIV enrolled in routine HIV care at clinics contributing data to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). METHODS: We estimated overall, sex, and race-stratified cumulative incidences using Turnbull estimation, and incidence rates using quasi-Poisson regression. T2DM was defined as glycosylated hemoglobin more than 6.5% or based on clinical diagnosis and medication use. Hypercholesterolemia was based on medication use or total cholesterol at least 200 mg/dl. Hypertriglyceridemia was based on medication use or fasting triglyceride at least 150 mg/dl or nonfasting at least 200 mg/dl. Hypertension was based on clinical diagnosis. CKD was defined as estimated glomerular filtration rates less than 90 ml/mi|1.73 m 2 for at least 3 months. RESULTS: Cumulative incidence by age 30 and incidence rates from age 18 to 30 (per 100 person-years) were T2DM: 19%, 2.9; hypercholesterolemia: 40%, 4.6; hypertriglyceridemia: 50%, 5.6; hypertension: 22%, 2.0; and CKD: 25%, 3.3. Non-Black women had the highest incidence of hypercholesterolemia and hypertriglyceridemia, Black adults had the highest hypertension incidence, and Black men had the highest CKD incidence. CONCLUSION: There was a high incidence of five chronic comorbidities among people with PHIV. Earlier screening at younger ages might be considered for this unique population to strengthen prevention strategies and initiate treatment in a timely way.

Preventive and Sexual Health in LGBTQ+ Older Adults.

Sexual health is an important but often overlooked health concern of LGBTQ + older adults. Multiple factors influence sexual health including intersecting identities; adverse life events; coping mechanisms; and psychological, social, and physical health domains. Thus, the use of a culturally competent and comprehensive person-centered approach to sexual health is warranted. In this review, we discuss approaches to engaging LGBTQ + older adults to ensure they are able to achieve their sexual health priorities and prevent new human immunodeficiency virus infections. We also discuss doxycycline postexposure prophylaxis to prevent other sexually transmitted infections and the impact of chemsex.

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.

Waitlist-controlled trial of an online intervention to address mental health among older people living with HIV.

Background: Older people living with HIV (PLWH) often experience elevated levels of depression, anxiety, and loneliness.Methods: This waitlist-controlled trial examined the effectiveness of online audio mindfulness lessons in impacting these feelings among older PLWH.Results: Among 214 participants, the mean (SD) age was 60.4 (5.9) years, 89% were male, and 69% were white. After 25 days, the intervention group showed significant improvements versus the waitlist control group in symptoms of depression (20.3% improvement, p < .01) and symptoms of anxiety (22.4% improvement, p = .03), but not in loneliness as measured by a Daily Diary (12.9% improvement, p = .07) or the 3-Item Loneliness Scale (4.8% improvement, p = .27). Secondary analyses among participants with elevated baseline symptoms of depression showed a 26.3% improvement (p < .01), with a moderate effect size (Hedge's g = 0.69). Similarly, those with elevated baseline symptoms of anxiety showed a 25.6% improvement (p < .01), a moderate effect size (g = 0.54), while those with moderate or severely elevated loneliness showed an 18.9% improvement in daily loneliness (p < .01), a moderate effect size (g = 0.55).Conclusion: This waitlist-controlled trial is the first to show that a series of brief, online audio mindfulness lessons improves mental health outcomes among older PLWH. For many patients, this intervention may offer relief that is both accessible and affordable.

The Impact of Number of Medications on Falls in Aging Persons with Human Immunodeficiency Virus.

We aimed to evaluate the impact of polypharmacy on the risk of having a fall in older persons with HIV (PWH). PWH at least 50 years of age who were seen at our institution from September 2012 to August 2017 were included. Unique participants were selected for either a case or control cohort depending on the presence of a documented fall during the study time period. Demographics, HIV-related measures, VACS score, number of medications, as well as the impact of taking benzodiazepines and opioids were compared between the two cohorts. Fall was documented for 637 patients compared to 1534 without a fall during the same time period. Multivariable logistic regression revealed that the total number of medications, having a higher VACS score, taking an opioid, being female sex assigned at birth, and having a lower nadir CD4 count were significantly associated with higher odds of having a fall. In this cohort of older PWH, taking a higher number of non-ARV medications significantly increased the odds of having a fall. In addition, taking an opioid resulted in the highest odds of having a fall. These results suggest the importance of deprescribing and addressing opioid use in reducing the risk of having a fall in older PWH.

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.

Qualitative Examination of the Impact of the COVID-19 Pandemic on Access and Adherence to Pre-exposure Prophylaxis (PrEP) Among Sexual and Gender Minorities.

During the COVID-19 pandemic, pre-exposure prophylaxis (PrEP) access and adherence decreased nationwide. This study examined pandemic-related disruptions to PrEP access and adherence among clients of a health center (Center) in Los Angeles, California. Clients (n = 25) and Center personnel (n = 11) completed qualitative interviews from March to July 2021. Although the Center provided options for remote PrEP care (i.e., telehealth, STI self-testing kits, and prescription delivery), clients experienced difficulty navigating services or lacked equipment for telehealth. More than half (n = 13) of clients discontinued PrEP during COVID-19 due to decreased sexual partners, relocation, or insurance status changes. Among those who continued PrEP, the majority reported no change in adherence, while a minority reported worsening adherence due to distractions/forgetting, prescription refill issues, lack of insurance coverage, and fear of completing in-person visits. Findings highlight the challenges of navigating PrEP services during COVID-19 and suggest PrEP services enhancement to adapt to crisis events.

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.

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.

Genome-wide CRISPR/Cas9 transcriptional activation screen identifies a histone acetyltransferase inhibitor complex as a regulator of HIV-1 integration.

The retrovirus human immunodeficiency virus-1 (HIV-1) is the causative agent of AIDS. Although treatment of HIV/AIDS with antiretroviral therapy provides suppression of viremia, latent reservoirs of integrated proviruses preclude cure by current antiviral treatments. Understanding the mechanisms of host-viral interactions may elucidate new treatment strategies. Here, we performed a CRISPR/Cas9 transcriptional activation screen using a high-complexity, genome-wide sgRNA library to identify cellular factors that inhibit HIV-1 infection of human CD4+ T cells. MT4 cells were transduced with a CRISPR/Cas9 sgRNA library and infected with nef-deficient HIV-1NL4-3 expressing ganciclovir-sensitive thymidine kinase, thus enabling selection of HIV-1-resistant cells for analysis of enriched sgRNAs. After validation of screen hits, multiple host factors essential for HIV-1 infection were identified, including SET (SET nuclear proto-oncogene) and ANP32A (acidic nuclear phosphoprotein 32A, PP32A), which together form a histone acetylase inhibitor complex. Using multiple human cell lines and peripheral blood mononuclear cells (PBMCs) from healthy donors and HIV-1-infected individuals, we demonstrate that SET depletion increased HIV-1 infectivity by augmenting DNA integration without significantly changing sites of integration. Conversely, SET overexpression decreased HIV-1 integration and infectivity. SET protein expression was significantly reduced in PBMCs from HIV-1-infected individuals and was downregulated by HIV-1 infection of healthy donor cells in vitro. Notably, HIV-1-induced downregulation of SET could be alleviated by inhibition of the protease granzyme A. Altogether, we have identified cellular inhibitors of HIV-1 infection on a genome-wide scale, which affords new insight into host-virus interactions and may provide new strategies for HIV-1 treatment.

Factors Associated With Severity of COVID-19 Disease in a Multicenter Cohort of People With HIV in the United States, March-December 2020.

BACKGROUND: Understanding the spectrum of COVID-19 in people with HIV (PWH) is critical to provide clinical guidance and risk reduction strategies. SETTING: Centers for AIDS Research Network of Integrated Clinic System, a US multisite clinical cohort of PWH in care. METHODS: We identified COVID-19 cases and severity (hospitalization, intensive care, and death) in a large, diverse HIV cohort during March 1, 2020-December 31, 2020. We determined predictors and relative risks of hospitalization among PWH with COVID-19, adjusted for disease risk scores. RESULTS: Of 16,056 PWH in care, 649 were diagnosed with COVID-19 between March and December 2020. Case fatality was 2%; 106 (16.3%) were hospitalized, and 12 died. PWH with current CD4 count <350 cells/mm 3 [aRR 2.68; 95% confidence interval (CI): 1.93 to 3.71; P < 0.001] or lowest recorded CD4 count <200 cells/mm 3 (aRR 1.67; 95% CI: 1.18 to 2.36; P < 0.005) had greater risks of hospitalization. HIV viral load and antiretroviral therapy status were not associated with hospitalization, although most of the PWH were suppressed (86%). Black PWH were 51% more likely to be hospitalized with COVID-19 compared with other racial/ethnic groups (aRR 1.51; 95% CI: 1.04 to 2.19; P = 0.03). Chronic kidney disease, chronic obstructive pulmonary disease, diabetes, hypertension, obesity, and increased cardiovascular and hepatic fibrosis risk scores were associated with higher hospitalization risk. PWH who were older, not on antiretroviral therapy, and with current CD4 count <350 cells/mm 3 , diabetes, and chronic kidney disease were overrepresented among PWH who required intubation or died. CONCLUSIONS: PWH with CD4 count <350 cells/mm 3 , and a history of CD4 count <200 cells/mm 3 , have a clear excess risk of severe COVID-19, accounting for comorbidities associated with severe outcomes. PWH with these risk factors should be prioritized for COVID-19 vaccination and early treatment and monitored closely for worsening illness.

Observed CD4 counts at entry into HIV care and at antiretroviral therapy prescription by age in the USA, 2004-18: a cohort study.

BACKGROUND: Adults aged 50 years or older comprise a majority of people with HIV in the USA. Our objective was to describe observed differences by age in CD4 count at entry into HIV care, timing of antiretroviral therapy (ART) prescription, and CD4 count at time of ART prescription before (2004-11) and during (2012-18) the current era of universal treatment. METHODS: For this descriptive study, we calculated median (IQR) CD4 count at entry into care, days from entry into care to ART prescription, and CD4 count at time of ART prescription among patients enrolled in US-based clinical cohorts of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD; see appendix). We excluded participants with no CD4 count recorded at entry into care, medical records that suggested previous ART use, or previous AIDS diagnosis. All calculations were stratified by age (≥50 and 18-50 years) and calendar year. FINDINGS: Of 35 293 ART-naive adult participants entering care between Jan 1, 2004 and Dec 31, 2018, 5794 (16%) were women and 29 499 (84%) were men; 15817 (45%) were Black, 11566 (33%) were White, 5538 (16%) were Hispanic (any race), 737 (2%) were Asian or Pacific Islander, 152 (0.4%) were Indigenous, and 98 (0.3%) were multiracial. Median age at entry into care was 39 years (IQR 29-49); 8004 (23%) were aged 50 years or older. Of 29 141 participants initially prescribed ART, 7274 (25%) were aged 50 years or older. From 2004 to 2018, median CD4 count at entry into care increased from 228 cells per µL (IQR 80-422) to 295 cells per µL (134-489) among adults aged 50 years and older, and from 297 cells per µL (119-480) to 378 cells per µL (202-564) among adults younger than 50 years. Median days from entry into care to ART prescription declined from 56 (IQR 17-658) to 6 (0-15) among adults older than 50 years, and from 61 (17-509) to 6 (0-16) among adults younger than 50 years. Median CD4 count at time of ART prescription increased from 139 cells per µL (IQR 59-257) to 311 cells per µL (137-504) among adults aged 50 years or older, and from 166 cells per µL (49-287) to 377 cells per µL (198-564) among adults younger than 50 years. INTERPRETATION: Before the release of universal treatment guidelines by the US Department of Health and Human Services in 2012, median time to ART prescription was already falling, leading to increases in median CD4 count at ART prescription for both age groups; both measures continued to improve in the treat-all era. However, median CD4 counts, both at entry into care and at ART prescription, among adults aged 50 years and older were lower than those of adults younger than 50 years throughout the study period. Furthermore, even into the treat-all era, over half of adults aged 50 years and older entered care with CD4 counts of less than 350 cells per µL, potentially because of factors including immunosenescence, delayed HIV diagnosis, and late presentation to care. Given that age-related immunological changes might not be fully avoidable, targeted strategies for increasing HIV risk awareness, routine testing, and immediate linkage to HIV care at diagnosis are particularly essential for this population. FUNDING: US National Institutes of Health grant U01AI069918.

Genital Inflammation Is Not Associated With Decreased Vaginal Tenofovir Concentrations in Women Taking Oral PrEP.

BACKGROUND: We evaluated the association of inflammation and dysbosis on cervicovaginal fluid (CVF) tenofovir (TFV) concentrations in women taking oral tenofovir disoproxil fumarate/emtricitable for HIV pre-exposure prophylaxis (PrEP) in the United States. SETTING: Thirty-five women in a HIV PrEP implementation study attended their week 24 visit at a San Diego research clinic and provided CVF specimens. METHODS: Women in the Adherence Enhancement Guided by Individualized Texting and Drug Levels study had their CVF specimens evaluated for (1) sexually transmitted bacterial (Neisseria gonorrhoeae, Chlamydia trachomatis, Gardnerella, and Trichomonas vaginalis), viral (human papillomavirus, cytomegalovirus and herpes simplex virus-1/2) and fungal (Candida) infections; (2) microbiome composition by 16 S sequencing (V3-V4 region); and (3) cytokine profiles by enzyme-linked immunoassay (Interleukin-8, macrophage Inflammatory protein-1a, macrophage Inflammatory Protein-1b and interferon-γ-inducible protein-10). Univariate statistical analysis was used to determine factors associated with CVF TFV concentrations. CVF TFV of 100-1000 ng/mL benchmarked typical genital concentrations and TFV-diphosphate in dried blood spots of 700 fmol/punch was considered adequate adherence. RESULTS: Thirty-five women had CVF specimens collected. No factor was associated with CVF TFV concentrations or discordance of blood and vaginal concentrations. Among 27 participants assessed for vaginosis (Candida, Gardnerella or Trichomonas), women with Gardnerella (n = 11) were more likely to have high (>1000 ng/mL) CVF TFV concentrations (82% versus 33%, P = 0.02). CONCLUSIONS: Presence of genital viruses, cytokines, or vaginal community state types were not associated with low CVF TFV concentrations in cisgender women taking oral tenofovir disoproxil fumarate/emtricitable for PrEP. The surprising association observed between presence of Gardnerella and higher vaginal TFV concentrations needs further evaluation.

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.

Factors associated with severity of COVID-19 disease in a multicenter cohort of people with HIV in the United States, March-December 2020.

BACKGROUND: Understanding the spectrum of SARS-CoV-2 infection and COVID-19 disease in people with HIV (PWH) is critical to provide clinical guidance and implement risk-reduction strategies. OBJECTIVE: To characterize COVID-19 in PWH in the United States and identify predictors of disease severity. DESIGN: Observational cohort study. SETTING: Geographically diverse clinical sites in the CFAR Network of Integrated Clinical Systems (CNICS). PARTICIPANTS: Adults receiving HIV care through December 31, 2020. MEASUREMENTS: COVID-19 cases and severity (hospitalization, intensive care, death). RESULTS: Of 16,056 PWH in care, 649 were diagnosed with COVID-19 between March-December 2020. Case fatality was 2%; 106 (16.3%) were hospitalized and 12 died. PWH with current CD4 count <350 cells/mm 3 (aRR 2.68; 95%CI 1.93-3.71; P<.001) or lowest recorded CD4 count <200 (aRR 1.67; 95%CI 1.18-2.36; P<.005) had greater risk of hospitalization. HIV viral load suppression and antiretroviral therapy (ART) status were not associated with hospitalization, although the majority of PWH were suppressed (86%). Black PWH were 51% more likely to be hospitalized with COVID-19 compared to other racial/ethnic groups (aRR 1.51; 95%CI 1.04-2.19, P=.03). Chronic kidney disease (CKD), chronic obstructive pulmonary disease, diabetes, hypertension, obesity, and increased cardiovascular and hepatic fibrosis risk scores were associated with higher risk of hospitalization. PWH who were older, not on ART, with current CD4 <350, diabetes, and CKD were overrepresented amongst PWH who required intubation or died. LIMITATIONS: Unable to compare directly to persons without HIV; underestimate of total COVID-19 cases. CONCLUSIONS: PWH with CD4 <350 cells/mm 3 , low CD4/CD8 ratio, and history of CD4 <200, have a clear excess risk of severe COVID-19, after accounting for comorbidities also associated with severe outcomes. PWH with these risk factors should be prioritized for COVID-19 vaccination, early treatment, and monitored closely for worsening illness.