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Abstract Background AIDS-associated cryptococcal meningitis has a high mortality. Fluconazole was the only systemic antifungal therapy available in our centre. From 1999–2001 we used low-dose fluconazole (200 mg daily initially), and did not offer therapy to patients perceived to have poor prognoses. In 2001 donated fluconazole became available, allowing us to use standard doses (400 mg daily initially). Antiretroviral therapy was not available during the study period. Methods Retrospective chart review of adult patients before and after the fluconazole donation. Results 205 patients fulfilled the inclusion criteria, 77 before and 128 after the donation. Following the donation fewer patients received no antifungal treatment (5% vs 19%, p = 0.002), and more patients received standard-dose fluconazole (90% vs 6%, p < 0.001). In-hospital mortality was 25%. Impaired consciousness, no antifungal treatment received and cerebrospinal fluid antigen titre > 1,000 were independent predictors of in-hospital mortality. Concomitant rifampicin did not affect in-hospital survival. Thirteen patients were referred to the tertiary referral hospital and received initial treatment with amphotericin B for a mean of 6 days – their in-hospital survival was not different from patients who received only fluconazole (p = 0.9). Kaplan-Meier analysis showed no differences in length of survival by initial treatment with standard or low doses of fluconazole (p = 0.27 log rank test); median survival was 76 and 82 days respectively. Conclusion Outcome of AIDS-associated cryptococcal meningitis is similar with low or standard doses of fluconazole. The early mortality is high. Initial therapy with amphotericin B and other measures may be needed to improve outcome.

Objectives: Tenofovir disoproxil fumarate (TDF) is associated with reduced bone mineral density (BMD). We evaluated changes in BMD in women who switched from TDF, emtricitabine and a nonnucleoside reverse transcriptase inhibitor (TDF/FTC/NNRTI) to abacavir, lamivudine and dolutegravir (ABC/3TC/DTG). Methods: We conducted a randomized controlled trial in which women aged ≥40 years were randomized 1:2 to continue TDF/FTC/NNRTI or switch to ABC/3TC/DTG. The primary endpoint was change in total hip BMD measured by dual‐energy X‐ray absorptiometry at week 48. Secondary endpoints were changes in BMD of the lumbar spine and femoral neck and markers of bone turnover and kidney function up to week 48. We conducted exploratory analyses of weight gain, insulin resistance and metabolic syndrome. Primary and secondary endpoints were analysed by linear regression, with multiple imputation for missing time points. Results: In all, 91 women [mean age = 50.4 (standard deviation [SD] = 6.6) years, median CD4 cell count = 600 (interquartile range: 479–800) cells/µL] were randomized. Women who switched to ABC/3TC/DTG maintained viral suppression and experienced improvements in total hip BMD (mean adjusted difference = 1%, P = 0.027) and lumbar spine BMD (3%, P = 0.002), with no change in specific markers of bone turnover or renal tubular function. Although participants in the ABC/3TC/DTG arm gained more weight (1.8 kg, P = 0.046), the switch strategy was not associated with reduced insulin sensitivity or new‐onset metabolic syndrome. Conclusions: Switching from TDF/FTC/NNRTI to ABC/3TC/DTG resulted in improved BMD. Although weight gain was common in women who switched from TDF/FTC/NNRTI to ABC/3TC/DTG, we did not detect adverse effects on glucose homeostasis. Larger studies need to confirm these findings. [ABSTRACT FROM AUTHOR]

Objectives: High rates of respiratory symptoms and chronic bronchitis (CB) are reported in people with HIV infection (PWH). We investigated the prevalence of respiratory symptoms and CB in PWH and HIV‐negative people in the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY) study. Methods: Assessment of respiratory symptoms and CB was undertaken using the modified form of the St. George's Respiratory Questionnaire for chronic obstructive pulmonary disease (COPD). Univariate (χ2 tests, Mann–Whitney U tests and Spearman's rank correlation) and multivariable (linear and logistic regression) analyses were performed to consider associations of respiratory symptoms with demographic, lifestyle and HIV‐related parameters, and with depressive symptoms and quality of life. Results: Among the 619 participants, respiratory Symptom scores were higher in older and younger PWH compared to older HIV‐negative people, with median (interquartile range) scores of 17.7 (6.2, 39.5), 17.5 (0.9, 30.0) and 9.0 (0.9, 17.5), respectively (P = 0.0001); these differences remained significant after confounder adjustment. Sixty‐three participants (10.2%) met the criteria for CB [44 (14.0%) older PWH, 14 (9.2%) younger PWH, and five (3.3%) older HIV‐negative people; P = 0.002], with these differences also remaining after adjustment for confounding variables, particularly smoking status [older vs. younger PWH: odds ratio (OR) 4.48 (95% confidence interval (CI) 1.64, 12.30); P = 0.004; older PWH vs. HIV‐negative people: OR 4.53 (95% CI 1.12, 18.28); P = 0.03]. Respiratory symptoms and CB were both associated with greater depressive symptom scores and poorer quality of life. No strong associations were reported between CB and immune function, HIV RNA or previous diagnosis of any AIDS event. Conclusions: Respiratory symptoms and CB are more common in PWH than in demographically and lifestyle‐similar HIV‐negative people and are associated with poorer mental health and quality of life. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to assess the effect of tenofovir alafenamide (TAF) on kidney and bone biomarkers in patients who developed proximal renal tubulopathy (PRT) while receiving tenofovir disoproxil fumarate (TDF). Methods: Individuals with a history of TDF‐associated PRT and currently suppressed HIV infection on a tenofovir‐sparing regimen were randomized 1:1 to continue current antiretroviral therapy or initiate emtricitabine (F)/TAF with discontinuation of nucleoside reverse transcriptase inhibitors (NRTIs) as appropriate. Renal and bone biomarkers were analysed at baseline, week 4 and week 12. The primary outcome was the mean difference between study arms in urine retinol‐binding protein:creatinine ratio (RBPCR) change from baseline to week 12. Data were analysed using linear regression, with robust standard errors (primary outcome), and repeated measures mixed effects models (secondary outcomes). The trial was registered under European Union Drug Regulating Authorities Clinical Trials Database 2016‐003345‐29. Results: We randomized 31 individuals [mean age 52.4 (standard deviation 0.3) years; 97% male; 90% white); all completed the study. At 12 weeks, there was no difference in change in RBPCR (β 19.6; 95% confidence interval −35.3, 74.5; P = 0.47), and no difference in change in estimated glomerular filtration rate (eGFR) (based on creatinine or cystatin C), albuminuria, proteinuria, renal phosphate or urea handling, (fasting) urine osmolality, parathyroid hormone and bone turnover markers in the control versus the F/TAF exposed groups. No cases of PRT were observed. Conclusions: In people with a history of proximal renal tubulopathy while on TDF, 12‐week exposure to TAF did not adversely affect renal tubular function. These data support continued evaluation of the long‐term safety of TAF in this group of patients. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to describe agreement between the QRISK2, Framingham and Data Collection on Adverse Events of Anti‐HIV Drugs (D:A:D) cardiovascular disease (CVD) risk calculators in a large UK study of people living with HIV (PLWH). Methods: PLWH enrolled in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study without a prior CVD event were included in this study. QRISK2, Framingham CVD and the full and reduced D:A:D CVD scores were calculated; participants were stratified into 'low' (< 10%), 'intermediate' (10–20%) and 'high' (> 20%) categories for each. Agreement between scores was assessed using weighted kappas and Bland–Altman plots. Results: The 730 included participants were predominantly male (636; 87.1%) and of white ethnicity (645; 88.5%), with a median age of 53 [interquartile range (IQR) 49–59] years. The median calculated 10‐year CVD risk was 11.9% (IQR 6.8–18.4%), 8.9% (IQR 4.6–15.0%), 8.5% (IQR 4.8–14.6%) and 6.9% (IQR 4.1–11.1%) when using the Framingham, QRISK2, and full and reduced D:A:D scores, respectively. Agreement between the different scores was generally moderate, with the highest level of agreement being between the Framingham and QRISK2 scores (weighted kappa = 0.65) but with most other kappa coefficients in the 0.50–0.60 range. Conclusions: Estimates of predicted 10‐year CVD risk obtained with commonly used CVD risk prediction tools demonstrate, in general, only moderate agreement among PLWH in the UK. While further validation with clinical endpoints is required, our findings suggest that care should be taken when interpreting any score alone. [ABSTRACT FROM AUTHOR]

While cognitive impairment is frequently reported in HIV-positive individuals and has historically been associated with poorer functional outcomes, the associations between cognitive impairment and patient-reported outcome measures (PROMs) in contemporary cohorts are unclear. Methods We tested cognitive function using a computerized battery (CogState™) in 290 HIV-positive and 97 HIV-negative individuals aged ≥ 50 years participating in the Pharmacokinetic and Clinical Observations in People Over Fifty (POPPY) study. Participants completed questionnaires detailing physical and mental health [Short Form Health Survey (SF-36)], cognitive function [European AIDS Clinical Society (EACS) questions], activities of daily living [Lawton Instrumental Activities of Daily Living (IADL)], depression [Patient Depression Questionnaire (PHQ-9) and Centres for Epidemiologic Studies Depression scale (CES-D)], falls and sexual desire. Cognitive impairment was defined using the Frascati criteria, global deficit score (GDS) and multivariate normative comparison (MNC). In the HIV-positive group, the classification performances of the different definitions of cognitive impairment and dichotomized questionnaire results were calculated. Results The prevalence of cognitive impairment in the HIV-positive group was 34.5% (GDS), 30.0% (Frascati) and 22.1% (MNC), with only 2% diagnosed with HIV-associated dementia. In general, the associations between cognitive impairment and PROMs were weak regardless of the definition used: mean c-statistics were 0.543 (GDS), 0.530 (MNC) and 0.519 (Frascati). Associations were similar using the global T-score to define cognitive impairment. Summary health scores (SF-36) were lower, but only significantly so for those with cognitive impairment identified using MNC, for both mental health (61.4 vs. 75.8; P = 0.03) and physical health (60.9 vs. 75.0; P = 0.03). Conclusions The associations between cognitive impairment and PROMs were weak, possibly because impairment was mild and therefore largely asymptomatic. Further work is needed to elucidate the clinical implications of cognitive impairment in HIV-disease. [ABSTRACT FROM AUTHOR]

Objectives The accuracy and precision of glomerular filtration rate ( GFR) estimating equations based on plasma creatinine ( GFRcr), cystatin C ( GFRcys) and the combination of these markers ( GFRcr-cys) have recently been assessed in HIV-infected individuals. We assessed the associations of GFR, estimated by these three equations, with clinical events in HIV-infected individuals. Methods We compared the associations of baseline GFRcr, GFRcys and GFRcr-cys [using the Chronic Kidney Disease Epidemiology Collaboration ( CKD-EPI) equations] with mortality, cardiovascular events ( CVEs) and opportunistic diseases ( ODs) in the Strategies for the Management of Antiretroviral Therapy ( SMART) study. We used Cox proportional hazards models to estimate unadjusted and adjusted hazard ratios per standard deviation ( SD) change in GFR. Results A total of 4614 subjects from the SMART trial with available baseline creatinine and cystatin C data were included in this analysis. Of these, 99 died, 111 had a CVE and 121 had an OD. GFRcys was weakly to moderately correlated with HIV RNA, CD4 cell count, high-sensitivity C-reactive protein, interleukin-6, and D-dimer, while GFRcr had little or no correlation with these factors. GFRcys had the strongest associations with the three clinical outcomes, followed closely by GFRcr-cys, with GFRcr having the weakest associations with clinical outcomes. In a model adjusting for demographics, cardiovascular risk factors, HIV-related factors and inflammation markers, a 1- SD lower GFRcys was associated with a 55% [95% confidence interval ( CI) 27−90%] increased risk of mortality, a 21% (95% CI 0−47%) increased risk of CVE, and a 22% (95% CI 0−48%) increased risk of OD. Conclusions Of the three CKD-EPI GFR equations, GFRcys had the strongest associations with mortality, CVE and OD. [ABSTRACT FROM AUTHOR]

Objectives: Our objective was to describe the prevalence of cardiovascular disease (CVD) risk factors in people of African ancestry with HIV in the UK., Methods: We conducted a cross-sectional analysis of CVD risk factors in Black people with HIV aged ≥40 years and estimated the 10-year CVD risk using QRISK®3-2018. Correlations between body mass index (BMI) and CVD risk factors were described using Pearson correlation coefficients, and factors associated with 10-year CVD risk ≥5% were described using logistic regression., Results: We included 833 Black people with HIV and a median age of 54 years; 54% were female, 50% were living with obesity (BMI ≥30 kg/m 2 ), 61% had hypertension, and 19% had diabetes mellitus. CVD risk >5% ranged from 2% in female participants aged 40-49 years to 99% in men aged ≥60 years, and use of statins ranged from 7% in those with CVD risk <2.5% to 64% in those with CVD risk ≥20%. BMI was correlated (R 2 0.1-0.2) with triglycerides and diastolic blood pressure in women and with glycated haemoglobin, systolic and diastolic blood pressure, and total:high-density lipoprotein (HDL) cholesterol ratio in men. In both female and male participants, older age, blood pressure, diabetes mellitus, and kidney disease were strongly associated with CVD risk ≥5%, whereas obesity, total:HDL cholesterol, triglycerides, and smoking status were variably associated with CVD risk ≥5%., Conclusions: We report a high burden of CVD risk factors, including obesity, hypertension, and diabetes mellitus, in people of African ancestry with HIV in the UK. BMI-focused interventions in these populations may improve CVD risk while also addressing other important health issues., (© 2024 The Author(s). HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Objective: Metabolic dysfunction associated fatty liver disease (MAFLD) is over-represented in people with HIV (PWH). Maraviroc (MVC) and/or metformin (MET) may reduce MAFLD by influencing inflammatory pathways and fatty acid metabolism., Design: Open-label, 48-week randomized trial with a 2 x 2 factorial design., Setting: Multicenter HIV clinics., Participants: Nondiabetic, virologically suppressed PLWH, aged at least 35 years, with confirmed/suspected MAFLD (≥1 biochemical/anthropometric/radiological/histological features)., Intervention: Adjunctive MVC; MET; MVC+MET vs. antiretroviral therapy (ART) alone., Primary Outcome: Change in liver fat fraction (LFF) between baseline and week-48 using magnetic resonance proton density fat fraction (MR PDFF)., Results: Six sites enrolled 90 participants (93% male; 81% white; median age 52 [interquartile range, IQR 47-57] years) between March 19, 2018, and November 11, 2019. Seventy percent had imaging/biopsy and at least one 1 MAFLD criteria. The analysis included 82/90 with week-0 and week-48 scans. Median baseline MR PDFF was 8.9 (4.6-17.1); 40, 38, 8, and 14% had grade zero, one, two, and three steatosis, respectively. Mean LFF increased slightly between baseline and follow-up scans: 2.22% MVC, 1.26% MET, 0.81% MVC+MET, and 1.39% ART alone. Prolonged intervention exposure (delayed week-48 scans) exhibited greater increases in MR PDFF (estimated difference 4.23% [95% confidence interval, 95% CI 2.97-5.48], P  < 0.001). There were no differences in predicted change for any intervention compared to ART alone: MVC (-0.42% [95% CI -1.53 to 0.68, P  = 0.45]), MET (-0.62 [-1.81 to 0.56, P  = 0.30]), and MVC+MET (-1.04 [-2.74 to 0.65, P  = 0.23]). Steatosis grade remained unchanged in 55% and increased in 24%., Conclusion: Baseline levels of liver fat were lower than predicted. Contrary to our hypothesis, neither MVC, MET, or the combination significantly reduced liver fat as measured by MRPDFF compared to ART alone., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Twenty-eight individuals who experienced proximal renal tubulopathy (PRT, Fanconi syndrome) while receiving tenofovir disoproxil initiated tenofovir alafenamide (TAF) and were followed for 5 years. None developed recurrent PRT or experienced significant changes in estimated glomerular filtration rate (by creatinine or cystatin-C), albuminuria, proteinuria, retinol-binding proteinuria, fractional excretion of phosphate, alkaline phosphatase, or bone mineral density at the lumbar spine. These data suggest that TAF is a well tolerated treatment option for individuals vulnerable to developing PRT., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To describe HIV care outcomes in people of Black ethnicities living in England during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus disease 2019 [COVID-19]) pandemic., Methods: This was an observational cohort study of people of self-reported Black ethnicities attending for HIV care at nine HIV clinics across England. The primary outcome was a composite of antiretroviral therapy (ART) interruption and HIV viraemia (HIV RNA ≥200 copies/mL) ascertained via self-completed questionnaires and review of medical records. We used multivariable logistic regression to explore associations between ART interruption/HIV viraemia and demographic factors, pre-pandemic HIV immunovirological control, comorbidity status, and COVID-19 disease and vaccination status., Results: We included 2290 people (median age 49.3 years; 56% female; median CD4 cell count 555 cells/mm 3 ; 92% pre-pandemic HIV RNA <200 copies/mL), of whom 302 (13%) reported one or more ART interruption, 312 (14%) had documented HIV viraemia ≥200 copies/mL, and 401 (18%) experienced the composite endpoint of ART interruption/HIV viraemia. In multivariable analysis, a pre-pandemic HIV RNA <200 copies/mL (odds ratio [OR] 0.21; 95% confidence interval [CI] 0.15-0.30) and being vaccinated against SARS-CoV-2 (OR 0.41; 95% CI 0.30-0.55) were associated with reduced odds of ART interruption/HIV viraemia; pandemic-related disruptions to HIV care were common self-reported additional factors., Conclusions: During the COVID-19 pandemic, one in six people of Black ethnicities in this HIV cohort experienced an ART interruption/HIV viraemia. Some of these episodes resulted from pandemic-related healthcare disruptions. Associations with suboptimal engagement in HIV care pre-pandemic and not being vaccinated against SARS-CoV-2 suggest that wider health beliefs and/or poor healthcare access may have been contributory factors., (© 2024 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: There are no validated waist circumference (WC) cut-offs to define metabolic syndrome in Black people with HIV., Methods: Cross-sectional analyses within the CKD-AFRICA study. We used Pearson correlation coefficients and receiver operating characteristic (ROC) curves to describe the relationship between WC and cardiometabolic parameters including triglycerides, cholesterol, glucose, glycated haemoglobin (HbA1c), and homeostatic model assessment for insulin resistance (HOMA-IR), and to identify optimal WC cut-offs for each of these outcomes., Results: We included 383 participants (55% female, median age 52 years) with generally well controlled HIV. Female and male participants had similar WC (median 98 vs. 97 cm, p = .16). Generally weak correlations (r 2 < 0.2) between WC and other cardiometabolic parameters were observed, with low (<0.7) areas under the ROC curves. The optimal WC cut-offs for constituents of the metabolic syndrome, HbA1c and HOMA-IR ranged from 92 to 101 cm in women and 89-98 cm in men, respectively; these cut-offs had variable sensitivity (52%-100%) and generally poor specificity (28%-72%)., Conclusions: In this cohort of Black people with HIV, WC cut-offs for cardiometabolic risk factors in male participants were in line with the recommended value of 94 cm while in female participants they vastly exceeded the recommended 80 cm for white women., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: LC, LD-D, LC, LH, JF and LG declared no competing interests. RPV reports grants and honoraria from Novo Nordisk, AstraZeneca, and Amarin Limited outside of this work. GKD reports research grants from Novo Nordisk and Diabetes Digital Media, and personal fees from Novo Nordisk, Rhythm Pharmaceuticals, Johnson&Johnson/Ethicon and Medtronic outside of this work. FAP reports grants and personal fees and non-financial support from Gilead, grants and personal fees and non-financial support from ViiV, grants and personal fees and non-financial support from MSD outside of the present study.

Background: People living with human immunodeficiency virus (HIV) are disproportionately impacted by socioeconomic deprivation and are at increased risk of developing other long-term conditions (LTCs). These illnesses require transformative action to tackle the adverse effects on their health. Data on lived experiences of LTCs among people living with HIV of Black African and Black Caribbean ethnicities are sparse, and how people with LTCs are impacted by social determinants of health (SDoH)., Methods: Through a phenomenological study design this qualitative study, conducted in 2022, comprised four focus group discussions (FGDs) with 20 people of Black ethnicities living with HIV were purposively invited from a community organisation (CO) in London, including four semistructured interviews with CO staff. Following transcription, qualitative data were analysed thematically and measures to validate the findings were implemented., Results: The findings are presented in terms of the following four levels of SDoH: (1) individual determinants (such as the impact of SDoH on lifestyle modification and self-management); (2) interpersonal determinants (such as positive experiences of accessing healthcare for LTCs); (3) clinical determinants (such as care pathway barriers) and (4) systemic determinants (such as systemic barriers related to race/ethnicity)., Conclusions: It is necessary to provide ongoing and interactive education to community members who live with HIV, focusing on risks and management of LTCs. Additionally, individuals would benefit from support to navigate increasingly complex and fragmented health services. Health Service staff require cultural competence when caring for patients of Black African and Black Caribbean ethnicities with complex health and psychosocial needs., Patient or Public Contribution: The research team collaborated with an HIV CO in South London from the very start of the project to agree the study design and learn about the realities of their daily lived experiences. Community collaborators helped to develop the semistructured interview and FGD topic guides, and were directly involved in the data gathering, analysis and validation., (© 2024 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Aims: Dolutegravir increases serum creatinine by inhibiting its renal tubular secretion and elimination. We investigated determinants of early changes in serum creatinine in a southern African cohort starting first-line dolutegravir-based antiretroviral therapy (ART)., Methods: We conducted a secondary analysis of data from participants in a randomized controlled trial of dolutegravir, emtricitabine and tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide fumarate (TAF) (ADVANCE, NCT03122262). We assessed clinical, pharmacokinetic and genetic factors associated with change in serum creatinine from baseline to Week 4 using linear regression models adjusted for age, sex, baseline serum creatinine, HIV-1 RNA concentration, CD4 T-cell count, total body weight and co-trimoxazole use., Results: We included 689 participants, of whom 470 had pharmacokinetic data and 315 had genetic data. Mean change in serum creatinine was 11.3 (SD 9.9) μmol.L -1 . Factors that were positively associated with change in serum creatinine at Week 4 were increased log dolutegravir area under the 24-h concentration-time curve (change in creatinine coefficient [β] = 2.78 μmol.L -1 [95% confidence interval (CI) 0.54, 5.01]), TDF use (β = 2.30 [0.53, 4.06]), male sex (β = 5.20 [2.92, 7.48]), baseline serum creatinine (β = -0.22 [-0.31, -0.12]) and UGT1A1 rs929596 A→G polymorphism with a dominant model (β = -2.33 [-4.49, -0.17]). The latter did not withstand correction for multiple testing., Conclusions: Multiple clinical and pharmacokinetic factors were associated with early change in serum creatinine in individuals initiating dolutegravir-based ART. UGT1A1 polymorphisms may play a role, but further research on genetic determinants is needed., (© 2024 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Objective: Social determinants of health (SDH) are important determinants of long-term conditions and multimorbidity in the general population. The intersecting relationship between SDH and multimorbidity in people with HIV remains poorly studied., Design: A cross-sectional study investigating the relationships between eight socio-economic parameters and prevalent comorbidities of clinical significance and multimorbidity in adults of African ancestry with HIV aged 18-65 years in South London, UK., Methods: Multivariable logistic regression analysis was used to evaluate associations between SDH and comorbidities and multimorbidity., Results: Between September 2020 and January 2022, 398 participants (median age 52 years, 55% women) were enrolled; 85% reported at least one SDH and 72% had at least one comorbidity. There were no associations between SDH and diabetes mellitus or kidney disease, few associations between SDH (job and food insecurity) and cardiovascular or lung disease, and multiple associations between SDH (financial, food, housing and job insecurity, low educational level, social isolation, and discrimination) and poor mental health or chronic pain. Associations between SDH and multimorbidity mirrored those for constituent comorbidities., Conclusion: We demonstrate strong associations between SDH and poor mental health, chronic pain and multimorbidity in people of black ethnicities living with HIV in the UK. These findings highlight the likely impact of enduring socioeconomic hardship in these communities and underlines the importance of holistic health and social care for people with HIV to address these adverse psychosocial conditions., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To describe the clinical epidemiology of COVID-19 in people of black ethnicity living with HIV in the UK., Methods: We investigated the incidence and factors associated with COVID-19 in a previously established and well-characterized cohort of black people with HIV. Primary outcomes were COVID-19 acquisition and severe COVID-19 disease (requiring hospitalization and/or resulting in death). Cumulative incidence was analysed using Nelson-Aalen methods, and associations between demographic, pre-pandemic immune-virological parameters, comorbidity status and (severe) COVID-19 were identified using Cox regression analysis., Results: COVID-19 status was available for 1847 (74%) of 2495 COVID-AFRICA participants (median age 49.6 years; 56% female; median CD4 cell count = 555 cells/μL; 93% HIV RNA <200 copies/mL), 573 (31%) of whom reported at least one episode of COVID-19. The cumulative incidence rates of COVID-19 and severe COVID-19 were 31.0% and 3.4%, respectively. Region of ancestry (East/Southern/Central vs. West Africa), nadir CD4 count and kidney disease were associated with COVID-19 acquisition. Diabetes mellitus [adjusted hazard ratio (aHR) = 2.39, 95% confidence interval (CI): 1.26-4.53] and kidney disease (aHR = 2.53, 95% CI: 1.26-4.53) were associated with an increased risk, and recent CD4 count >500 cells/μL (aHR = 0.49, 95% CI: 0.25-0.93) with a lower risk of severe COVID-19., Conclusions: Region of ancestry was associated with COVID-19 acquisition, and immune and comorbidity statuses were associated with COVID-19 disease severity in people of black ethnicity living with HIV in the UK., (© 2024 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: The combination of dolutegravir plus rilpivirine has been studied in people with virologically suppressed HIV with no previous history of treatment failure or resistance. We investigated the potential to maintain viral suppression with dolutegravir plus rilpivirine in people with Lys103Asn mutations whose HIV was previously managed with other treatment regimens., Methods: In this open-label pilot trial at 32 clinical sites in seven European countries, virologically suppressed, HBsAg-negative adults aged 18 years or older with HIV-1 and Lys103Asn mutations were randomly assigned (2:1) to switch to 50 mg dolutegravir plus 25 mg rilpivirine (given as a single tablet) once daily or to continue their current antiretroviral therapy regimen (control group). After 48 weeks, participants in the control group also switched to dolutegravir plus rilpivirine. Randomisation was stratified by country, and a computer-generated randomisation list with permuted blocks within strata was used to assign participants to treatment groups. The primary endpoints were virological failure (ie, two consecutive measurements of 50 copies or more of HIV RNA per mL at least 2 weeks apart) and virological suppression (the proportion of participants with fewer than 50 copies of HIV RNA per mL) at week 48 (week 96 data will be reported separately). Analyses were done in the modified intention-to-treat population, which included all participants who received at least one dose of the study medication. This trial is registered with ClinicalTrials.gov, NCT05349838, and EudraCT, 2017-004040-38., Findings: Between Nov 5, 2018, and Dec 9, 2020, 140 participants were enrolled and randomly assigned, 95 to the dolutegravir plus rilpivirine group and 45 to the control group. Virological failure was recorded in three participants (3·2%, 95% CI 0·7 to 9·0) in the the dolutegravir plus rilpivirine group and one (2·2%, 0·1 to 11·8) in the control group. The proportion of participants in whom virological suppression was maintained at week 48 was 88·4% (80·2 to 94·1) in the dolutegravir plus rilpivirine group versus 88·9% (75·9 to 96·3) in the control group (difference -0·5, -11·7 to 10·7). Significantly more adverse events were recorded in the dolutegravir plus rilpivirine group than in the control group (234 vs 72; p=0·0034), but the proportion of participants who reported at least one adverse event was similar between groups (76 [80%] of 95 vs 33 [73%] of 45; p=0·39). The frequency of serious adverse events was low and similar between groups., Interpretation: Virological suppression was maintained at week 48 in most participants with Lys103Asn mutations when they switched from standard regimens to dolutegravir plus rilpivirine. The results of this pilot study, if maintained when the week 96 data are reported, support conduct of a large, well-powered trial of dolutegravir plus rilpivirine., Funding: ViiV Healthcare., Competing Interests: Declaration of interests GM has received fees for educational activities or advisory services from Gilead, Merck Sharp & Dohme, Theratechnologies, and ViiV Healthcare. AC has received fees for educational activities and consultancies, and financial support for attending conferences from Gilead, Janssen-Cilag, Merck Sharp & Dohme, and ViiV Healthcare. SR has received honoraria for presentations and scientific advice from Merck Sharp & Dohme, Theratechnologies, GSK, Janssen Cilag, ViiV Healthcare, and Gilead, and research grants paid to his institution from Janssen Cilag, ViiV Healthcare, and Gilead. MM has participated in lectures and advisory boards for ViiV Healthcare, Janssen, and MSD. BJ is a ViiV Healthcare employee and holds GSK stock. RG is an employee of GSK and owns shares in the company. AP has delivered lectures and participated in advisory boards for ViiV Healthcare, Janssen, Gilead, and MSD. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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/m 2 ). 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., (© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)