The Impact of Time between Booster Doses on Humoral Immune Response in Solid Organ Transplant Recipients Vaccinated with BNT162b2 Vaccines.

As solid organ transplant (SOT) recipients remain at risk of severe outcomes after SARS-CoV-2 infections, vaccination continues to be an important preventive measure. In SOT recipients previously vaccinated with at least three doses of BNT162b2, we investigated humoral responses to BNT162b2 booster doses. Anti-SARS-CoV-2 receptor binding domain (RBD) immunoglobulin G (IgG) was measured using an in-house ELISA. Linear mixed models were fitted to investigate the change in the geometric mean concentration (GMC) of anti-SARS-CoV-2 RBD IgG after vaccination in participants with intervals of more or less than six months between the last two doses of vaccine. We included 107 SOT recipients vaccinated with a BNT162b2 vaccine. In participants with an interval of more than six months between the last two vaccine doses, we found a 1.34-fold change in GMC per month (95% CI 1.25-1.44), while we found a 1.09-fold change in GMC per month (95% CI 0.89-1.34) in participants with an interval of less than six months between the last two vaccine doses, resulting in a rate ratio of 0.82 (95% CI 0.66 to 1.01, p = 0.063). In conclusion, the administration of identical COVID-19 mRNA vaccine boosters within six months to SOT recipients may result in limited humoral immunogenicity of the last dose.

Exploring the concept of unmet need within sexual and reproductive health in England: A qualitative Delphi exercise.

BACKGROUND: Unmet need within sexual and reproductive health (SRH) is a concept that is difficult to define and measure. This qualitative Delphi exercise was used to ascertain the opinions of SRH professionals on the conceptualisation and measurement of unmet need within SRH. METHODS: This exercise was carried out in two rounds. In the first round, respondents responded narratively to three prompts, which were then used to create a series of statements. In the second round, participants responded narratively to the statements created in the first round. Responses from both rounds were then coded and analysed thematically. RESULTS: Participants felt that an understanding of unmet need is an important part of SRH service design and provision, and believed that certain populations are often underrepresented within the datasets that are used to assess unmet need. Many respondents felt that a full understanding of unmet need within SRH would only come from involvement of relevant stakeholders in the process of investigating unmet need, and that qualitative methods may also have a role to play in gaining a more holistic understanding of unmet need within SRH. CONCLUSIONS: Respondents within this study felt that unmet need is complex concept that has a significant impact on service delivery and the outcomes and experiences of the most vulnerable populations. We need to improve our understanding of unmet need and prioritise stakeholder voices if we want to create interventions that address unmet need within SRH.

Inequalities in sexual and reproductive outcomes among women aged 16-24 in England (2012-2019).

BACKGROUND: Women aged 16-24 in England have a high burden of sexual and reproductive morbidity, with particularly poor outcomes among people living in more deprived areas (including racially minoritised populations). This analysis used national data to examine the disparities within sexual and reproductive outcomes among this population and to assess whether the patterns of inequality were consistent across all outcomes. METHODS: Within this ecological study, univariable and multivariable Poisson regression analyses of neighbourhood-level data from national data sets were carried out to investigate the relationships of deprivation and ethnicity with each of six dependent variables: gonorrhoea and chlamydia testing rates, gonorrhoea and chlamydia test positivity rates, and abortion and repeat abortion rates. RESULTS: When comparing Index of Multiple Deprivation (IMD) decile 1 (most deprived) and IMD decile 10 (least deprived), chlamydia (RR 0.65) and gonorrhoea (0.79) testing rates, chlamydia (0.70) and gonorrhoea (0.34) positivity rates, abortion rates (0.45) and repeat abortion rates (0.72) were consistently lower in IMD decile 10 (least deprived). Similarly, chlamydia (RR 1.24) and gonorrhoea positivity rates (1.92) and repeat abortion rates (1.31) were higher among black women than white women. Results were similar when both ethnicity and deprivation were incorporated into multivariable analyses. CONCLUSION: We found similar patterns of outcome inequality across a range of sexual and reproductive outcomes, despite multiple differences in the drivers of each outcome. Our analysis suggests that there are broad structural causes of inequality across sexual and reproductive health that particularly impact the health of deprived and black populations.

Improving 1-Year Mortality Following Intensive Care Unit Admission in Adults with HIV: A 20-Year Observational Study.

BACKGROUND: Despite widespread use of combination antiretroviral therapy, people with HIV (PWH) continue to have an increased risk of admission to and mortality in the intensive care unit (ICU). Mortality risk after hospital discharge is not well described. Using retrospective data on adult PWH (≥18 years) admitted to ICU from 2000-2019 in an HIV-referral centre, we describe trends in 1-year mortality after ICU admission. METHODS: One-year mortality was calculated from index ICU admission to date of death; with follow-up right-censored at day 365 for people remaining alive at 1 year, or day 7 after ICU discharge if lost-to-follow-up after hospital discharge. Cox regression was used to describe the association with calendar year before and after adjustment for patient characteristics (age, sex, Acute Physiology and Chronic Health Evaluation II [APACHE II] score, CD4+ T-cell count, and recent HIV diagnosis) at ICU admission. Analyses were additionally restricted to those discharged alive from ICU using a left-truncated design, with further adjustment for respiratory failure at ICU admission in these analyses. RESULTS: Two hundred and twenty-one PWH were admitted to ICU (72% male, median [interquartile range] age 45 [38-53] years) of whom 108 died within 1-year (cumulative 1-year survival: 50%). Overall, the hazard of 1-year mortality was decreased by 10% per year (crude hazard ratio (HR): 0.90 (95% confidence interval: 0.87-0.93)); the association was reduced to 7% per year (adjusted HR: 0.93 (0.89-0.98)) after adjustment. Conclusions were similar among the subset of 136 patients discharged alive (unadjusted: 0.91 (0.84-0.98); adjusted 0.92 (0.84, 1.02)). CONCLUSIONS: Between 2000 and 2019, 1-year mortality after ICU admission declined at this ICU. Our findings highlight the need for multi-centre studies and the importance of continued engagement in care after hospital discharge among PWH.

Identifying missed opportunities for hepatitis C virus antenatal testing and diagnosis in England.

New case-finding opportunities are needed to achieve hepatitis C virus (HCV) elimination in England by the year 2030. HCV antenatal testing is not offered universally in England but is recommended for women with risk factors for HCV (e.g. injecting drug use, being born in a high-prevalence country). The aim of this analysis was to investigate the missed opportunities for HCV antenatal testing among women who had given birth and were subsequently diagnosed with HCV at some time after childbirth. By linking data on live births (2010-2020) to laboratory reports of HCV diagnoses (1995-2021), we identified all women who were diagnosed with HCV after the date of their first childbirth. This group was considered to potentially have experienced a missed opportunity for HCV antenatal testing; HCV-RNA testing and treatment outcomes were also obtained for these women. Of the 32,295 women who gave birth between 2010 and 2020 with a linked diagnosis of HCV (median age: 34 years, 72.1% UK-born), over half (n = 17,123) were diagnosed after childbirth. In multivariable analyses, the odds of being diagnosed with HCV after childbirth were higher in those of Asian Bangladeshi, Black African or Chinese ethnicity and among those born in Africa. Over four-fifths (3510/4260) of those eligible for treatment were linked to treatment, 30.7% (747/2435) of whom had a liver scarring level of at least moderate and 9.4% (228/2435) had cirrhosis. Given the potential opportunity to identify cases of HCV with targeted case-finding through antenatal services, universal opt-out testing should be considered in these settings.

Hepatic steatosis in people older and younger than fifty who are living with HIV and HIV-negative controls: A cross-sectional study nested within the POPPY cohort.

BACKGROUND: Hepatic steatosis is a major cause of chronic liver disease associated with several negative health outcomes. We compared the prevalence of and factors associated with steatosis in people living with and without HIV. METHODS: Older (>50 years) and younger (<50 years) people with HIV and older HIV-negative controls (>50 years) underwent liver transient elastography examination with controlled attenuation parameter (steatosis ≥238 dB/m, moderate/severe steatosis ≥280 dB/m, liver fibrosis ≥7.1 kPa). We compared groups using logistic regression/Chi-squared/Fisher's exact/Kruskal-Wallis tests. RESULTS: In total, 317 participants (109 older people with HIV; 101 younger people with HIV; 107 HIV-negative controls) were predominantly white (86%) and male (76%), and 21% were living with obesity (body mass index ≥30 kg/m2 ). Most (97%) people with HIV had undetectable HIV RNA. The prevalence of fibrosis was 8.4%, 3.0%, and 6.5% in the three groups, respectively (p = 0.26). Fibrosis was predominately (>65%) mild. The prevalence of steatosis was the same in older people with HIV (66.4%) and controls (66.4%) but lower in younger people with HIV (37.4%; p < 0.001). After adjustment, younger people with HIV were less likely to have steatosis (odds ratio [OR] 0.26; 95% confidence interval [CI] 0.14-0.52) than controls, but male sex (OR 2.45; 95% CI 1.20-4.50) and high waist-to-hip ratio (OR 3.04; 95% CI 1.74-5.33) were associated with an increased odds of steatosis. We found no association between steatosis and HIV-related variables. CONCLUSIONS: The prevalence of hepatic steatosis and fibrosis was similar between older participants regardless of HIV status. Age, sex, and abdominal obesity, but not HIV-related variables, were associated with steatosis. Interventions for controlling obesity should be integrated into routine HIV care.

Understanding the conditions included in data-driven patterns of multimorbidity: a scoping review.

BACKGROUND: Despite the growing utilization of data-driven methods to investigate multimorbidity patterns, there is currently no consensus or guidance on the conditions to include when identifying patterns. This scoping review aims to systematically examine the nature of conditions included in existing studies using data-driven techniques. METHODS: A comprehensive search of three electronic databases (MEDLINE, Web of Science and Scopus) was conducted to identify relevant publications from inception to 28 February 2022 using predefined search terms and inclusion/exclusion criteria. The reference lists and citations of relevant papers were also searched. RESULTS: Among 7326 search results, 5444 relevant articles were identified. After screening against the eligibility criteria, 60 articles were included in the review. Half of the reviewed studies reported selection criteria for conditions, with prevalence in the population of interest being the most common criterion (40%). Most studies included at least one neurological [59 (98.3%)], musculoskeletal [58 (96.7%)], respiratory [57 (95.0%)] or mental health [56 (93.3%)] condition. In contrast, only a small proportion of studies included skin [17 (28.3%)], infections [14 (23.3%)] or autoimmune conditions [10 (16.7%)]. Nine conditions (hypertension, diabetes, cancer, arthritis, COPD, asthma, depression, stroke and osteoporosis) were included by more than half of the studies. CONCLUSIONS: This review highlights the considerable heterogeneity among the conditions included in analyses of multimorbidity patterns. Researchers should provide a clear rationale for the selection of conditions to facilitate comparisons across studies and ensure reproducibility, as well as consider selecting a diverse range of conditions to capture the complexity of multimorbidity.

HIV pre-exposure prophylaxis and its implementation in the PrEP Impact Trial in England: a pragmatic health technology assessment.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV acquisition. To enable routine commissioning of PrEP in England, we aimed to establish population need, duration of need, PrEP uptake, and duration of use in attendees of sexual health services (SHS) in England. METHODS: The Impact Trial was a prospective, open-label, single-arm, multicentre trial conducted at 157 SHS across England between Oct 13, 2017, and July 12, 2020. Clinicians assessed HIV-negative attendees for their risk of HIV acquisition to identify those who were eligible to participate and receive either daily or event-based oral PrEP (tenofovir disoproxil maleate with emtricitabine), as appropriate. Eligible participants were aged 16 years or older, considered HIV-negative on the day of enrolment, and willing to adhere to the trial procedures. Non-trial attendees are mutually exclusive of trial participants and included SHS attendees who were not recruited to the Impact Trial at any point. They include HIV-negative individuals aged 16 years or older who attended a participating SHS at least once after recruitment at that SHS had begun and before Feb 29, 2020. The main outcomes assessed were PrEP need, uptake, and use, and HIV and sexually transmitted infection (STI) incidence. Data are presented up to Feb 29, 2020, before the introduction of COVID-19 control measures. The study is registered with ClinicalTrials.gov, NCT03253757. FINDINGS: In this analysis, we include 21 356 of 24 268 participants enrolled before Feb 29, 2020. 20 403 participants (95·5%) were men who have sex with men (MSM). Uptake of PrEP among SHS attendees clinically assessed and coded as eligible was 21 292 (57·1%) of 37 289. 18 400 trial participants had at least one post-enrolment visit and a median of 361 days of follow-up (IQR 143-638); 14 039 (75·9%) of these had enough PrEP prescribed to provide protection for 75% of their follow-up time. Among MSM, HIV incidence was 0·13 (95% CI 0·08-0·19) per 100 person-years in trial participants (27 seroconversions) and 0·95 (95% CI 0·88-1·03) per 100 person-years in non-trial attendees (587 seroconversions; proportionate reduction of 86·8%, 95% CI 80·2-91·6). 18 607 bacterial STIs were recorded (incidence 68·1 per 100 person-years in trial participants who were MSM). 4343 (24·4%) MSM participants were diagnosed with two or more STIs, accounting for 14 800 (79·5%) of all 18 607 diagnoses. INTERPRETATION: PrEP need was higher than initially estimated by an expert stakeholder group. The high proportion of follow-up time protected by PrEP suggests that the need for protection persisted throughout trial participation for most participants. HIV incidence among MSM trial participants was low. The large unmet need for PrEP suggests that greater provision is required to maximise the potential of a national programme. The high incidence of bacterial STIs among participants, concentrated within a subgroup of PrEP users, presents an opportunity for tailored STI control measures. FUNDING: NHS England.

Anti-Hepatitis C (HCV) test positivity and new HCV diagnoses among women tested in antenatal services in England between 2015-2019.

OBJECTIVE: To determine associations with hepatitis C virus (HCV) positivity, new HCV diagnoses and subsequent linkage to HCV treatment services among pregnant women in England. METHOD: A retrospective cohort using routine laboratory tests for HCV-specific antibody (anti-HCV) and HCV-RNA undertaken during antenatal attendances England. All women receiving at least one anti-HCV test during an antenatal clinic attendance between 2015 and 2019 were included. Multivariable logistic regression was used to investigate sociodemographic associations with anti-HCV test positivity among pregnant women who did (PWIDs) and did not (non-PWIDs) inject drugs, as well as to identify sociodemographic factors associated with being newly diagnosed during pregnancy. Linkage to antiviral treatment services and treatment outcomes were determined for those women who tested HCV-RNA positive. RESULTS: 32,088 women (median age 32 years, 19,664 (61 %) UK-born, 337 (1.1 %) PWID) received an anti-HCV test among whom 814 (2.5 %) had a positive anti-HCV test (95 % confidence interval [2.4-2.7 %]). Anti-HCV test positivity was 2.1 % [2.0-2.3 %] among non-PWIDs and 40 % [35-46 %] among PWIDs. In multivariable analyses among non-PWIDs, anti-HCV test positivity was associated with older age, living in more deprived areas, and varied by ethnicity and country of birth. Among PWIDs, anti-HCV test positivity was associated with older age only. Three hundred and twenty (39 %) of the women testing anti-HCV positive were new diagnoses; those who were newly diagnosed were younger and lived in less deprived than those with a prior diagnosis whereas PWIDs were less likely to be newly diagnosed. HCV-RNA positivity was 52 % (n = 330/640, 95 %CI[47.6-55.5 %]) among those with an HCV-RNA test within 30 days, and 75 % (n = 220/293, 95 %CI[69.7-79.9 %]) of those eligible for treatment had engaged in HCV treatment services after antenatal testing. CONCLUSIONS: Antenatal testing for HCV provides an opportunity for new case findings and engagement with treatment services where needed. Therefore, universal opt-out testing for HCV antenatally should be reconsidered.

Integrase strand-transfer inhibitor use and cardiovascular events in adults with HIV: an emulation of target trials in the HIV-CAUSAL Collaboration and the Antiretroviral Therapy Cohort Collaboration.

BACKGROUND: A recent observational study suggested that the risk of cardiovascular events could be higher among antiretroviral therapy (ART)-naive individuals with HIV who receive integrase strand-transfer inhibitor (INSTI)-based ART than among those who receive other ART regimens. We aimed to emulate target trials separately in ART-naive and ART-experienced individuals with HIV to examine the effect of using INSTI-based regimens versus other ART regimens on the 4-year risk of cardiovascular events. METHODS: We used routinely recorded clinical data from 12 cohorts that collected information on cardiovascular events, BMI, and blood pressure from two international consortia of cohorts of people with HIV from Europe and North America. For the target trial in individuals who had previously never used ART (ie, ART-naive), eligibility criteria were aged 18 years or older, a detectable HIV-RNA measurement while ART-naive (>50 copies per mL), and no history of a cardiovascular event or cancer. Eligibility criteria for the target trial in those with previous use of non-INSTI-based ART (ie, ART-experienced) were the same except that individuals had to have been on at least one non-INSTI-based ART regimen and be virally suppressed (≤50 copies per mL). We assessed eligibility for both trials for each person-month between January, 2013, and January, 2023, and assigned individuals to the treatment strategy that was compatible with their data. We estimated the standardised 4-year risks of cardiovascular events (myocardial infarction, stroke, or invasive cardiovascular procedure) via pooled logistic regression models adjusting for time and baseline covariates. In per-protocol analyses, we censored individuals if they deviated from their assigned treatment strategy for more than 2 months and weighted uncensored individuals by the inverse of their time-varying probability of remaining uncensored. The denominator of the weight was estimated via a pooled logistic model that included baseline and time-varying covariates. FINDINGS: The analysis in ART-naive individuals included 10 767 INSTI initiators and 8292 non-initiators of INSTI. There were 43 cardiovascular events in INSTI initiators (median follow-up of 29 months; IQR 15-45) and 52 in non-initiators (39 months; 18-47): standardised 4-year risks were 0·76% (95% CI 0·51 to 1·04) in INSTI initiators and 0·75% (0·54 to 0·98) in non-INSTI initiators; risk ratio 1·01 (0·57 to 1·57); risk difference 0·0089% (-0·43 to 0·36). The analysis in ART-experienced individuals included 7875 INSTI initiators and 373 965 non-initiators. There were 56 events in INSTI initiators (median follow-up 18 months; IQR 9-29) and 3103 events (808 unique) in non-INSTI initiators (26 months; 15-37) in non-initiators: standardised 4-year risks 1·41% (95% CI 0·88 to 2·03) in INSTI initiators and 1·48% (1·28 to 1·71) in non-initiators; risk ratio 0·95 (0·60 to 1·36); risk difference -0·068% (-0·60 to 0·52). INTERPRETATION: We estimated that INSTI use did not result in a clinically meaningful increase of cardiovascular events in ART-naive and ART-experienced individuals with HIV. FUNDING: National Institute of Allergy and Infectious Diseases and National Institute on Alcohol Abuse and Alcoholism.

HIV-1 drug resistance in people on dolutegravir-based antiretroviral therapy: a collaborative cohort analysis.

BACKGROUND: The widespread use of the integrase strand transfer inhibitor (INSTI) dolutegravir in first-line and second-line antiretroviral therapy (ART) might facilitate emerging resistance. The DTG RESIST study combined data from HIV cohorts to examine patterns of drug resistance mutations (DRMs) and identify risk factors for dolutegravir resistance. METHODS: We included cohorts with INSTI resistance data from two collaborations (ART Cohort Collaboration, International epidemiology Databases to Evaluate AIDS in Southern Africa), and the UK Collaborative HIV Cohort. Eight cohorts from Canada, France, Germany, Italy, the Netherlands, Switzerland, South Africa, and the UK contributed data on individuals who were viraemic on dolutegravir-based ART and underwent genotypic resistance testing. Individuals with unknown dolutegravir initiation date were excluded. Resistance levels were categorised using the Stanford algorithm. We identified risk factors for resistance using mixed-effects ordinal logistic regression models. FINDINGS: We included 599 people with genotypic resistance testing on dolutegravir-based ART between May 22, 2013, and Dec 20, 2021. Most had HIV-1 subtype B (n=351, 59%), a third had been exposed to first-generation INSTIs (n=193, 32%), 70 (12%) were on dolutegravir dual therapy, and 18 (3%) were on dolutegravir monotherapy. INSTI DRMs were detected in 86 (14%) individuals; 20 (3%) had more than one mutation. Most (n=563, 94%) were susceptible to dolutegravir, seven (1%) had potential low, six (1%) low, 17 (3%) intermediate, and six (1%) high-level dolutegravir resistance. The risk of dolutegravir resistance was higher on dolutegravir monotherapy (adjusted odds ratio [aOR] 34·1, 95% CI 9·93-117) and dolutegravir plus lamivudine dual therapy (aOR 9·21, 2·20-38·6) compared with combination ART, and in the presence of potential low or low (aOR 5·23, 1·32-20·7) or intermediate or high-level (aOR 13·4, 4·55-39·7) nucleoside reverse transcriptase inhibitor (NRTI) resistance. INTERPRETATION: Among people with viraemia on dolutegravir-based ART, INSTI DRMs and dolutegravir resistance were rare. NRTI resistance substantially increased the risk of dolutegravir resistance, which is of concern, notably in resource-limited settings. Monitoring is important to prevent resistance at the individual and population level and ensure the long-term sustainability of ART. FUNDING: US National Institutes of Health, Swiss National Science Foundation.

A scoping review of media campaign strategies used to reach populations living with or at high risk for Hepatitis C in high income countries to inform future national campaigns in the United Kingdom.

BACKGROUND: With the advent of direct acting antivirals, the World Health Organisation proposed eliminating Hepatitis C as a public health threat by 2030. To achieve this, countries need to diagnose, engage in care and treat their undiagnosed populations. This will require sensitisation campaigns. However previous media campaigns have had mixed impact. We conducted a scoping review to identify and understand the impact of previous Hepatitis C media campaigns. These findings could inform the delivery of future campaigns. METHODS: We searched five electronic databases for published literature on media campaigns conducted for Hepatitis C awareness, testing, and treatment in Organisation for Economic Co-operation and Development (OECD) countries since 2010. Two independent reviewers screened citations for inclusion. Additionally, we spoke to stakeholders in the Hepatitis C field in the UK and conducted a Google search to identify any unpublished literature. A quantitative synthesis was conducted to identify targeted populations, strategies and media used, aims and impact of the campaigns. RESULTS: A title and year of publication screening of 3815 citations resulted in 113 papers that had a full abstract screen. This left 50 full-text papers, 18 were included of which 9 (50%) were from Europe. 5 (27.8%) of campaigns targeted minority ethnicities, and 9 (50%) aimed to increase testing. A Google search identified 6 grey literature sources. Most campaigns were not evaluated for impact. Discussions with stakeholders identified several barriers to successful campaigns including lack of targeted messaging, stigmatising or accusatory messaging, and short-lived or intermittent campaign strategies. CONCLUSION: Future campaigns will likely need to be multifaceted and have multiple tailored interventions. Campaigns will need to be sizeable and robust, integrated into health systems and viewed as an ongoing service rather than one-offs.

Anticholinergic medications associated with falls and frailty in people with HIV.

BACKGROUND: Anticholinergic medications (ACMs) are associated with poorer age-related outcomes, including falls and frailty. We investigate associations between ACM use and recurrent falls and frailty among older (aged ≥50 years) people with HIV in the POPPY study. METHODS: Anticholinergic potential of co-medications at study entry was coded using the anticholinergic burden score, anticholinergic risk score, and Scottish Intercollegiate Guidelines Network score; drugs scoring ≥1 on any scale were defined as ACM. Associations with recurrent falls (two or more falls in the previous 28 days) and frailty (modified Fried's) were assessed using logistic regression adjusting for (1) possible demographic/lifestyle confounders and (2) clinical factors and depressive symptoms (Patient Health Questionnaire-9). RESULTS: ACM use was reported by 193 (28%) of 699 participants, with 64 (9%) receiving two or more ACM; commonly prescribed ACMs were codeine (12%), citalopram (12%), loperamide (9%), and amitriptyline (7%). Falls were reported in 63/673 (9%), and 126/609 (21%) met the frailty criteria. Both recurrent falls and frailty were more common in ACM users than in non-users (recurrent falls: 17% in users vs. 6% in non-users, p < 0.001; frailty: 32% vs. 17%, respectively, p < 0.001). Use of two or more ACMs was associated with increased odds of falls after adjustment for demographic/lifestyle factors (odds ratio [OR] 4.53; 95% confidence interval [CI] 2.06-9.98) and for clinical factors (OR 3.58; 95% CI 1.37-9.38). Similar albeit weaker associations were seen with frailty (OR 2.26; 95% CI 1.09-4.70 and OR 2.12; 95% CI 0.89-5.0, respectively). CONCLUSIONS: ACM are commonly prescribed for people living with HIV, and evidence exists for an association with recurrent falls and frailty. Clinicians should be alert to this and reduce ACM exposure where possible.

Changes in short-term (in-ICU and in-hospital) mortality following intensive care unit admission in adults living with HIV: 2000-2019.

OBJECTIVE: Limited data suggest intensive care unit (ICU) outcomes have improved in people with HIV (PWH). We describe trends in in-ICU/in-hospital mortality among PWH following admission to ICU in a single UK-based HIV referral centre, from 1 January 2000 to 31 December 2019. METHODS: Modelling of associations between ICU admission and calendar year of admission was done using logistic regression with adjustment for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, CD4 + T-cell count and diagnosis of HIV at/within the past 3 months. RESULTS: Among 221 PWH (71% male, median [interquartile range (IQR)] age 45 years [38-53]) admitted to ICU, median [IQR] APACHE II score and CD4 + T-cell count were 19 [14-25] and 122 cells/µl [30-297], respectively; HIV-1 viral load was ≤50 copies/ml in 46%. The most common ICU admission diagnosis was lower respiratory tract infection (30%). In-ICU and in-hospital, mortality were 29 and 38.5%, respectively. The odds of in-ICU mortality decreased over the 20-year period by 11% per year [odds ratio (OR): 0.89 (95% confidence interval (CI): 0.84-0.94)] with in-hospital mortality decreasing by 14% per year [0.86 (0.82-0.91)]. After adjusting for patient demographics and clinical factors, both estimates were attenuated, however, the odds of in-hospital mortality continued to decline over time [in-ICU mortality: adjusted OR: 0.97 (0.90-1.05); in-hospital mortality: 0.90 (0.84-0.97)]. CONCLUSION: Short-term mortality of critically ill PWH admitted to ICU has continued to decline in the ART era. This may result from changing indications for ICU admission, advances in critical care and improvements in HIV-related immune status.

Biomarkers of central and peripheral inflammation mediate the association between HIV and depressive symptoms.

People living with HIV are at increased risk for depression, though the underlying mechanisms for this are unclear. In the general population, depression is associated with peripheral and central inflammation. Given this, and since HIV infection elicits inflammation, we hypothesised that peripheral and central inflammatory biomarkers would at least partly mediate the association between HIV and depressive symptoms. People living with HIV (n = 125) and without HIV (n = 79) from the COmorBidity in Relation to AIDS (COBRA) cohort were included in this study. Participants living with and without HIV had similar baseline characteristics. All participants living with HIV were on antiretroviral therapy and were virally suppressed. Plasma, CSF, and brain MR spectroscopy (MRS) biomarkers were measured. Using logistic regression models adjusted for sociodemographic factors, we found that participants with HIV were more likely to have Any Depressive Symptoms (Patient Health Questionnaire [PHQ-9] score >4) (odds ratio [95% confidence interval] 3.27 [1.46, 8.09]). We then sequentially adjusted the models for each biomarker separately to determine the mediating role of each biomarker, with a >10% reduction in OR considered as evidence of potential mediation. Of the biomarkers analysed, MIG (-15.0%) and TNF-α (-11.4%) in plasma and MIP1-α (-21.0%) and IL-6 (-18.0%) in CSF mediated the association between HIV and depressive symptoms in this sample. None of the other soluble or neuroimaging biomarkers substantially mediated this association. Our findings suggest that certain biomarkers of central and peripheral inflammation may at least partly mediate the relationship between HIV and depressive symptoms.

sHIV-1 drug resistance in people on dolutegravir-based ART: Collaborative analysis of cohort studies.

Background: The widespread use of the integrase strand transfer inhibitor (INSTI) dolutegravir (DTG) in first- and second-line antiretroviral therapy (ART) may facilitate emerging resistance. We combined data from HIV cohorts to examine patterns of drug resistance mutations (DRMs) and identify risk factors for DTG resistance. Methods: Eight cohorts from Canada, Europe, and South Africa contributed data on individuals with genotypic resistance testing on DTG-based ART. Resistance levels were categorised using the Stanford algorithm. We identified risk factors for resistance using mixed-effects ordinal logistic regression models. Results: We included 750 people with genotypic resistance testing on DTG-based ART between 2013 and 2022. Most had HIV subtype B (N=444, 59·2%) and were treatment-experienced; 134 (17.9%) were on DTG dual and 19 (2.5%) on DTG monotherapy. INSTI DRMs were detected in 100 (13·3%) individuals; 21 (2·8%) had more than one mutation. Most (N=713, 95·1%) were susceptible to DTG, 8 (1·1%) had potential-low, 5 (0·7%) low, 18 (2·4%) intermediate and 6 (0·8%) high-level DTG resistance. The risk of DTG resistance was higher on DTG monotherapy (adjusted odds ratio (aOR) 37·25, 95% CI 11·17 to 124·2) and DTG lamivudine dual therapy (aOR 6·59, 95% CI 1·70 to 25·55) compared to combination ART, and higher in the presence of potential-low/low (aOR 4.62, 95% CI 1.24 to 17.2) or intermediate/high-level (aOR 7·01, 95% CI 2·52 to 19·48) nucleoside reverse transcriptase inhibitors (NRTI) resistance. Viral load on DTG showed a trend towards increased DTG resistance (aOR 1·42, 95% CI 0·92 to 2·19 per standard deviation of log10 area under the viral load curve). Interpretation: Among people experiencing virological failure on DTG-based ART, INSTI DRMs were uncommon, and DTG resistance was rare. DTG monotherapy and NRTI resistance substantially increased the risk for DTG resistance, which is of concern, notably in resource-limited settings.

Life expectancy after 2015 of adults with HIV on long-term antiretroviral therapy in Europe and North America: a collaborative analysis of cohort studies.

BACKGROUND: The life expectancy of people with HIV taking antiretroviral therapy (ART) has increased substantially over the past 25 years. Most previous studies of life expectancy were based on data from the first few years after starting ART, when mortality is highest. However, many people with HIV have been successfully treated with ART for many years, and up-to-date prognosis data are needed. We aimed to estimate life expectancy in adults with HIV on ART for at least 1 year in Europe and North America from 2015 onwards. METHODS: We used data for people with HIV taking ART from the Antiretroviral Therapy Cohort Collaboration and the UK Collaborative HIV Cohort Study. Included participants started ART between 1996 and 2014 and had been on ART for at least 1 year by 2015, or started ART between 2015 and 2019 and survived for at least 1 year; all participants were aged at least 16 years at ART initiation. We used Poisson models to estimate the associations between mortality and demographic and clinical characteristics, including CD4 cell count at the start of follow-up. We also estimated the remaining years of life left for people with HIV aged 40 years who were taking ART, and stratified these estimates by variables associated with mortality. These estimates were compared with estimates for years of life remaining in a corresponding multi-country general population. FINDINGS: Among 206 891 people with HIV included, 5780 deaths were recorded since 2015. We estimated that women with HIV at age 40 years had 35·8 years (95% CI 35·2-36·4) of life left if they started ART before 2015, and 39·0 years (38·5-39·5) left if they started ART after 2015. For men with HIV, the corresponding estimates were 34·5 years (33·8-35·2) and 37·0 (36·5-37·6). Women with CD4 counts of fewer than 49 cells per µL at the start of follow-up had an estimated 19·4 years (18·2-20·5) of life left at age 40 years if they started ART before 2015 and 24·9 years (23·9-25·9) left if they started ART after 2015. The corresponding estimates for men were 18·2 years (17·1-19·4) and 23·7 years (22·7-24·8). Women with CD4 counts of at least 500 cells per µL at the start of follow-up had an estimated 40·2 years (39·7-40·6) of life left at age 40 years if they started ART before 2015 and 42·0 years (41·7-42·3) left if they started ART after 2015. The corresponding estimates for men were 38·0 years (37·5-38·5) and 39·2 years (38·7-39·7). INTERPRETATION: For people with HIV on ART and with high CD4 cell counts who survived to 2015 or started ART after 2015, life expectancy was only a few years lower than that in the general population, irrespective of when ART was started. However, for people with low CD4 counts at the start of follow-up, life-expectancy estimates were substantially lower, emphasising the continuing importance of early diagnosis and sustained treatment of HIV. FUNDING: US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council.

Investigating rates and risk factors for hepatitis C virus reinfection in people receiving antiviral treatment in England.

England has committed to the World Health Organization target to eliminate hepatitis C virus (HCV) as a public threat by the year 2030. Given successful treatments for HCV in recent years, it is unclear whether HCV reinfection will impact England's ability to achieve HCV elimination. We aimed to estimate the HCV reinfection rate among a cohort of patients receiving antiviral treatment using available surveillance data. Linkage between a treatment dataset from 2015 to 2019 and an HCV RNA testing dataset were used to identify people who experienced reinfection using three criteria. A Cox proportional hazards model was used to determine risk factors associated with HCV reinfection among a cohort who received treatment and had follow-up HCV RNA testing. The reinfection rate among those receiving HCV treatment was 7.91 per 100 person-years (PYs, 95% confidence interval (CI) 7.37-8.49) and highest among current injecting drug users (22.55 per 100 PYs, 95% CI 19.98-25.46) and people who had been in prison (20.42 per 100 PYs, 95% CI 17.21-24.24). In the adjusted model, women had a significantly reduced risk of reinfection. Being of younger age, current injecting drug users, and receipt of first treatment in prison were each significantly associated with increased risk of reinfection. Two-fifths of those with reinfection (43%, n = 329/767) were linked to treatment after reinfection, and of those starting treatment, three quarters (75%, n = 222/296) achieved a sustained virologic response. Guidance for testing groups at risk of reinfection and harm reduction strategies to minimize transmission should be implemented if England is to achieve HCV elimination targets.

Defining multimorbidity in people with HIV - what matters most?

PURPOSE OF REVIEW: Although multimorbidity (defined as the coexistence of multiple conditions) presents significant health challenges to people with HIV, there is currently no consensus on how it should be defined among this population. This review aimed to examine the definition of multimorbidity in existing studies among people with HIV ( n  = 22). RECENT FINDINGS: Variation in the definition of multimorbidity (in terms of the number and nature of conditions included) across studies among people with HIV was observed, with less than half (45%) reporting a selection criteria for conditions. The number of conditions considered ranged from 4 to 65. Certain conditions (e.g. stroke, myocardial infarction and chronic kidney disease) and risk factors (e.g. hypertension) were more frequently included, while other symptoms (e.g. joint pain, peripheral neuropathy and sleeping problems) and mental health conditions (e.g. anxiety and panic attacks) were rarely included in the definition of multimorbidity. SUMMARY: The definition of multimorbidity among people with HIV is highly variable, with certain conditions overlooked. We propose recommendations that researchers should consider when defining multimorbidity among this population to not only enable comparisons between studies/settings but also to ensure studies consider a person-centred approach that can accurately capture multimorbidity among people with HIV.

Prevalence of pain in women living with HIV aged 45-60: associated factors and impact on patient-reported outcomes.

As the population of women with HIV ages, an increasing proportion are experiencing the menopause, with potential associated pain. Among 844 participants in the Positive Transitions Through the Menopause (PRIME) study (72.3% black African; median age 49 (interquartile-range 47-53) years; 20.9%, 44.0% and 35.1% pre-, peri- and post-menopausal), 376 (44.6%) and 73 (8.7%) reported moderate or extreme pain. Women had been diagnosed with HIV for 14 (9-18) years, 97.7% were receiving antiretroviral therapy and 88.4% had a suppressed viral load. In adjusted ordinal logistic regression, peri-menopausal status (adjusted odds ratio (1.80) [95% confidence interval 1.22-2.67]), current smoking (1.85 [1.11-3.09]), number of comorbid conditions (1.95 [1.64-2.33] /condition) and longer duration of HIV (1.12 [1.00-1.24]/5 years) were independently associated with increased reported pain, whereas being in full-time work (0.61 [0.45-0.83]) and having enough money for basic needs (0.47 [0.34-0.64]) were associated with decreased pain reporting. Increasing pain was independently related to insomnia symptoms (moderate: 2.76 [1.96-3.90]; extreme: 8.09 [4.03-16.24]) and severe depressive symptoms (PHQ4 ≥ 6; moderate: 3.96 [2.50-6.28]; extreme: 9.13 [4.45-18.72]). Whilst our analyses cannot determine the direction of any associations, our findings point to the importance of eliciting a history of pain and addressing symptoms in order to improve wellbeing.