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Background While national adoption of universal HIV treatment guidelines has led to improved, timely uptake of antiretroviral therapy (ART), longer-term care outcomes are understudied. There is little data from real-world service delivery settings on patient attrition, viral load (VL) monitoring, and viral suppression (VS) at 24 and 36 months after HIV treatment initiation. Methods and findings For this retrospective cohort analysis, we used observational data from 25 countries in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium's Asia-Pacific, Central Africa, East Africa, Central/South America, and North America regions for patients who were ART naïve and aged [greater than or equal to]15 years at care enrollment between 24 months before and 12 months after national adoption of universal treatment guidelines, occurring 2012 to 2018. We estimated crude cumulative incidence of loss-to-clinic (CI-LTC) at 12, 24, and 36 months after enrollment among patients enrolling in care before and after guideline adoption using competing risks regression. Guideline change-associated hazard ratios of LTC at each time point after enrollment were estimated via cause-specific Cox proportional hazards regression models. Modified Poisson regression was used to estimate relative risks of retention, VL monitoring, and VS at 12, 24, and 36 months after ART initiation. There were 66,963 patients enrolling in HIV care at 109 clinics with [greater than or equal to]12 months of follow-up time after enrollment (46,484 [69.4%] enrolling before guideline adoption and 20,479 [30.6%] enrolling afterwards). More than half (54.9%) were females, and median age was 34 years (interquartile range [IQR]: 27 to 43). Mean follow-up time was 51 months (standard deviation: 17 months; range: 12, 110 months). Among patients enrolling before guideline adoption, crude CI-LTC was 23.8% (95% confidence interval [95% CI] 23.4, 24.2) at 12 months, 31.0% (95% CI [30.6, 31.5]) at 24 months, and 37.2% (95% [CI 36.8, 37.7]) at 36 months after enrollment. Adjusting for sex, age group, enrollment CD4, clinic location and type, and country income level, enrolling in care and initiating ART after guideline adoption was associated with increased hazard of LTC at 12 months (adjusted hazard ratio [aHR] 1.25 [95% CI 1.08, 1.44]; p = 0.003); 24 months (aHR 1.38 [95% CI 1.19, 1.59]; p < .001); and 36 months (aHR 1.34 [95% CI 1.18, 1.53], p < .001) compared with enrollment before guideline adoption, with no before-after differences among patients with no record of ART initiation by end of follow-up. Among patients retained after ART initiation, VL monitoring was low, with marginal improvements associated with guideline adoption only at 12 months after ART initiation. Among those with VL monitoring, VS was high at each time point among patients enrolling before guideline adoption (86.0% to 88.8%) and afterwards (86.2% to 90.3%), with no substantive difference associated with guideline adoption. Study limitations include lags in and potential underascertainment of care outcomes in real-world service delivery data and potential lack of generalizability beyond IeDEA sites and regions included in this analysis. Conclusions In this study, adoption of universal HIV treatment guidelines was associated with lower retention after ART initiation out to 36 months of follow-up, with little change in VL monitoring or VS among retained patients. Monitoring long-term HIV care outcomes remains critical to identify and address causes of attrition and gaps in HIV care quality., Author(s): Ellen Brazier 1,2,*, Olga Tymejczyk 1, Kara Wools-Kaloustian 3, Awachana Jiamsakul 4, Marco Tulio Luque Torres 5, Jennifer S. Lee 6, Lisa Abuogi 7, Vohith Khol 8, Fernando Mejía [...]

Introduction: Females of childbearing age with hepatitis C virus (HCV) face increased marginalisation with intersecting, sex‐specific barriers to direct acting antiviral (DAA) therapy. We assessed the factors associated with uptake of DAA therapy among females of childbearing age, including those with evidence of recent drug dependence. Methods: HCV notifications in New South Wales, Australia (1995–2017) were linked to opioid agonist therapy (OAT), hospitalisations, incarcerations, perinatal, HIV notifications, deaths and prescription databases. Recent drug dependence was defined as hospitalisation due to injectable drugs or receipt of OAT occurring in the DAA era (2016–2018). Logistic regression was used to analyse factors associated with DAA uptake among females of childbearing age (18–44), including those with recent drug dependence. Results: Among 57,467 people with evidence of chronic HCV in the DAA era (2016–2018), 20,161 (35%) were female, including 33% (n = 6563/20,161) of childbearing age (18–44). Among all females of childbearing age (n = 6563) and those with evidence of recent drug dependence (n = 2278/6563, 35%), DAA uptake was lower among those who had given birth in the DAA era (vs. no birth record, all females of childbearing age; aOR: 0.74, 95% CI 0.61, 0.89; those with recent drug dependence; aOR 0.69, 95% CI 0.51, 0.93) and Aboriginal and Torres Strait Islander peoples (all females of childbearing age; aOR 0.81, 95% CI 0.71, 0.93; those with recent drug dependence aOR 0.75, 95% CI 0.62, 0.90). Conclusion: Females of childbearing age should be considered a key population for DAA therapy. Enhancing antenatal and postnatal HCV care may be critical in the pursuit towards elimination. [ABSTRACT FROM AUTHOR]

Background Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active antiretroviral therapy (ART) and increase risk of malignancies. The prognostic role of low CD4:CD8 ratio and elevated CD8 cell counts on the risk of cancer remains unclear. Methods We investigated the association of CD4:CD8 ratio on the hazard of non-AIDS defining malignancy (NADM), AIDS-defining malignancy (ADM) and most frequent group of cancers in ART-treated people with HIV (PWH) with a CD4 and CD8 cell counts and viral load measurements at baseline. We developed Cox proportional hazard models with adjustment for known confounders of cancer risk and time-dependent cumulative and lagged exposures of CD4:CD8 ratio to account for time-evolving risk factors and avoid reverse causality. Results CD4:CD8 ratios below 0.5, compared to above 1.0, were independently associated with a 12-month time-lagged higher risk of ADM and infection-related malignancies (adjusted hazard ratio 2.61 [95% confidence interval {CI }1.10–6.19] and 2.03 [95% CI 1.24–3.33], respectively). CD4 cell counts below 350 cells/μL were associated with an increased risk of NADMs and ADMs, as did infection, smoking, and body mass index-related malignancies. Conclusions In ART-treated PWH low CD4:CD8 ratios were associated with ADM and infection-related cancers independently from CD4 and CD8 cell counts and may alert clinicians for cancer screening and prevention of NADM. [ABSTRACT FROM AUTHOR]

Introduction: Non-prescription antibiotic dispensing is prevalent among community pharmacies in several low- and middle-income countries. We evaluated the impact of a multi-faceted intervention to address this challenge in urban community pharmacies in Indonesia., Methods: A pre-post quasi-experimental study was carried out in Semarang city from January to August 2022 to evaluate a 7-month long intervention comprising: (1) online educational sessions for pharmacists; (2) awareness campaign targeting customers; (3) peer visits; and (4) pharmacy branding and pharmacist certification. All community pharmacies were invited to take part with consenting pharmacies assigned to the participating group and all remaining pharmacies to the non-participating group. The primary outcome (rate of non-prescription antibiotic dispensing) was measured by standardised patients displaying symptoms of upper respiratory tract infection, urinary tract infection (UTI) and seeking care for diarrhoea in a child. χ 2 tests and multivariate random-effects logistic regression models were conducted. Thirty in-depth interviews were conducted with pharmacists, staff and owners as well as other relevant stakeholders to understand any persistent barriers to prescription-based dispensing of antibiotics., Findings: Eighty pharmacies participated in the study. Postintervention, non-prescription antibiotics were dispensed in 133/240 (55.4%) consultations in the participating group compared with 469/570 (82.3%) in the non-participating group (p value <0.001). The pre-post difference in the non-prescription antibiotic dispensing rate in the participating group was 20.9% (76.3%-55.4%) compared with 2.3% (84.6%-82.3%) in the non-participating group (p value <0.001).Non-prescription antibiotics were less likely to be dispensed in the participating group (OR=0.19 (95% CI 0.09 to 0.43)) and more likely to be dispensed for the UTI scenario (OR=3.29 (95% CI 1.56 to 6.94)). Barriers to prescription-based antibiotic dispensing included fear of losing customers, customer demand, and no supervising pharmacist present., Interpretation: Multifaceted interventions targeting community pharmacies can substantially reduce non-prescription antibiotic dispensing. Future studies to evaluate the implementation and sustainability of this intervention on a larger scale are needed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Monitoring hepatitis B virus (HBV) and hepatitis C virus (HCV) liver-related morbidity and mortality is key to evaluate progress towards elimination targets., Methods: HBV and HCV notifications in NSW, Australia (1995-2022) were linked to hospital and mortality records. Temporal trends in decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), and mortality were evaluated among people notified for HBV and HCV. Segmented Poisson regression models were used to assess the impact of the viral hepatitis elimination era (1 January 2015-31 December 2022) on advanced liver disease and mortality., Findings: During 1995-2022, there were 64,865 people with an HBV notification and 112,277 people with an HCV notification in NSW. Between 2002 and 2022, there were significant reductions in age-adjusted HBV- and HCV-related DC, HCC, and liver-related mortality. Among those with HBV, age-standardised incidence per 1000 person-years (py) in 2002, 2015, and 2022 was 3.08, 1.47, and 1.16 for DC (p < 0.001); 2.97, 1.45, and 0.75 for HCC (p < 0.001); and 2.84, 1.93, and 1.40 for liver-related mortality (p < 0.001). Among those with HCV, age-standardised incidence per 1000 py in 2002, 2015, and 2022, was 5.53, 4.57, and 2.31 for DC (p < 0.001); 2.22, 2.59, and 1.87 for HCC (p < 0.001); and 3.89, 4.73, and 3.16 for liver-related mortality (p < 0.001). In 2022, absolute liver-related mortality per 100,000 population was 0.95 for HBV and 3.56 for HCV. In adjusted analyses, older age, comorbidity, and a history of alcohol use disorder were associated with increased liver-related mortality among those with HBV and HCV., Interpretation: This population-level study demonstrated declining risks of DC, HCC, and mortality, with HBV-related declines commencing well before elimination era while HCV-related declines were mostly during elimination era. Population liver mortality indicates elimination target achieved for combined viral hepatitis and HBV, but not HCV., Funding: The Kirby Institute, UNSW Sydney, and New South Wales Ministry of Health, Australia., Competing Interests: GD reports research support from Gilead and Abbvie. HV has received honoraria from Gilead Sciences. JGe received consulting fees from NovoNordisk, participated on a Data Safety Monitoring Board for AbbVie, Gilead Sciences, BMS, Pharmaxis, Novartis, Cincera, Pfizer, Roche, NovoNordisk, Eisai and Bayer. JGr has received research grants from AbbVie, Biolytical, Cepheid, Gilead and Hologic, and has received honoraria from AbbVie, Abbott, Cepheid, Gilead and Roche outside the submitted work. GM reports grants from ViiV and Janssen, received honororia from ViiV and Gilead and participated on a Data Safety Monitoring Board for ViiV. All remaining authors have no potential conflicts to declare. Disclaimer: All inferences, opinions, and conclusions drawn in this publication are those of the author(s), and do not necessarily reflect the opinions or policies of the Australian Government Department of Health., (Crown Copyright © 2024 Published by Elsevier Ltd.)

With over 1.5 million new cases annually, skin cancers are the most commonly diagnosed group of cancers worldwide. Among these, melanoma and keratinocyte cancers (KC), comprising squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), are predominant. Retinol, a vitamin A derivative, is essential in the regulation of growth and differentiation of epidermal cells. Moreover, retinol exhibits antioxidant properties, protecting the skin against ultra-violet (UV) radiation induced oxidative damage. Existing research on the impact of retinol on melanoma, SCC and BCC development shows mixed results. Several dietary intake studies have suggested that higher retinol levels reduce skin cancer risk, however, others have failed to find this association. We used two-sample Mendelian randomization (MR) to explore if there is a causal relationship between retinol and the risk of developing melanoma, SCC or BCC. Genetically predicted circulating retinol levels were obtained from a genome wide association study (GWAS) meta-analysis of the INTERVAL (N=11,132) and METSIM (N=6,136) cohorts. Melanoma (30,134 cases and 375,188 controls), SCC (10,557 cases and 537,850 controls) and BCC (36,479 cases and 540,185 controls) risks were derived from published GWAS meta-analyses. We conducted two MR approaches. In the first MR we used a single SNP (rs10882283) that is associated with the levels of Retinol Binding Protein 4 (RBP4) as an instrument variable (IV) for circulating retinol levels. In the second MR we used all independent genetic variants that were strongly associated (P < 5 × 10 -8 ) with retinol levels as IVs. Odds ratios (OR) for skin cancer were calculated for a one standard deviation (SD) increase in genetically predicted retinol levels. The single IV approach revealed that retinol levels were not significantly associated with risk of melanoma (OR = 1.04 [95% confidence interval 0.83, 1.31], P = 0.72), SCC (OR = 1.15 [0.87, 1.51], P = 0.32) or BCC (OR = 1.06 [0.90, 1.23], P = 0.50). Similar null results were observed with the multiple IV approach for melanoma (OR = 1.03 [0.95, 1.11], P = 0.54), SCC (OR = 1.01 [0.91, 1.13], P = 0.83), and BCC (OR = 1.04 [0.96, 1.12], P = 0.38). In conclusion, we found no evidence that circulating retinol levels were causally associated with the development of melanoma, SCC and BCC., Competing Interests: Competing Interests None to declare.

Background: With integrase strand transfer inhibitor (INSTI) use associated with increased body mass index (BMI) and BMI increases associated with higher diabetes mellitus (DM) risk, this study explored the relationship between INSTI/non-INSTI regimens, BMI changes, and DM risk., Methods: RESPOND participants were included if they had CD4, HIV RNA, and ≥ 2 BMI measurements during follow up. Those with prior DM were excluded. DM was defined as a random blood glucose ≥ 11·1 mmol/L, HbA1c ≥ 6·5%/48 mmol/mol, use of antidiabetic medication, or site reported clinical diagnosis. Poisson regression assessed the association between natural log (ln) of time-updated BMI, current INSTI/non-INSTI, and their interactions, on DM risk., Results: Among 20,865 people with HIV included, most were male (74%) and White (73%). Baseline median age was 45 years (IQR 37-52), with a median BMI of 24 kg/m2 (IQR 22-26). There were 785 DM diagnoses with a crude rate of 0·73 (95%CI 0·68-0·78)/100 PYFU. Ln(BMI) was strongly associated with DM (adjusted incidence rate ratio (aIRR) 16·54 per log increase, 95%CI 11·33-24·13; p<0·001). Current INSTI use associated with increased DM risk (IRR 1·58, 95%CI 1·37-1·82; p<0·001) in univariate analyses, only partially attenuated when adjusted for variables including ln(BMI) (aIRR 1·48, 95%CI 1·29-1·71; p<0·001). There was no interaction between ln(BMI), INSTI and non-INSTI use, and DM (p=0·130)., Conclusions: In RESPOND, compared with non-INSTIs, current use of INSTIs was associated with an increased DM risk, which partially attenuated when adjusted for BMI changes and other variables., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Cutaneous melanoma incidence varies consistently across body sites between men and women, but the underlying causes of the differences remain unclear. To date, no prospective studies have examined risk factors for melanoma separately for men and women according to body site., Methods: We compared the association between constitutional, genetic and environmental risk factors for invasive melanoma on different body sites separately for men and women in a population-based prospective cohort study of 17,774 men and 21,070 women aged between 40 and 69 years and residents of Queensland, Australia at baseline in 2011. Participants were followed until December 2021.We examined risk factors including hair colour, tanning ability, naevus density, and proxies for high cumulative sun exposure, all self-reported at baseline. We also examined polygenic risk score (PRS) derived from summary statistics from a melanoma genome-wide association study meta-analysis., Results: During a median 10.4 years of follow-up, 455 men and 331 women developed an incident invasive melanoma; the mean age at diagnosis was lower in women than in men (62.6 vs. 65.0, respectively). The most common body site was the trunk in men (45.1%), and the upper (36.8%) and lower limbs (27.4%) in women. High naevus density and proxy measures of high cumulative sun exposure were similarly associated with melanoma at all sites in men and women. In both sexes, high genetic risk was associated with melanoma on all body sites except the head and neck. We observed differences between men and women in the association between PRS and melanoma of the trunk (highest vs. lowest tertile of PRS: HR 2.78, 95% CI 1.64-4.69 for men; 1.55, 95% CI 0.63-3.80 for women), and non-significant but large differences for the lower limbs (HR 5.25, 95% CI 1.80-15.27 for men; 1.75, 95% CI 0.88-3.47 for women)., Conclusions: While there are a number of potential explanations for these findings, this raises the possibility that genetic factors other than those related to pigmentation and naevus phenotypes may play a role in the predilection for melanoma to arise on different sites between the sexes., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Introduction: Gonorrhoea, the sexually transmissible infection caused by Neisseria gonorrhoeae , has a substantial impact on sexual and reproductive health globally with an estimated 82 million new infections each year worldwide. N. gonorrhoeae antimicrobial resistance continues to escalate, and disease control is largely reliant on effective therapy as there is no proven effective gonococcal vaccine available. However, there is increasing evidence from observational cohort studies that the serogroup B meningococcal vaccine four-component meningitis B vaccine (4CMenB) (Bexsero), licensed to prevent invasive disease caused by Neisseria meningitidis , may provide cross-protection against the closely related bacterium N. gonorrhoeae . This study will evaluate the efficacy of 4CMenB against N. gonorrhoeae infection in men (cis and trans), transwomen and non-binary people who have sex with men (hereafter referred to as GBM+)., Methods and Analysis: This is a double-blind, randomised placebo-controlled trial in GBM+, either HIV-negative on pre-exposure prophylaxis against HIV or living with HIV (CD4 count >350 cells/mm 3 ), who have had a diagnosis of gonorrhoea or infectious syphilis in the last 18 months (a key characteristic associated with a high risk of N. gonorrhoeae infection). Participants are randomised 1:1 to receive two doses of 4CMenB or placebo 3 months apart. Participants have 3-monthly visits over 24 months, which include testing for N. gonorrhoeae and other sexually transmissible infections, collection of demographics, sexual behaviour risks and antibiotic use, and collection of research samples for analysis of N. gonorrhoeae -specific systemic and mucosal immune responses. The primary outcome is the incidence of the first episode of N. gonorrhoeae infection, as determined by nucleic acid amplification tests, post month 4. Additional outcomes consider the incidence of symptomatic or asymptomatic N. gonorrhoeae infection at different anatomical sites (ie, urogenital, anorectum or oropharynx), incidence by N. gonorrhoeae genotype and antimicrobial resistance phenotype, and level and functional activity of N. gonorrhoeae -specific antibodies., Ethics and Dissemination: Ethical approval was obtained from the St Vincent's Hospital Human Research Ethics Committee, St Vincent's Hospital Sydney, NSW, Australia (ref: 2020/ETH01084). Results will be disseminated in peer-reviewed journals and via presentation at national and international conferences., Trial Registration Number: NCT04415424., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)