THE ASSOCIATION OF ANEMIA WITH SURVIVAL AMONG PEOPLE WITH HIV FOLLOWING ANTIRETROVIRAL INITIATION IN THE NA-ACCORD 2007-2016.

BACKGROUND: Anemia is an independent predictor of mortality, which may be utilized as a signal of deteriorating health. We estimated the association between anemia severity categories and mortality following the initiation of antiretroviral therapy (ART) among people with HIV (PWH) in North America. METHODS: Within the NA-ACCORD, annual median hemoglobin measurements between 01/01/2007-12/31/2016 were categorized using World Health Organization criteria into mild (11.0-12.9g/dL men, 11.0-11.9g/dL women), moderate (8.0-10.9g/dL men/women) and severe (<8.0g/dL men/women) anemia. Discrete time-to-event analyses using complementary log-log link models estimated mortality hazards ratios adjusted for demographics, comorbidities, and HIV clinical markers with 95% confidence intervals for the association between anemia and mortality. RESULTS: Among 67,228 PWH contributing a total of 320,261 annual median hemoglobin measurements, 257,293 (80%) demonstrated no anemia, 44,041 (14%) mild, 18,259 (6%) moderate, and 668 (0.2%) severe anemia during follow-up. Mortality risk was 5.6-fold higher among PWH with (vs. without) anemia. The association was greater among males (aHR=5.8 [5.4, 6.2]) versus females (aHR=4.1 [3.2, 5.4]). Mortality risk was 3.8-fold higher among PWH with mild anemia, 13.7-fold higher with moderate anemia, and 34.5-fold higher with severe anemia (vs. no anemia). Median hemoglobin levels significantly declined within 4 years prior to death, with the maximum decrease the year prior to death. Macrocytic anemia was associated with an increased and microcytic anemia a decreased mortality risk (vs. normocytic anemia). CONCLUSIONS: Anemia among PWH who have initiated ART is an important predictive marker for mortality with macrocytic anemia having an increased and microcytic anemia a decreased association with mortality compared with normocytic anemia.

Evaluation of mean corpuscular volume among anemic people with HIV in North America following ART initiation.

BACKGROUND: Anemia is common and associated with increased morbidity among people with HIV (PWH). Classification of anemia using the mean corpuscular volume (MCV) can help investigate the underlying causative factors of anemia. We characterize anemia using MCV among PWH receiving antiretroviral therapy (ART), and identify the risk factors for normocytic, macrocytic, and microcytic anemias. METHODS: Including PWH with anemia (hemoglobin measure < 12.9 g/dL among men and < 11.9 g/dL among women) in the NA-ACCORD from 01/01/2007 to 12/31/2017, we estimated the annual distribution of normocytic (80-100 femtolitre (fL)), macrocytic (> 100 fL) or microcytic (< 80 fL) anemia based on the lowest hemoglobin within each year. Poisson regression models with robust variance and general estimating equations were used to estimate crude and adjusted prevalence ratios and 95% confidence intervals for risk factors for macrocytic (vs. normocytic) and microcytic (vs. normocytic) anemia stratified by sex. RESULTS: Among 37,984 hemoglobin measurements that identified anemia in 14,590 PWH, 27,909 (74%) were normocytic, 4257 (11%) were microcytic, and 5818 (15%) were macrocytic. Of the anemic PWH included over the study period, 1910 (13%) experienced at least one measure of microcytic anemia and 3208 (22%) at least one measure of macrocytic anemia. Normocytic anemia was most common among both males and females, followed by microcytic among females and macrocytic among males. Over time, the proportion of anemic PWH who have macrocytosis decreased while microcytosis increased. Macrocytic (vs. normocytic) anemia is associated with increasing age and comorbidities. With increasing age, microcytic anemia decreased among females but not males. A greater proportion of PWH with normocytic anemia had CD4 counts ≤ 200 cells/mm3 and had recently initiated ART. CONCLUSION: In anemic PWH, normocytic anemia was most common. Over time macrocytic anemia decreased, and microcytic anemia increased irrespective of sex. Normocytic anemia is often due to chronic disease and may explain the greater risk for normocytic anemia among those with lower CD4 counts or recent ART initiation. Identified risk factors for type-specific anemias including sex, age, comorbidities, and HIV factors, can help inform targeted investigation into the underlying causes.

Antibiotic duration and route for treatment of adults with uncomplicated streptococcal bloodstream infections: a retrospective study in a large healthcare system.

Data guiding the duration and route of streptococcal bloodstream infection (BSI) treatment are lacking. We conducted a retrospective cohort study of adults hospitalized with uncomplicated streptococcal BSI in a large integrated healthcare system from 2013 to 2020. The exposures of interest were antibiotic duration (5-10 days vs. 11-15 days) and antibiotic route (oral switch vs. entirely intravenous). The primary outcome was a composite 90-day outcome comprised of all-cause mortality, recurrent streptococcal BSI, or readmission. We performed non-inferiority analyses for each exposure. Separate multivariable Cox proportional hazards regression models were constructed for each exposure. The antibiotic duration analysis included 1,407 patients (5-10 days, n = 246; 11-15 days, n = 1,161). We found that 5-10-day courses were non-inferior to 11-15-day courses (P = 0.047). The antibiotic route analysis included 1,461 patients (oral switch, n = 1,112; entirely intravenous, n = 349). Oral step-down therapy did not meet the criteria for non-inferiority (P = 0.06). In the adjusted models, no significant difference was found in the primary outcome rate by antibiotic duration or antibiotic route at discharge. We found that 5-10-day courses were non-inferior to longer courses, and thus may be a safe and effective treatment option in the treatment of uncomplicated streptococcal bacteremia. Randomized controlled trials are needed to confirm the equivalent outcomes with shorter regimens and to definitively determine the optimal antibiotic route on discharge.

COVID-19 vaccination initiation and completion in a multicenter cohort study of insured US transgender and cisgender adults.

PURPOSE: Transgender and gender-diverse (TGD) people may have been disproportionately impacted by the COVID-19 pandemic, yet little is known about vaccination status in this population. This multicenter cohort study of insured adults examined the rates of COVID-19 vaccine initiation and completion in TGD persons compared to matched cisgender persons. METHODS: A cohort of TGD persons and matched cisgender persons enrolled in Kaiser Permanente health plans in Northern and Southern California between 12/1/2020 and 7/31/2021 were analyzed. COVID-19 vaccination initiation and completion rates were compared across groups using Cox regression models. RESULTS: Among transmasculine persons, the HR (95 % CI) estimates for COVID-19 vaccination initiation and completion were, respectively, 1.35 (1.30-1.40) and 1.78 (1.71-1.85) compared with cisgender women and 1.34 (1.29-1.40) and 1.81 (1.73-1.88) compared with cisgender men. Among transfeminine persons, the corresponding HRs (95 % CIs) for vaccination initiation and completion were 1.35 (1.30-1.40) and 1.78 (1.71-1.85) compared with cisgender women and 1.34 (1.29-1.40) and 1.81 (1.73-1.88) compared with cisgender men. CONCLUSION: Findings from this cohort of insured adults demonstrated that TGD persons initiated and completed COVID-19 vaccination at higher rates compared to matched cisgender persons. Further work is needed to understand vaccination rates and determinants in the broader TGD populations.

Discrimination of the Veterans Aging Cohort Study Index 2.0 for Predicting Cause-specific Mortality Among Persons With HIV in Europe and North America.

Background: Predicting cause-specific mortality among people with HIV (PWH) could facilitate targeted care to improve survival. We assessed discrimination of the Veterans Aging Cohort Study (VACS) Index 2.0 in predicting cause-specific mortality among PWH on antiretroviral therapy (ART). Methods: Using Antiretroviral Therapy Cohort Collaboration data for PWH who initiated ART between 2000 and 2018, VACS Index 2.0 scores (higher scores indicate worse prognosis) were calculated around a randomly selected visit date at least 1 year after ART initiation. Missingness in VACS Index 2.0 variables was addressed through multiple imputation. Cox models estimated associations between VACS Index 2.0 and causes of death, with discrimination evaluated using Harrell's C-statistic. Absolute mortality risk was modelled using flexible parametric survival models. Results: Of 59 741 PWH (mean age: 43 years; 80% male), the mean VACS Index 2.0 at baseline was 41 (range: 0-129). For 2425 deaths over 168 162 person-years follow-up (median: 2.6 years/person), AIDS (n = 455) and non-AIDS-defining cancers (n = 452) were the most common causes. Predicted 5-year mortality for PWH with a mean VACS Index 2.0 score of 38 at baseline was 1% and approximately doubled for every 10-unit increase. The 5-year all-cause mortality C-statistic was .83. Discrimination with the VACS Index 2.0 was highest for deaths resulting from AIDS (0.91), liver-related (0.91), respiratory-related (0.89), non-AIDS infections (0.87), and non-AIDS-defining cancers (0.83), and lowest for suicides/accidental deaths (0.65). Conclusions: For deaths among PWH, discrimination with the VACS Index 2.0 was highest for deaths with measurable physiological causes and was lowest for suicide/accidental deaths.

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.

Care interruptions and mortality among adults in Europe and North America.

OBJECTIVE: Interruptions in care of people with HIV (PWH) on antiretroviral therapy (ART) are associated with adverse outcomes, but most studies have relied on composite outcomes. We investigated whether mortality risk following care interruptions differed from mortality risk after first starting ART. DESIGN: Collaboration of 18 European and North American HIV observational cohort studies of adults with HIV starting ART between 2004 and 2019. METHODS: Care interruptions were defined as gaps in contact of ≥365 days, with a subsequent return to care (distinct from loss to follow-up), or ≥270 days and ≥545 days in sensitivity analyses. Follow-up time was allocated to no/preinterruption or postinterruption follow-up groups. We used Cox regression to compare hazards of mortality between care interruption groups, adjusting for time-updated demographic and clinical characteristics and biomarkers upon ART initiation or re-initiation of care. RESULTS: Of 89 197 PWH, 83.4% were male and median age at ART start was 39 years [interquartile range (IQR): 31-48)]. 8654 PWH (9.7%) had ≥1 care interruption; 10 913 episodes of follow-up following a care interruption were included. There were 6104 deaths in 536 334 person-years, a crude mortality rate of 11.4 [95% confidence interval (CI): 11.1-11.7] per 1000 person-years. The adjusted mortality hazard ratio (HR) for the postinterruption group was 1.72 (95% CI: 1.57-1.88) compared with the no/preinterruption group. Results were robust to sensitivity analyses assuming ≥270-day (HR 1.49, 95% CI: 1.40-1.60) and ≥545-day (HR 1.67, 95% CI: 1.48-1.88) interruptions. CONCLUSIONS: Mortality was higher among PWH reinitiating care following an interruption, compared with when PWH initially start ART, indicating the importance of uninterrupted care.

Factors associated with suicidal ideation among people with HIV engaged in care.

BACKGROUND: People with HIV (PWH) are at elevated risk for suicidal ideation (SI), yet few studies have examined how substance use, clinical and sociodemographic factors are associated with SI among PWH. METHOD: We used substance use (Tobacco, Alcohol, Prescription Medication, and Other Substance Use [TAPS]) and depression (PHQ-9) data from computerized screening of adult PWH in primary care clinics in Northern California, combined with health record data on psychiatric diagnoses, HIV diagnosis, treatment, and control (HIV RNA, CD4), insurance, and neighborhood deprivation index (NDI) to examine factors associated with SI (PHQ-9 item 9 score > 0). Adjusted odds ratios (aOR) for SI were obtained from logistic regression models. RESULTS: Among 2829 PWH screened (92 % male; 56 % white; mean (SD) age of 54 (13) years; 220 (8 %) reported SI. Compared with no problematic use, SI was higher among those reporting one (aOR = 1.65, 95 % CI = 1.17, 2.33), two (aOR = 2.23, 95 % CI = 1.42, 3.49), or ≥ 3 substances (aOR = 4.49, 95 % CI = 2.41, 8.39). SI risk was higher for those with stimulant use (aOR = 3.55, 95 % CI = 2.25, 5.59), depression (aOR = 4.18, 95 % CI = 3.04, 5.74), and anxiety diagnoses (aOR = 1.67, 95 % CI = 1.19, 2.34), or Medicaid (aOR = 2.11, 95%CI = 1.24, 3.60) compared with commercial/other insurance. SI was not associated with HIV-related measures or NDI. LIMITATIONS: SI was assessed with a single PHQ-9 item. Simultaneous SI and exposure data collection restricts the ability to establish substance use as a risk factor. CONCLUSIONS: HIV care providers should consider multiple substance use, stimulant use, depression or anxiety, and public insurance as risk factors for SI and provide interventions when needed.

Cardiovascular Risk Estimation Is Suboptimal in People With HIV.

BACKGROUND: Established cardiovascular disease (CVD) risk prediction functions may not accurately predict CVD risk in people with HIV. We assessed the performance of 3 CVD risk prediction functions in 2 HIV cohorts. METHODS AND RESULTS: CVD risk scores were calculated in the Mass General Brigham and Kaiser Permanente Northern California HIV cohorts, using the American College of Cardiology/American Heart Association atherosclerotic CVD function, the FHS (Framingham Heart Study) hard coronary heart disease function and the Framingham Heart Study hard CVD function. Outcomes were myocardial infarction or coronary death for FHS hard coronary heart disease function; and myocardial infarction, stroke, or coronary death for American College of Cardiology/American Heart Association and FHS hard CVD function. We calculated regression coefficients and assessed discrimination and calibration by sex; predicted to observed risk of outcome was also compared. In the combined cohort of 9412, 158 (1.7%) had a coronary heart disease event, and 309 (3.3%) had a CVD event. Among women, CVD risk was generally underestimated by all 3 risk functions. Among men, CVD risk was underestimated by the American College of Cardiology/American Heart Association and FHS hard CVD function, but overestimated by the FHS hard coronary heart disease function. Calibration was poor for women using the FHS hard CVD function and for men using all functions. Discrimination in all functions was good for women (c-statistics ranging from 0.78 to 0.90) and moderate for men (c-statistics ranging from 0.71 to 0.72). CONCLUSIONS: Established CVD risk prediction functions generally underestimate risk in people with HIV. Differences in model performance by sex underscore the need for both HIV-specific and sex-specific functions. Development of CVD risk prediction models tailored to HIV will enhance care for aging people with HIV.

Recent and projected incidence trends and risk of anal cancer among people with HIV in North america.

BACKGROUND: Anal cancer risk is elevated among people with HIV (PWH). Recent anal cancer incidence patterns among PWH in the United States (US) and Canada remain unclear. It is unknown how the incidence patterns may evolve in future years. METHODS: Using data from the North American AIDS Cohort Collaboration on Research and Design, we investigated absolute anal cancer incidence and incidence trends in the US, Canada, and different US regions. We further estimated relative risk compared with persons without HIV, relative risk among various subgroups, and projected future anal cancer burden among US PWH. RESULTS: During 2001-2016, in the US, age-standardized anal cancer incidence declined 2.2%/year (95%CI=-4.4% to -0.1%), particularly in the Western region (-3.8%/year [95%CI=-6.5% to -0.9%]. In Canada, incidence remained stable. Considerable geographic variation in risk was observed by US regions (eg, over four-fold risk in the Midwest and Southeast compared to the Northeast among men who have sex with men [MSM] with HIV). Anal cancer risk increased with a decrease in nadir CD4 count and was elevated among those with opportunistic illnesses. Anal cancer burden among US PWH is expected to decrease in future years (through 2035), but >70% of cases will continue to occur in MSM with HIV and people with AIDS. CONCLUSION: Geographic variation in anal cancer risk and trends may reflect underlying differences in screening practices and HIV epidemic. MSM with HIV and PWH with AIDS will continue to bear most anal cancer burden, highlighting the importance of precision prevention.

Life and Disability Insurance for People with or at Risk of HIV: Aligning Policy with Evidence.

Antiretroviral medications have substantially improved life expectancy for people with HIV. These medications are also highly effective in preventing HIV acquisition in people who do not have HIV, a strategy known as HIV preexposure prophylaxis (PrEP). Despite these advances, some life and disability insurers continue to deny or limit coverage for people with HIV, and some have even refused to cover people who are using PrEP to protect themselves. These policies unfairly deny people with HIV, PrEP users, and their families the peace of mind and financial protection that can come with life and disability insurance coverage. This article summarizes the current evidence on HIV treatment and prevention, arguing that underwriting decisions by life and disability insurers should not be made based on HIV status or use of PrEP.

Association between gender-affirming hormone therapy and measures of glucose metabolism: A longitudinal study.

CONTEXT: The long-term effect of gender-affirming hormone therapy (GAHT) on glucose metabolism is an area of priority in transgender health research. OBJECTIVES: To evaluate the relation between GAHT and changes in fasting blood glucose (FG) and glycosylated hemoglobin (HbA1c) in transmasculine (TM) and transfeminine (TF) persons relative to the corresponding temporal changes in presumably cisgender persons (i.e. without any evidence of TGD status). DESIGN: Retrospective cohort study. SETTING: Three large integrated health systems. PARTICIPANTS: 2,425 TF and 2,127 TM persons compared with 33,995 cisgender males (CM) and 38,913 cisgender females (CF) enrolled in the same health plans. OUTCOMES/MEASURES: Temporal changes in FG and HbA1c levels examined using linear mixed models with main results expressed as ratios-of-ratios. RESULTS: The pre- versus post-GAHT ratios-of-ratio (95% confidence interval) estimates adjusted for age, race/ethnicity, study site, and body mass index in the model comparing TF and CM groups were 1.05 (1.01, 1.09) for FG and 1.03 (0.99, 1.06) for HbA1c. By contrast, the corresponding results in the models contrasting TM and cisgender cohort members were in the 0.99-1.00 range. The ratio-of-ratios comparing post-GAHT changes among transgender and cisgender persons were close to the null and without a discernable pattern. CONCLUSION: Though the within-transgender cohort data suggest an increase in the levels of FG and HbA1c following feminizing GAHT initiation, these changes were no longer evident when compared with the corresponding changes in cisgender referents. Based on these results, clinically important effects of GAHT on routine laboratory markers of glucose metabolism appear unlikely.

Self-reported pain severity and use of cannabis and opioids in persons with HIV in an urban primary care setting in Northern California: A cross-sectional study.

Persons with HIV (PWH) experience high levels of pain. We examined the relationship of pain severity with use of cannabis and prescription opioids among PWH. This cross-sectional study evaluated associations between self-reported pain (moderate/severe vs mild/none) and cannabis and prescription opioid use in a primary care sample of PWH enrolled in an alcohol use treatment study at Kaiser Permanente, San Francisco. Prevalence ratios (PR) for moderate/severe pain associated with cannabis, opioid use, or both in the prior 30 days were obtained from Poisson regression models. Adjusted models included race/ethnicity, education, employment, HIV ribonucleic acid levels, depression, and anxiety. Overall, 614 PWH completed baseline questionnaires from May 2013 to May 2015, among whom 182/614 (29.6%) reported moderate/severe pain. The prevalence of moderate/severe pain varied by substances: 19.1% moderate/severe pain among study participants who reported neither cannabis or opioids, 30.2% for cannabis alone, 41.2% for opioids alone, and 60.9% for those reporting both substances. In adjusted models, compared with PWH who reported neither substance (reference), prevalence of moderate/severe pain was higher for those using cannabis alone (PR 1.54; 95% CI 1.13-2.09), opioids alone (PR 1.96; 95% CI 1.31-2.94), and those reporting both (PR 2.66; 95% CI 1.91-3.70). PWH who reported opioid and/or cannabis use were more likely to report moderate/severe pain compared with PWH who did not report use of these substances. To improve patient care, it is vital to assess patients' approaches to pain management including substance use and target appropriate interventions to reduce pain in PWH.

Using Electronic Health Records to Improve HIV Preexposure Prophylaxis Care: A Randomized Trial.

BACKGROUND: Preexposure prophylaxis (PrEP) use remains limited and inequitable, and strategies are needed to improve PrEP provision in primary care. METHODS: We conducted a cluster randomized trial at Kaiser Permanente, San Francisco, to evaluate the effectiveness of a clinical decision support intervention guided by an electronic health record (EHR)-based HIV risk prediction model to improve PrEP provision. Primary care providers (PCPs) were randomized to usual care or intervention, with PCPs who provide care to people with HIV balanced between arms. PCPs in the intervention arm received an EHR-based staff message with prompts to discuss HIV prevention and PrEP before upcoming in-person or video visits with patients whose predicted 3-year HIV risk was above a prespecified threshold. The main study outcome was initiation of PrEP care within 90 days, defined as PrEP discussions, referrals, or prescription fills. RESULTS: One hundred twenty-one PCPs had 5051 appointments with eligible patients (2580 usual care; 2471 intervention). There was a nonsignificant increase in initiation of PrEP care in the intervention arm (6.0% vs 4.5%, HR 1.32, 95% CI: 0.84 to 2.1). There was a significant interaction by HIV provider status, with an intervention HR of 2.59 (95% CI: 1.30 to 5.16) for HIV providers and 0.89 (95% CI: 0.59 to 1.35) for non-HIV providers (P-interaction <0.001). CONCLUSION: An EHR-based intervention guided by an HIV risk prediction model substantially increased initiation of PrEP care among patients of PCPs who also care for people with HIV. Higher-intensity interventions may be needed to improve PrEP provision among PCPs less familiar with PrEP and HIV care.

Changes in Body Mass Index Over Time in People With and Without HIV Infection.

Background: Excess weight gain is an important health concern among people with HIV (PWH) on antiretroviral therapy (ART). The extent to which ART contributes to body mass index (BMI) changes is incompletely understood. Methods: We conducted a retrospective study of PWH initiating ART and demographically matched people without HIV (PWoH). Data on baseline BMI (kg/m2; categorized as underweight/normal, overweight, or obese) and ART class (integrase strand transfer inhibitor [INSTI], non-nucleoside reverse transcriptase inhibitor [NNRTI], protease inhibitor [PI]) were obtained from electronic health records. BMI was evaluated longitudinally using piecewise linear splines in mixed effects models by HIV status, baseline BMI, and ART class. Models were adjusted for sociodemographics, comorbidities, and substance use. Results: The study included 8256 PWH and 129 966 PWoH (mean baseline age, 40.9 and 42.2 years, respectively; 88% men). In adjusted models, the average annual change in BMI in the first 2 years after ART initiation was 0.53 for PWH and 0.12 for PWoH (P < .001). BMI increases among PWH were observed for all ART classes: 0.69 for INSTIs, 0.69 for PIs, and 0.40 for NNRTIs vs 0.12 among PWoH. For PWH initiating INSTIs, BMI increases were observed regardless of baseline BMI. Overall BMI changes >2 years after ART initiation were similar by HIV status (0.02 average annual increase for PWH and PWoH). Conclusions: PWH initiating ART gained excess weight in the first 2 years, emphasizing the importance of monitoring weight and cardiometabolic health among ART-treated PWH.

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.

Longitudinal trends in causes of death among adults with HIV on antiretroviral therapy in Europe and North America from 1996 to 2020: a collaboration of cohort studies.

BACKGROUND: Mortality rates among people with HIV have fallen since 1996 following the widespread availability of effective antiretroviral therapy (ART). Patterns of cause-specific mortality are evolving as the population with HIV ages. We aimed to investigate longitudinal trends in cause-specific mortality among people with HIV starting ART in Europe and North America. METHODS: In this collaborative observational cohort study, we used data from 17 European and North American HIV cohorts contributing data to the Antiretroviral Therapy Cohort Collaboration. We included data for people with HIV who started ART between 1996 and 2020 at the age of 16 years or older. Causes of death were classified into a single cause by both a clinician and an algorithm if International Classification of Diseases, Ninth Revision or Tenth Revision data were available, or independently by two clinicians. Disagreements were resolved through panel discussion. We used Poisson models to compare cause-specific mortality rates during the calendar periods 1996-99, 2000-03, 2004-07, 2008-11, 2012-15, and 2016-20, adjusted for time-updated age, CD4 count, and whether the individual was ART-naive at the start of each period. FINDINGS: Among 189 301 people with HIV included in this study, 16 832 (8·9%) deaths were recorded during 1 519 200 person-years of follow-up. 13 180 (78·3%) deaths were classified by cause: the most common causes were AIDS (4203 deaths; 25·0%), non-AIDS non-hepatitis malignancy (2311; 13·7%), and cardiovascular or heart-related (1403; 8·3%) mortality. The proportion of deaths due to AIDS declined from 49% during 1996-99 to 16% during 2016-20. Rates of all-cause mortality per 1000 person-years decreased from 16·8 deaths (95% CI 15·4-18·4) during 1996-99 to 7·9 deaths (7·6-8·2) during 2016-20. Rates of all-cause mortality declined with time: the average adjusted mortality rate ratio per calendar period was 0·85 (95% CI 0·84-0·86). Rates of cause-specific mortality also declined: the most pronounced reduction was for AIDS-related mortality (0·81; 0·79-0·83). There were also reductions in rates of cardiovascular-related (0·83, 0·79-0·87), liver-related (0·88, 0·84-0·93), non-AIDS infection-related (0·91, 0·86-0·96), non-AIDS-non-hepatocellular carcinoma malignancy-related (0·94, 0·90-0·97), and suicide or accident-related mortality (0·89, 0·82-0·95). Mortality rates among people who acquired HIV through injecting drug use increased in women (1·07, 1·00-1·14) and decreased slightly in men (0·96, 0·93-0·99). INTERPRETATION: Reductions of most major causes of death, particularly AIDS-related deaths among people with HIV on ART, were not seen for all subgroups. Interventions targeted at high-risk groups, substance use, and comorbidities might further increase life expectancy in people with HIV towards that in the general population. FUNDING: US National Institute on Alcohol Abuse and Alcoholism.

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.