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BACKGROUND: Understanding the reasons for and consequences of bodyweight change in people living with HIV initiating antiretroviral therapy (ART) is crucial to optimising long-term health and wellbeing. We aimed to examine bodyweight trends and associated factors among individuals with well estimated dates of HIV-1 seroconversion. METHODS: In this cohort study, we pooled retrospective data from clinical records of participants in CASCADE aged 16 years and older recruited from clinics in France, Greece, the Netherlands, Spain, Sweden, the UK, and Canada. All participants had well estimated dates of HIV-1 seroconversion, seroconverted between Jan 1, 2007, and Dec 31, 2022 (HIV-1 positive antibody test within 12 months of an HIV-1 negative antibody test, or other laboratory evidence of seroconversion), initiated ART within 1 year of seroconversion, and were previously ART-naive. Participants were followed up to the time of data pooling (May 31, 2023). We modelled bodyweight changes after ART initiation by ART class, BMI categories, and other demographic characteristics using linear mixed models. FINDINGS: Of 15 755 potentially eligible participants, 5698 met inclusion criteria. Of those, 5148 (90·3%) were assigned male at birth, 517 (9·1%) were assigned female at birth, and 33 (0·6%) had sex not known. 2778 (48·8%) participants initiated integrase strand transfer inhibitor (INSTI)-based ART regimens, 1809 (31·7%) initiated protease inhibitor-based regimens, and 1111 (19·5%) initiated non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. The majority of participants were men who have sex with men (MSM; 4519 [79·3%]). Median age at seroconversion was 33·7 years (IQR 26·9-43·2). Bodyweight changes differed significantly by ART class within all baseline BMI categories (BMI <18·5 kg/m2 p=0·026, BMI 18·5-24·9 kg/m2 p<0·0001, BMI 25·0-29·9 kg/m2 p=0·0021, and BMI ≥30·0 kg/m2 p=0·0033; ART class and BMI interaction p=0·011). Participants with BMI less than 30 kg/m2 on regimens including both INSTI and tenofovir alafenamide gained 4·76 kg (95% CI 4·05-5·46) or more at 3 years. Of those with baseline BMI 18·5-24·9 kg/m2, 31·3% (95% CI 29·5-33·1) on INSTI-based regimens, 25·3% (23·0-27·7) on protease inhibitor-based regimens, 20·4% (18·8-22·9) on NNRTI-based regimens, 37·4% (33·9-40·9) on tenofovir alafenamide-based regimens, and 38·4% (34·6-42·1) on tenofovir alafenamide and INSTI-based regimens had gained more than 10% of their baseline bodyweight at 3 years. The greatest 3-year bodyweight gains by individuals on INSTI-based regimens and with BMI 18·5-24·9 kg/m2 were in women (5·63 kg [95% CI 4·92-6·35]), and people originating from sub-Saharan African (5·76 kg [5·06-6·46]), compared with MSM (3·82 kg [3·50-4·13]). INTERPRETATION: Our findings suggest a direct effect of INSTIs and tenofovir alafenamide on bodyweight gain, rather than a return to health effect. Given the known risk for cardiometabolic disease, bodyweight management needs to be part of the overall care of individuals prescribed these drugs. FUNDING: ViiV Healthcare UK, Janssen Pharmaceutica, and Merck Sharp & Dohme.
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OBJECTIVES: Although hepatitis A virus (HAV) and hepatitis B virus (HBV) immunisation is recommended in the UK for gay, bisexual and other men who have sex with men (GBMSM), data on immunisation coverage are limited. We aimed to determine the seroprevalence of HAV and HBV immunity among a sample of GBMSM attending sexual health services (SHS) in England. METHODS: Residual serum samples from HIV/syphilis testing for adult GBMSM attending eight SHS in London and one in Leeds were tested for markers of HAV immunity (HAV IgG) and HBV immunity (anti-HBs) using an unlinked anonymous approach. We estimated seroprevalence of HAV and HBV immunity overall and stratified by individuals' characteristics, which we obtained from the Genitourinary Medicine Clinic Activity Dataset Sexually Transmitted Infection (STI) Surveillance System. We used logistic regression to calculate crude and adjusted ORs between seropositivity and demographic and clinical characteristics. RESULTS: Seroprevalence of immunity to HAV (74.5% of 2577) and HBV (77.1% of 2551) was high. In adjusted analysis, HAV IgG seroprevalence varied by clinic and WHO region of birth (global p<0.001 for each), increased with older age (ORs of 1.50 (95% CI 1.18 to 1.86), 2.91 (2.17 to 3.90) and 3.40 (2.44 to 4.75) for ages 26-35, 36-45 and >46 vs 18-25 years (global p<0.001), was higher in those with an STI in the past year (1.58 (1.25 to 2.00); p<0.001) and those who were living with HIV (1.82 (1.25 to 2.64); p<0.001). Anti-HBs seroprevalence varied by clinic (global p<0.001), increased with older age (global p<0.001) and was higher in those with an STI in the past year (1.61 (1.27 to 2.05); p<0.001). CONCLUSION: Our findings provide a baseline seroprevalence from which to monitor serial levels of immunity to HBV and HAV in GBMSM accessing SHS. Levels of immunity for both viruses are high, noting samples were taken after recent widespread outbreaks and vaccination campaigns. High vaccine coverage in all GBMSM should be maintained to prevent further outbreaks.
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Hepatitis A , Hepatitis B , Homosexualidad Masculina , Humanos , Masculino , Estudios Seroepidemiológicos , Hepatitis A/epidemiología , Hepatitis A/inmunología , Adulto , Inglaterra/epidemiología , Hepatitis B/epidemiología , Hepatitis B/inmunología , Londres/epidemiología , Persona de Mediana Edad , Adulto Joven , Homosexualidad Masculina/estadística & datos numéricos , Adolescente , Minorías Sexuales y de Género/estadística & datos numéricos , Anticuerpos contra la Hepatitis B/sangre , Instituciones de Atención Ambulatoria/estadística & datos numéricos , Salud Sexual , Inmunoglobulina G/sangreRESUMEN
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.
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Anticuerpos Antivirales , Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , Inmunidad Humoral , Inmunización Secundaria , Inmunoglobulina G , Trasplante de Órganos , SARS-CoV-2 , Receptores de Trasplantes , Humanos , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , COVID-19/prevención & control , COVID-19/inmunología , Masculino , Femenino , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Persona de Mediana Edad , SARS-CoV-2/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Anciano , Adulto , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacunación , Glicoproteína de la Espiga del Coronavirus/inmunologíaRESUMEN
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.
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Técnica Delphi , Necesidades y Demandas de Servicios de Salud , Investigación Cualitativa , Servicios de Salud Reproductiva , Salud Reproductiva , Salud Sexual , Humanos , Inglaterra , Servicios de Salud Reproductiva/normas , Femenino , Masculino , Evaluación de Necesidades , Actitud del Personal de SaludRESUMEN
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.
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Infecciones por VIH , Unidades de Cuidados Intensivos , Humanos , Masculino , Femenino , Infecciones por VIH/mortalidad , Infecciones por VIH/tratamiento farmacológico , Persona de Mediana Edad , Unidades de Cuidados Intensivos/estadística & datos numéricos , Adulto , Estudios Retrospectivos , Mortalidad Hospitalaria , Alta del Paciente/estadística & datos numéricos , Modelos de Riesgos Proporcionales , APACHE , Admisión del Paciente/estadística & datos numéricosRESUMEN
The Global Task Force on Chronic Pain in HIV published seven research priorities in the field of HIV-associated chronic pain in 2019: (1) causes; (2) management; (3) treatment individualization and integration with addiction treatment; (4) mental and social health factors; (5) prevalence; (6) treatment cost effectiveness; and (7) prevention. The current study used a web-based survey to determine whether the research topics were aligned with the priorities of adults with lived experiences of HIV and chronic pain. We also collected information about respondents' own pain and treatment experiences. We received 311 survey responses from mostly US-based respondents. Most respondents reported longstanding, moderate to severe, multisite pain, commonly accompanied by symptoms of anxiety and/or depression. The median number of pain treatments tried was 10 (IQR = 8, 13), with medications and exercise being the most common modalities, and opioids being viewed as the most helpful. Over 80% of respondents considered all research topics either "extremely important" or "very important". Research topic #2, which focused on optimizing management of pain in people with HIV, was accorded the greatest importance by respondents. These findings suggest good alignment between the priorities of researchers and US-based people with lived experience of HIV-associated chronic pain.
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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.
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Infecciones por Chlamydia , Gonorrea , Humanos , Femenino , Inglaterra/epidemiología , Adolescente , Adulto Joven , Gonorrea/epidemiología , Infecciones por Chlamydia/epidemiología , Infecciones por Chlamydia/diagnóstico , Embarazo , Aborto Inducido/estadística & datos numéricos , Disparidades en el Estado de Salud , Factores Socioeconómicos , Disparidades en Atención de SaludRESUMEN
BACKGROUND: Mortality among people with HIV declined with the introduction of combination antiretroviral therapy. We investigated trends over time in all-cause and cause-specific mortality in people with HIV from 1999-2020. METHODS: Data were collected from the D:A:D cohort from 1999 through January 2015 and RESPOND from October 2017 through 2020. Age-standardized all-cause and cause-specific mortality rates, classified using Coding Causes of Death in HIV (CoDe), were calculated. Poisson regression models were used to assess mortality trends over time. RESULTS: Among 55716 participants followed for a median of 6 years (IQR 3-11), 5263 participants died (crude mortality rate [MR] 13.7/1000 PYFU; 95%CI 13.4-14.1). Changing patterns of mortality were observed with AIDS as the most common cause of death between 1999- 2009 (n = 952, MR 4.2/1000 PYFU; 95%CI 4.0-4.5) and non-AIDS defining malignancy (NADM) from 2010 -2020 (n = 444, MR 2.8/1000 PYFU; 95%CI 2.5-3.1). In multivariable analysis, all-cause mortality declined over time (adjusted mortality rate ratio [aMRR] 0.97 per year; 95%CI 0.96, 0.98), mostly from 1999 through 2010 (aMRR 0.96 per year; 95%CI 0.95-0.97), and with no decline shown from 2011 through 2020 (aMRR 1·00 per year; 95%CI 0·96-1·05). Mortality due all known causes except NADM also declined over the entire follow-up period. CONCLUSION: Mortality among people with HIV in the D:A:D and/or RESPOND cohorts decreased between 1999 and 2009 and was stable over the period from 2010 through 2020. The decline in mortality rates was not fully explained by improvements in immunologic-virologic status or other risk factors.
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Background: The 2022-2024 global mpox outbreak, occurring primarily in the sexual networks of gay, bisexual and other men who have sex with men (GBMSM), has not been accompanied by a focus on patient perspectives of illness. We explore the experiences of GBMSM diagnosed with mpox in England to understand needs for social and clinical support. Methods: In-depth interviews (March/July 2023) were conducted with 22 GBMSM diagnosed with mpox in 2022, randomly selected from a national mpox surveillance database, and 4 stakeholders from clinical/community-based organisations. Interviews covered experiences of illness, testing, diagnosis, treatment and contact tracing, and were recorded, transcribed and analysed with a thematic framework. Findings: Media coverage drawing on homophobic stereotypes around sex between men contributed to feelings of stigma and shame. GBMSM living with HIV appeared to cope better with mpox stigma, drawing on their experiences of being diagnosed with HIV for resilience. Younger GBMSM with less experience of stigmatising illness found mpox diagnosis more traumatic and sometimes required support beyond what was provided. Accessing testing could be complicated when healthcare professionals did not recognise mpox symptoms. Men felt information on course of illness, isolation and vaccination after recovery was often inconsistent and contradictory. GBMSM described that care from sexual health and infectious disease units usually better met their emotional and medical needs. This was frequently linked by men to these services having skills in working with the GBMSM community and managing infection risk sensitively. General hospital services and centralised contact tracing could increase feelings and experiences of stigma as some staff were perceived to lack skills in supporting GBMSM and, sometimes, clinical knowledge. Long-term impacts described by men included mental health challenges, urethral/rectal symptoms and life-changing disability. Interpretation: In this study stigma was a central feature of mpox illness among GBMSM and could be exacerbated or lessened depending on the clinical and social support provided. Involving communities affected by outbreaks in co-producing, planning and delivering care (including contact-tracing) may help improve support provided. Funding: TCW, AJR, AS and FMB received support from the National Institute for Health and Care Research (NIHR) under its Programme Grants for Applied Research Programme (Ref: NIHR202038). CS and JS receive support from the National Institute for Health and Care Research Health Protection Research Unit (NIHR HPRU) in Blood Borne and Sexually Transmitted Infections at UCL in partnership with UKHSA; RV receives support from the NIHR HPRU in Emerging and Zoonotic Infections and NIHR HPRU in Gastrointestinal Infections. The views expressed are those of the author(s) and not necessarily those of the NIHR, UK Health Security Agency, World Health Organization or the Department of Health and Social Care.
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INTRODUCTION: Pre-exposure prophylaxis (PrEP) is an effective medication to reduce the risk of acquiring HIV. PrEP is available free of charge in the UK from sexual health clinics. Expanding PrEP delivery to community pharmacies holds promise and aligns with UK government goals to eliminate new cases of HIV by 2030. The aim of this scoping review was to describe the existing evidence about the barriers to and facilitators of community pharmacy oral PrEP delivery, for pharmacists and pharmacy clients, as aligned with the Capacity Opportunity, Motivation Behaviour (COM-B) Model. METHODS: Five bibliographic and five review databases were searched from inception to August 2023. Literature of any study design was included if it discussed barriers and facilitators of community pharmacy PrEP delivery. Trial registrations, protocols and news articles were excluded. RESULTS: A total of 649 records were identified, 73 full texts were reviewed and 56 met the inclusion criteria, predominantly from high-income/westernized settings. Most of the included literature was original research (55%), from the United States (77%) conducted during or after the year 2020 (63%). Barriers to PrEP delivery for pharmacists included lack of knowledge, training and skills (capability), not having the necessary facilities (opportunity), concern about the costs of PrEP and believing that PrEP use could lead to risk behaviours and sexually transmitted infections (motivation). Facilitators included staff training (capability), time, the right facilities (opportunity), believing PrEP could be a source of profit and could reduce new HIV acquisitions (motivation). For clients, barriers included a lack of PrEP awareness (capability), pharmacy facilities (opportunity) and not considering pharmacists as healthcare providers (motivation). Facilitators included awareness of PrEP and pharmacist's training to deliver it (capability), the accessibility of pharmacies (opportunity) and having an interest in PrEP (motivation). DISCUSSION: To effectively enhance oral PrEP delivery in UK community pharmacies, the identified barriers and facilitators should be explored for UK relevance, addressed and leveraged at the pharmacy team, client and care pathway level. CONCLUSIONS: By comprehensively considering all aspects of the COM-B framework, community pharmacies could become crucial providers in expanding PrEP accessibility, contributing significantly to HIV prevention efforts.
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Fármacos Anti-VIH , Infecciones por VIH , Farmacias , Humanos , Estados Unidos , Infecciones por VIH/prevención & control , Infecciones por VIH/tratamiento farmacológico , Motivación , Renta , Fármacos Anti-VIH/uso terapéuticoRESUMEN
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.
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Hepacivirus , Hepatitis C , Humanos , Femenino , Embarazo , Adulto , Hepacivirus/genética , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Hepatitis C/tratamiento farmacológico , Factores de Riesgo , Inglaterra/epidemiología , Cirrosis Hepática , PrevalenciaRESUMEN
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.
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Diagnóstico por Imagen de Elasticidad , Hígado Graso , Infecciones por VIH , Papaver , Humanos , Masculino , Anciano , Estudios Transversales , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Infecciones por VIH/patología , Hígado Graso/epidemiología , Hígado Graso/patología , Hígado/diagnóstico por imagen , Cirrosis Hepática/epidemiología , Cirrosis Hepática/complicaciones , Obesidad/complicaciones , Obesidad/epidemiología , Diagnóstico por Imagen de Elasticidad/efectos adversosRESUMEN
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.
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Diabetes Mellitus , Hipertensión , Accidente Cerebrovascular , Humanos , Multimorbilidad , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Recent studies have shown a decrease in CD4 count during adolescence in young people with perinatally acquired human immunodeficiency virus (HIV, PHIV). METHODS: Young people with PHIV in the United Kingdom, followed in the Collaborative HIV Paediatric Study who started antiretroviral therapy (ART) from 2000 onward were included. Changes in CD4 count over time from age 10 to 20 years were analyzed using mixed-effects models, and were compared to published CD4 data for the gerneral population. Potential predictors were examined and included demographics, age at ART start, nadir CD4 z score (age-adjusted) in childhood, and time-updated viral load. RESULTS: Of 1258 young people with PHIV included, 669 (53%) were female, median age at ART initiation was 8.3 years, and the median nadir CD4 z score was -4.0. Mean CD4 count was higher in young people with PHIV who started ART before age 10 years and had a nadir CD4 z score ≥-4; these young people with PHIV had a decline in CD4 count after age 10 that was comparable to that of the general population. Mean CD4 count was lower in young people with PHIV who had started ART before age 10 and had a nadir CD4 z score <-4; for this group, the decline in CD4 count after age 10 was steeper over time. CONCLUSIONS: In children, in addition to starting ART at an early age, optimizing ART to maintain a higher CD4 z score during childhood may be important to maximizing immune reconstitution later in life.
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Fármacos Anti-VIH , Infecciones por VIH , Adolescente , Niño , Femenino , Humanos , Masculino , Adulto Joven , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos , VIH , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Carga ViralRESUMEN
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 21â356 of 24â268 participants enrolled before Feb 29, 2020. 20â403 participants (95·5%) were men who have sex with men (MSM). Uptake of PrEP among SHS attendees clinically assessed and coded as eligible was 21â292 (57·1%) of 37â289. 18â400 trial participants had at least one post-enrolment visit and a median of 361 days of follow-up (IQR 143-638); 14â039 (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). 18â607 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 14â800 (79·5%) of all 18â607 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.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Enfermedades de Transmisión Sexual , Masculino , Humanos , Femenino , Homosexualidad Masculina , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Infecciones por VIH/diagnóstico , Profilaxis Pre-Exposición/métodos , Fármacos Anti-VIH/uso terapéutico , Estudios Prospectivos , Evaluación de la Tecnología Biomédica , Enfermedades de Transmisión Sexual/epidemiología , Inglaterra/epidemiologíaRESUMEN
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.
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Hepatitis C , Abuso de Sustancias por Vía Intravenosa , Humanos , Femenino , Embarazo , Adulto , Hepacivirus/genética , Estudios Retrospectivos , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/terapia , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Hepatitis C/complicaciones , Inglaterra , Anticuerpos contra la Hepatitis C , ARNRESUMEN
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 10â767 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 373â965 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.
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Enfermedades Cardiovasculares , Infecciones por VIH , Inhibidores de Integrasa VIH , Adulto , Humanos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/efectos adversos , América del Norte , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Integrasas/uso terapéuticoRESUMEN
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.
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Infecciones por VIH , Inhibidores de Integrasa VIH , Seropositividad para VIH , VIH-1 , Humanos , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Inhibidores de Integrasa VIH/uso terapéutico , Inhibidores de Integrasa VIH/farmacología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/farmacología , Lamivudine/uso terapéutico , Estudios de Cohortes , Seropositividad para VIH/tratamiento farmacológico , Farmacorresistencia Viral/genéticaRESUMEN
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.
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Hepatitis C Crónica , Hepatitis C , Humanos , Países Desarrollados , Antivirales , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Hepatitis C/prevención & control , Grupos MinoritariosRESUMEN
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 45âyears [38-53]) admitted to ICU, median [IQR] APACHE II score and CD4 + T-cell count were 19 [14-25] and 122âcells/µl [30-297], respectively; HIV-1 viral load was ≤50âcopies/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.