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.

Age group differences in substance use, social support, and physical and mental health concerns among people living with HIV two years after receiving primary care-based alcohol treatment.

Objectives: People living with HIV (PWH) have seen reduction in HIV-associated morbidity and increase in near-normal life expectancy, yet unhealthy alcohol use poses substantial risks to older as well as younger adults. Further research regarding age-associated physical and mental health concerns among PWH who drink alcohol is needed to inform services, given the expanding age range of patients in care.Methods: We compared age group differences (18-34, 35-44, 45-54, ≥55 years old) in two-year patient-reported outcomes and HIV viral control among PWH enrolled in a primary care-based behavioral alcohol intervention trial; with 90% follow up from baseline.Results: Of 553 PWH, 50 (9%) were 18-34, 85 (15%) were 35-44, 197 (36%) were 45-54, and 221 (40%) were ≥55 years old. Most were men (97%) and White (64%). At two years, PWH ≥55 reported less substance use in the prior 30 days, fewer social contacts, and more pain; younger PWH had lower antiretroviral therapy (ART) adherence. In adjusted analyses, PWH ages 18-34 had higher odds of unhealthy alcohol use, tobacco, cannabis, or other substances compared to those ≥55; with higher odds of anxiety among PWH 35-44 compared with those ≥55; and physical quality of life was worse among those ≥55 compared with younger groups.Conclusions: While older PWH report less substance use than younger PWH and have better ART adherence post-treatment, they are more likely to experience limited social support and worse physical quality of life. Findings can inform interventions to address varying needs of PWH across the lifespan.

Timing of Antiretroviral Therapy Initiation and Risk of Cancer Among Persons Living With Human Immunodeficiency Virus.

BACKGROUND: Persons living with human immunodeficiency virus (HIV; PLWH) experience a high burden of cancer. It remains unknown which cancer types are reduced in PLWH with earlier initiation of antiretroviral therapy (ART). METHODS: We evaluated AIDS-free, ART-naive PLWH during 1996-2014 from 22 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. PLWH were followed from first observed CD4 of 350-500 cells/µL (baseline) until incident cancer, death, lost-to-follow-up, or December 2014. Outcomes included 6 cancer groups and 5 individual cancers that were confirmed by chart review or cancer registry linkage. We evaluated the effect of earlier (in the first 6 months after baseline) versus deferred ART initiation on cancer risk. Marginal structural models were used with inverse probability weighting to account for time-dependent confounding and informative right-censoring, with weights informed by subject's age, sex, cohort, baseline year, race/ethnicity, HIV transmission risk, smoking, viral hepatitis, CD4, and AIDS diagnoses. RESULTS: Protective results for earlier ART were found for any cancer (adjusted hazard ratio [HR] 0.57; 95% confidence interval [CI], .37-.86), AIDS-defining cancers (HR 0.23; 95% CI, .11-.49), any virus-related cancer (HR 0.30; 95% CI, .16-.54), Kaposi sarcoma (HR 0.25; 95% CI, .10-.61), and non-Hodgkin lymphoma (HR 0.22; 95% CI, .06-.73). By 15 years, there was also an observed reduced risk with earlier ART for virus-related NADCs (0.6% vs 2.3%; adjusted risk difference -1.6; 95% CI, -2.8, -.5). CONCLUSIONS: Earlier ART initiation has potential to reduce the burden of virus-related cancers in PLWH but not non-AIDS-defining cancers (NADCs) without known or suspected viral etiology.

HIV Stigma and Its Associations with Longitudinal Health Outcomes Among Persons Living with HIV with a History of Unhealthy Alcohol Use.

This study examined the demographic and clinical correlates of HIV stigma and evaluated how HIV stigma was associated with physical and mental health outcomes one year later in a primary-care based cohort of persons living with HIV (PLHIV; N = 584). HIV stigma was measured using a modified Berger HIV stigma scale, which includes four subscales: (1) personalized stigma; (2) disclosure concerns; (3) negative self-image; and (4) concerns around public attitudes towards PLHIV. Physical and mental health were assessed using the 12-item short form survey (SF-12). Compared to whites, African Americans were more likely to have higher personalized stigma scores (adjusted prevalence ratio [aPR] 1.54 [95% confidence interval 1.10-2.15]), disclosure concerns (aPR 1.40 [1.03-1.92]), and concerns with public attitudes about PLHIV (aPR 1.61 [1.11-2.34]). Hispanic/Latinx participants were more likely to have concerns around public attitudes towards PLHIV (aPR 1.50 [1.11-2.02]) than whites. Compared to men, women were more likely to have higher negative self-image scores (aPR 1.50 [1.08-2.08]). Higher stigma scores were associated with poorer subsequent self-reported physical and mental health functional status. Our findings highlight the substantial need for addressing HIV stigma, particularly among minority subgroups.

RESUMEN: El objetivo de este estudio era examinar la correlación del estigma del VIH con aspectos demográficos y clínicos. Se buscaba evaluar la asociación del estigma del VIH con los efectos de la salud física y mental luego de un año en un cohorte de personas viviendo con VIH (PVV; N = 584) provenientes de una clínica de servicios primarios. El estigma del VIH se midió utilizando la escala modificada de estigma del VIH de Berger que incluye cuatro sub-escalas: (1) estigma personalizado; (2) preocupaciones por revelación de diagnóstico; (3) auto-imagen negativa; y (4) preocupaciones acerca de actitudes hacia PVV. La salud física y mental fue evaluada utilizando una encuesta corta de 12 ítems. En comparación con las personas blancas, entre las personas Afroamericanas había más probabilidad de obtener una mayor puntuación en las escalas de estigma personalizado (razón de prevalencia ajustada [aRP] 1.54 [95% intervalo de confianza 1.10­2.15]), preocupaciones por revelación de diagnóstico (aRP 1.40 [1.03­1.92]), y preocupacionespor actitudes negativas hacia PVV (aRP 1.61 [1.11­2.34]). Participantes Hispanos/Latinos tenían más probabilidad de tener preocupaciones por las actitudes negativas hacia PVV (aRP 1.50 [1.11­2.02]) en comparación con personas blancas. En comparación con los hombres, las mujeres tenían mayor probabilidad de tener un resultado más alto en la escala de auto-imagen negativa (aRP 1.50 [1.08­2.08]). Resultados mayores estuvieron asociados a estatus más pobres de funcionalidad de salud física y mental. Nuestros resultados destacan la necesidad substancial de atender asuntos de estigma por el VIH, particularmente en grupos minoritarios.

Association of Immunosuppression and Human Immunodeficiency Virus (HIV) Viremia With Anal Cancer Risk in Persons Living With HIV in the United States and Canada.

BACKGROUND: People living with human immunodeficiency virus (HIV; PLWH) have a markedly elevated anal cancer risk, largely due to loss of immunoregulatory control of oncogenic human papillomavirus infection. To better understand anal cancer development and prevention, we determined whether recent, past, cumulative, or nadir/peak CD4+ T-cell count (CD4) and/or HIV-1 RNA level (HIV RNA) best predict anal cancer risk. METHODS: We studied 102 777 PLWH during 1996-2014 from 21 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. Using demographics-adjusted, cohort-stratified Cox models, we assessed associations between anal cancer risk and various time-updated CD4 and HIV RNA measures, including cumulative and nadir/peak measures during prespecified moving time windows. We compared models using the Akaike information criterion. RESULTS: Cumulative and nadir/peak CD4 or HIV RNA measures from approximately 8.5 to 4.5 years in the past were generally better predictors for anal cancer risk than their corresponding more recent measures. However, the best model included CD4 nadir (ie, the lowest CD4) from approximately 8.5 years to 6 months in the past (hazard ratio [HR] for <50 vs ≥500 cells/µL, 13.4; 95% confidence interval [CI], 3.5-51.0) and proportion of time CD4 <200 cells/µL from approximately 8.5 to 4.5 years in the past (a cumulative measure; HR for 100% vs 0%, 3.1; 95% CI, 1.5-6.6). CONCLUSIONS: Our results are consistent with anal cancer promotion by severe, prolonged HIV-induced immunosuppression. Nadir and cumulative CD4 may represent useful markers for identifying PLWH at higher anal cancer risk.

Alcohol and drug use, partner PrEP use and STI prevalence among people with HIV.

OBJECTIVES: People with HIV (PWH) have a high burden of bacterial sexually transmitted infections (STIs). We examined the relationship of alcohol and drug use and partner pre-exposure prophylaxis (PrEP) use to STI prevalence in a cohort of PWH with a history of unhealthy alcohol use. METHODS: We analysed data from a primary care-based alcohol intervention study at Kaiser Permanente Northern California (KPNC). Participants were recruited between April 2013 and May 2015 and were followed for up to 24 months. We linked participant responses to questions from the 24 month follow-up interview, including alcohol and drug use and partner PrEP use, with STI test results (ie, syphilis, chlamydia, gonorrhoea) in the KPNC electronic health record. Prevalence ratios (PR) were estimated using Poisson models fitted with robust variance estimators to evaluate the association of substance use and partner use of PrEP with STIs. RESULTS: In the analytic sample (n=465), the median age was 52 years (IQR 45-59); 67% were white; 95% were men who have sex with men. Thirty-two per cent of participants had HIV-positive partners only; 31% had HIV-negative partners with at least one on PrEP in the previous year and 37% had HIV-negative partners without any on PrEP. Twenty-three per cent reported alcohol and drug use prior to sex in the last 6 months. Eight per cent of participants had an STI. Partner PrEP use (adjusted PR (aPR) 2.99 (95% CI 1.11 to 8.08)) was independently associated with higher STI prevalence. Participants who reported use of alcohol (aPR 1.53 (0.61 to 3.83)), drugs (aPR 1.97 (0.71 to 5.51)) or both (aPR 1.93 (0.75 to 4.97)) prior to sex had a higher STI prevalence. CONCLUSIONS: The higher prevalence of STIs among PWH with unhealthy alcohol use who have partners on PrEP suggests that this subgroup may be a high-yield focus for targeted outreach, STI screening and sexual health counselling.

Changes in Days of Unhealthy Alcohol Use and Antiretroviral Therapy Adherence, HIV RNA Levels, and Condomless Sex: A Secondary Analysis of Clinical Trial Data.

In a sample of people with HIV (PWH) enrolled in an alcohol intervention trial and followed for 12 months, we examined the association of changes in days (i.e., decrease, increase, no change [reference]) of unhealthy drinking (consuming ≥ 4/≥ 5 drinks for women/men) with antiretroviral therapy adherence (≥ 95% adherent), viral suppression (HIV RNA < 75 copies/mL), condomless sex with HIV-negative/unknown status partners, and dual-risk outcome (HIV RNA ≥ 75 copies/mL plus condomless sex). The sample included 566 PWH (96.8% male; 63.1% White; 93.9% HIV RNA < 75 copies/mL) who completed baseline, 6-, and 12-month assessments. Decrease in days of unhealthy drinking was associated with increased likelihood of viral suppression (odds ratio [OR] 3.78; 95% confidence interval [CI] 1.06, 13.51, P = .04) versus no change. Increase in days of unhealthy drinking was associated with increased likelihood of condomless sex (OR 3.13; 95% CI 1.60, 6.12, P < .001). Neither increase nor decrease were associated with adherence or dual-risk outcome. On a continuous scale, for each increase by 1 day of unhealthy drinking in the prior month, the odds of being 95% adherent decreased by 6% (OR 0.94, 95% CI 0.88, 1.00, P = 0.04).

Interventions to Reduce Unhealthy Alcohol Use among Primary Care Patients with HIV: the Health and Motivation Randomized Clinical Trial.

BACKGROUND: Unhealthy alcohol use has adverse effects on HIV treatment. Screening, brief intervention, and referral to treatment (SBIRT) has some evidence of efficacy but may not be sufficient for those with low motivation or comorbid substance use. OBJECTIVE: To examine the effectiveness of motivational interviewing (MI) and emailed feedback (EF) among primary care HIV-positive patients, compared with treatment as usual care (UC) only, which included SBIRT. DESIGN: Randomized clinical trial. PARTICIPANTS: Six hundred fourteen adult HIV-positive patients in Kaiser Permanente Northern California who reported prior-year unhealthy alcohol use. INTERVENTION: Participants were randomized to either three sessions of MI (one in person and two by phone), information regarding alcohol risks via EF through a patient portal, or UC alone. MI and EF participants who reported unhealthy alcohol use at 6 months were offered additional MI and EF treatment, respectively. MAIN MEASURES: Participant-reported unhealthy alcohol use (defined as ≥ 4/≥ 5 drinks per day for women/men), alcohol problems at 12 months, based on blinded telephone interviews. Secondary outcomes included drug use and antiretroviral (ART) adherence. KEY RESULTS: At 12 months, there were no overall group differences, but in all three arms, there were declines in unhealthy alcohol use and alcohol-related problems (p < 0.001). Participants reporting low motivation to reduce drinking at baseline were less likely to report unhealthy alcohol use if they received MI vs. EF and UC (p = 0.013). At 6 months, reported illegal drug use/misuse of prescription drugs other than marijuana was lower in the MI arm than EF or UC (p = 0.012). There were no differences in ART adherence between groups. CONCLUSIONS: In a randomized trial of HIV-positive patients using two behavioral interventions compared with SBIRT alone, participants in all three conditions reduced unhealthy alcohol use. MI may provide added benefit for patients with low motivation or who report illegal drug use/misuse of prescription drugs. TRIAL REGISTRATION: NCT01671501 ( ClinicalTrials.gov ).

Declining relative risk for myocardial infarction among HIV-positive compared with HIV-negative individuals with access to care.

Concerns remain for an increased myocardial infarction (MI) risk among individuals infected with human immunodeficiency virus (HIV). We conducted a cohort study evaluating MI risk from 1996 to 2011 by HIV status. The adjusted MI rate ratio for HIV status declined over time, reaching 1.0 (95% confidence interval, .7-1.4) in 2010-2011, the most recent study period.

Antiretroviral Therapy Adherence and Use of an Electronic Shared Medical Record Among People Living with HIV.

Electronic shared medical records (SMR) are emerging healthcare technologies that allow patients to engage in their healthcare by communicating with providers, refilling prescriptions, scheduling appointments, and viewing portions of medical records. We conducted a pre-post cohort study of HIV-positive adults who used and did not use SMR in two integrated healthcare systems. We compared the difference in antiretroviral refill adherence between SMR users and age- and sex-frequency matched non-users from the 12-month period prior to SMR useto the 12-month period starting 6 months after initiation of SMR use. High adherence was maintained among SMR users (change = -0.11 %) but declined among non-users (change = -2.05 %; p = 0.003). Among SMR users, there was a steady improvement in adherence as monthly frequency of SMR use increased (p = 0.009). SMR use, particularly more frequent use, is associated with maintaining high adherence and non-use is associated with declines in adherence over time among patients with access to these online services.

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.

Primary HPV screening compared with other cervical cancer screening strategies in women with HIV: a cost-effectiveness study.

OBJECTIVE: To compare the model-predicted benefits, harms, and cost-effectiveness of cytology, cotesting, and primary HPV screening in U.S. women living with HIV (WLWH). DESIGN: We adapted a previously published Markov decision model to simulate a cohort of U.S. WLWH. SETTING: United States. SUBJECTS, PARTICIPANTS: A hypothetical inception cohort of WLWH. INTERVENTION: We simulated five screening strategies all assumed the same strategy of cytology with HPV triage for ASCUS for women aged 21 to 29 years. The different strategies noted are for women aged 30 and older as the following: continue cytology with HPV triage, cotesting with repeat cotesting triage, cotesting with HPV16/18 genotyping triage, primary hrHPV testing with cytology triage, and primary hrHPV testing with HPV16/18 genotyping triage. MAIN OUTCOME MEASURES: The outcomes include colposcopies, false-positive results, treatments, cancers, cancer deaths, life-years and costs, and lifetime quality-adjusted life-years. RESULTS: Compared with no screening, screening was cost-saving, and > 96% of cervical cancers and deaths could be prevented. Cytology with HPV triage dominated primary HPV screening and cotesting. At willingness-to-pay thresholds under $250,000, probabilistic sensitivity analyses indicated that primary HPV testing was more cost-effective than cotesting in over 98% of the iterations. CONCLUSIONS: Our study suggests the current cytology-based screening recommendation is cost-effective, but that primary HPV screening could be a cost-effective alternative to cotesting. To improve the cost-effectiveness of HPV-based screening, increased acceptance of the HPV test among targeted women is needed, as are alternative follow-up recommendations to limit the harms of high false-positive testing.

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.

Initial antiretroviral therapy regimen and risk of heart failure.

OBJECTIVES: Heart failure risk is elevated in people with HIV (PWH). We investigated whether initial antiretroviral therapy (ART) regimens influenced heart failure risk. DESIGN: Cohort study. METHODS: PWH who initiated an ART regimen between 2000 and 2016 were identified from three integrated healthcare systems. We evaluated heart failure risk by protease inhibitor, nonnucleoside reverse transcriptase inhibitors (NNRTI), and integrase strand transfer inhibitor (INSTI)-based ART, and comparing two common nucleotide reverse transcriptase inhibitors: tenofovir disoproxil fumarate (tenofovir) and abacavir. Follow-up for each pairwise comparison varied (i.e. 7 years for protease inhibitor vs. NNRTI; 5 years for tenofovir vs. abacavir; 2 years for INSTIs vs. PIs or NNRTIs). Hazard ratios were from working logistic marginal structural models, fitted with inverse probability weighting to adjust for demographics, and traditional cardiovascular risk factors. RESULTS: Thirteen thousand six hundred and thirty-four PWH were included (88% men, median 40 years of age; 34% non-Hispanic white, 24% non-Hispanic black, and 24% Hispanic). The hazard ratio (95% CI) were: 2.5 (1.5-4.3) for protease inhibitor vs. NNRTI-based ART (reference); 0.5 (0.2-1.8) for protease inhibitor vs. INSTI-based ART (reference); 0.1 (0.1-0.8) for NNRTI vs. INSTI-based ART (reference); and 1.7 (0.5-5.7) for tenofovir vs. abacavir (reference). In more complex models of cumulative incidence that accounted for possible nonproportional hazards over time, the only remaining finding was evidence of a higher risk of heart failure for protease inhibitor compared with NNRTI-based regimens (1.8 vs. 0.8%; P  = 0.002). CONCLUSION: PWH initiating protease inhibitors may be at higher risk of heart failure compared with those initiating NNRTIs. Future studies with longer follow-up with INSTI-based and other specific ART are warranted.

Comparison of Stage I Non-Small-Cell Lung Cancer Treatments for Patients Living With HIV: A Simulation Study.

INTRODUCTION: Non-small-cell lung cancer (NSCLC) is a leading cause of death for people living with HIV (PWH). Nevertheless, there are no clinical trial data regarding the management of early-stage lung cancer in PWH. Using data from large HIV and cancer cohorts we parameterized a simulation model to compare treatments for stage I NSCLC according to patient characteristics. MATERIALS AND METHODS: To parameterize the model we analyzed PWH and NSCLC patient outcomes and quality of life data from several large cohort studies. Comparative effectiveness of 4 stage I NSCLC treatments (lobectomy, segmentectomy, wedge resection, and stereotactic body radiotherapy) was estimated using evidence synthesis methods. We then simulated trials comparing treatments according to quality adjusted life year (QALY) gains by age, tumor size and histology, HIV disease characteristics and major comorbidities. RESULTS: Lobectomy and segmentectomy yielded the greatest QALY gains among all simulated age, tumor size and comorbidity groups. Optimal treatment strategies differed by patient sex, age, and HIV disease status; wedge resection was among the optimal strategies for women aged 80 to 84 years with tumors 0 to 2 cm in size. Stereotactic body radiotherapy was included in some optimal strategies for patients aged 80 to 84 years with multimorbidity and in sensitivity analyses was a non-inferior option for many older patients or those with poor HIV disease control. CONCLUSION: In simulated comparative trials of treatments for stage I NSCLC in PWH, extensive surgical resection was often associated with the greatest projected QALY gains although less aggressive strategies were predicted to be non-inferior in some older, comorbid patient groups.

Fracture Risk and Association With TDF Use Among People With HIV in Large Integrated Health Systems.

BACKGROUND: Greater decline in bone health among people with HIV (PWH) has been documented but fracture risk and the impact of specific antiretroviral therapy (ART) regimens remain unclear. SETTING: Retrospective analyses of electronic health record data from 3 US integrated health care systems. METHODS: Fracture incidence was compared between PWH aged 40 years or older without prior fracture and demographically matched people without HIV (PWoH), stratified by age, sex, and race/ethnicity. Multivariable Cox proportional hazards models were used to estimate fracture risk associated with HIV infection. The association of tenofovir disoproxil fumarate (TDF) use and fracture risk was evaluated in a subset of PWH initiating ART. RESULTS: Incidence of fracture was higher in PWH [13.6/1000 person-years, 95% confidence interval (CI): 13.0 to 14.3, n = 24,308] compared with PWoH (9.5, 95% CI: 9.4 to 9.7, n = 247,313). Compared with PWoH, the adjusted hazard ratio (aHR) for fracture among PWH was 1.24 (95% CI: 1.18 to 1.31). The association between HIV infection and fracture risk increased with age, with the lowest aHR (1.17, 95% CI: 1.10 to 1.25) among those aged 40-49 years and the highest aHR (1.89, 95% CI: 1.30 to 2.76) among those aged 70 years or older. Among PWH initiating ART (n = 6504), TDF was not associated with significant increase in fracture risk compared with non-TDF regimens (aHR: 1.18, 95% CI: 0.89 to 1.58). CONCLUSIONS: Among people aged 40 years or older, HIV infection is associated with increased risk of fractures. Bone health screening from the age of 40 years may be beneficial for PWH. Large cohort studies with longer follow-up are needed to evaluate TDF effect and the potential benefit of early screening.

Variation in Heart Failure Risk by HIV Severity and Sex in People With HIV Infection.

BACKGROUND: HIV is an independent risk factor for heart failure (HF). However, the association of HIV severity with incident HF and the potential interaction with sex are incompletely understood. SETTING: Integrated health care system. METHODS: We conducted a cohort study of people with HIV (PWH) and matched people without HIV (PWoH), all aged ≥ 21 years and with no previous HF. Poisson regression was used to compare incident HF by HIV status, with PWH stratified by severity of HIV infection [defined by recent (<6 months) CD4 count, nadir CD4 count, or recent HIV RNA level]. Models were adjusted for sociodemographic characteristics, substance use, and HF risk factors. Analyses were conducted for men and women combined, then by sex. RESULTS: The study included 38,868 PWH and 386,569 PWoH (mean baseline age = 41.0 ± 10.8 years; 88% men). Compared with PWoH, incident HF risk was higher among PWH with lower recent CD4 [200-499 cells/µL, adjusted rate ratio (aRR) = 1.82, 95% confidence interval (CI) = 1.50 to 2.21 and <200 cells/µL, aRR = 3.26 (2.47 to 4.30)] and a low nadir CD4 [<200 cells/µL, aRR = 1.56 (1.37 to 1.79)] but not among PWH with normal CD4 [≥500 cells/µL, aRR = 1.14 (0.90 to 1.44)]. Higher incident HF risk was observed among PWH at all HIV RNA levels, with greater HF risk at higher HIV RNA levels. The excess HF risk associated with low CD4 (recent or nadir) and high HIV RNA was stronger among women than men (P interactions=0.05, 0.08, and 0.01, respectively). CONCLUSIONS: Given the association of HIV severity with HF, optimizing HIV treatment and management may be important for HF prevention among PWH.

Comparison of dementia incidence and prevalence between individuals with and without HIV infection in primary care from 2000 to 2016.

OBJECTIVE: To compare dementia incidence and prevalence after age 50 years by HIV status. DESIGN: Observational cohort, 2000-2016. METHODS: People with HIV (PWH) on antiretroviral therapy (ART) and demographically similar people without HIV (PWoH), all aged 50 years and older, were identified from Kaiser Permanente healthcare systems in Northern California, Southern California, and Mid-Atlantic States (Maryland, Virginia, Washington DC). Dementia diagnoses were obtained from electronic health records. Incidence and prevalence of dementia, overall and by time period (i.e. 2000-2002, 2003-2004, …, 2015-2016), were calculated using Poisson regression. Trends were examined using Joinpoint regression. Rate ratios were used to compare dementia by HIV status with adjustment for sociodemographics, substance use, and clinical factors. RESULTS: The study included 13 296 PWH and 155 354 PWoH (at baseline: for both, mean age = 54 years, 89% men; for PWH, 80% with HIV RNA <200 copies/ml). From 2000 to 2016, overall incidence of dementia was higher among PWH [adjusted incidence rate ratio (aIRR) = 1.80, 95% confidence interval (CI) = 1.60-2.04]. Dementia incidence decreased among both PWH and PWoH (-8.0 and -3.1% per period, respectively) but remained higher among PWH in the most recent time period, 2015-2016 (aIRR = 1.58, 95% CI = 1.18-2.12). The overall prevalence of dementia from 2000 to 2016 was higher among PWH [adjusted prevalence ratio (aPR) = 1.86, 95% CI = 1.70-2.04] and was also higher among PWH in 2015-2016 (aPR = 1.75, 95% CI = 1.56-1.97). CONCLUSION: Reductions in dementia incidence are encouraging and may reflect ART improvement, but PWH are still more likely to have dementia than PWoH. Monitoring the burden of dementia among PWH is important as this population ages.

SARS-CoV-2 Testing and Positivity Among Persons With and Without HIV in 6 US Cohorts.

BACKGROUND: It is not definitively known if persons with HIV (PWH) are more likely to be SARS-CoV-2 tested or test positive than persons without HIV (PWoH). We describe SARS-CoV-2 testing and positivity in 6 large geographically and demographically diverse cohorts of PWH and PWoH in the United States. SETTING: The Corona Infectious Virus Epidemiology Team comprises 5 clinical cohorts within a health system (Kaiser Permanente Northern California, Oakland, CA; Kaiser Permanente Mid-Atlantic States, Rockville, MD; University of North Carolina Health, Chapel Hill, NC; Vanderbilt University Medical Center, Nashville, TN; and Veterans Aging Cohort Study) and 1 interval cohort (Multicenter AIDS Cohort Study/Women's Interagency HIV Study Combined Cohort Study). METHODS: We calculated the proportion of patients SARS-CoV-2 tested and the test positivity proportion by HIV status from March 1 to December 31, 2020. RESULTS: The cohorts ranged in size from 1675 to 31,304 PWH and 1430 to 3,742,604 PWoH. The proportion of PWH who were tested for SARS-CoV-2 (19.6%-40.5% across sites) was significantly higher than PWoH (14.8%-29.4%) in the clinical cohorts. However, among those tested, the proportion of patients with positive SARS-CoV-2 tests was comparable by HIV status; the difference in proportion of SARS-CoV-2 positivity ranged from 4.7% lower to 1.4% higher. CONCLUSIONS: Although PWH had higher testing proportions compared with PWoH, we did not find evidence of increased positivity in 6 large, diverse populations across the United States. Ongoing monitoring of testing, positivity, and COVID-19-related outcomes in PWH are needed, given availability, response, and durability of COVID-19 vaccines; emergence of SARS-CoV-2 variants; and latest therapeutic options.