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BackgroundAnemia is common among people living with HIV infection (PLWH) and is associated with adverse health outcomes. Information on risk factors for anemia incidence in the current antiretroviral therapy (ART) era is lacking.MethodsWithin a prospective clinical cohort of adult PLWH receiving care at eight sites across the United States between 1/2010-3/2018, Cox proportional hazards regression analyses were conducted among a) PLWH free of anemia at baseline and b) PLWH free of severe anemia at baseline to determine associations between time-updated patient characteristics and development of anemia (hemoglobin

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

Little is known about the psychometric properties of depression instruments among persons infected with HIV. We analyzed data from a large sample of patients in usual care in two US cities (n=1467) using the nine-item Patient Health Questionnaire (PHQ-9) from the PRIME-MD. The PHQ-9 had curvilinear scaling properties and varying levels of measurement precision along the continuum of depression measured by the instrument. In our cohort, the scale showed a prominent floor effect and a distribution of scores across depression severity levels. Three items had differential item functioning (DIF) with respect to race (African-American vs. white); two had DIF with respect to sex; and one had DIF with respect to age. There was minimal individual-level DIF impact. Twenty percent of the difference in mean depression levels between African-Americans and whites was due to DIF. While standard scores for the PHQ-9 may be appropriate for use with individual HIV-infected patients in cross-sectional settings, these results suggest that investigations of depression across groups and within patients across time may require a more sophisticated analytic framework. [ABSTRACT FROM AUTHOR]

Numerous antiretroviral therapy (ART) regimens are recommended for first-line and subsequent HIV care, but regimen selection for clinical use may not represent the full range of options. We hypothesized that despite an increase in available antiretrovirals, clinical trial data on regimen efficacy and fixed-dose combination options have lead to uniformity in initial ART. We evaluated regimen selection for ART-naïve patients at the University of Alabama at Birmingham (UAB) 1917 Clinic between January 2000 and December 2007. The annual number of unique initial regimens was quantified. Initial regimen variability was expressed as regimens per 100 patients. Subsequent ART regimens were characterized for complexity via regimen sequence trees detailing the first three generations of regimens for patients starting the two most common initial combinations. Four hundred eighty-two ART-naïve patients were treated with 39 unique initial regimens (8.0 regimens per 100 patients). Variability in initial regimen selection was highest in the first 6 years (14.9-24.4 regimens per 100 patients). A sharp decline was observed in 2006 (16.1 regimens per 100 patients) and 2007 (6.5 regimens per 100 patients). The most dramatic shift in drug selection involved an increase in emtricitabine plus tenofovir plus efavirenz, from 0% in 2003 to 85% in 2007. During the study period, 205 of 482 (43%) patients required a change in initial therapy. Of these, 156 of 205 (76%) had a unique sequence of regimens. A shift toward homogeneity of initial ART was observed (85% of patients received the same first-line regimen in 2007). In contrast, regimen sequencing beyond the first regimen remained complex. These shifts in ART prescribing patterns may have implications for collaborative HIV care. [ABSTRACT FROM AUTHOR]

Background. The ability to control human immunodeficiency virus (HIV) replication in vivo in the absence of antiretroviral therapy (ART) is a measure of the efficiency of antiviral immunity. In a study of patients with chronic, ART-suppressed HIV infection, AIDS Clinical Trials Group 5068 investigated the effects of immunization with an exogenous HIV vaccine and pulse exposure to the subject's unique viral epitopes, by means of structured treatment interruptions (STIs), on the dynamics of viral rebound during a subsequent analytical treatment interruption (ATI). Methods. Ninety-seven subjects receiving stable ART with an HIV-1 RNA load <50 copies/mL and CD4(+) T lymphocyte count >400 cells/mm(3) were randomized to undergo continued ART, STIs, ALVAC-HIV vCP1452 immunization, or STIs and ALVAC-HIV vCP1452 immunization. Results. Subjects in the 2 STI arms had a significantly longer median doubling time in the period of the initial rise of viral load, a significantly lower median peak viral load, a significantly lower median end-of-ATI viral load set point, and a greater proportion of subjects with an end-of-ATI viral load set point <1000 copies/mL, compared with the subjects in the 2 arms without STIs. With an immunization schedule of 3 sets of 3 weekly injections, ALVAC-HIV vCP1452 did not affect viral load measures. Conclusions. In this randomized, controlled study of intermittent STI as a therapeutic autoimmunization strategy, evidence of enhanced immunologic control of HIV replication was demonstrated. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Context: Guidelines for antiretroviral therapy are important for clinicians worldwide given the complexity of the field and the varied clinical situations in which these agents are used. The International AIDS Society-USA panel has updated its recommendations as warranted by new developments in the field.Objective: To provide physicians and other human immunodeficiency virus (HIV) clinicians with current recommendations for the use of antiretroviral therapy in HIV-infected adults in circumstances for which there is relatively unrestricted access to drugs and monitoring tools. The recommendations are centered on 4 key issues: when to start antiretroviral therapy; what to start; when to change; and what to change. Antiretroviral therapy in special circumstances is also described.Data Sources and Study Selection: A 16-member noncompensated panel was appointed, based on expertise in HIV research and patient care internationally. Data published or presented at selected scientific conferences from mid 2004 through May 2006 were identified and reviewed by all members of the panel.Data Extraction and Synthesis: Data that might change previous guidelines were identified and reviewed. New guidelines were drafted by a writing committee and reviewed by the entire panel.Conclusions: Antiretroviral therapy in adults continues to evolve rapidly, making delivery of state-of-the-art care challenging. Initiation of therapy continues to be recommended in all symptomatic persons and in asymptomatic persons after the CD4 cell count falls below 350/microL and before it declines to 200/microL. A nonnucleoside reverse transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir each combined with 2 nucleoside (or nucleotide) reverse transcriptase inhibitors is recommended with choice being based on the individual patient profile. Therapy should be changed when toxicity or intolerance mandate it or when treatment failure is documented. The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL. Adherence to antiretroviral therapy in the short-term and the long-term is crucial for treatment success and must be continually reinforced. [ABSTRACT FROM AUTHOR]

Context: The Zambian Ministry of Health has scaled-up human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) care and treatment services at primary care clinics in Lusaka, using predominately nonphysician clinicians.Objective: To report on the feasibility and early outcomes of the program.Design, Setting, and Patients: Open cohort evaluation of antiretroviral-naive adults treated at 18 primary care facilities between April 26, 2004, and November 5, 2005. Data were entered in real time into an electronic patient tracking system.Intervention: Those meeting criteria for antiretroviral therapy (ART) received drugs according to Zambian national guidelines.Main Outcome Measures: Survival, regimen failure rates, and CD4 cell response.Results: We enrolled 21,755 adults into HIV care, and 16,198 (75%) started ART. Among those starting ART, 9864 (61%) were women. Of 15,866 patients with documented World Health Organization (WHO) staging, 11,573 (73%) were stage III or IV, and the mean (SD) entry CD4 cell count among the 15,336 patients with a baseline result was 143/microL (123/microL). Of 1142 patients receiving ART who died, 1120 had a reliable date of death. Of these patients, 792 (71%) died within 90 days of starting therapy (early mortality rate: 26 per 100 patient-years), and 328 (29%) died after 90 days (post-90-day mortality rate: 5.0 per 100 patient-years). In multivariable analysis, mortality was strongly associated with CD4 cell count between 50/microL and 199/microL (adjusted hazard ratio [AHR], 1.4; 95% confidence interval [CI], 1.0-2.0), CD4 cell count less than 50/microL (AHR, 2.2; 95% CI, 1.5-3.1), WHO stage III disease (AHR, 1.8; 95% CI, 1.3-2.4), WHO stage IV disease (AHR, 2.9; 95% CI, 2.0-4.3), low body mass index (<16; AHR,2.4; 95% CI, 1.8-3.2), severe anemia (<8.0 g/dL; AHR, 3.1; 95% CI, 2.3-4.0), and poor adherence to therapy (AHR, 2.9; 95% CI, 2.2-3.9). Of 11,714 patients at risk, 861 failed therapy by clinical criteria (rate, 13 per 100 patient-years). The mean (SD) CD4 cell count increase was 175/microL (174/microL) in 1361 of 1519 patients (90%) receiving treatment long enough to have a 12-month repeat.Conclusion: Massive scale-up of HIV and AIDS treatment services with good clinical outcomes is feasible in primary care settings in sub-Saharan Africa. Most mortality occurs early, suggesting that earlier diagnosis and treatment may improve outcomes. [ABSTRACT FROM AUTHOR]

To compare long-term virologic benefits of antiretroviral regimens in persons with advanced human immunodeficiency virus (HIV) disease, a randomized, open-label study was conducted of 517 subjects with no or limited previous experience with antiretroviral therapy. Subjects received lamivudine plus zidovudine and indinavir (indinavir group), efavirenz plus indinavir (efavirenz + indinavir group), or nelfinavir plus indinavir (nelfinavir + indinavir group) and were monitored for 2.1 years. Virologic failure was lower in the efavirenz + indinavir group (P=.04) and higher in the nelfinavir + indinavir group (P=.006), compared with that in the indinavir group. No difference in grade 3 or 4 adverse event rates in the efavirenz + indinavir group (P=.97) and a trend toward an increased rate in the nelfinavir + indinavir group (P=.07), compared with the indinavir group, were noted. A 4-drug regimen containing efavirenz plus indinavir resulted in a superior virologic response, whereas one containing nelfinavir plus indinavir resulted in an inferior response and a greater likelihood of toxicity. Copyright © 2003 The University of Chicago [ABSTRACT FROM AUTHOR]

Objective: To provide current recommendations for antiretroviral therapy for human immunodeficiency virus (HIV) disease.Participants: The original International AIDS Society-USA 13-member panel representing international expertise in antiretroviral research and care of patients with HIV infection.Evidence: The following were considered: Newly available clinical and basic science study results, including phase 3 controlled trials; clinical, virological, and immunologic end-point data; interim analyses of studies presented at national and international research conferences; studies of HIV pathophysiology; and expert opinions of panel members. Recommendations were limited to the drugs available in mid 1997.Process: The full panel met on a regular basis (July 1996, September 1996, November 1996, January 1997, and April 1997) since the publication of its initial recommendations in mid 1996 to review new research reports and interim results. The panel discussed whether and how new information changed its initial recommendations. The recommendations contained herein were determined by group consensus.Conclusions: New data have provided a stronger rationale for earlier initiation of more aggressive therapy than previously recommended and reinforce the importance of careful selection of initial drug regimen for each patient for optimal long-term clinical benefit and adherence. The plasma viral load is a crucial element of clinical management for assessing prognosis and the effectiveness of therapy, and such testing must be done properly. Treatment failure is most readily indicated by a rising plasma HIV RNA level and should be confirmed prior to a change of treatment. Therapeutic approaches must be updated as new data, particularly on the long-term clinical effect of aggressive antiretroviral treatment, continue to emerge. [ABSTRACT FROM AUTHOR]

Objective: To provide clinical recommendations for antiretroviral therapy for human immunodeficiency virus (HIV) disease with currently (mid 1996) available drugs. When to start therapy, what to start with, when to change, and what to change to were addressed.Participants: A 13-member panel representing international expertise in antiretroviral research and HIV patient care was selected by the international AIDS Society-USA.Evidence: Available clinical and basic science data, including phase 3 controlled trials, clinical endpoint data, virologic and immunologic endpoint data, interim analyses, studies of HIV pathophysiology, and expert opinions of panel members were considered. Recommendations were limited to drugs available in mid 1996.Process: For each question posed, 1 or more member(s) reviewed and presented available data. Recommendations were determined by group consensus (January 1996); revisions as warranted by new data were incorporated by group consensus (February-May 1996).Conclusions: Recent data on HIV pathogenesis, methods to determine plasma HIV RNA, clinical trial data, and availability of new drugs point to the need for new approaches to treatment. Therapy is recommended based on CD4+ cell count, plasma HIV RNA level, or clinical status. Preferred initial drug regimens include nucleoside combinations; at present protease inhibitors are probably best reserved for patients at higher progression risk. For treatment failure or drug intolerance, subsequent regimen considerations include reasons for changing therapy, available drug options, disease stage, underlying conditions, and concomitant medication(s). Therapy for primary (acute) infection, high-risk exposures to HIV, and maternal-to-fetal transmission are also addressed. Therapeutic approaches need to be updated as new data continue to emerge. [ABSTRACT FROM AUTHOR]

Objective: Falls are a significant public health concern, particularly among older adults and people with HIV (PWH). This study examines the association between alcohol consumption and falls in PWH., Methods: The PROSPER-HIV study recruited PWH from four US sites. Participants were categorized based on Alcohol Use Disorders Identification Test Consumption (AUDIT-C) scores: none, non-hazardous, and hazardous drinking. Data collection included demographics, medical history (i.e., comorbidities, treated hypertension, eGFR), alcohol consumption using AUDIT-C, daily alcohol recall in grams, and self-reported falls over the previous year. Physical performance was measured using the Short Performance Physical Battery (SPPB). Statistical analyses included Pearson's correlation and Poisson regression models to estimate fall prevalence ratios (PR), adjusting for confounders (SPPB, comorbidities, treated hypertension, and eGFR)., Results: The study included 315 PWH, aged 52 ± 12 years, with 78% male participants. Thirty-three percent were classified as non-drinking, 50% non-hazardous, and 17% hazardous drinking. Poisson regression showed a significantly higher risk of falls (PR: 2.12, 95% CI: 1.11-4.03) and recurrent falls (PR: 3.54, 95% CI: 1.21-10.3) among hazardous drinking compared to non-hazardous drinking, even after adjusting for confounders. The PR for falls per daily intake in grams was not statistically significant., Conclusions: There is a significant association between hazardous alcohol consumption and increased fall risk in PWH using AUDIT-C, but not when accessing recall of alcohol consumption in grams., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Smoking is a myocardial infarction (MI) risk factor among people with HIV (PWH). Questions persist regarding the role of smoking behaviors and measurements (e.g., intensity, duration) on MI risk. We used Cox proportional hazards regression to compare the association of smoking parameterization with incidents of type 1 and type 2 MI and whether smoking intensity or duration improves MI risk prediction among PWH. Among 11,637 PWH, 37% reported currently smoking, and there were 346 MIs. Current smoking was associated with type 1 (84% increased risk) but not type 2 MI in adjusted analyses. The type 1 MI model with pack years had the best goodness of fit compared with other smoking parameterizations. Ever or never parameterization and smoking diagnosis data had significantly poorer model fit. These results highlight the importance of differentiating MI types and performing patient-based smoking assessments to improve HIV care and research rather than relying on smoking status from diagnoses., (Copyright © 2024 Association of Nurses in AIDS Care.)

Substance use is associated with decreased antiretroviral therapy (ART) adherence among people with HIV (PWH). Adherence plays a significant role in mediating the negative effects of substance use on HIV suppression and is a principal modifiable patient-level factor in improving HIV suppression and reducing ART drug resistance. Understanding substance use and ART adherence, particularly with rapidly changing substance use epidemiology and ART regimens, is vital to improving HIV care. Among 10,557 PWH (2010-2021) from 8 academic clinical sites nationally we examined longitudinal associations of substance use severity and number of substances used (measured using AUDIT-C and modified ASSIST) with patient-reported ART adherence (visual analog scale). Alcohol (68% any use, 18% unhealthy use [AUDIT-C > 4 men, > 3 women]), marijuana (33%), and methamphetamine (9%) use were most reported. Polysubstance use was common (32%). Both higher severity substance use and higher number of substances used were associated with lower ART adherence. Severity of methamphetamine use had the strongest dose-response association with ART adherence (low severity [ASSIST 1-3]: -3.05%, 95% CI: -4.23%, -1.87%; moderate [ASSIST 4-26]: -6.20%, 95% CI: -7.08%, -5.33%; high [ASSIST > 26]: -10.77%, 95% CI: -12.76%, -8.78%). Severe substance use, especially methamphetamine, and higher number of illicit drugs used were associated with declines in adherence at levels that were likely clinically meaningful in the modern era of ART. Findings support integrating substance use care with HIV care and potential benefits of harm reduction strategies for improving adherence such as encouraging lower levels of substance use and fewer number of substances used., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Frailty occurs at higher rates and younger ages among people with HIV (PWH) compared to the general population and is often attributed to chronic inflammation and subsequent immune exhaustion. We assessed how inflammatory biomarkers are associated with frailty among PWH., Methods: The Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort is comprised of adult PWH in care at 10 sites, and harmonizes demographic, clinical, and patient-reported outcomes (PRO) data. A panel of 13 inflammatory biomarkers was collected from a subset of virally suppressed PWH once per person between 2010-2018. Frailty was measured with a validated PRO phenotype, scored 0-4, from biomarker collection date through July 2022. With adjusted linear mixed models, we estimated longitudinal associations between standard deviation-scaled log2-transformed biomarkers and frailty score., Results: Among 273 PWH, most were male (91%), average age at baseline was 45, 42% were non-Hispanic White while 35% were non-Hispanic Black, and average follow-up time was 5.5 years. Several biomarkers were associated with higher frailty, including those linked to microbial translocation (sCD14, LBP, KT ratio) and systemic inflammation (CRP, IL-6, suPAR, sTNFR1, sTNFR2). Higher IL-6 was associated with a 0.25-point higher frailty score (95%CI:0.12-0.39). Higher sTNFR1 (0.35 [0.13-0.56]), sCD14 (0.21 [0.11-0.31]), and suPAR (0.24 [0.11-0.36]) levels were also associated with higher frailty scores over follow-up., Conclusions: Higher levels of biomarkers linked to microbial translocation and systemic inflammation are associated with higher average frailty scores over time in a cohort of virally suppressed PWH, highlighting these pathways as potential interventional targets for mitigating frailty in PWH., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Since its global reemergence in 2022, monkeypox (mpox) has demonstrated increased incidence and severity among people with human immunodeficiency virus (HIV [PWH]). Predictors of mpox diagnosis, vaccination, and outcomes among PWH are limited., Methods: We included PWH with primary care visits after 1 January 2022 at 9 US sites participating in the Centers for AIDS Research Network of Integrated Clinic Systems Network. We identified mpox diagnosed between 1 June 2022 and 31 May 2023, through a combination of polymerase chain reaction result, diagnosis code, and/or tecovirimat receipt. We examined validated clinical diagnoses, laboratory results, vaccine data, and patient reported outcomes. We evaluated relative risks (RR) of mpox diagnosis, hospitalization, tecovirimat treatment, and vaccine receipt., Findings: Among 19 777 PWH in care, 413 mpox cases (all male sex at birth) occurred (2.2 cases/100 person-years). Age <40 years, geographic region, Hispanic/Latine ethnicity, lack of antiretroviral therapy, detectable HIV viral load, and recent bacterial sexually transmitted infection predicted mpox diagnosis. PWH with CD4 200-349 cells/mm3 were most likely to be hospitalized (adjusted RR, 3.20; 95% confidence interval: 1.44-7.09) compared to CD4 ≥500, but half as likely as those with CD4 <200 to receive tecovirimat. Overall, smallpox/mpox vaccine effectiveness of ≥1 vaccine was 71% (adjusted RR, 0.29; 95% confidence interval: .14-.47) at preventing mpox, and 86% or better with CD4 ≥350 or HIV viral suppression. Non-Hispanic Black PWH were less likely to be vaccinated than other racial/ethnic identities., Interpretation: PWH not on antiretroviral therapy or with unsuppressed HIV were more likely to be diagnosed with, and hospitalized for, mpox. Mpox/smallpox vaccine effectiveness was high, inclusive of those with low CD4 count and HIV viremia., Competing Interests: Potential conflicts of interest. A. E. S. received funding from Merck as a clinical trial investigator for unrelated work. K. A. C. has been a medical advisory board member for Gilead Sciences and a workshop participant for Janssen outside of this work. R. B. I. is on a Scientific Advisory Board for AbbVie and received research funding from Enanta Pharmaceutics and Ascentage Pharma through her institution, unrelated to this work. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Low food security is common among people with HIV (PWH) and is associated with poorer health outcomes. Frailty, an aging-related outcome that is increasingly prevalent among PWH, may be stimulated by low food security. We assessed associations between food security and frailty among PWH., Methods: The Impact of Physical Activity Routines and Dietary Intake on the Longitudinal Symptom Experience of People Living with HIV (PROSPER-HIV) study follows PWH to evaluate how diet and physical activity impact symptoms. We utilized food security and frailty data from PROSPER-HIV Year 1 visits (January 2019 to July 2022) to estimate associations. Food security was measured via the validated two-item Food Security Questionnaire and categorized as Food Secure, Low Food Security, or Very Low Food Security. Frailty was measured with the Fried frailty phenotype, and categorized as robust, prefrail, and frail. We used relative risk regression to estimate associations between food security and frailty status, adjusted for demographic characteristics., Results: Among 574 PWH, nearly one-quarter were women (22%), mean age was 52 years old, 8% were frail, and 46% prefrail. Low food security was reported among nearly one-third of PWH: 13% Low Food Security and 18% Very Low Food Security. Compared with being Food Secure, we found Low Food Security was associated with frailty [prevalence ratio: 4.06 (95% confidence interval (CI) 2.16-7.62] and Very Low Food Security was associated with both prefrailty [1.48 (1.23-1.78)] and frailty [5.61 (3.14-10.0)], as compared with robust status., Conclusion: Low food security was associated with increased frailty among PWH in this study, suggesting a potential intervention point to promote healthy aging., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: Although stroke risk associated with HIV may be greater for women than men, little is known about whether the impact of different factors on cerebrovascular risk varies by sex in people with HIV (PWH) and contributes to stroke risk disparities in this population. The primary objective of this study was to examine whether sex modifies the effect of demographics, cardiometabolic factors, health-related behaviors, and HIV-specific variables on stroke risk in PWH from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort., Methods: In this observational cohort study, we analyzed data from clinical encounters for PWH followed at 5 CNICS sites from approximately 2005 to 2020. All potential stroke events were adjudicated by neurologists. Patient-reported outcomes collected at clinic visits, including substance use and depression, were also available. We used Cox proportional hazards models to determine whether sex modified the association of predictors of interest with incident stroke., Results: Among 13,573 PWH (19% female sex at birth, mean age 44 years, mean follow-up 5.6 years), female sex was associated with a higher risk of stroke only among individuals aged 50 years or younger (hazard ratio [HR] 2.01 at age 40 [1.25-3.21] vs HR 0.60 at age 60 [0.34-1.06]; p = 0.001 for the interaction). Younger female participants who developed a stroke were more likely to have treated hypertension, a higher cardiovascular risk score, and detectable HIV than younger male participants whereas these factors were comparable by sex among older participants who developed a stroke. Sex modified the effect of detectable HIV (HR 4.66 for female participants [2.48-8.74] vs HR 1.30 for male participants [0.83-2.03]; p = 0.001 for the interaction), methamphetamine use (HR 4.78 for female participants [1.47-15.56] vs HR 1.19 for male participants [0.62-2.29]; p = 0.04 for the interaction), and treated hypertension (HR 3.44 for female participants [1.74-6.81] vs HR 1.66 for male participants [1.14-2.41]; p = 0.06 for the interaction) on stroke risk., Discussion: Younger female participants with HIV were at elevated cerebrovascular risk compared with younger male participants. Several risk factors had a greater adverse effect on stroke risk in female participants than in male participants, including HIV viremia, methamphetamine use, and treated hypertension. These findings underscore the importance of a personalized approach to predict and prevent cerebrovascular risk among PWH.

Background: Few studies have examined which subgroups of people with HIV (PWH) carry the greatest burden of internalized HIV stigma (IHS), which may be important to care provision and interventions., Methods: PWH in the CFAR Network of Integrated Clinical Systems (CNICS) longitudinal, US-based, multisite, clinical care cohort completed tablet-based assessments during clinic visits including a four-item, Likert scale (low 1-5 high), IHS instrument. Associations between sociodemographic characteristics and IHS scores were assessed in adjusted linear regression models., Results: Twelve thousand six hundred and fifty-six PWH completed the IHS assessment at least once from February 2016 to November 2022, providing 28 559 IHS assessments. At baseline IHS assessment, the mean age was 49 years, 41% reported White, 38% Black/African American, and 16% Latine race/ethnicity, and 80% were cisgender men. The mean IHS score was 2.04, with all subgroups represented among those endorsing IHS. In regression analyses, younger PWH and those in care fewer years had higher IHS scores. In addition, cisgender women vs. cisgender men, PWH residing in the West vs. the Southeast, and those with sexual identities other than gay/lesbian had higher IHS scores. Compared with White-identifying PWH, those who identified with Black/African American or Latine race/ethnicity had lower IHS scores. Age stratification revealed patterns related to age category, including specific age-related differences by gender, geographic region and race/ethnicity., Discussion: IHS is prevalent among PWH, with differential burden by subgroups of PWH. These findings highlight the benefits of routine screening for IHS and suggest the need for targeting/tailoring interventions to reduce IHS among PWH., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Substance use in people with HIV (PWH) negatively impacts antiretroviral therapy (ART) adherence. However, less is known about this in the current treatment era and the impact of specific substances or severity of substance use. We examined the associations of alcohol, marijuana, and illicit drug use (methamphetamine/crystal, cocaine/crack, illicit opioids/heroin) and their severity of use with adherence using multivariable linear regression in adult PWH in care between 2016 and 2020 at 8 sites across the US. PWH completed assessments of alcohol use severity (AUDIT-C), drug use severity (modified ASSIST), and ART adherence (visual analogue scale). Among 9400 PWH, 16% reported current hazardous alcohol use, 31% current marijuana use, and 15% current use of ≥1 illicit drugs. In multivariable analysis, current methamphetamine/crystal use, particularly common among men who had sex with men, was associated with 10.1% lower mean ART adherence ( p  < 0.001) and 2.6% lower adherence per 5-point higher severity of use (ASSIST score) ( p  < 0.001). Current and more severe use of alcohol, marijuana, and other illicit drugs were also associated with lower adherence in a dose-dependent manner. In the current HIV treatment era, individualized substance use treatment, especially for methamphetamine/crystal, and ART adherence should be prioritized.

Objective: There is limited real-world evidence about the effectiveness of semaglutide for weight loss among people with HIV (PWH). We aimed to investigate weight change in a US cohort of PWH who initiated semaglutide treatment., Design: Observational study using the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort., Methods: We identified adult PWH who initiated semaglutide between 2018 and 2022 and with at least two weight measurements. The primary outcome was within-person bodyweight change in kilograms at 1 year. The secondary outcome was within-person Hemoglobin A1c percentage (HbA1c) change. Both outcomes were estimated using multivariable linear mixed model., Results: In total, 222 new users of semaglutide met inclusion criteria. Mean follow-up was 1.1 years. Approximately 75% of new semaglutide users were men, and at baseline, mean age was 53 years [standard deviation (SD): 10], average weight was 108 kg (SD: 23), mean BMI was 35.5 kg/m 2 , mean HbA1c was 7.7% and 77% had clinically recognized diabetes. At baseline, 97% were on ART and 89% were virally suppressed (viral load < 50 copies/ml). In the adjusted mixed model analysis, treatment with semaglutide was associated with an average weight loss of 6.47 kg at 1 year (95% CI -7.67 to -5.18) and with a reduction in HbA1c of 1.07% at 1 year (95% CI -1.64 to -0.50) among the 157 PWH with a postindex HbA1c value., Conclusion: Semaglutide was associated with significant weight loss and HbA1c reduction among PWH, comparable to results of previous studies from the general population., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: People with HIV (PWH) are at increased risk for venous thromboembolism (VTE). We conducted this study to characterize VTE including provoking factors among PWH in the current treatment era., Methods: We included PWH with VTE between 2010 and 2020 at 6 sites in the CFAR Network of Integrated Clinical Systems cohort. We ascertained for possible VTE using diagnosis, VTE-related imaging, and VTE-related procedure codes, followed by centralized adjudication of primary data by expert physician reviewers. We evaluated sensitivity and positive predictive value of VTE ascertainment approaches. VTEs were classified by type and anatomic location. Reviewers identified provoking factors such as hospitalizations, infections, and other potential predisposing factors such as smoking., Results: We identified 557 PWH with adjudicated VTE: 239 (43%) had pulmonary embolism with or without deep venous thrombosis, and 318 (57%) had deep venous thrombosis alone. Ascertainment with clinical diagnoses alone missed 6% of VTEs identified with multiple ascertainment approaches. DVTs not associated with intravenous lines were most often in the proximal lower extremities. Among PWH with VTE, common provoking factors included recent hospitalization (n = 134, 42%), infection (n = 133, 42%), and immobilization/bed rest (n = 78, 25%). Only 57 (10%) PWH had no provoking factor identified. Smoking (46%), HIV viremia (27%), and injection drug use (22%) were also common., Conclusions: We conducted a robust adjudication process that demonstrated the benefits of multiple ascertainment approaches followed by adjudication. Provoked VTEs were more common than unprovoked events. Nontraditional and modifiable potential predisposing factors such as viremia and smoking were common., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: "Sick quitting," a phenomenon describing reductions in alcohol consumption following poor health, may explain observations that alcohol appears protective for frailty risk. We examined associations between frailty and reductions in drinking frequency among people with HIV (PWH). At six Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites between January 2012 and August 2021, we assessed whether frailty, measured through validated modified frailty phenotype, precedes reductions in drinking frequency. We associated time-updated frailty with quitting and reducing frequency of any drinking and heavy episodic drinking (HED), adjusted for demographic and clinical characteristics in Cox models. Among 5,654 PWH reporting drinking, 60% reported >monthly drinking and 18% reported ≥monthly HED. Over an average of 5.4 years, frail PWH had greater probabilities of quitting (HR: 1.56, 95% confidence interval [95% CI] [1.13-2.15]) and reducing (HR: 1.35, 95% CI [1.13-1.62]) drinking frequency, as well as reducing HED frequency (HR: 1.58, 95% CI [1.20-2.09]) versus robust PWH. Sick quitting likely confounds the association between alcohol use and frailty risk, requiring investigation for control., (Copyright © 2024 Association of Nurses in AIDS Care.)

Background: The prevalence of substance use in people with HIV (PWH) in the United States is higher than in the general population and is an important driver of HIV-related outcomes. We sought to assess if previously identified genetic associations that contribute to substance use are also observed in a population of PWH., Methods: We performed genome-wide association studies (GWAS) of alcohol, smoking, and cannabis use phenotypes in a multi-ancestry population of 7,542 PWH from the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). We conducted multi-ancestry GWAS for individuals of African (n = 3,748), Admixed American (n = 1,334), and European (n = 2,460) ancestry. Phenotype data were self-reported and collected using patient reported outcomes (PROs) and three questions from AUDIT-C, an alcohol screening tool. We analyzed nine phenotypes: 1) frequency of alcohol consumption, 2) typical number of drinks on a day when drinking alcohol, 3) frequency of five or more alcoholic drinks in a 30-day period, 4) smoking initiation, 5) smoking cessation, 6) cigarettes per day, 7) cannabis use initiation, 8) cannabis use cessation, 9) frequency of cannabis use during the previous 30 days. For each phenotype we considered a) variants previously identified as associated with a substance use trait and b) novel associations., Results: We observed evidence for effects of previously reported single nucleotide polymorphisms (SNPs) related to alcohol (rs1229984, p = 0.001), tobacco (rs11783093, p = 2.22E-4), and cannabis use (rs2875907, p = 0.005). We also report two novel loci (19p13.2, p = 1.3E-8; and 20p11.21, p = 2.1E-8) associated with cannabis use cessation., Conclusions: Our analyses contribute to understanding the genetic bases of substance use in a population with relatively higher rates of use compared to the general population., Competing Interests: KMJ was employed by Bristol-Myers Squibb during the drafting of this manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors report no conflicts of interest to disclose., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Objective: To evaluate the association between medication for opioid use disorder (MOUD) initiation and addiction consultation and outcomes for patients hospitalized with infectious complications of injecting opioids., Method: This was a retrospective cohort study performed at four academic medical centers in the United States. The participants were patients who had been hospitalized with infectious complications of injecting opioids in 2018. Three hundred and twenty-two patients were included and their individual patient records were manually reviewed to identify inpatient receipt of medication for opioid use disorder (MOUD), initiation of MOUD, and addiction consultation. The main outcomes of interest were premature discharge, MOUD on discharge, linkage to outpatient MOUD, one-year readmission and death., Results: Three hundred and twenty-two patients were predominately male (59%), white (66%), and median age 38 years, with 36% unstably housed, and 30% uninsured. One hundred and forty-five (45%) patients received MOUD during hospitalization, including only 65 (28%) patients not on baseline MOUD. Discharge was premature for 64 (20%) patients. In the year following discharge, 27 (9%) patients were linked to MOUD, and 159 (50%) patients had at least one readmission. Being on MOUD during hospitalization was significantly associated with higher odds of planned discharge [odds ratio (OR) 3.87, P  < 0.0001], MOUD on discharge (OR 129.7, P  < 0.0001), and linkage to outpatient MOUD (OR 1.25, P  < 0.0001), however, was not associated with readmission. Study limitations were the retrospective nature of the study, so post-discharge data are likely underestimated., Conclusion: There was dramatic undertreatment with MOUD from inpatient admission to outpatient linkage, and high rates of premature discharge and readmission. Engagement in addiction care during hospitalization is a critical first step in improving the care continuum for individuals with opioid use disorder; however, additional interventions may be needed to impact long-term outcomes like readmission.

Background: Tobacco smoking increases frailty risk among the general population and is common among people with HIV (PWH) who experience higher rates of frailty at younger ages than the general population., Methods: We identified 8608 PWH across 6 Centers for AIDS Research Network of Integrated Clinical Systems sites who completed ≥2 patient-reported outcome assessments, including a frailty phenotype measuring unintentional weight loss, poor mobility, fatigue, and inactivity, and scored 0-4. Smoking was measured as baseline pack-years and time-updated never, former, or current use with cigarettes/day. We used Cox models to associate smoking with risk of incident frailty (score ≥3) and deterioration (frailty score increase by ≥2 points), adjusted for demographics, antiretroviral medication, and time-updated CD4 count., Results: The mean follow-up of PWH was 5.3 years (median: 5.0), the mean age at baseline was 45 years, 15% were female, and 52% were non-White. At baseline, 60% reported current or former smoking. Current (HR: 1.79; 95% confidence interval: 1.54 to 2.08) and former (HR: 1.31; 95% confidence interval: 1.12 to 1.53) smoking were associated with higher incident frailty risk, as were higher pack-years. Current smoking (among younger PWH) and pack-years, but not former smoking, were associated with higher risk of deterioration., Conclusions: Among PWH, smoking status and duration are associated with incident and worsening frailty., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Plasma vascular endothelial growth factor (VEGF) coreceptor neuropilin-1 (NRP-1) had the largest association with coronary plaque in the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) proteomics analysis. With little known about NRP-1 in people with human immunodeficiency virus (PWH), we explored its relation to other proteins in REPRIEVE and validated our findings through a Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) case-cohort study by assessing its relation to host factors and incident cardiovascular disease and cancer. Within REPRIEVE, NRP-1 was associated with proteins involved in angiogenesis, signal transduction, immunoregulation, and cell migration/adhesion. Within CNICS, NRP-1 was associated with key host factors, including older age and male sex. NRP-1 was associated with an increased hazard of multiple cancers but a decreased prostate cancer risk. Finally, NRP-1 was most strongly associated with mortality and type 2 myocardial infarction. These data suggest that NRP-1 is part of a clinically relevant immunoregulatory pathway related to multiple comorbidities in PWH. Clinical Trials Registration . NCT02344290., Competing Interests: Potential conflicts of interest. S. R. S. reports grant support through his institution from NIH/NIAID. M. V. Z. reports grant support through her institution from NIH/NIAID and Gilead Sciences, relevant to the conduct of the study, and grants from NIH/NIAID and NIH/NHLBI, outside the submitted work. M. T. reports grant support from NIH/NHLBI, American Heart Association, and Robert Wood Johnson Foundation, outside the submitted work. C. J. F. reports grant support through his institution from Gilead Sciences, ViiV Healthcare, GSK, Janssen, AbbVie, Merck, Amgen, and Cytodyn, outside the submitted work. J. J. E. reports grant support through his institution from Gilead Sciences, ViiV Healthcare, and Janssen and personal fees from ViiV Healthcare, Merck, and Gilead Sciences, outside the submitted work. J. M. J. reports grant support through his institution from NIH/NIAID. K. H. M. reports unrestricted research grants to his institution from Gilead Sciences, Merck, and ViiV Healthcare and has served on scientific advisory boards for Gilead and Merck, outside the submitted work. C. M. reports institutional research support by Lilly and honoraria from ViiV Healthcare and Gilead Sciences for advisory board membership, outside the submitted work. R. D. M. reports grant support to his institution from NIH/NIAID and NIH/National Institute on Drug Abuse (NIDA) relevant to the conduct of the study. T. U. reports grant support from NIH/NHLBI and Kowa Pharmaceuticals during the conduct of the study and grants from NIH/NIAID and NIH/National Institute on Aging (NIA), outside the submitted work. M. S. S. reports grant support from NIH/NIAID relevant to the conduct of the study. J. A. A. reports institutional research support for clinical trials from Emergent Biosolutions, Frontier Technologies, Gilead Sciences, GlaxoSmithKline, Janssen, Macrogenics, Merck, Pfizer, Regeneron, and ViiV Healthcare; personal fees for advisory boards from GlaxoSmithKline and Merck; and data and safety monitoring board membership for Kintor Pharmaceuticals, outside the submitted work. J. S. C. reports consulting fees from Merck and Co and Resvirlogix. J. A. C. D. reports through to his institution from NIH/NHLBI, outside the submitted work. H. J. R. reports grants from NIH/NIAID and NIH/NHLBI during the conduct of the study, as well as grants from NIH/NIAID, NIH/NHLBI, NIH/National Institute of Diabetes and Digestive and Kidney Diseases, and NIH/NIA, outside the submitted work. H. M. C. reports grants from NIH/NHLBI during the conduct of this study; grants through her institution from NIH/NIDA, the Agency for Healthcare Research and Quality, and ViiV Healthcare; and advisory board membership for Gilead, outside the submitted work. P. W. H. reports grant support through his institution from Gilead Sciences; drug donation for an NIH-sponsored clinical trial he is leading from Merck; and personal fees from ViiV Healthcare, Gilead Sciences, and Merck. S. K. G. reports grant support through his institution from Kowa Pharmaceuticals America, Gilead Sciences, and ViiV Healthcare for the conduct of the study; and grants from Theratechnologies and Navidea, personal fees from Theratechnologies and ViiV, and service on the scientific advisory board of Marathon Asset Management, all outside the submitted work. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: People with human immunodeficiency virus (HIV) infection (PWH) are at higher risk of myocardial infarction (MI) than those without HIV. About half of MIs in PWH are type 2 (T2MI), resulting from mismatch between myocardial oxygen supply and demand, in contrast to type 1 MI (T1MI), which is due to primary plaque rupture or coronary thrombosis. Despite worse survival and rising incidence in the general population, evidence-based treatment recommendations for T2MI are lacking. We used polygenic risk scores (PRS) to explore genetic mechanisms of T2MI compared to T1MI in PWH., Methods: We derived 115 PRS for MI-related traits in 9541 PWH enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems cohort with adjudicated T1MI and T2MI. We applied multivariate logistic regression analyses to determine the association with T1MI and T2MI. Based on initial findings, we performed gene set enrichment analysis of the top variants composing PRS associated with T2MI., Results: We found that T1MI was strongly associated with PRS for cardiovascular disease, lipid profiles, and metabolic traits. In contrast, PRS for alcohol dependence and cholecystitis, significantly enriched in energy metabolism pathways, were predictive of T2MI risk. The association remained after the adjustment for actual alcohol consumption., Conclusions: We demonstrate distinct genetic traits associated with T1MI and T2MI among PWH further highlighting their etiological differences and supporting the role of energy regulation in T2MI pathogenesis., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Randomized controlled trials (RCTs) from low- and middle-income settings suggested that early initiation of antiretroviral therapy (ART) leads to higher mortality rates among people with HIV (PWH) who present with cryptococcal meningitis (CM). There is limited information about the impact of ART timing on mortality rates in similar people in high-income settings., Methods: Data on ART-naive PWH with CM diagnosed from 1994 to 2012 from Europe/North America were pooled from the COHERE, NA-ACCORD, and CNICS HIV cohort collaborations. Follow-up was considered to span from the date of CM diagnosis to earliest of the following: death, last follow-up, or 6 months. We used marginal structural models to mimic an RCT comparing the effects of early (within 14 days of CM) and late (14-56 days after CM) ART on all-cause mortality, adjusting for potential confounders., Results: Of 190 participants identified, 33 (17%) died within 6 months. At CM diagnosis, their median age (interquartile range) was 38 (33-44) years; the median CD4+ T-cell count, 19/μL (10-56/μL); and median HIV viral load, 5.3 (4.9-5.6) log10 copies/mL. Most participants (n = 157 [83%]) were male, and 145 (76%) started ART. Mimicking an RCT, with 190 people in each group, there were 13 deaths among participants with an early ART regimen and 20 deaths among those with a late ART regimen. The crude and adjusted hazard ratios comparing late with early ART were 1.28 (95% confidence interval, .64-2.56) and 1.40 (.66-2.95), respectively., Conclusions: We found little evidence that early ART was associated with higher mortality rates among PWH presenting with CM in high-income settings, although confidence intervals were wide., Competing Interests: Potential conflicts of interest. J. M. M. has received consulting honoraria and/or research grants from AbbVie, Angelini, Contrafect, Cubist, Genentech, Gilead Sciences, Jansen, Medtronic, MSD, Novartis, Pfizer, and ViiV Healthcare, outside the submitted work, as well as consulting fees from Lysovant. L. E. C. has stock or stock options and is an employee of AbbVie. C. Sabin reports payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, or educational events from Gilead Sciences and ViiV Healthcare (payments to the author for preparation of educational materials); participation on a data and safety monitoring board (DSMB) or advisory board for Gilead Sciences and ViiV Healthcare (paid to the author); and service as vice chair of the British HIV Association. H. S. reports consulting fees from ViiV and MSD and payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing or educational events from MSD, ViiV, and Gilead. P. R., through his institution, has received independent scientific grant support from Gilead Sciences, Janssen Pharmaceuticals, Merck, and ViiV Healthcare and has served on scientific advisory boards for Gilead Sciences, ViiV Healthcare, and Merck, honoraria for which were all paid to his institution (all support outside the submitted work). V. B. reports support for attending meetings and/or travel from Gilead and Janssen and has stock or stock options in DWS Biotech LC Fond (private self-investment; no payments to author or institution received from any third party). F. V. received research or teaching grants from Gilead Sciences, ViiV Healthcare, and MSD, unrelated to the submitted work. N. O. reports grants or contracts from Simonsens Fond (paid to the institution). A. M. reports travel support, lecture fees, honorarium and consultancy fees from ViiV, Gilead, Eiland, and Bonnin, all outside the submitted work. L. W. reports grants or contracts from ANRS MIE. R. T. reports a research grant from Gilead Science; payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, or educational events from Gilead Science (payment for lectures), Janssen (payment for lectures), and ViiV Healthcare (payment for lectures); support for travel from Gilead Science and Janssen; and participation on an advisory board for Gilead Science. A. D. M. reports consulting fees from ViiV, Gilead, and Janssen (paid to the author); payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing or educational events from Gilead and ViiV (paid to the author); and participation on a DSMB or advisory board for Janssen, Gilead, and ViiV (payment to the author). C. M. reports research grant from Gilead; payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, or educational events from ViiV and Gilead; and participation on a DSMB or advisory board for Corimuno, Gilead, ViiV, Janssen, and MSD. H. F.’s institution received educational grants from AbbVie, ViiV, Gilead, MSD, Sandoz, and Pfizer, all outside the submitted work. M. S. S. reports research grants from Gilead Sciences and ViiV Healthcare (paid to the institution); payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing; or educational events from IAS-USA (not-for-profit organization); serving on the DSMB for the I-Spy COVID trial; and serving as board chair for IAS-USA. H. M. C. reports grants or contracts from the National Institutes of Health (NIH), the Agency for Healthcare Research and Quality, and ViiV (paid to institution); consulting fees from ViiV (pending); and participation on the Office of AIDS Research Scientific Advisory Board. J. J. E. reports grants or contracts from ViiV Healthcare, Gilead Sciences, and Janssen; consulting fees from Merck, ViiV Healthcare, Gilead Science, and Janssen; and leadership or fiduciary roles in other boards, societies, committees, or advocacy groups for the IAS-USA antiretroviral therapy guidelines committee. K. N. A. reports grants or contracts from the NIH (paid to institution), royalties or licenses from Coursera, consulting fees from the NIH (for the All of US Study), and payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, or educational events for DC HIV Cohort (author served on the DC HIV Cohort’s external advisory board). M. J. G. reports consulting fees from Merck, Gilead, and ViiV (with occasional honoraria for ad hoc membership on human immunodeficiency virus advisory boards). H. C. B., in the 36 months before the submission of the current manuscript, has received grants, support for traveling, consultancy fees, and honoraria from Gilead, BMS, ViiV Healthcare, Roche, and Pfizer, unrelated to the current work. He served as the president of the Association Contre le HIV et Autres Infections Transmissibles until June 2022; in this function he received support for the Swiss HIV Cohort Study from ViiV Healthcare, Gilead, BMS, and MSD. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: People with HIV have a higher risk of myocardial infarction (MI) than the general population, with a greater proportion of type 2 MI (T2MI) due to oxygen demand-supply mismatch compared with type 1 (T1MI) resulting from atherothrombotic plaque disruption. People living with HIV report a greater prevalence of cigarette and alcohol use than do the general population. Alcohol use and smoking as risk factors for MI by type are not well studied among people living with HIV. We examined longitudinal associations between smoking and alcohol use patterns and MI by type among people living with HIV., Design and Methods: Using longitudinal data from the Centers for AIDS Research Network of Integrated Clinical Systems cohort, we conducted time-updated Cox proportional hazards models to determine the impact of smoking and alcohol consumption on adjudicated T1MI and T2MI., Results: Among 13 506 people living with HIV, with a median 4 years of follow-up, we observed 177 T1MI and 141 T2MI. Current smoking was associated with a 60% increase in risk of both T1MI and T2MI. In addition, every cigarette smoked per day was associated with a 4% increase in risk of T1MI, with a suggestive, but not significant, 2% increase for T2MI. Cigarette use had a greater impact on T1MI for men than for women and on T2MI for women than for men. Increasing alcohol use was associated with a lower risk of T1MI but not T2MI. Frequency of heavy episodic alcohol use was not associated with MI., Conclusions: Our findings reinforce the prioritization of smoking reduction, even without cessation, and cessation among people living with HIV for MI prevention and highlight the different impacts on MI type by gender., (© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Objective: Frailty is common among people with HIV (PWH), so we developed frail risk in the short-term for care (RISC)-HIV, a frailty prediction risk score for HIV clinical decision-making., Design: We followed PWH for up to 2 years to identify short-term predictors of becoming frail., Methods: We predicted frailty risk among PWH at seven HIV clinics across the United States. A modified self-reported Fried Phenotype captured frailty, including fatigue, weight loss, inactivity, and poor mobility. PWH without frailty were separated into training and validation sets and followed until becoming frail or 2 years. Bayesian Model Averaging (BMA) and five-fold-cross-validation Lasso regression selected predictors of frailty. Predictors were selected by BMA if they had a greater than 45% probability of being in the best model and by Lasso if they minimized mean squared error. We included age, sex, and variables selected by both BMA and Lasso in Frail RISC-HIV by associating incident frailty with each selected variable in Cox models. Frail RISC-HIV performance was assessed in the validation set by Harrell's C and lift plots., Results: Among 3170 PWH (training set), 7% developed frailty, whereas among 1510 PWH (validation set), 12% developed frailty. BMA and Lasso selected baseline frailty score, prescribed antidepressants, prescribed antiretroviral therapy, depressive symptomology, and current marijuana and illicit opioid use. Discrimination was acceptable in the validation set, with Harrell's C of 0.76 (95% confidence interval: 0.73-0.79) and sensitivity of 80% and specificity of 61% at a 5% frailty risk cutoff., Conclusions: Frail RISC-HIV is a simple, easily implemented tool to assist in classifying PWH at risk for frailty in clinics., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The relationship between chronic obstructive pulmonary disease (COPD) and cardiovascular disease in people with HIV (PWH) is incompletely understood. We determined whether COPD is associated with risk of myocardial infarction (MI) among PWH, and if this differs for type 1 (T1MI) and type 2 (T2MI)., Design: We utilized data from five sites in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort, a multisite observational study., Methods: Our primary outcome was an adjudicated MI, classified as T1MI or T2MI. We defined COPD based on a validated algorithm requiring COPD diagnosis codes and at least 90-day continuous supply of inhalers. We conducted time-to-event analyses to first MI and used multivariable Cox proportional hazards models to measure associations between COPD and MI., Results: Among 12 046 PWH, 945 had COPD. Overall, 309 PWH had an MI: 58% had T1MI ( N  = 178) and 42% T2MI ( N  = 131). In adjusted models, COPD was associated with a significantly increased risk of all MI [adjusted hazard ratio (aHR) 2.68 (95% confidence interval (CI) 1.99-3.60)] even after including self-reported smoking [aHR 2.40 (95% CI 1.76-3.26)]. COPD was also associated with significantly increased risk of T1MI and T2MI individually, and with sepsis and non-sepsis causes of T2MI. Associations were generally minimally changed adjusting for substance use., Conclusion: COPD is associated with a substantially increased risk for MI, including both T1MI and T2MI, among PWH. Given the association with both T1MI and T2MI, diverse mechanistic pathways are involved. Future strategies to decrease risk of T1MI and T2MI in PWH who have COPD are needed., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Modifications to Fried's frailty phenotype (FFP) are common. We evaluated a self-reported modified frailty phenotype (Mod-FP) used among people with HIV (PWH). Among 522 PWH engaged in two longitudinal studies, we assessed validity of the four-item Mod-FP compared with the five-item FFP. We compared the phenotypes via receiver operator characteristic curves, agreement in classifying frailty, and criterion validity via association with having experienced falls. Mod-FP classified 8% of PWH as frail, whereas FFP classified 9%. The area under the receiver operator characteristic curve for Mod-FP classifying frailty was 0.93 (95% CI = 0.91-0.96). We observed kappa ranging from 0.64 (unweighted) to 0.75 (weighted) for categorizing frailty status. Both definitions found frailty associated with a greater odds of experiencing a fall; FFP estimated a slightly greater magnitude (i.e., OR) for the association than Mod-FP. The Mod-FP has good performance in measuring frailty among PWH and is reasonable to use when the gold standards of observed assessments (i.e., weakness and slowness) are not feasible., (Copyright © 2023 Association of Nurses in AIDS Care.)

Importance: Recent advances in treatment and prevention of HIV warrant updated recommendations to guide optimal practice., Objective: Based on a critical evaluation of new data, to provide clinicians with recommendations on use of antiretroviral drugs for the treatment and prevention of HIV, laboratory monitoring, care of people aging with HIV, substance use disorder and HIV, and new challenges in people with HIV, including COVID-19 and monkeypox virus infection., Evidence Review: A panel of volunteer expert physician scientists were appointed to update the 2020 consensus recommendations. Relevant evidence in the literature (PubMed and Embase searches, which initially yielded 7891 unique citations, of which 834 were considered relevant) and studies presented at peer-reviewed scientific conferences between January 2020 and October 2022 were considered., Findings: Initiation of antiretroviral therapy (ART) is recommended as soon as possible after diagnosis of HIV. Barriers to care should be addressed, including ensuring access to ART and adherence support. Integrase strand transfer inhibitor-containing regimens remain the mainstay of initial therapy. For people who have achieved viral suppression with a daily oral regimen, long-acting injectable therapy with cabotegravir plus rilpivirine given as infrequently as every 2 months is now an option. Weight gain and metabolic complications have been linked to certain antiretroviral medications; novel strategies to ameliorate these complications are needed. Management of comorbidities throughout the life span is increasingly important, because people with HIV are living longer and confronting the health challenges of aging. In addition, management of substance use disorder in people with HIV requires an evidence-based, integrated approach. Options for preexposure prophylaxis include oral medications (tenofovir disoproxil fumarate or tenofovir alafenamide plus emtricitabine) and, for the first time, a long-acting injectable agent, cabotegravir. Recent global health emergencies, like the SARS-CoV-2 pandemic and monkeypox virus outbreak, continue to have a major effect on people with HIV and the delivery of services. To address these and other challenges, an equity-based approach is essential., Conclusions and Relevance: Advances in treatment and prevention of HIV continue to improve outcomes, but challenges and opportunities remain.

Objective: To examine associations between frailty and drug, alcohol, and tobacco use among a large diverse cohort of people with HIV (PWH) in clinical care in the current era., Methods: PWH at 7 sites across the United States completed clinical assessments of patient-reported measures and outcomes between 2016 and 2019 as part of routine care including drug and alcohol use, smoking, and other domains. Frailty was assessed using 4 of the 5 components of the Fried frailty phenotype and PWH were categorized as not frail, pre-frail, or frail. Associations of substance use with frailty were assessed with multivariate Poisson regression., Results: Among 9336 PWH, 43% were not frail, 44% were prefrail, and 13% were frail. Frailty was more prevalent among women, older PWH, and those reporting current use of drugs or cigarettes. Current methamphetamine use (1.26: 95% CI 1.07-1.48), current (1.65: 95% CI 1.39-1.97) and former (1.21:95% CI 1.06-1.36) illicit opioid use, and former cocaine/crack use (1.17: 95% CI 1.01-1.35) were associated with greater risk of being frail in adjusted analyses. Current smoking was associated with a 61% higher risk of being frail vs. not frail (1.61: 95% CI 1.41-1.85) in adjusted analyses., Conclusions: We found a high prevalence of prefrailty and frailty among a nationally distributed cohort of PWH in care. This study identified distinct risk factors that may be associated with frailty among PWH, many of which, such as cigarette smoking and drug use, are potentially modifiable., Competing Interests: Conflict of interest All authors report that they have no relevant conflicts of interest to disclose., (Copyright © 2022. Published by Elsevier B.V.)

Among 14 049 people with human immunodeficiency virus in care in 2019-2020, 96% were treated with antiretroviral therapy (ART). Current antiretroviral treatment patterns highlight high uptake of guideline-recommended ART regimens including second-generation integrase strand transfer inhibitors (dolutegravir and bictegravir) and tenofovir alafenamide, especially in antiretroviral-naive individuals initiating ART., Competing Interests: Potential conflicts of interest. K. C. is a member of the medical advisory board for Gilead Sciences and reports grants or contracts from Gilead Sciences to their institution, outside the submitted work. G. A. B. has received research grant support from Merck Foundation and Eli Lilly, consulting fees from Med IQ, and payment or honoraria from StateServ and the University of Kentucky. J. K. reports a past relationship with the American Board of Internal Medicine, as an infectious disease specialty board member. J. J. E. reports contracts to their institution from ViiV Healthcare, Gilead Sciences, and Janssen; is an ad hoc consultant to Merck, Gilead Sciences, ViiV, and Janssen; and is an investigator for clinical trials at the University of North Carolina, which receives funding from Gilead, ViiV, and Janssen. E. R. C. has received unrestricted research grants paid to UC Reagents from Gilead Sciences for an unrelated hepatitis C virus project and from Merck Sharp & Dohme for an unrelated project and has received payment or honoraria from Gilead Science. M. S. S. reports money paid to their institution from ViiV and Gilead for clinical trials that are now closed, outside the submitted work; reports participation on the data science monitoring board for the I-SPY COVID trial; and reports serving on the board of directors for International Antiviral Society-USA. H. M. C. has received research grant support from ViiV and the Agency for Healthcare Research and Quality paid to their institution, outside the submitted work, and reports participation on the National Institutes of Health Office of AIDS Research Advisory Council. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)