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Studies have suggested CD8 lymphocytes may be a possible marker for inflammation, which is believed to be a contributing factor to neurocognitive impairment. Individuals enrolled in the MSM Neurocog Study were analysed. Those with depression, anxiety or mood disorders were excluded. Individuals with neurocognitive impairment were identified using the Brief NeuroCognitive Screen and compared to those with normal scores. CD4 and CD8 T cell values and CD4:CD8 ratios were compared between groups. In all, 144 men, aged 18–50 years, were included in the analysis. Twenty were diagnosed with neurocognitive impairment. We were unable to identify any significant difference between current, nadir or peak CD4 and CD8 counts. CD4:CD8 ratios and CD4:CD8 ratio inversion (<1) were also found to be similar between both groups. However, neurocognitive impairment subjects were 8% more likely to have inversion of CD4:CD8 ratio and higher median peak CD8 cell counts reported compared to non-impaired subjects. Analysis of data from the MSM Neurocog Study, demonstrated trends in peripheral CD8 counts and CD4:CD8 ratios. However, we are unable to demonstrate any significant benefit. Plasma biomarkers of neurocognitive impairment in HIV-infected subjects would be of great benefit over current methods of invasive CSF analysis and technical neuroimaging used in the diagnosis of neurocognitive impairment. Future, prospective, longitudinal work with large numbers of neurocognitive impairment subjects is required to further investigate the role of peripheral CD8 T cells as markers of neurocognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Selection of protease mutations on antiretroviral therapy (ART) including a ritonavir-boosted protease inhibitor (PI) has been reported infrequently. Scarce data exist from long-term cohorts on resistance incidence or mutational patterns emerging to different PIs.Methods: We studied UK patients receiving lopinavir/ritonavir as their first PI, either while naive to ART or having previously received non-PI-based ART. Virological failure was defined as viral load ≥ 400 copies/mL after previous suppression <400 copies/mL, or failure to achieve <400 copies/mL during the first 6 months. pol sequences whilst failing lopinavir or within 30 days after stopping were analysed. Major and minor mutations (IAS-USA 2008-after exclusion of polymorphisms) were considered. Predicted susceptibility was determined using the Stanford HIVdb algorithm.Results: Three thousand and fifty-six patients were followed for a median (IQR) of 14 (6-30) months, of whom 811 (27%) experienced virological failure. Of these, resistance test results were available on 291 (36%). One or more protease mutations were detected in 32 (11%) patients; the most frequent were I54V (n = 12), M46I (n = 11), V82A (n = 7) and L76V (n = 3). No association with viral subtype was evident. Many patients retained virus predicted to be susceptible to lopinavir (14, 44%), tipranavir (26, 81%) and darunavir (27, 84%).Conclusions: This study reflects the experience of patients in routine care. Selection of protease gene mutations by lopinavir/ritonavir occurred at a much higher rate than in clinical trials. The mutations observed showed only partial overlap with those previously identified by structural chemistry models, serial cell culture passage and genotype-phenotype analyses. There remained a low degree of predicted cross-resistance to other widely used PIs. [ABSTRACT FROM AUTHOR]

The Conference on Retroviruses and Opportunistic Infections (CROI) is usually the most significant HIV conference of the year in terms of basic and clinical scientific output. CROI 2024 in Denver, USA, felt very much back to 'business as usual' following COVID-19 disruptions that had impacted preceding years, but also felt more global and outward- facing. The British HIV Association supports a working group to attend CROI annually and deliver feedback in the UK. This article summarizes the highlights from that meeting., (© 2024 British HIV Association.)

Introduction: The equity-focused ILANA study evaluated feasibility, acceptability, appropriateness of delivering on-label two-monthly cabotegravir and rilpivirine (CAB+RPV) injections for HIV-1 therapy in clinics and community settings., Methods: The study, which mandated inclusive recruitment, was conducted May-December 2022 at six UK sites. Injections were delivered in clinic (months 1-6), and in clinic or community setting according to patient choice (months 6-12). Surveys were completed at baseline, M4 and M12 using validated measures for feasibility (FIM), acceptability (AIM), and appropriateness (IAM). Primary endpoint: proportion of participants agreeing that the injection and community setting were feasible (FIM>4) at M12. Fourteen participants completed interviews at baseline and M12., Results: Community settings offered by sites included: home visits (n=3), HIV support organisations (n=2), community clinic (n=1). Of 114 participants,54% were female, 70% racially minoritised and 40% aged >50. 27/114 chose to receive injections in community settings. FIM/AIM/IAM scores at M12 were high for the injection (79.0-87.4%) and lower for the community setting (44.2-47.4%) overall. Subgroup analyses indicated differences in scores by gender and ethnicity. Among those who attended the community, FIM/AIM/IAM scores for the community setting at M12 were high (73.1-80.8%). Concerns about stigma, inconvenience, and losing access to trusted clinicians negatively influenced perceptions of receiving injections at community settings, amongst other factors., Conclusion: CAB+RPV injections were considered highly feasible, acceptable, and appropriate, however few chose community delivery. Those that chose community delivery found it highly acceptable and feasible. Further exploration of CAB+RPV delivery in alternative community sites not offered (e.g. primary care or pharmacies) is warranted., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Opt-out Emergency Department blood borne virus (EDBBV) screening was introduced at the Royal Free Hospital under the NHSEI (NHS England and NHS Improvement) programme to expand opt-out testing in local authority areas with high HIV prevalence. This initiative was part of the "Toward Zero" policy towards ending HIV transmission in England by 2030., Methods: All patients attending the Royal Free Hospital Emergency Department (ED) aged 16 and over were screened for blood borne viruses (HIV/HBV/HCV) unless they opted out. We looked at HIV data from patients seen in ED between the initiation of EDBBV testing on the 12 th of April and 12 th of August 2022. Hepatitis B and C data was reviewed in a separate study., Outcome: A total of 12,208 samples from 10,641 patients were screened for HIV. Amongst these samples there were 88 which were positive, giving a seroprevalence of 0.84 %. There were 48 patients who were already known to local HIV services, 35 were known to HIV services outside of our Trust and 5 were new diagnoses., Conclusion: Our results confirmed our local HIV prevalence to be very high, as per the UK Health Security Agency and supports the need for HIV testing. Opt-out ED BBV screening has been a highly effective method for identifying people living with HIV who are unaware of their status., Competing Interests: Declaration of competing interest 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., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Long-acting injectable cabotegravir + rilpivirine (CAB + RPV LAI) was approved for use in virally suppressed adults in the England and Wales national health service in November 2021. We describe a service evaluation of delivery processes and outcomes in 12 clinics., Methods: Centres populated a database using information from local policies and clinical records. Services were asked to describe approval processes, clinic pathways, and adherence to national guidelines. Additional data were collected on reasons for regimen choice, treatment discontinuations, and management of viraemia., Results: In total, 518 adults from 12 clinics were approved for CAB + RPV LAI between February 2022 and December 2023. Of the 518 people approved for CAB + RPV LAI, 423 received at least one injection. Median duration on CAB + RPV was 7.5 months (interquartile range 3.7-11.3). In total, 97% of injections were administered within the ±7-day window. Virological failure occurred in 0.7%, and 6% discontinued CAB + RPV., Conclusion: In this large UK-based cohort, robust approval processes and clinic protocols facilitated on-time injections and low rates of both discontinuation and virological failure., (© 2024 The Author(s). HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Previous research has documented the various challenges people living with HIV face as they navigate intimate relationships, including what is often referred to as disclosure. In studies of gay, bisexual and other men who have sex with men, the issue of telling or not telling others about an HIV-positive status has been examined primarily in relation to communication with sexual partners, with few studies focusing on other aspects of intimacy. Drawing on interviews with gay men living with HIV, conducted in four clinics in London, this article explores the narratives of men who have been asked by female friends about the possibility of being a sperm donor. The narratives highlight layers of complexity which have received little attention, not only in research on HIV but also in studies of sperm donation and co-parenting. The article advances dialogue between these two largely separate bodies of work. Our data suggest that reluctance to share an HIV-positive status with others can be an important factor in deciding how to answer the 'sperm donor question'. Examining reproductive relationships of a specific kind - those based on friendships between women and gay men - the article develops the understanding of how secrecy about HIV shapes intimate lives.

Undiagnosed HIV infection is a prominent clinical issue throughout Europe that requires the continuous attention of all healthcare professionals and policymakers to prevent missed testing opportunities and late diagnosis. This systematic review aimed to evaluate interventions to increase HIV testing rates and case detection in European hospitals. Out of 4598 articles identified, 29 studies fulfilled the selection criteria. Most of the studies were conducted in single Western European capital cities, and only one study was from Eastern Europe. The main interventions investigated were test-all and indicator-condition-based testing strategies. Overall, the prevalence of undiagnosed HIV was well above 0.1%. The studied interventions increased the HIV testing rate and the case detection rate. The highest prevalence of undiagnosed HIV was found with the indicator-condition-driven testing strategy, whereas the test-all strategy had the most profound impact on the proportion of late diagnoses. Nevertheless, the HIV testing rates and case-finding varied considerably across studies. In conclusion, effective strategies to promote HIV testing in European hospitals are available, but relevant knowledge gaps regarding generalizability and sustainability remain. These gaps require the promotion of adherence to HIV testing guidelines, as well as additional larger studies representing all European regions.

Natural killer (NK) cell subsets with adaptive properties are emerging as regulators of vaccine-induced T and B cell responses and are specialized towards antibody-dependent functions contributing to SARS-CoV-2 control. Although HIV-1 infection is known to affect the NK cell pool, the additional impact of SARS-CoV-2 infection and/or vaccination on NK cell responses in people living with HIV (PLWH) has remained unexplored. Our data show that SARS-CoV-2 infection skews NK cells towards a more differentiated/adaptive CD57 + FcεRIγ - phenotype in PLWH. A similar subset was induced following vaccination in SARS-CoV-2 naïve PLWH in addition to a CD56 bright population with cytotoxic potential. Antibody-dependent NK cell function showed robust and durable responses to Spike up to 148 days post-infection, with responses enriched in adaptive NK cells. NK cell responses were further boosted by the first vaccine dose in SARS-CoV-2 exposed individuals and peaked after the second dose in SARS-CoV-2 naïve PLWH. The presence of adaptive NK cells associated with the magnitude of cellular and humoral responses. These data suggest that features of adaptive NK cells can be effectively engaged to complement and boost vaccine-induced adaptive immunity in potentially more vulnerable groups such as PLWH., (© 2023. The Author(s).)

Background: To investigate the impact of the M184V/I mutation on virologic response to dolutegravir plus lamivudine (DTG + 3TC) in suppressed-switch populations, a meta-analysis was performed using virologic outcomes from people with human immunodeficiency virus type 1 (PWH) with and without M184V/I before DTG + 3TC switch in real-world studies identified via systematic literature review. Sensitivity analyses were performed using data from PWH with M184V/I in interventional studies identified via targeted literature review., Methods: Single-arm meta-analyses using common- and random-effects models were used to estimate proportions of PWH with virologic failure (VF) among real-world populations with and without M184V/I and interventional study participants with M184V/I at 24, 48, and 96 weeks., Results: Literature reviews identified 5 real-world studies from 3907 publications and 51 abstracts meeting inclusion criteria and 5 interventional studies from 1789 publications and 3 abstracts. All time points had low VF incidence in PWH with M184V/I (real-world: 1.43%-3.81%; interventional: 0.00%) and without (real-world: 0.73%-2.37%). Meta-analysis-estimated proportions (95% confidence interval) with VF were low at weeks 24, 48, and 96, respectively, for PWH with M184V/I (real-world: 0.01 [.00-.04], 0.03 [.01-.06], and 0.04 [.01-.07]; interventional: 0.00 [.00-.02], 0.00 [.00-.01], and 0.00 [.00-.03]) and without (real-world: 0.00 [.00-.02], 0.02 [.01-.04], and 0.02 [.00-.05]). One real-world study (n = 712) reported treatment-emergent M184V at VF in 1 of 652 (0.15%) PWH without prior M184V/I., Conclusions: Results suggest that prior M184V/I has minimal impact on virologic suppression after switching to DTG + 3TC and provide reassurance when considering switching regimens in virologically suppressed PWH with incomplete treatment history or limited treatment options., Competing Interests: Potential conflicts of interest. M. K. was a complimentary worker for ViiV Healthcare at the time of the analysis. G. V. is an employee of ViiV Healthcare. C. M. P., B. J., C. O., J. Pr., and E. L. are employees of ViiV Healthcare and own stock in GSK. T. J. B. has received grants from Gilead, MSD, Roche, and ViiV Healthcare; consulting fees and honoraria from Gilead, GSK, Janssen, MSD, Roche, Theratechnologies, and ViiV Healthcare; and travel support from Gilead and ViiV Healthcare. C. A. has received honoraria from Gilead, MSD, and ViiV Healthcare; has received travel support from Gilead and MSD; and is a member of the CPP Ouest IV Ethics Committee. A.-G. M. has received grants and honoraria from Gilead, MSD, and ViiV Healthcare; consulting fees from GSK; and travel support from Gilead. J. Pa. has received honoraria from Gilead, Janssen-Cilag, MSD, and ViiV Healthcare and travel support from Gilead and Janssen-Cilag. N. G. has received grants, honoraria, and travel support from Gilead, Janssen-Cilag, MSD, and ViiV Healthcare. J. M. L. has received grants from Gilead and ViiV Healthcare; has received speaker honoraria from Gilead, Janssen-Cilag, and ViiV Healthcare; and is a member of the Spanish Antiretroviral Treatment Guidelines panel. D. R.-C. has received honoraria from Gilead and ViiV Healthcare and travel support from Gilead. R. D. M.-B. has received speaker fees from Gilead and ViiV Healthcare and travel support from ViiV Healthcare. G. B. has received honoraria and travel support from ViiV Healthcare. M. T., C. H., and T. W. are employees of HEOR Ltd, which received funding from ViiV Healthcare to support this analysis. S. D. G. reports no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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.

Although microbubbles are used primarily in the medical industry as ultrasonic contrast agents, they can also be manipulated by acoustic waves for targeted drug delivery, sonothrombolysis and sonoporation. Acoustic waves can also potentially remove microbubbles from tubing systems (e.g., in hemodialysis) to prevent the negative effects associated with circulating microbubbles. A deeper understanding of the interactions between the acoustic radiation force, the microbubble and the channel wall could greatly benefit these applications. In this study, single air-filled microbubbles were injected into a flowing (polydimethylsiloxane) channel and monitored by a high-speed camera while passing through a pulsed ultrasonic wave zone (0.5 MHz). This study compared various bubble sizes, flow rates and acoustic pressure amplitudes to better understand the three physical regimes observed: free bubble translation (away from the wall); on-wall translation; and bubble-wall attachment. Comparison with a theoretical model revealed that the acoustic radiation force needs to exceed the combined repulsive forces (shear lift, wall lubrication and repulsive Van der Waal forces) for the dead state of bubble-wall attachment. The bubble dynamics revealed through this investigation provide an opportunity for efficient positioning of microbubbles in a channel flow, for either in vivo manipulation or removal in biological applications., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2022 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: Since 2015, we prescribed dolutegravir (DTG)-based two drug regimens (DTG-2DR) for 620 people [total cohort 3133 (19.8%)]., Method: Clinic database search 1 January 15 to 31 October 21. Demographic, tolerability and HIV related data analysed., Results: In total, 620 people identified; 561 had complete data. 446 male (79.5%); median age 54 years (interquartile range 46, 59). 343 (61.1%) MSM. Nine people who initiated naïvely achieved viral suppression (100%). 546/552 (99.0%) switched or continued and were suppressed at data censor. 460/552 (83.3%) received DTG-lamivudine (DTG/3TC), 74/552 (13.4%) received DTG-rilpivirine (DTG/RPV) and 18/552 (3.3%) received DTG-emtricitabine (DTG/FTC). 70 (12.5%) switched off DTG-2DR (55 DTG/3TC, 13 DTG/RPV, two DTG/FTC) due to side-effects. 41 episodes of blip (1 off >50 copies/ml) occurred in 30 people (5.3%). 11/41 on DTG-RPV [ n  = 7 multi-tablet regimen (MTR), n  = 4 single tablet regimen (STR)]. 27/41 DTG-3TC, 3/41 DTG/FTC ( n  = 26 MTR, n  = 4 STR). Six people (1.1%) failed (confirmed viral load >200 copies/ml or persistent low level viraemia) ( n  = 4 DTG-3TC STR, n  = 1 DTG-3TC MTR, n  = 1 DTG-RPV MTR). Four failures due to low level viraemia, one due to non-adherence and one due to high viral load. Resistance tests performed for 5/6 - mutations detected only in latter person with high viral load failure (on DTG-3TC MTR) who developed triple class resistance., Conclusion: Majority of experience is in DTG/3TC stable switch. Minority of patients developed side-effects. Low number of virological failures, one developed integrase inhibitor resistance. Viral failure associated with MTR, commensurate with trial data showing no failure with resistance if DTG/3TC STR used. Overall DTG-2DR demonstrates high efficacy in real-world setting., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

We assessed a cohort of people living with human immunodeficiency virus (PLWH) (n = 110) and HIV negative controls (n = 64) after 1, 2 or 3 SARS-CoV-2 vaccine doses. At all timepoints, PLWH had significantly lower neutralizing antibody (nAb) titers than HIV-negative controls. We also observed a delayed development of neutralization in PLWH that was underpinned by a reduced frequency of spike-specific memory B cells (MBCs). Improved neutralization breadth was seen against the Omicron variant (BA.1) after the third vaccine dose in PLWH but lower nAb responses persisted and were associated with global MBC dysfunction. In contrast, SARS-CoV-2 vaccination induced robust T cell responses that cross-recognized variants in PLWH. Strikingly, individuals with low or absent neutralization had detectable functional T cell responses. These PLWH had reduced numbers of circulating T follicular helper cells and an enriched population of CXCR3 + CD127 + CD8 + T cells after two doses of SARS-CoV-2 vaccination., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Purpose: The proportion of people living with HIV being older adults is increasing and due to high rates of multimorbidity and frailty within this group geriatricians are well placed to contribute to their care. However, little is known about how geriatricians feel about this new opportunity., Methods: A scoping review was performed following the Arksey & O'Malley's methodological framework with nine databases searched in December 2021 for studies reporting the experiences or views of geriatricians on caring for people living with HIV. Study inclusion was not limited by language or year of publication. Narrative reviews were excluded. Two reviewers independently performed the extraction using predetermined criteria. A descriptive analysis of extracted information was performed., Results: Six publications reporting four studies, all conducted in the USA, were identified. The current barriers to geriatricians being involved in the care of older people living with HIV are: their current experience in managing people living with HIV, their knowledge of HIV, specific issues related to older people living with HIV and screening for HIV in older people as well as their attitudes to people living with HIV and experience of managing older LGBTQ + people., Conclusion: Prior to geriatricians being routinely involved in the care of older people living with HIV further research outside of the USA is required. Geriatricians will also require specific training which should be incorporated into geriatric medicine training curricula as well as the creation of learning tools and quality clinical practice guidelines ideally created in collaboration with HIV organisations., (© 2022. The Author(s).)

Ukraine is one of the countries in Europe most affected by HIV. The escalation of open war on the European continent has affected HIV care in Ukraine in an unprecedented way. Treating physicians in Europe have little experience on how to handle HIV-specific care under these circumstances. A framework is urgently needed that both defines and sets out strategies to handle the specific challenges for emergency support for people living with HIV, both those staying in Ukraine and those becoming displaced. The optimal allocation of the few available medical resources, primarily antiretroviral therapy, is necessary to best prevent individual morbidity and achieve population transmission control. Professional HIV networks play a central role to create, optimise, and execute support strategies. Through a rapid literature review we identified the key strategies needed to create a support framework, adapted to Ukraine's HIV epidemiology. We produce a unified support framework aiming to reduce the inevitable impact on Ukraine's HIV care cascade now, and when rebuilding it after the war., Competing Interests: Declaration of interests JIB declares grants or contracts from Gilead, Janssen, MSD, and ViiV healthcare; and consulting frees from Gilead, Janssen, MSD, and ViiV healthcare. OS declares grants and honoraria from Gilead. AL declares grants or contracts from Gilead, My Cartis, and ViiV healthcare; consulting fees from Janssen and ViiV healthcare; and payment of honoraria from Gilead, Janssen-Cilag, and ViiV healthcare. AC declares grants or contracts from Gilead; and payment or honoraria from Gilead, Janssen-Cilag, MSD, and ViiV healthcare. CDS declares payment or honoraria from AbbVie, AstraZeneca, Cepheid, Formycon, Gilead, GSK, Janssen, Molecular Partners, MSD, Roche, Swedish Orphan Biovitrium, and ViiV Healthcare; and support for attending meetings or travel, or both, from AbbVie, AstraZeneca, Cepheid, Formycon, Gilead, GSK, Janssen, Molecular partners, MSD, Roche, Swedish Orphan Biovitrium, and ViiV Healthcare. SN declares grants or contracts from Gilead and ViiV healthcare; consulting fees from Gilead, Janssen, MSD, and ViiV healthcare; payment or honoraria from Gilead, Janssen, MSD, and ViiV healthcare; and support for attending meetings or travel, or both, from Janssen, Gilead, and ViiV healthcare. AW declares grants and consulting fees from Gilead, Janssen, and ViiV healthcare. TJB declares grants or contracts from Gilead, Janssen, MSD, Roche, Thera, and ViiV healthcare; support for attending meetings or travel, or both, from Gilead, Janssen, MSD, Roche, Thera, and ViiV healthcare; consulting fees from Gilead, MSD, Roche, Thera, and ViiV healthcare; and payment or honoraria from Gilead, Janssen, MSD, Roche, Thera, and ViiV healthcare. LW declares consulting fees from Cipla, Gilead, Merck, Mylan, Theratech, ViiV healthcare; payment or honoraria from Gilead, Janssen, Merck, Mylan, Theratech, and ViiV healthcare; and research grants from Gilead, Janssen, and ViiV healthcare. SB declares consulting fees and honoraria from Gilead, MSD, Roche, Sobi, ViiV healthcare. CR declares support for the present manuscript from Aidsfonds and Dutch Federation Medical Specialists; grants or contracts from Erasmus MC Fellowship, Gilead, Health~Holland, Janssen, MSD, ViiV healthcare, and ZonMW; consulting fees from Gilead and ViiV healthcare; and payment or honoraria from Gilead, ViiV healthcare, and Virology Education. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In 2020, 37.7 million (30.2-45.1 million) people were living with HIV globally, with 27.5 million (26.5-27.7 million) accessing antiretroviral therapy. Women and girls accounted for half of all new HIV infections. HIV is now a treatable chronic health condition, and people diagnosed with HIV can expect to live long and healthy lives with access to antiretroviral therapy. There is evidence, however, that people with HIV are more likely to develop certain age-related diseases, including cardiovascular disease, chronic airway disease, kidney failure, liver failure, cancer, type 2 diabetes and other complications. People with HIV also continue to experience intersecting social stigma, which affects their health outcomes compared with the general population. Amid the coronavirus disease (COVID-19) pandemic, new opportunities and challenges are emerging in HIV medicine and emphasize the need for clinicians to maintain a working knowledge of HIV and its potential complications., (© 2022 Published by Elsevier Ltd.)

Competing Interests: JL has received payments or honoraria for lectures, presentations, or speaker’s bureaus from Janssen-Cilag, Gilead Sciences, and ViiV Healthcare, outside of the present work. PC has received research grants from Richmond and ViiV Healthcare, consulting fees from ViiV Healthcare; has received honoraria for speaker fees from ViiV Healthcare and Novartis; and has participated in data safety monitoring/advisory boards for Moderna, ViiV Healthcare, and Merck. TB has received conference support, speaker fees, and advisory board honoraria from Gilead Sciences, Janssen, MSD, Roche, Theratech, and ViiV Healthcare, and holds research and educational grants from Gilead Sciences, Roche, and ViiV Healthcare.

Objectives: By 2030 the majority of the people living with HIV in the United Kingdom will be over the age of 50. HIV services globally must adapt to manage people living with HIV as they age. Currently these services are often designed based on data from the wider population or from the experiences of HIV clinicians. This article aims to help clinicians designing inclusive HIV services by presenting the most common needs identified during the first year of a specialist clinic for older people living with HIV at the Ian Charleson Day Centre, Royal Free Hospital in London, United Kingdom., Methods: The records of all thirty-five patients attending the inaugural nine sessions were reviewed., Results: The median age of attendees was 69 (53-93) with 77% being male, 63% being White, 49% being heterosexual and 97% being virally suppressed respectively. The majority (83%) met the criteria for frailty using the Fried frailty phenotype. Eighteen issues linked to ageing were identified with the most common being affective symptoms (51%), memory loss (37%) and falls (29%)., Conclusions: Whilst older people living with HIV are a heterogeneous group frailty is common and appears to present earlier. HIV services either need to adapt to meet these additional needs or must support users in transitioning to existing services. We feel that our multidisciplinary model is successful in identifying problems associated with ageing in people living with HIV and could be successfully replicated elsewhere., (© 2021 British HIV Association.)

Background: The 2-drug regimen dolutegravir plus lamivudine has demonstrated long-term noninferior efficacy vs 3-/4-drug regimens (3/4DRs) in phase 3 trials. This systematic literature review summarizes clinical trial and real-world evidence evaluating impact of dolutegravir plus lamivudine on inflammatory and atherogenesis biomarkers in people with human immunodeficiency virus type 1 (PWH)., Methods: Using Ovid MEDLINE, Embase, PubMed, and Cochrane library databases and conference proceedings, we searched for studies published from 1 January 2013 to 14 July 2021, reporting changes in inflammatory and atherogenesis biomarkers with dolutegravir plus lamivudine in antiretroviral therapy-experienced, virologically suppressed PWH aged ≥18 years., Results: Four records representing 2 randomized controlled trials (RCTs) and 6 records of real-world evidence met eligibility criteria. All real-world studies evaluated CD4 + /CD8 +  ratio, while only 1 assessed inflammatory biomarkers. Across both RCTs, no consistent pattern of change in biomarkers was observed between dolutegravir/lamivudine and 3/4DR comparators. There were significant changes in soluble CD14 favoring dolutegravir/lamivudine in TANGO at weeks 48 and 144 and SALSA at week 48, and in interleukin-6 favoring the control group in TANGO at weeks 48 and 144. In the real-world study evaluating inflammatory biomarkers, median soluble CD14 significantly decreased 48 weeks postswitch to dolutegravir plus lamivudine ( P  < .001), while other biomarkers remained stable. In all 6 real-world studies, increases in CD4 + /CD8 +  ratio were reported after switch to dolutegravir plus lamivudine (follow-up, 12-60 months)., Conclusions: Results show that dolutegravir plus lamivudine has a comparable impact on inflammatory and atherogenesis biomarkers vs 3/4DRs, with no consistent pattern of change after switch in virologically suppressed PWH., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Purpose of Review: The HIV population is ageing with rising rates of frailty though strategies of how best to manage it remain ill-defined. It also remains unclear what the prevalence of frailty is within this cohort, how best to diagnose it and what factors are associated., Recent Findings: The prevalence of frailty remains unclear because of heterogenous results. Routine screening in those 50+ is recommended and whilst the Fried Frailty Phenotype is currently preferred the Clinical Frailty Scale could be considered. No biomarkers are currently recommended. Looking at associated factors, HIV neurocognitive impairment and long-term alcohol usage has been shown to be associated with developing frailty whilst those who are frail have been shown to be less active and more likely to fall. NAFLD with fibrosis has been shown to be an indicator of metabolic age and the Pooled Cohort Equations has been shown to be more effective in diagnosing cardiovascular risk in frail people living with HIV., Summary: Whilst the prevalence of frailty differs between countries, with the addition of prefrailty, this represents a large proportion of people living with HIV. Services must ensure strategies are in place to support those living with HIV and frailty. Further longitudinal studies are required., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Research on HIV and reproduction has focused largely on women and heterosexual men. This article examines whether it is relevant to address parenthood in HIV care with gay men and what ways of doing so are most appropriate., Methods: Qualitative interviews were conducted at four London clinics with 25 men living with HIV, aged 20-45, who did not have children, and 16 HIV clinicians. A thematic analysis identified potential reasons why parenthood was rarely discussed with gay men in HIV care., Results: Two sets of ideas contributed to a lack of conversations about parenthood: clinicians' ideas about what matters to gay men and men's ideas about what it means to be HIV-positive. Both sets of ideas largely excluded having children, with patients and practitioners similarly unlikely to raise the topic of parenthood in the clinic. Contrary to what clinician commonly assumed, many men expressed interest in receiving more information, highlighting the importance of reassuring people upon diagnosis that it is possible to become parents while living with HIV., Conclusions: Parenting desires and intentions were rarely discussed with men in HIV care. Our findings illuminate the potentially beneficial effects of emphasising that having children is a possibility at diagnosis, regardless of patients' gender or sexuality. Conveying this information seems meaningful, not only to men who want to become parents in the future but also to others, as it appears to alleviate fears about mortality and ill health., (© 2021. The Author(s).)

Competing Interests: TJB has received speaker or advisory fees and conference support from MSD, ViiV, Gilead, Roche, and Theratech, and holds educational or research grants from ViiV, Gilead and Roche. LJW has received speaker or advisory fees from MSD, ViiV, Janssen, Gilead, Theratech, Cipla & Mylan and is an investigator on trials sponsored by Gilead & Janssen.

It is now established that people living with HIV who have an undetectable viral load and adhere to antiretroviral treatment cannot transmit HIV to their sexual partners. Previous research has shown that 'being undetectable' changes how HIV-positive gay men experience their sex lives. But how does it affect gay men's reproductive behaviours? And what influence does it have on views about parenthood at a time when gay fatherhood has become more socially accepted and publicly visible? Drawing on qualitative interviews with patients and clinicians at four HIV clinics in London, we identify differences in how interviewees talked about the possibility of having children for HIV-positive men. Both groups, unprompted, frequently referred to sperm washing as a method enabling safe conception. However, whereas clinicians talked about sperm washing as an historical technique, which is no longer necessary, patients spoke of it as a current tool. The men rarely mentioned being undetectable as relevant to parenthood and, when prompted, some said that they did not fully understand the mechanics of HIV transmission. Our findings offer new insights into how biomedical knowledge is incorporated into people's understandings of living with HIV, raising important questions about how the meanings of being undetectable are communicated., (© 2020 The Authors. Sociology of Health & Illness published by John Wiley & Sons Ltd on behalf of Foundation for SHIL (SHIL).)

Pre-exposure prophylaxis (PrEP) is the provision of antiretroviral drugs before HIV exposure to prevent infection for those in whom it is indicated. We conducted an online survey about PrEP in a national sample of infectious diseases physicians in Turkey. They were surveyed from March to April 2019 and they were asked about their attitudes, knowledge and clinical practise about PrEP. Overall, 209 of 2100 (10%) completed the survey, of whom 66.3% were female, 69.5% were specialist and 41.1% were working at education and research hospitals. Most of the participants reported their PrEP knowledge as 'low'. Men who have sex with men was the most suitable group for PrEP according to participants. 27.9% of them were requested to prescribe PrEP which was to be paid by individuals themselves and 24.2% of the participants had recommended PrEP in their clinical practice. The primary concerns among those who would not recommend PrEP were the possible increase in sexually transmitted infections, the potential low cost-effectiveness of PrEP, the ineffectiveness of PrEP in HIV transmission and the time lost to following-up the individuals taking PrEP. Developing a national guideline would support clinicians in order to change their attitudes and to find answers to their concerns.

Background and Objective: The use of patient-specific CFD modelling for arteriovenous fistulae (AVF) has shown great clinical potential for improving surveillance, yet the use of imaging modes such as MRI and CT for the 3D geometry acquisition presents high costs and exposure risks, preventing regular use. We have developed an ultrasound based procedure to bypass these limitations., Methods: A scanning procedure and processing pipeline was developed specifically for CFD modelling of AVFs, using a freehand ultrasound setup combining B-mode scanning with 3D probe motion tracking. The scanning procedure involves sweeping along the vasculature to create a high density stack of B-mode frames containing the lumen geometry. This stack is converted into a continuous volume and transient flow waveforms are recorded at the boundaries, synchronised with ECG and automatically digitised, forming realistic boundary conditions for the CFD models. This is demonstrated on a diseased patient-specific AVF., Results: The three scans obtained using this procedure varied in geometry and flow behaviour, with regions of disease located in the first two scans. The outcome of the second procedure seen in the third scan indicated successful restoration with no sites of disease and higher flow. The models gave insight into the lumenal changes in diameter for both the artery and vein segments, as well as characterising hemodynamic behaviours in both the diseased and restored states. Vascular segment resistances obtained from the CFD models indicate a significant reduction once disease was removed, resulting in much higher flows enabling the patient to resume dialysis., Conclusion: The methodology described in this study allowed for a multifaceted analysis and high level tracking in terms of both geometry and flow behaviours for a patient case, demonstrating significant clinical utility and practicality, as well as enabling further research into vascular disease progression in AVFs through longitudinal analysis., (Copyright © 2019. Published by Elsevier B.V.)

Globally, around 2.6 million people receive renal replacement therapy (RRT), and a further 4.9-9.7 million people need, but do not have access to, RRT [1]. The next generation RRT devices will certainly be in demand due to the increasing occurrence of diabetes, atherosclerosis and the growing population of older citizens. This review provides a comprehensive, yet concise overview of the cleared and remaining hurdles in the development of artificial kidneys to move beyond traditional dialysis technology-the current baseline of renal failure treatment. It compares and contrasts the state-of-the-art in 'cell-based' and 'non-cell-based' approaches. Based on this study, a new engineering perspective on the future of artificial kidneys is described. This review suggests that stem-cell-based artificial kidneys represent a long-term, complete solution but it can take years of development due to the limitations of current cell seeding technology, viability and complicated behaviour control. Alternatively, there is much potential for near- and medium- term solutions with the development of non-cell-based wearable and implantable devices to support current therapies. Based on recent fundamental advances in microfluidics, membranes and related research, it may be possible to integrate these technologies to enable implantable artificial kidneys (iAK) in the near future.

Prior numerical studies have shown that the blood flow patterns surrounding drug-eluting stents can enhance drug uptake in stented arteries. However, these studies employed steady-state simulations, wherein flow and drug transport parameters remained constant with respect to time. In the present study, numerical simulations and in-vitro experiments were performed to determine whether luminal blood flow patterns can truly enhance drug uptake in stented arteries. Unlike the aforementioned studies, the time-varying depletion of drug within the stent coating was modelled and the simulation results were validated qualitatively with the in-vitro experiments. The simulations showed that the non-Newtonian properties of blood, its complex near-wall behavior, and the pulsatility of its flow all affect drug uptake only modestly. Furthermore, flow-mediated drug transport was found to be negligible due to the rapid rate at which drug depletes at the stent coating surfaces that are exposed to arterial blood flow. For fluid dynamicists, these results show that steady-state simulations must be avoided when modelling drug transport in stented arteries. For device designers, these results may be used to optimize the shape of drug-eluting stent struts and coatings to improve stent efficacy.

Competing Interests: Competing interests: Some authors work for organisations involved in supporting parenting options described.