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Objectives: Initial antiretroviral therapy (ART) causes loss of bone mineral density (BMD) over the first 1–2 years. Whether this loss continues with longer therapy is unclear. We determined changes in bone and spine BMD over 5 years in adults receiving immediate or deferred initial ART. Methods: In the Strategic Timing of Antiretroviral Therapy (START) BMD substudy, ART‐naïve adults with CD4 counts > 500 cells/μL were randomized to immediate or deferred ART. Deferred group participants not yet on ART were offered ART after May 2015. Mean per cent changes in total hip and lumbar spine BMD (measured annually by dual‐energy X‐ray absorptiometry) were compared between groups using longitudinal mixed models. Fracture rates were also compared between groups for all START participants. Results: Substudy participants (immediate group, n = 201; deferred group, n = 210; median age 32 years; 80% non‐white; 24% female) were followed for a mean 4.5 years until December 2016. In the immediate group, > 96% used ART throughout. In the deferred group, 16%, 58% and 94% used ART at years 1, 3 and 5, respectively. BMD decreased more in the immediate group initially; groups had converged by year 3 at the spine and year 4 at the hip by intent‐to‐treat (ITT). BMD changes after year 1 were similar in the immediate group and in those off ART in the deferred group [mean difference: spine, 0.03% per year; 95% confidence interval (CI) −0.4, 0.4; P = 0.88; hip, −0.2% per year; 95% CI −0.7, 0.3; P = 0.37]. Fracture incidence did not differ significantly between groups (immediate group, 0.86/100 person‐years versus deferred group, 0.85/100 person‐years; hazard ratio 1.01; 95% CI 0.76, 1.35; P = 0.98). Conclusions: Significant ART‐induced bone loss slowed after the first year of ART and became similar to that in untreated HIV infection. [ABSTRACT FROM AUTHOR]

Objectives This study's objective was to determine the prevalence of body shape changes and metabolic abnormalities in an ambulant population with HIV infection. Three different definitions of lipodystrophy were used to assess these changes. Patients' anthropometric measures and dual-energy X-ray absorptiometry (DEXA) scans were compared in order to estimate fat distribution in this population. We sought to evaluate potential predictors for lipodystrophy according to each of the three definitions. Methods We performed a cross-sectional study in the outpatient clinic of a tertiary referral hospital in Melbourne, Australia. We enrolled a total of 167 HIV-infected ambulatory patients over 3 months in mid-1998. Data on 159 males, 149 of whom were receiving triple combination antiretroviral therapy, were evaluated. Anthropometric measures, clinical examination, self-report of body shape changes, biochemical measures and DEXA scan were used to assess lipodystrophy and risk factors for cardiovascular disease. Patients described body shape changes in the face, trunk, arms and legs. Laboratory parameters measured included fasting triglyceride (TG), cholesterol, high-density lipoproteins (HDL), glucose, insulin, CD4 cell count and plasma HIV RNA. Current and past antiretroviral therapies were ascertained. Results According to one proposed Australian national definition of lipodystrophy (LDNC), the prevalence of lipodystrophy in this population was 650%. This definition included an objective assessment with major and minor criteria. Patient-defined lipodystrophy (LDP), which involved a subjective assessment of thinning arms and legs and central adiposity, occurred in 19%. Patient-defined lipoatrophy (LAP), which involved a subjective assessment of thinning arms and legs without central adiposity, occurred in 21.3%. No change in body habitus was noted by 37% of the cohort. Hypercholesterolaemia was recorded in 44%, hypertriglyceridaemia in 52% and elevated insulin levels... [ABSTRACT FROM AUTHOR]

Objective A Swiss nonoccupational post-exposure prophylaxis ( NPEP) source-tracing study successfully reduced unnecessary NPEP prescriptions by recruiting and testing source partners of unknown HIV serostatus. The Victorian NPEP Service in Australia attempted to replicate this study with the addition of HIV rapid testing and a mobile service. Methods Patients presenting to two busy NPEP sites who reported a source partner of unknown HIV status were routinely asked if their source could be traced. If the exposed person indicated that their source partner was traceable they were asked to contact them and discuss the possibility of having an HIV test. Results No sources were enrolled and the study was terminated. Conclusion We hypothesize that there are a number of differences between Australia and Switzerland that make source tracing unfeasible in Australia. [ABSTRACT FROM AUTHOR]

Young people aged 18-29 are considered "adult" within the Australian HIV health service context. However, evidence increasingly defines this age group as distinct from the broader adult population such that the needs of young people living with HIV may be overlooked in the context of HIV service design and delivery. This analysis draws on the Young + Positive study, a national study in Australia that documented the perspectives of young people (aged 18-29) living with HIV. Data were collected via survey (n = 60) and interview (n = 25) methods between 2018 and 2019. The data were analysed using descriptive statistics and thematic analysis, exploring the inner- and outer-world factors influencing participant engagement with HIV care and support. Using the multi-dimensional framework by Harms [2021. Understanding human development (3rd ed.). Oxford University Press], we found that both inner- and outer-world factors influenced participants' ability and motivations to engage with specialist HIV treatment and support. Inner-world factors included psychological outlook, and perceptions of HIV and HIV services. Outer-world factors included workforce competencies of service providers, physical space of the service and hours of service operation. These research findings confirm that opportunities exist to better meet the treatment and care needs of young people living with HIV.

While HIV infection and clonal hematopoiesis (CH) have been linked with inflammatory dysregulation and an increased risk of aging-related comorbidities, their relationship with clinical geriatric syndromes has not been well defined. In the Age-related Clonal Haematopoiesis in an HIV Evaluation Cohort (ARCHIVE) study (NCT04641013), we measure associations between HIV and CH and geriatric syndromes. Of 345 participants (176 with HIV and 169 without HIV), 23% had at least one mutation associated with CH: 27% with HIV and 18% without HIV (p = 0.048). In adjusted analyses, HIV infection is independently associated with increased phenotypic age acceleration (coefficient 1.73, 95% confidence interval [CI] 0.3, 3.16) and CH is independently associated with being frail (vs. pre-frail/robust; odds ratio 2.38, 95% CI 1.01, 5.67) and with having reduced quality of life (coefficient -2.18, 95% CI -3.92, -0.44). Our findings suggest that HIV is associated with increased biological age and that CH may be used as a biomarker for adverse geriatric outcomes., Competing Interests: Declaration of interests M.B. has received funding from Gilead Sciences and ViiV Healthcare for lecturing and traveling to scientific meetings and medical advisory boards. D.A.B. has received funding and travel grants from and served on advisory boards for ViiV Healthcare and Gilead. D.E.S. has received consultancy fees and lecturing honorarium from ViiV Healthcare and Gilead Sciences. J.F.H.’s institution has received reimbursement for her participation in advisory boards for Gilead Sciences and ViiV Healthcare. I.W.’s institution has received financial or in-kind support for his role in clinical studies from Moderna, CSL, MSD, Gilead, and ViiV. G.V.M. has received research funding from Gilead, AbbVie, Janssen, and ViiV, has served on advisory boards for AstraZeneca and ViiV, and has provided consultancy and received travel support from Gilead. M.N.P. has received research funding from ViiV, Janssen, and Gilead (awarded to institution), research support (in kind) from ViiV, Janssen, BMS, Verastem, ASTEX, Grifols, CSL Behring, Takeda, and Emergent (in kind, to institution) and has served on the advisory board for AstraZeneca and Gilead. P.Y. has received speaker honoraria from Astellas Pharma for unrelated projects., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Owing to widespread availability of potent and tolerable antiretroviral therapy, life expectancy of people with human immunodeficiency virus (HIV) has significantly increased. Consequently, the population of people with HIV are ageing, with over 50% over the age of 50 years, and it is expected that 25% will be over the age of 65 years by 2030. People diagnosed with HIV at older age tend to have more advanced disease, and may already be experiencing comorbidities that will influence the choice of initial antiretroviral treatment. Despite the well described changes in pharmacokinetics associated with ageing, there are a paucity of pharmacokinetics studies of contemporary antiretroviral drugs to help guide treatment for HIV. Irrespective of this, integrase inhibitor-based regimens have been shown to have similar treatment outcomes in older and young adults and are the preferred regimens for initiation and switching therapy in older adults. Non-acquired immunodeficiency syndrome (AIDS) comorbidities are more common in people with HIV owing to chronic immune activation and inflammation even in the presence of virological suppression on antiretroviral treatment. Screening and risk assessment of comorbidities is crucial as the presence of geriatric syndrome, frailty or neurocognitive impairment may impact medication adherence. Simplification of complex regimens, both antiretroviral and comorbidity treatments, is recommended to improve adherence. Regular medication reviews under the guidance of an experienced HIV pharmacist are recommended to identify adverse drug-drug interactions and inappropriate prescribing of drugs with potential adverse effects, such as falls risk. Antiretroviral stewardship has been shown to improve patient outcomes and quality of life for ageing people with HIV., Competing Interests: Declarations. Funding: No funding was provided for writing this manuscript Conflict of interest: J.F.H.’s institution received reimbursement for her time spent on advisory boards for Gilead Sciences and ViiV Healthcare. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable. Availability of data and material: Not applicable. Code availability: Not applicable. Author contributions: J.F.H. performed literature review, wrote and reviewed the manuscript and approved the final version., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose of Review: Potent, well tolerated and simple to administer antiretroviral therapy (ART) has resulted in significant improvement in life expectancy for people with HIV. The increased lifespan does not necessarily equate to improved healthspan with increased rates of comorbidities, frailty and geriatric syndrome experienced by older people with HIV. This review explores the challenges in prevention and management of multimorbidity and geriatric syndrome with the ultimate goal of improving health and quality of life through holistic care., Recent Findings: Recent studies have drawn attention to the multifactorial nature of most comorbidities experienced by people with HIV. Adverse effects of contemporary ART, combined with lifestyle factors of smoking, excess alcohol and other substance use, chronic immune activation and inflammation associated with chronic HIV infection and other co-infections, all impact multimorbidity and geriatric syndromes. The complex healthcare needs of the aging population of people with HIV will require comprehensive, multidisciplinary integrated models of care., Competing Interests: Declarations. Human and Animal Rights and Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors. Competing Interests: JH’s institution received reimbursement for her time on Advisory Boards for Gilead Sciences and ViiV Healthcare., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: New data and new antiretroviral drugs and formulations continue to become available for the prevention and management of HIV infection., Objective: To provide updated recommendations for HIV treatment and clinical management and HIV prevention., Methods: A panel of volunteer expert physician scientists were appointed to provide updated consensus recommendations for 2024. Relevant evidence in the literature since the last report was identified from PubMed and Embase searches (which initially yielded 3998 unique citations, of which 249 were considered relevant); from ongoing monitoring of the literature by the panel members; from data submitted by product manufacturers; and from studies presented at peer-reviewed scientific conferences between June 2022 and October 2024., Findings: Antiretroviral therapy continues to be recommended for all individuals with HIV. For most people with HIV, initial regimens composed of an integrase strand transfer inhibitor (InSTI), specifically bictegravir or dolutegravir, with 2 (and in some cases 1) nucleoside or nucleotide reverse transcriptase inhibitors are recommended. Recommendations are made for those with particular clinical circumstances, such as pregnancy and active opportunistic diseases, as well as for those unable to take InSTIs. Regimens may need to be changed for virologic failure, adverse effects, convenience, or cost, among other reasons. Long-acting injectable therapy is available for those who prefer not to take daily oral medications and for people struggling with adherence to daily therapy. Recommendations are provided for laboratory monitoring, management of substance use disorders and weight changes, as well as use of statins for cardiovascular disease prevention. For HIV prevention, oral (daily or intermittent) and injectable long-acting medications are effective options for people at increased likelihood of HIV exposure. Further, new tools for maintaining health and well-being among people with HIV, such as doxycycline postexposure prophylaxis to avert sexually transmitted infection, and strategies to treat substance use disorders, are recommended. Disparities in HIV acquisition and care access are discussed and solutions proposed., Conclusions: New approaches for treating and preventing HIV offer additional tools to help end the HIV epidemic, but achieving this goal depends on addressing disparities and inequities in access to care.

This single-centre substudy of a double-blind, randomized, placebo-controlled trial aimed to determine the effect of 96 weeks of rosuvastatin on pulse wave velocity (PWV) in men (n = 55, 54 years) with HIV at moderate cardiovascular risk (Framingham risk score 10-15%). PWV increased in both rosuvastatin [0.54 m/s standard error of difference (SED) 0.26] and placebo [0.50 m/s (SED 0.26), P = 0.896] arms, leading to no difference in PWV at week 96 [rosuvastatin 9.40 m/s (SE 0.31); placebo 9.21 m/s (SE0.31), P = 0.676]., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Lateral epicondylitis is a common cause of elbow pain that is generally self-limiting. For patients who have persistent symptoms refractory to conservative treatment, there is still no clear consensus on the most favorable treatment modality. The purpose of this systematic review was to synthesize the available literature regarding both nonoperative and operative treatment modalities for recalcitrant lateral epicondylitis (RLE) to provide insight into the efficacy of treatment options., Methods: A systematic review was performed in accordance with the 2020 Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, where the PubMed, MEDLINE/Ovid, CINAHL, Cochrane, and Scopus databases were queried to identify studies evaluating treatment options for RLE., Results: A total of 27 studies with 1,958 patients were included. Of the reviewed studies, there were a wide variety of treatments including platelet-rich plasma injections, percutaneous tenotomies, and various arthroscopic and open procedures., Conclusion: There are a wide variety of treatment modalities available for RLE that have promising efficacy in the short, medium, and long terms. A comprehensive approach combining evidence-based and patient-centered care is critical for effective management of refractory symptoms., Level of Evidence: Level IV. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/B128)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Medical school clerkship grades are used to evaluate orthopedic surgery residency applicants, however, high interinstitutional variability in grade distribution calls into question the utility of clerkship grades when evaluating applicants from different medical schools. This study aims to evaluate the variability in grade distribution among medical schools and look for trends in grade distribution over recent years., Methods: Applications submitted to Rush University's orthopedic surgery residency program from 2015, 2019, and 2022 were collected from the Electronic Residency Application Service. Applications from the top 100 schools according to the 2023-2024 U.S. News and World Report Research Rankings were reviewed. The percentage of "honors" grades awarded by medical schools for the surgery and internal medicine clerkships were extracted from applicants' Medical Student Performance Evaluation letters., Results: The median percentage of honors given in 2022 was 36.0 % (range 10.0-82.0) for the surgery clerkship and 33.0 % (range 6.7-80.0) for the internal medicine clerkship. Honors were given 6.6 % more in the surgery clerkship in 2022 compared to 2015. There was a negative correlation between a higher (worse) U.S. News and World Report research ranking and the percentage of honors awarded in 2022 for the surgery and internal medicine clerkships., Conclusion: There is substantial interinstitutional variability in the rate that medical schools award an "honors" grade with evidence of grade inflation in the surgery clerkship. Residency programs using clerkship grades to compare applicants should do so cautiously provided the variability demonstrated in this study., Competing Interests: None., (© 2024 The Authors.)

Purpose: This study seeks to assess the quality and reliability of YouTube videos on Dupuytren's contracture., Methods: The first 50 unique videos on Dupuytren's contracture were evaluated by searching YouTube for Dupuytren's contracture. Video metrics, source, and content type were recorded. Video reliability was assessed using the Journal of American Medical Association (JAMA) Benchmark criteria. Video educational quality was assessed using the Global Quality Score (GQS) and a Dupuytren's Contracture-Specific Score (DC-SS)., Results: The total number of views for all 50 videos evaluated was 1,908,608 (mean, 38,172.16 ± 5,502.45 views). The mean reliability (JAMA) score was 2.21 ± 0.69 (range 0-4), the mean educational quality (GQS) score was 2.80 ± 1.28 (range 1-5), and the mean disease-specific (DC-SS) score was 6.05 ± 2.17 (range 0-15). Nonphysician health care professionals had the most popular videos, but the lowest DC-SS. GQS varied based on the video source, with physician-uploaded videos having the highest average quality scores. Physician source was an independent positive predictor of higher quality (GQS) (β = 0.477)., Conclusions: Videos on Dupuytren's contracture were frequently viewed on YouTube but had overall low educational quality and reliability. Of the videos that discussed collagenase as a treatment option, 40% failed to mention percutaneous needle aponeurotomy. Patients may be exposed to an incomplete set of treatment options. Educational content on YouTube should be interpreted cautiously and proper in-office education and high-quality resources for Dupuytren's contracture should be provided by physicians., Type of Study/level of Evidence: Therapeutic IV., Competing Interests: No benefits in any form have been received or will be received related directly to this article., (© 2024 The Authors.)

Purpose: Distal radioulnar joint (DRUJ) injuries can be devastating and challenging to manage. The multiplanar curvature exhibited by the ulna impacts the morphology of the DRUJ, making it difficult to assess through two-dimensional radiographs alone. We used full-length, three-dimensional (3D) computed tomography angiography scans to assess the relationship between ulnar bowing, DRUJ ulnar variance (UV), and sigmoid notch angle. The goal of this study was to establish normal anatomic ranges for these landmarks to improve treatment for forearm traumas and DRUJ pathologies., Methods: Eighty-two intact upper extremity computed tomography angiography scans were examined and reconstructed into 3D models. We characterized ulnar bowing and DRUJ metrics using computer-aided design software. Measures of central tendency and Pearson correlation coefficients were calculated for comparative analysis., Results: The study yielded an average ulnar length of 272.3 mm. We identified the proximal ulnar bow at 36.7% of the bone's total length, possessing a depth of 10.3 mm, a proximal angle of 6.6°, and a distal angle of 3.9°. The distal ulnar bow appeared at 75.3% of the bone's length, characterized by a depth of 4.2 mm, a proximal angle of 2°, and a distal angle of 4.3°. In the coronal plane, the proximal angle of the proximal ulnar bow correlated positively with UV (r = 0.39, P < .001), whereas the distal angle of the distal ulnar bow correlated negatively (r = -0.48, P < .001). We also found significant correlations between the depths of both proximal and distal bows with UV (r = 0.38, P < .001; r = -0.34, P < .001, respectively). Moreover, UV within the DRUJ strongly correlated with the sigmoid notch angle (r = -0.77, P  = .01). In contrast, the sagittal plane metrics did not show meaningful correlations with UV., Conclusion: Sagittal alignment and translation at the DRUJ articulation are directly related to ulna bowing at the distal ulna. A nuanced understanding of these 3D relationships can enhance preoperative planning when correcting ulnar-side pathology., Type of Study/level of Evidence: Therapeutic IV., Competing Interests: No benefits in any form have been received or will be received related directly to this article., (© 2024 The Authors.)

Competing Interests: JFH reports reimbursement to her institution for her participation on advisory boards for Gilead Sciences and ViiV Healthcare. All other authors declare no competing interests.

Background: People living with HIV (PLHIV) are at increased risk for coronary artery disease (CAD). This study aimed to describe the features associated with CAD in PLHIV., Methods: A case ([n =160] PLHIV with CAD) control ([n =317] PLHIV matched by age and sex without CAD) study was performed at the Alfred Hospital, Melbourne, Australia (January 1996 and December 2018). Data collected included CAD risk factors, duration of HIV infection, nadir and at-event CD4+ T-cell counts, CD4:CD8 ratio, HIV viral load, and antiretroviral therapy exposure., Results: Participants were predominantly male (n =465 [97.4%]), with a mean age of 53years. Traditional risk factors associated with CAD in univariate analysis included hypertension (OR 11.4 [95%CI 5.01, 26.33], P <0.001), current cigarette smoking (OR 2.5 [95% CI 1.22, 5.09], P =0.012), and lower high-density lipoprotein cholesterol (OR 0.14 [95%CI 0.05, 0.37], P <0.001). There was no association between duration of HIV infection, nadir or current CD4 cell count. However, current and ever exposure to abacavir (cases: 55 [34.4%]; controls: 79 [24.9%], P =0.023 and cases: 92 [57.5%]; controls: 154 [48.6%], P =0.048, respectively) was associated with CAD. In conditional logistic regression analysis, current abacavir use, current smoking, and hypertension remained significantly associated (aOR=1.87 [CI=1.14, 3.07], aOR=2.31 [1.32, 4.04], and aOR=10.30 [5.25, 20.20] respectively)., Conclusion: Traditional cardiovascular risk factors and exposure to abacavir were associated with CAD in PLHIV. This study highlights that aggressive management of cardiovascular risk factors remains critical for reducing risk in PLHIV.

Introduction: Antiretroviral therapy for people living with HIV-1 must be taken lifelong due to the persistence of latent virus in long-lived and proliferating CD4 + T cells. Vitamin D 3 is a steroidal gene transcription regulator which exerts diverse effects on immune and epithelial cells including reductions in CD4 + T cell proliferation and improvement in gut barrier integrity. We hypothesised that a high dose of vitamin D 3 would reduce the size of the HIV-1 reservoir by reducing CD4 + T cell proliferation., Methods: We performed a randomised placebo-controlled trial evaluating the effect of 24 weeks of vitamin D 3 (10,000 international units per day) on the HIV-1 reservoir and immunologic parameters in 30 adults on antiretroviral therapy; participants were followed for 12 weeks post-treatment. The primary endpoint was the effect on total HIV-1 DNA at week 24. Parameters were assessed using mixed-effects models., Results: We found no effect of vitamin D 3 on the change in total HIV-1 DNA from week 0 to week 24 relative to placebo. There were also no changes in integrated HIV-1 DNA, 2-long-terminal repeat (2-LTR) circles or cell-associated HIV-1 RNA. Vitamin D 3 induced a significant increase in the proportion of central memory CD4 + and CD8 + T cells, a reduction in the proportion of senescent CD8 + T cells and a reduction in the natural killer cell frequency at all time points including week 36, 12 weeks after the study drug cessation. At week 36, there was a significant reduction in total HIV-1 DNA relative to placebo and persistently elevated 25-hydroxyvitamin D levels. No significant safety issues were identified., Conclusions: Vitamin D 3 administration had a significant impact on the T cell differentiation but overall effects on the HIV-1 reservoir were limited and a reduction in HIV-1 DNA was only seen following cessation of the study drug. Additional studies are required to determine whether the dose and duration of vitamin D 3 can be optimised to promote a continued depletion of the HIV-1 reservoir over time., Trial Registration: ClinicalTrials.gov NCT03426592., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

ABSTRACT Globally the community of people with HIV is ageing, and some of these have increasingly complex care needs, with a known excess of non-HIV related comorbidities and related issues including consequent polypharmacy. At the 2022 International AIDS Conference in Montréal, Canada, the "Silver Zone" was created in the Global Village as a safe space for older people with HIV. As part of the Silver Zone activities, a session discussing global models of care for in this group was held. HIV treatment providers and advocates from diverse resource settings and with a diversity of expertise were invited to share their experience, reflections, and ideas, and this consensus statement was formed based on these discussions. Different approaches to care emerged, based on local needs and resources, and it became clear that issues of complexity and frailty need not be age limited. Despite clear regional differences, some common themes became apparent, and a consensus was established on basic principles that may be considered in diverse settings. These are discussed here, with agreement on necessary proximal steps to develop bespoke person-centred care models.

Background: Previous studies have reported impairment in systolic and diastolic function in people with HIV (PWHIV). Our aim was to determine if echocardiographically measured left ventricular (LV) global longitudinal strain (GLS) is abnormal in asymptomatic PWHIV., Methods: A cross-sectional study of PWHIV ( n  = 98, 89% male, median age 53 years) and HIV-negative people ( n  = 50, median age 53 years) without known cardiovascular disease were recruited from a single centre. All participants completed a health/lifestyle questionnaire, provided a fasting blood sample, and underwent a comprehensive echocardiogram for assessment of diastolic and systolic LV function, including measurement of GLS., Results: All PWHIV were receiving antiretroviral therapy (ART) for a median of 12 years (IQR: 6.9, 22.4), the majority with good virological control (87% suppressed) and without immunological compromise (median CD4 598 cells/µl, IQR: 388, 841). Compared with controls of similar age and gender, there was no difference in GLS [mean GLS -20.3% (SD 2.5%) vs. -21.0% (SD 2.5%), p  = 0.14] or left ventricular ejection fractions [65.3% (SD 6.3) vs. 64.8% (SD 4.8), p  = 0.62]. Following adjustment for covariates (gender, heart rate, systolic and diastolic blood pressure, and fasting glucose), the difference in GLS remained non-significant. There were no differences in LV diastolic function between the groups. Exposure to at least one mitochondrially toxic ART drug (didanosine, stavudine, zidovudine, or zalcitabine) was not associated with impairment of LV systolic function., Conclusion: No clinically significant impairment of myocardial systolic function, as measured by LV GLS, was detected in this predominantly Caucasian male population of PWHIV on long-term ART, with no history of cardiovascular disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Hoy, Lee, Trevillyan, Dewar, Roney, Dart and Yang.)

Purpose of Review: People with HIV (PWHIV) are at increased risk for osteoporosis and fractures, because of the effects of HIV and inflammation and antiretroviral therapy (ART) initiation as well as traditional risk factors. This review from recent literature focuses on sex differences in rates of bone disease, risk of fractures, and effects of ART., Recent Findings: Women with HIV in resource-constrained settings experience bone loss because of the additive effect of initiating TDF-containing ART during pregnancy, lactation, and menopause. Children and adolescents experience lower bone accrual during the pubertal growth years. There has been less focus on bone health in recent trials of ART containing tenofovir alafenamide and/or integrase inhibitors. Very few clinical trials or studies compare sex-specific changes in inflammation, immune activation, response to ART and bone turnover or change in BMD resulting in significant knowledge gaps., Summary: More data is needed to determine changes in prevalence of osteopenia, osteoporosis, and fractures in the era of immediate initiation of ART at high CD4 cell counts and the use of more bone-friendly ART. The long-term effects of ART and low bone mass on fractures in the ageing population of PWHIV is yet to be realized., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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.

Background: There are more than 7,800 people living with human immunodeficiency virus (HIV) in Victoria, Australia. Crucial in maximising the individual and population level benefits from antiretroviral therapy (ART) is understanding how to achieve patient retention in care and the factors that drive it. This study was an expansion of a 2015 assessment of HIV-care retention in Victoria, which sought out to determine whether the inclusion of a broader range of HIV-healthcare sites would yield more accurate estimates of retention in HIV-care. We aimed to improve our understanding of HIV-care retention in Victoria, Australia, identify people living with HIV (PLHIV) with unknown outcomes, and attempt to re-engage PLHIV in care., Methods: A network of 15 HIV-care sites was established in Victoria, Australia across diverse care settings which ranged from low-caseload rural sites to high-caseload metropolitan GP clinics and hospitals. Individuals who had an HIV viral load (VL) performed in both calendar years of 2016 and 2017 were classified as retained in care. Individuals with a VL test in 2016 but not in 2017 were considered to potentially have unknown outcomes as they may have been receiving care elsewhere, have disengaged from care or died. For this group, an intervention of cross-referencing partially de-identified data between healthcare sites, and contact tracing individuals who still had unknown outcomes was performed., Results: For 5223 individuals considered to be retained in care across 15 healthcare sites in the study period, 49 had unconfirmed transfers of care to an alternative provider and 79 had unknown outcomes. After the intervention, the number of unconfirmed care transfers was reduced to 17 and unknown outcomes reduced to 51. These changes were largely attributed to people being reclassified as confirmed transfers of care. Retention in care estimates that did not include the patient outcome of confirmed transfer of care ranged from 76.2 to 95.8% and did not alter with the intervention. However, retention in care estimates which considered confirmed transfers and those that re-entered care at a new site as retained in care significantly increased across five of the sites with estimates ranging from 80.9 to 98.3% pre-intervention to 83.3-100% post-intervention. Individuals whose outcomes remained unknown post-intervention were more often men who have sex with men (MSM) when compared to other categories (person who injects drugs (PWID), combined PWID/MSM, men who identify as heterosexual or unknown) (74.5% vs. 53.5%, [p = 0.06]) and receiving ART at their last HIV-care visit (84.3% vs. 67.8% [p = 0.09])., Conclusion: This study confirmed high retention in HIV-care and low numbers of people disengaged from HIV-care in Victoria. This was demonstrated across a larger number of sites with varying models of care than a prior assessment in 2015. These data align with national and state targets aiming for 95% of PLHIV retained in HIV-care., (© 2022. The Author(s).)

Backgroud: Antiretroviral (ARV) side effects are a critical determinant of adherence among people living with HIV (PLWH). Integrase strand transfer inhibitors (INSTIs), a commonly used ARV, have been reported to cause weight gain. We determined the relative importance of weight gain compared with other side effects from the perspective of PLWH., Setting: Melbourne Sexual Health Centre and the Alfred Hospital in Victoria, Australia., Methods: We conducted a discrete choice experiment survey to explore PLWH's preferences for 8 short-term side effects (eg, weight gain and depression) and 4 long-term side effects (eg, long-term weight gain and risks of heart attack). We sent an anonymous survey link through short message service (SMS) and postcards to PLWH attending both centers between July and August 2021. The choice data were analyzed using random parameter logit (RPL) and latent class (LCM) models., Results: Three hundred thirty-five respondents were included: most were male (88.1%). In the RPL analyses, weight gain was the second most important attribute after depression for short-term side effects and the third most important attribute after risk of heart attack and kidney problem for long-term side effects. In the LCM analyses, 23.9% were most sensitive to short-term weight gain, whereas 16.0% were most sensitive to long-term weight gain., Conclusions: Weight gain was the second most important short-term side effect and the third most important long-term side effect in a cohort of Australian PLWH. However, weight gain was the most important side effect of ARV for a significant minority., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The incidence of end-stage organ disease in people living with human immunodeficiency virus (HIV) (PLWH) is increasing, as people live longer due to potent, tolerable antiretroviral therapy (ART). Consequently, the number of PLWH who would benefit from solid organ transplant (SOT) is rising. The SOT experience in PLWH in Australia remains limited. Aim To retrospectively review the outcomes for SOT in PLWH at our service, in Victoria, Australia., Methods: A retrospective cohort study of PLWH undergoing SOT over a 15-year period was performed. Adult PLWH age >18 years were eligible and identified from the Victorian HIV Service database. Descriptive statistics were used to summarise baseline demographics and clinical data, and outcomes following SOT., Results: Nine virologically suppressed PLWH underwent SOT from HIV-negative donors (five kidneys, two livers and two bilateral sequential lung transplants). All patients were male, with a median age of 57.3 years (interquartile range (IQR) = 54.3-60.1) and CD4 count of 485 (IQR = 342-835) at transplantation, and comorbidities were common at baseline. After a median follow up of 3.9 years (IQR = 2.7-7.6), 8 (89%) patents were alive, 7 (78%) had functioning grafts, although 5 (56%) experienced organ rejection. Infections were common. Two patients required modification to their ART due to significant drug-drug interactions prior to transplant, while 5 (56%) had modifications post-SOT. No patients experienced HIV virologic failure., Conclusion: PLWH with end-stage organ disease experience good clinical and functional outcomes and should be considered for SOT where indicated. However, multidisciplinary planning and care is essential to optimise care in this patient group., (© 2021 Royal Australasian College of Physicians.)

Background: Gay and bisexual men (GBM) are a key population affected by human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection. We aimed to measure HCV treatment effectiveness and to determine the population impact of treatment scale-up on HCV prevalence and incidence longitudinally among GBM., Methods: The co-EC Study (Enhancing Care and Treatment Among HCV/HIV Coinfected Individuals to Eliminate Hepatitis C Transmission) was an implementation trial providing HCV direct-acting antiviral treatment in Melbourne, Australia, during 2016-2018. Individuals with HCV/HIV coinfection were prospectively enrolled from primary and tertiary care services. HCV viremic prevalence and HCV antibody/viremic incidence were measured using a statewide, linked, surveillance system., Results: Among 200 participants recruited, 186 initiated treatment during the study period. Sustained virological response in primary care (98% [95% confidence interval {CI}, 93%-100%]) was not different to tertiary care (98% [95% CI, 86%-100%]). From 2012 to 2019, between 2434 and 3476 GBM with HIV infection attended our primary care sites annually, providing 13 801 person-years of follow-up; 50%-60% received an HCV test annually, and 10%-14% were anti-HCV positive. Among those anti-HCV positive, viremic prevalence declined 83% during the study (54% in 2016 to 9% in 2019). HCV incidence decreased 25% annually from 1.7/100 person-years in 2012 to 0.5/100 person-years in 2019 (incidence rate ratio, 0.75 [95% CI, .68-.83]; P < .001)., Conclusions: High treatment effectiveness by nonspecialists demonstrates the feasibility of treatment scale-up in this population. Substantial declines in HCV incidence and prevalence among GBM provides proof-of-concept for HCV microelimination., Clinical Trials Registration: NCT02786758., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Most studies assessing the HIV care cascade have typically been cross-sectional analyses, which do not capture the transition time to subsequent stages. We aimed to assess the longitudinal HIV cascade of care in Australia, and changes over time in transition times and associated factors., Methods: In this longitudinal cohort study, we included linked data for gay and bisexual men (GBM) with a new HIV diagnosis who attended clinics participating in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance in New South Wales and Victoria between Jan 1, 2012, and Dec 31, 2019. We assessed three cascade transition periods: diagnosis to linkage to care (stage 1 transition); linkage to care to antiretroviral therapy (ART) initiation (stage 2 transition); and ART initiation to virological suppression (viral load ≤200 copies per mL; stage 3 transition). We also calculated the probability of remaining virologically suppressed after the first recorded viral load of less than 200 copies per mL. We used the Kaplan-Meier method to estimate transition times and cumulative probability of stage transition., Findings: We included 2196 GBM newly diagnosed with HIV between 2012 and 2019 contributing 6747 person-years of follow-up in our analysis. Median time from HIV diagnosis to linkage to care (stage 1 transition) was 2 days (IQR 1-3). Median time from linkage to care to ART initiation (stage 2 transition) was 33 days (30-35). Median time from ART initiation to first recorded virological suppression (stage 3 transition) was 49 days (47-52). The cumulative probability of ART initiation within 90 days of linkage to care increased from 36·9% (95% CI 32·9-40·6) in the 2012-13 calendar period to 94·1% (91·2-96·0) in the 2018-19 calendar period and cumulative probability of virological suppression within 90 days of ART initiation increased from 54·3% (48·8-59·3) in the 2012-13 calendar period to 82·9% (78·4-86·4) in the 2018-19 calendar period. 91·6% (90·1-93·1) of GBM remained virologically supressed up to 2 years after their first recorded virological suppression event., Interpretation: In countries with high cross-sectional cascade estimates such as Australia, the impact of treatment as prevention is better estimated using longitudinal cascade analyses., Funding: National Health and Medical Research Council Australia., Competing Interests: Declaration of interests MWT has received honoraria for scientific meetings from Gilead Sciences. JHM and JFH have received grants via their institutions from Gilead Sciences, ViiV Health Care, and Merck Sharpe Dohme for the conduct of clinical trials and participation on advisory boards. MH has received funding for investigator-initiated research from Gilead Sciences and AbbVie, unrelated to this work. RG has received research support funding from Gilead Sciences. MS has received funding for investigator-initiated research from Gilead Sciences and AbbVie unrelated to this work; and consultancy fees from Gilead Sciences for activities unrelated to this work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Statins may help prevent cardiovascular disease (CVD) in people with human immunodeficiency virus (PWH) with chronic inflammation owing to their pleotropic lipid-lowering and anti-inflammatory properties., Methods: The impact of 48 weeks of rosuvastatin therapy on inflammation and immune activation in a double-blind, placebo-controlled trial in PWH at moderate cardiovascular disease risk was assessed., Results: Rosuvastatin did not alter plasma levels of interleukin 6, soluble tumor necrosis factor receptor type 2, CXCL10, soluble CD14, or soluble vascular cellular adhesion molecule 1 (P ≥ .1 for all). Proportions of CD16+ monocyte subsets were increased in PWH receiving rosuvastatin., Conclusions: The potential benefits of statin use in PWH with normal lipid levels requires further clinical outcome research., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Ambitious World Health Organization targets for disease elimination require monitoring of epidemics using routine health data in settings of decreasing and low incidence. We evaluated 2 methods commonly applied to routine testing results to estimate incidence rates that assume a uniform probability of infection between consecutive negative and positive tests based on 1) the midpoint of this interval and 2) a randomly selected point in this interval. We compared these with an approximation of the Poisson binomial distribution, which assigns partial incidence to time periods based on the uniform probability of occurrence in these intervals. We assessed bias, variance, and convergence of estimates using simulations of Weibull-distributed failure times with systematically varied baseline incidence and varying trend. We considered results for quarterly, half-yearly, and yearly incidence estimation frequencies. We applied the methods to assess human immunodeficiency virus (HIV) incidence in HIV-negative patients from the Treatment With Antiretrovirals and Their Impact on Positive and Negative Men (TAIPAN) Study, an Australian study of HIV incidence in men who have sex with men, between 2012 and 2018. The Poisson binomial method had reduced bias and variance at low levels of incidence and for increased estimation frequency, with increased consistency of estimation. Application of methods to real-world assessment of HIV incidence found decreased variance in Poisson binomial model estimates, with observed incidence declining to levels where simulation results had indicated bias in midpoint and random-point methods., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

People with human immunodeficiency virus (HIV) have higher rates of certain comorbidities, particularly cardiovascular disease and cancer, than people without HIV 1-5 . In view of observations that somatic mutations associated with age-related clonal hematopoiesis (CH) are linked to similar comorbidities in the general population 6-10 , we hypothesized that CH may be more prevalent in people with HIV. To address this issue, we established a prospective cohort study, the ARCHIVE study (NCT04641013), in which 220 HIV-positive and 226 HIV-negative participants aged 55 years or older were recruited in Australia. Demographic characteristics, clinical data and peripheral blood were collected to assess the presence of CH mutations and to identify potential risk factors for and clinical sequelae of CH. In total, 135 CH mutations were identified in 100 (22.4%) of 446 participants. CH was more prevalent in HIV-positive participants than in HIV-negative participants (28.2% versus 16.8%, P = 0.004), overall and across all age groups; the adjusted odds ratio for having CH in those with HIV was 2.16 (95% confidence interval 1.34-3.48, P = 0.002). The most common genes mutated overall were DNMT3A (47.4%), TET2 (20.0%) and ASXL1 (13.3%). CH and HIV infection were independently associated with increases in blood parameters and biomarkers associated with inflammation. These data suggest a selective advantage for the emergence of CH in the context of chronic infection and inflammation related to HIV infection.

Background: People living with HIV-1 (PLHIV) are at increased risk for cardiovascular disease., Objective: This study aimed to determine if PLHIV would benefit from starting statins at a lower threshold than currently recommended in the general population., Design: A double-blind multicentre, randomised, placebo-controlled trial was performed., Methods: Participants (n = 88) with well controlled HIV, at moderate cardiovascular risk (Framingham score of 10-15%), and not recommended for statins were recruited from Australia and Switzerland. They were randomized 1 : 1 to rosuvastatin (n = 44) 20 mg daily, 10 mg if co-administered with ritonavir/cobicistat-boosted antiretroviral therapy, or placebo (n = 40) for 96 weeks. Assessments including fasting blood collection and carotid--intima media thickness (CIMT) were performed at baseline, and weeks 48 and 96. The primary outcome was the change from baseline to week 96 in CIMT (clinicaltrials.gov: NCT01813357)., Results: Participants were predominantly men [82 (97.6%); mean age 54 years (SD 6.0)]. At 96 weeks, there was no difference in the progression of CIMT between the rosuvastatin (mean 0.004 mm, SE 0.0036) and placebo (0.0062 mm, SE 0.0039) arms (P = 0.684), leading to no difference in CIMT levels between groups at week 96 [rosuvastatin arm, 0.7232 mm (SE 0.030); placebo arm 0.7785 mm (SE 0.032), P = 0.075].Adverse events were common (n = 146) and predominantly in the rosuvastatin arm [108 (73.9%)]. Participants on rosuvastatin were more likely to cease study medication because of an adverse event [7 (15.9%) vs. 2 (5.0%), P = 0.011]., Conclusion: In PLHIV, statins prescribed at a lower threshold than guidelines did not lead to improvements in CIMT but was associated with significant adverse events., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Markers of HIV disease severity are associated with increased liver fibrosis in HIV/Hepatitis C virus (HCV) co-infected individuals. HCV treatment may reverse liver fibrosis, but evidence among HIV/HCV-co-infected populations and the impact of HIV parameters on fibrosis regression is limited. We aimed to assess the influence of surrogate markers of HIV-infection and other determinants of liver stiffness before HCV treatment and changes after HCV cure in people living with HIV., Methods: We used data from an HCV treatment implementation study aiming for HCV micro-elimination among gay and bisexual men with HIV in Melbourne, Australia (co-EC Study). We obtained liver stiffness measurements (LSM) before and after direct-acting antiviral treatment using transient elastography (FibroScan). Linear mixed models were used to evaluate determinants of pretreatment LSM and changes in LSM following cure with duration in years between pre- and post-LSM assessment as main exposure variable., Results: At least one LSM was available in 173 participants, and 98 participants had 2 LSMs. Median pre- and post-treatment LSMs were 5.7 and 5.1 kPa, respectively. Median time between transient elastography measurements was 1.3 years (interquartile range = 0.9-2.1). In multivariable analysis, longer duration of known HIV infection, a lower CD4 and CD8 T-cell count and hazardous alcohol consumption were associated with higher LSM values before treatment initiation. Successfully treated patients had a 6% (95% confidence interval = -10% to -2%) annual decrease (0.34 kPa predicted decrease) in LSM following cure. Changes in LSM values did not depend on any of the pretreatment HIV markers or other factors., Conclusion: Low levels of liver stiffness were observed before treatment initiation and a small decrease (6%) in LSM following HCV cure in people living with HIV. No clear predictors affecting change in LSM following cure were found in this study, including markers of HIV infection. However, markers of advanced HIV immunodeficiency and hazardous alcohol consumption remained associated with higher LSM values even after HCV cure.

Importance: Data on the use of antiretroviral drugs, including new drugs and formulations, for the treatment and prevention of HIV infection continue to guide optimal practices., Objective: To evaluate new data and incorporate them into current recommendations for initiating HIV therapy, monitoring individuals starting on therapy, changing regimens, preventing HIV infection for those at risk, and special considerations for older people with HIV., Evidence Review: New evidence was collected since the previous International Antiviral (formerly AIDS) Society-USA recommendations in 2018, including data published or presented at peer-reviewed scientific conferences through August 22, 2020. A volunteer panel of 15 experts in HIV research and patient care considered these data and updated previous recommendations., Findings: From 5316 citations about antiretroviral drugs identified, 549 were included to form the evidence basis for these recommendations. Antiretroviral therapy is recommended as soon as possible for all individuals with HIV who have detectable viremia. Most patients can start with a 3-drug regimen or now a 2-drug regimen, which includes an integrase strand transfer inhibitor. Effective options are available for patients who may be pregnant, those who have specific clinical conditions, such as kidney, liver, or cardiovascular disease, those who have opportunistic diseases, or those who have health care access issues. Recommended for the first time, a long-acting antiretroviral regimen injected once every 4 weeks for treatment or every 8 weeks pending approval by regulatory bodies and availability. For individuals at risk for HIV, preexposure prophylaxis with an oral regimen is recommended or, pending approval by regulatory bodies and availability, with a long-acting injection given every 8 weeks. Monitoring before and during therapy for effectiveness and safety is recommended. Switching therapy for virological failure is relatively rare at this time, and the recommendations for switching therapies for convenience and for other reasons are included. With the survival benefits provided by therapy, recommendations are made for older individuals with HIV. The current coronavirus disease 2019 pandemic poses particular challenges for HIV research, care, and efforts to end the HIV epidemic., Conclusion and Relevance: Advances in HIV prevention and management with antiretroviral drugs continue to improve clinical care and outcomes among individuals at risk for and with HIV.

: Integrase strand transfer inhibitor-based antiretroviral therapy can cause weight gain. It is unknown if this is a class effect, with limited data regarding raltegravir. In 37 virologically suppressed adults (36 men, mean age 49 years) who switched from tenofovir disoproxil fumarate to raltegravir 400 mg twice daily, mean weight changes from baseline at weeks 24, 48 and 96 were not significant (maximum 0.8 kg at week 24; all P ≥ 0.16). Weight gain may not occur with all integrase strand transfer inhibitors.

Objective: People living with HIV have an increased risk of cardiovascular disease (CVD) despite effective antiretroviral therapy (ART). Monocytes play a key role in the early stages of atherosclerosis-driven CVD by forming lipid-laden foam cells within artery walls. HIV infection potentiates foam cell formation ex vivo, but the mechanisms contributing to this are not known., Methods: We investigated the atherosclerosis-promoting potential of monocytes from 39 virologically suppressed men living with HIV (MLHIV) on ART and no evidence of CVD, and 25 HIV-uninfected controls of comparable age, sex, smoking status and CVD risk., Results: Despite absence of clinical atherosclerosis in both MLHIV and uninfected cohorts (evidenced by a carotid intima-media thickness of 0.6 mm for both groups; P = 0.254), monocytes from MLHIV showed increased potential to form atherosclerosis-promoting foam cells compared with controls in an ex-vivo assay (36.6% vs. 27.6%, respectively, P = 0.003). Consistent with observations of persistent inflammation and immune/endothelial activation in ART-treated HIV infection, levels of soluble tumour necrosis factor receptor II, CXCL10 and soluble VCAM-1 were elevated in MLHIV (P ≤ 0.005 for all), but were not significantly associated with foam cell formation. Foam cell formation was associated with an impaired ability of monocytes to undergo reverse transmigration, and a reduced ability to efflux cholesterol ex vivo (P < 0.05 for both). Importantly, foam cell formation declined significantly with duration of viral suppression (P = 0.004)., Conclusion: These findings highlight the persistence of HIV-related changes to the atherogenic potential of monocytes despite long-term viral suppression, and provide insights into mechanisms potentially driving increased CVD in ART-treated HIV infection.

Combination antiretroviral therapy (ART) is effective at suppressing HIV viremia to achieve persistently undetectable levels in peripheral blood in the majority of individuals with access and ability to maintain adherence to treatment. However, evidence suggests that ART is less effective at eliminating HIV-associated inflammation and innate immune activation. To the extent that residual inflammation and immune activation persist, virologically suppressed people living with HIV (PLWH) may have increased risk of inflammatory co-morbidities, and adjunctive therapies may need to be considered to reduce HIV-related inflammation and fully restore the health of virologically suppressed HIV+ individuals. Cardiovascular disease (CVD) is the single leading cause of death in the developed world and is becoming more important in PLWH with access to ART. Arterial disease due to atherosclerosis, leading to acute myocardial infarction (AMI) and stroke, is a major component of CVD. Atherosclerosis is an inflammatory disease, and epidemiological comparisons of atherosclerosis and AMI show a higher prevalence and suggest a greater risk in PLWH compared to the general population. The reasons for greater prevalence of CVD in PLWH can be broadly grouped into four categories: (a) the higher prevalence of traditional risk factors e.g., smoking and hypertension (b) dyslipidemia (also a traditional risk factor) caused by off-target effects of ART drugs (c) HIV-related inflammation and immune activation and (d) other undefined HIV-related factors. Management strategies aimed at reducing the impact of traditional risk factors in PLWH are similar to those for the general population and their effectiveness is currently being evaluated. Together with improvements in ART regimens and guidelines for treatment, and a greater awareness of its impact on CVD, the HIV-related risk of AMI and stroke is decreasing but remains elevated compared to the general community. Monocytes are key effector cells which initiate the formation of atherosclerotic plaques by migrating into the intima of coronary arteries and accumulating as foam cells full of lipid droplets. This review considers the specific role of monocytes as effector cells in atherosclerosis which progresses to AMI and stroke, and explores mechanisms by which HIV may promote an atherogenic phenotype and function independent of traditional risk factors. Altered monocyte function may represent a distinct HIV-related factor which increases risk of CVD in PLWH.

Importance: Emerging evidence suggests that risk of bacterial sexually transmitted infections (STIs) increases among gay and bisexual men following initiation of HIV preexposure prophylaxis (PrEP)., Objective: To describe STI incidence and behavioral risk factors among a cohort of predominantly gay and bisexual men who use PrEP, and to explore changes in STI incidence following PrEP commencement., Design, Setting, and Participants: The Pre-exposure Prophylaxis Expanded (PrEPX) Study, a multisite, open-label intervention study, was nested within the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance (ACCESS) clinic network. A total of 4275 participants were enrolled (July 26, 2016-April 1, 2018) in Victoria, Australia. Of these, 2981 enrolled at 5 ACCESS clinics (3 primary care, 1 sexual health, and 1 community-based HIV rapid testing service), had at least 1 follow-up visit, and were monitored until April 30, 2018., Exposures: Upon enrollment, participants received daily oral tenofovir disoproxil fumurate and emtricitabine for HIV PrEP, quarterly HIV and STI testing, and clinical monitoring., Main Outcomes and Measures: The primary outcome was incidence of chlamydia, gonorrhea, or syphilis. Incidence rates and hazard ratios describing behavioral risk factors of STI diagnosis were calculated. Incidence rate ratios (IRRs), adjusted for change in testing frequency, described changes in STI incidence from 1-year preenrollment to study follow-up among participants with preenrollment testing data (n = 1378)., Results: Among the 2981 individuals (median age, 34 years [interquartile range, 28-42]), 98.5% identified as gay or bisexual males, 29% used PrEP prior to enrollment, 89 (3%) withdrew and were censored at date of withdrawal, leaving 2892 (97.0%) enrolled at final follow-up. During a mean follow-up of 1.1 years (3185.0 person-years), 2928 STIs were diagnosed among 1427 (48%) participants (1434 chlamydia, 1242 gonorrhea, 252 syphilis). STI incidence was 91.9 per 100 person-years, with 736 participants (25%) accounting for 2237 (76%) of all STIs. Among 2058 participants with complete data for multivariable analysis, younger age, greater partner number, and group sex were associated with greater STI risk, but condom use was not. Among 1378 participants with preenrollment testing data, STI incidence increased from 69.5 per 100 person-years prior to enrollment to 98.4 per 100 person-years during follow-up (IRR, 1.41 [95% CI, 1.29-1.56]). After adjusting for testing frequency, the increase in incidence from 1 year preenrollment to follow-up was significant for any STI (adjusted IRR, 1.12 [95% CI, 1.02-1.23]) and for chlamydia (adjusted IRR, 1.17 [95% CI, 1.04-1.33])., Conclusions and Relevance: Among gay and bisexual men using PrEP, STIs were highly concentrated among a subset, and receipt of PrEP after study enrollment was associated with an increased incidence of STIs compared with preenrollment. These findings highlight the importance of frequent STI testing among gay and bisexual men using PrEP.

Objective: To compare the effects of switching tenofovir disoproxil fumarate (TDF) or treatment with an intravenous bisphosphonate on bone mineral density (BMD) in HIV-positive adults with low bone mass., Design: Two-year, randomized, open-label study at 10 sites in Australia and Spain., Participants: Of 112 adults on TDF-based antiretroviral therapy (ART) screened, 87 with low BMD (T-score < -1.0 at hip or spine by dual-energy X-ray absorptiometry) and undetectable plasma HIV viral load were randomized to either switch TDF to another active antiretroviral drug or to continue TDF-based ART and receive intravenous zoledronic acid (ZOL) 5 mg annually for 2 years., Primary Outcome Measure: Change in lumbar spine BMD at 24 months by intention-to-treat analysis. Secondary outcomes included changes in femoral neck and total hip BMD, fractures, safety, and virological failure., Results: Forty-four participants were randomized to TDF switch and 43 to ZOL, mean age 50 years (SD 11), 96% men, mean TDF duration 5.9 years (SD 3.1), and mean spine and hip T-scores -1.6 and -1.3, respectively. At 24 months, mean spine BMD increased by 7.4% (SD 4.3%) with ZOL vs. 2.9% (SD 4.5%) with TDF-switch (mean difference 4.4%, 95% CI 2.6-6.3; P < 0.001). Mean total hip BMD increased by 4.6 (SD 2.6%) and 2.6% (SD 4%), respectively (mean difference 1.9%, 95% CI 0.5-3.4; P = 0.009). There was one fracture in the ZOL group vs. seven fractures in four TDF-switch participants. Virological failure occurred in one TDF-switch participant. Other safety endpoints were similar., Conclusion: ZOL is more effective than switching TDF at increasing BMD in HIV-positive adults with low bone mass.

Introduction: HIV and antiretroviral therapy (ART) have been associated with increased cardiovascular disease and important changes in lipid metabolism. Advances in mass-spectrometry technology allow for the detailed assessment of individual lipid species which may illuminate the mechanisms underlying increased cardiovascular risk. We describe the change in plasma lipidome with initiation of antiretroviral therapy and compare these by regimen., Methods: Plasma lipid profiling (by electrospray isonisation-tandem mass spectrometry) was performed on ARV-naive HIV positive participants randomised to one of three regimens; tenofovir/emtricitabine with efavirenz, ritonavir-boosted atazanavir (atazanavir/r) or zidovudine/abacavir. Participants (n = 115) who remained on their randomised regimen with complete samples available at baseline, week 12 and 48 were included. 306 lipid species from 22 lipid classes were analysed., Results: Initiation of ART led to significant changes in lipidome which were partly dependent on the randomised regimen received. This led to significant differences in 72 lipid species and 7 classes (cholesterol ester, free cholesterol, phosphatidylcholine, GM3 ganglioside, trihexosylceramide, monohexosylceramide, and ceramides) by arm at week 48. Consistently higher lipid concentrations were seen with efavirenz compared with atazanavir/r or zidovudine/abacavir. Twelve of the lipid species and two lipid classes (cholesterol esters and ceramides) that were significantly increased in the efavirenz arm compared with the atazanavir/r or zidovudine/abacavir arms have previously been associated with future cardiovascular events in HIV positive patients. Change in HIV viral load was predictive of change in 3 lipid species., Conclusions: Initiation of ART lead to significant changes in the plasma lipidome that were greatest in those receiving efavirenz., Competing Interests: No authors have a significant conflicts of interest related to this work but we would like to declare that Professor Jennifer Hoy’s institution has received reimbursement for her participation in Advisory Boards for Gilead Science, Merck Sharp & Dohme, ViiV Healthcare and Abbott. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: The current study aimed to validate existing risk prediction scores and identify predictors of chronic kidney disease (CKD) in the setting of HIV., Design and Methods: A retrospective cohort study of HIV-positive individuals (n = 748) with baseline estimated glomerular filtration rate (eGFR) more than 60 ml/min was conducted at the Alfred Hospital, Melbourne, Australia. Multivariable regression analysis was performed to determine factors associated with development of CKD, defined as two consecutive measurements of eGFR less than 60 ml/min. The performance of CKD risk scores proposed by the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study Group and Scherzer and colleagues were estimated by the area under the receiver operator curve (AUROC)., Results: CKD developed in 37 individuals (5.0%), at a median of 4.7 (interquartile range 2.2, 6.2) years. Older age [odds ratio (OR) 3.03, 95% confidence interval (CI): 1.20, 7.65, P = 0.02] and lower baseline eGFR (OR 10.39, 95% CI: 4.73, 22.83, P < 0.001) were associated with the development of CKD. Neither current, nor cumulative tenofovir disoproxil fumarate (TDF) use was associated with progression to CKD [current TDF hazard ratio (HR) 1.05, 95% CI: 0.54, 2.07, P = 0.88; cumulative TDF HR 1.03, 95% CI: 0.86, 1.24, P = 0.75]. The short D:A:D and Scherzer scores were well calibrated, with the short D:A:D score demonstrating superior discrimination (short D:A:D AUROC 0.85, Scherzer AUROC 0.78, P = 0.02)., Conclusion: Older individuals and those with a lower baseline eGFR are at higher risk for CKD. Risk prediction tools may be useful in identifying those at greatest risk, who may benefit from aggressive management of risk factors.

Importance: Antiretroviral therapy (ART) is the cornerstone of prevention and management of HIV infection., Objective: To evaluate new data and treatments and incorporate this information into updated recommendations for initiating therapy, monitoring individuals starting therapy, changing regimens, and preventing HIV infection for individuals at risk., Evidence Review: New evidence collected since the International Antiviral Society-USA 2016 recommendations via monthly PubMed and EMBASE literature searches up to April 2018; data presented at peer-reviewed scientific conferences. A volunteer panel of experts in HIV research and patient care considered these data and updated previous recommendations., Findings: ART is recommended for virtually all HIV-infected individuals, as soon as possible after HIV diagnosis. Immediate initiation (eg, rapid start), if clinically appropriate, requires adequate staffing, specialized services, and careful selection of medical therapy. An integrase strand transfer inhibitor (InSTI) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) is generally recommended for initial therapy, with unique patient circumstances (eg, concomitant diseases and conditions, potential for pregnancy, cost) guiding the treatment choice. CD4 cell count, HIV RNA level, genotype, and other laboratory tests for general health and co-infections are recommended at specified points before and during ART. If a regimen switch is indicated, treatment history, tolerability, adherence, and drug resistance history should first be assessed; 2 or 3 active drugs are recommended for a new regimen. HIV testing is recommended at least once for anyone who has ever been sexually active and more often for individuals at ongoing risk for infection. Preexposure prophylaxis with tenofovir disoproxil fumarate/emtricitabine and appropriate monitoring is recommended for individuals at risk for HIV., Conclusions and Relevance: Advances in HIV prevention and treatment with antiretroviral drugs continue to improve clinical management and outcomes for individuals at risk for and living with HIV.

Background: Pre-exposure prophylaxis (PrEP) is the use of HIV anti-retroviral therapy to prevent HIV transmission in people at high risk of HIV acquisition. PrEP is highly efficacious when taken either daily, or in an on-demand schedule. In Australia co-formulated tenofovir-emtricitabine is registered for daily use for PrEP, however, this co-formulation is not listed yet on the national subsidized medicines list. We describe a study protocol that aims to demonstrate if the provision of PrEP to up to 3800 individuals at risk of HIV in Victoria, Australia reduces HIV incidence locally by 25% generally and 30% among GBM. Methods: PrEPX is a population level intervention study in Victoria, Australia in which generic PrEP will be delivered to 3800 individuals for up to 36 months. Study eligibility is consistent with the recently updated 2017 Australian PrEP guidelines. Participants will attend study clinics, shared care clinics, or outreach clinics for quarterly HIV/STI screening, biannual renal function tests and other clinical care as required. Study visits and STI diagnoses will be recorded electronically through the ACCESS surveillance system. At each study visit participants will be invited to complete behavioral surveys that collect demographics and sexual risk data. Diagnosis and behavioral data will be compared between PrEPX participants and other individuals testing within the ACCESS surveillance system. A subset of participants will complete in depth surveys and interviews to collect attitudes, beliefs and acceptability data. Participating clinics will provide clinic level data on implementation and management of PrEPX participants. The population level impact on HIV incidence will be assessed using Victorian HIV notification data. Discussion: This study will collect evidence on the real world impact of delivery of PrEP to 3800 individuals at risk of acquiring HIV in Victoria. This study will provide important information for the broader implementation of PrEP planning upon listing of the tenofovir-emtricitabine on the national subsidized list of medicines. The study is registered on the Australian New Zealand Clinical Trials Registry (ACTRN12616001215415).