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People living with HIV (PLHIV) have an elevated risk of atherosclerotic cardiovascular disease (ASCVD) compared to their uninfected peers. Expanding statin use may help alleviate this burden. We evaluated the cost-effectiveness of reducing the recommend statin initiation threshold for primary ASCVD prevention among PLHIV in Thailand. Our decision analytic microsimulation model randomly selected (with replacement) individuals from the TREAT Asia HIV Observational Database (data collected between 1/January/2013 and 1/September/2019). Direct medical costs and quality-adjusted life-years were assigned in annual cycles over a lifetime horizon and discounted at 3% per year. We assumed the Thai healthcare sector perspective. The study population included PLHIV aged 35-75 years, without ASCVD, and receiving antiretroviral therapy. Statin initiation thresholds evaluated were 10-year ASCVD risk [greater than or equal to]10% (control), [greater than or equal to]7.5% and [greater than or equal to]5%. A statin initiation threshold of ASCVD risk [greater than or equal to]7.5% resulted in accumulation of 0.015 additional quality-adjusted life-years compared with an ASCVD risk threshold [greater than or equal to]10%, at an extra cost of 3,539 Baht ( US113), giving an incremental cost-effectiveness ratio of 239,000 Baht ( US7,670)/quality-adjusted life-year gained. The incremental cost-effectiveness ratio comparing ASCVD risk [greater than or equal to]5% to [greater than or equal to]7.5% was 349,000 Baht ( US11,200)/quality-adjusted life-year gained. At a willingness-to-pay threshold of 160,000 Baht ( US5,135)/quality-adjusted life-year gained, a 30.8% reduction in the average cost of low/moderate statin therapy led to the ASCVD risk threshold [greater than or equal to]7.5% becoming cost-effective compared with current practice. Reducing the recommended 10-year ASCVD risk threshold for statin initiation among PLHIV in Thailand would not currently be cost-effective. However, a lower threshold could become cost-effective with greater preference for cheaper statins.

Objectives. To estimate the combined effect of California’s Tobacco 21 law (enacted June 2016) and$2-per-pack cigarette excise tax increase (enacted April 2017) on cigarette prices and sales, compared with matched comparator states. Methods. We used synthetic control methods to compare cigarette prices and sales after the policies were enacted, relative to what we would have expected without the policy reforms. To estimate the counterfactual, we matched pre-reform covariate and outcome trends between California and control states to construct a “synthetic” California. Results. Compared with the synthetic control in 2018, cigarette prices in California were $ 1.89 higher ( $7.86 vs $ 5.97; P < .001), and cigarette sales were 16.6% lower (19.9 vs 16.6 packs per capita; P < .001). This reduction in sales equates to 153.9 million fewer packs being sold between 2017 and 2018. Conclusions. California’s new cigarette tax was largely passed on to consumers. The new cigarette tax, combined with the Tobacco 21 law, have contributed to a rapid and substantial reduction in cigarette consumption in California.

Hypertension has been rapidly growing in Bangladesh. However, there has been limited analysis of differences in the hypertension cascade across socio-demographic groups. This study was a secondary analysis of the 2017–18 Bangladesh Demographic and Health Survey. Four dichotomous outcome variables – hypertension prevalence, awareness among those with hypertension, treatment among those aware, and control among those treated – were analyzed. The variation of each outcome was assessed across socio-demographic factors. The association between socio-demographic characteristics and outcomes was analyzed using logistic regression. Less than half of the hypertensive individuals were aware of their hypertension (42.5%), and awareness was higher among those who were older, female, of higher household wealth, and living in urban areas. Among those aware, most were receiving treatment (87.4%), and this proportion was higher in older individuals (89.2% among 65 + , 70.4% among 18–24; p < 0.001). One-third of those treated (33.8%) had their blood pressure controlled, and this was higher among younger and more educated individuals. In multivariable models stratified by rural/urban community, most of the aforementioned trends remained with additional differences between communities. Notably, the association of higher education level with treatment odds differed in rural and urban communities (OR 0.34 [95%CI 0.16, 0.75] in rural; OR 2.83 [95%CI 1.04, 7.73] in urban). Efforts to improve hypertension awareness among individuals who are younger, male, of lower household wealth, and in rural areas are required to address disparities in care. Socio-demographic variations in hypertension awareness, treatment, and control must be considered to design targeted interventions for each step of the cascade.

Background The number of people aged greater than 65 years per 100 people aged 20–64 years is expected to almost double in The Kingdom of Saudi Arabia (KSA) between 2020 and 2030. We therefore aimed to quantify the growing non-communicable disease (NCD) burden in KSA between 2020 and 2030, and the impact this will have on the national health budget. Methods Ten priority NCDs were selected: ischemic heart disease, stroke, type 2 diabetes, chronic obstructive pulmonary disease, chronic kidney disease, dementia, depression, osteoarthritis, colorectal cancer, and breast cancer. Age- and sex-specific prevalence was projected for each priority NCD between 2020 and 2030. Treatment coverage rates were applied to the projected prevalence estimates to calculate the number of patients incurring treatment costs for each condition. For each priority NCD, the average cost-of-illness was estimated based on published literature. The impact of changes to our base-case model in terms of assumed disease prevalence, treatment coverage, and costs of care, coming into effect from 2023 onwards, were explored. Results The prevalence estimates for colorectal cancer and stroke were estimated to almost double between 2020 and 2030 (97% and 88% increase, respectively). The only priority NCD prevalence projected to increase by less than 60% between 2020 and 2030 was for depression (22% increase). It is estimated that the total cost of managing priority NCDs in KSA will increase from USD 19.8 billion in 2020 to USD 32.4 billion in 2030 (an increase of USD 12.6 billion or 63%). The largest USD value increases were projected for osteoarthritis (USD 4.3 billion), diabetes (USD 2.4 billion), and dementia (USD 1.9 billion). In scenario analyses, our 2030 projection for the total cost of managing priority NCDs varied between USD 29.2 billion - USD 35.7 billion. Conclusions Managing the growing NCD burden in KSA’s aging population will require substantial healthcare spending increases over the coming years.

Introduction Antiretroviral therapy (ART) initiation, regardless of CD4 count, has been recommended in Thailand since 2014, with same‐day initiation recommended since 2021. We assessed HIV treatment outcomes among Thai people living with HIV (PLHIV) by the time from HIV diagnosis to ART initiation under the Universal Health Coverage (UHC) programme and identified factors associated with virological failure (VF). Methods PLHIV aged ≥15 years initiating ART between 2014 and 2022 were included from the UHC database. We categorized participants into four groups using the duration from HIV diagnosis to ART initiation: (1) ≤ 7 days (same‐day ART); (2) 8 days to <1 month; (3) 1–3 months; and (4) >3 months. Viral load (VL) was measured 6 months after starting ART, and annually thereafter. VF was defined as VL ≥1000 copies/ml. Factors associated with VF were analysed using competing risk models considering death and loss to follow‐up (LTFU) as competing events. Results Among 252,239 PLHIV who started ART, the median age at initiation was 34 years (interquartile range [IQR]: 26–43 years). The median (IQR) pre‐ART CD4 count was 233 (76–420) cells/mm3. ART initiation occurred within 7 days for 25% (17% on the same day, 8% in 2–7 days), 24% in 8 days to <1 month, 23% in 1–3 months and 28% in >3 months. ART initiation within 7 days increased from 20% (2014–2016) to 32% (2021–2022). VF occurred with a rate of 3.11 (95% CI 3.07–3.159) per 100 person‐years (PYs). PLHIV initiating ART 8 days to 1 month were at lower risk of VF (aSHR 0.52, 95% CI 0.50–0.54) when compared to ART initiation >3 months. ART initiation within 7 days resulted in the lowest mortality (6%: 1.28 [95% CI 1.24–1.32] per 100 PYs), but the highest rate of LTFU (12%: 2.69 [95% CI 2.63–2.75] per 100 PYs) when compared to other ART initiation groups. Conclusions Although ART initiation within 7 days has increased in Thailand, the overall rate of early initiation remains low. ART initiation within 1 month significantly lowered the risk of VF. ART initiation within 7 days significantly reduced mortality. To further optimize health outcomes, innovative strategies are urgently needed to promote earlier ART initiation in Thailand.

Background Rural parts of Mali carry a disproportionate burden of the country’s high under-five mortality rate. A range of household factors are associated with poor under-five health in resource-limited settings. However, it is unknown which most influence the under-five mortality rate in rural Mali. We aimed to describe household factors associated with under-five mortality in Bankass, a remote region in central Mali. Methods We analysed baseline household survey data from a trial being conducted in Bankass. The survey was administered to households between December 2016 and January 2017. Under-five deaths in the five years prior to baseline were documented along with detailed information on household factors and women’s birth histories. Factors associated with under-five mortality were analysed using Cox regression. Results Our study population comprised of 17,408 under-five children from 8322 households. In the five years prior to baseline, the under-five mortality rate was 152.6 per 1000 live births (158.8 and 146.0 per 1000 live births for males and females, respectively). Living a greater distance from a primary health center was associated with a higher probability of under-five mortality for both males (adjusted hazard ratio [aHR] 1.53 for ≥10 km versus < 2 km, 95% confidence interval [CI] 1.25–1.88) and females (aHR 1.59 for ≥10 km versus < 2 km, 95% CI 1.27–1.99). Under-five male mortality was additionally associated with lower household wealth quintile (aHR 1.47 for poorest versus wealthiest, 95%CI 1.21–1.78), lower reading ability among women of reproductive age in the household (aHR 1.73 for cannot read versus can read, 95%CI 1.04–2.86), and living in a household with access to electricity (aHR 1.16 for access versus no access, 95%CI 1.00–1.34). Conclusions U5 mortality is very high in Bankass and is associated with living a greater distance from healthcare and several other household factors that may be amenable to intervention or facilitate program targeting.

Integrins have emerged as key sensory molecules that translate chemical and physical cues from the extracellular matrix (ECM) into biochemical signals that regulate cell behavior. Integrins function by clustering into adhesion plaques, but the molecular mechanisms that drive integrin clustering in response to interaction with the ECM remain unclear. To explore how deformations in the cell-ECM interface influence integrin clustering, we developed a spatial-temporal simulation that integrates the micro-mechanics of the cell, glycocalyx, and ECM with a simple chemical model of integrin activation and ligand interaction. Due to mechanical coupling, we find that integrin-ligand interactions are highly cooperative, and this cooperativity is sufficient to drive integrin clustering even in the absence of cytoskeletal crosslinking or homotypic integrin-integrin interactions. The glycocalyx largely mediates this cooperativity and hence may be a key regulator of integrin function. Remarkably, integrin clustering in the model is naturally responsive to the chemical and physical properties of the ECM, including ligand density, matrix rigidity, and the chemical affinity of ligand for receptor. Consistent with experimental observations, we find that integrin clustering is robust on rigid substrates with high ligand density, but is impaired on substrates that are highly compliant or have low ligand density. We thus demonstrate how integrins themselves could function as sensory molecules that begin sensing matrix properties even before large multi-molecular adhesion complexes are assembled.

To the Editor: The findings of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), reported by Grinspoon et al. (Aug. 24 issue),1 put statins at the forefront on reducing the excess risk of atherosclerotic cardiovascular disease among persons with human immunodeficiency virus (HIV) infection. We recently developed a model of atherosclerotic cardiovascular disease in persons with HIV infection.2 Applying the REPRIEVE results to our model shows that if pitavastatin is priced competitively with generic statins, expanded use among persons with HIV infection is likely to be cost-effective in the United States. However, this finding is sensitive to assumptions . . .

Abstract Background Human immunodeficiency virus (HIV)–positive gay and bisexual men (GBM) in Australia are well engaged in care. The World Health Organization’s (WHO) hepatitis C virus (HCV) elimination target of an 80% reduction in incidence by 2030 may be reachable ahead of time in this population. Methods We predicted the effect of treatment and behavioral changes on HCV incidence among HIV-positive GBM up to 2025 using a HCV transmission model parameterized with Australian data. We assessed the impact of changes in behavior that facilitate HCV transmission in the context of different rates of direct-acting antiviral (DAA) use. Results HCV incidence in our model increased from 0.7 per 100 person-years in 2000 to 2.5 per 100 person-years in 2016 and had the same trajectory as previously reported clinical data. If the proportion of eligible (HCV RNA positive) patients using DAAs stays at 65% per year between 2016 and 2025, with high-risk sexual behavior and injecting drug use remaining at current levels, HCV incidence would drop to 0.4 per 100 person-years (85% decline from 2016). In the same treatment scenario but with substantial increases in risk behavior, HCV incidence would drop to 0.6 per 100 person-years (76% decline). If the proportion of eligible patients using DAAs dropped from 65% per year in 2016 to 20% per year in 2025 and risk behavior did not change, HCV incidence would drop to 0.7 per 100 person-years (70% reduction). Conclusions Reaching the WHO HCV elimination target by 2025 among HIV-positive GBM in Australia is achievable. Hepatitis C virus (HCV) incidence among Australia’s human immunodeficiency virus (HIV)–positive gay and bisexual population is likely to decline sharply with direct-acting antiviral use, even with increases in risk behavior. Our model suggests that reaching the World Health Organization HCV elimination target ahead of time among this population is achievable.

Background In the Northern Territory (NT) of Australia, First Nations people with chronic hepatitis B (CHB) are infected with a unique sub-genotype, C4, which contains mutations linked to progressive fibrosis and hepatocellular carcinoma. This cohort study aimed to investigate disease progression in C4 sub-genotype infection and estimate how many untreated individuals may benefit from antiviral therapy with broadening treatment indications. Methods Included individuals were part of Hep B PAST, a co-designed program to improve the cascade of care for people living with CHB in the NT. Disease phase and cirrhotic status were determined algorithmically using clinical and laboratory data at two time points. Loss of HBV antigens was assessed longitudinally. Treatment need was assessed cross-sectionally in the cohort at study completion. Key outcomes were estimated rates of HBsAg/HBeAg loss in sub-genotype C4 infection and quantification of how many untreated individuals qualify for therapy under current Australian and expanded global treatment guidelines. Results HBsAg and HBeAg loss occurred at a rate of 1·04 and 8·06 events/100 person-years respectively (7342·6 and 545·6 years follow up). 783 people living with CHB were included (40% female, median age 48 years). Of these, 16% had cirrhosis (an additional 6% having FibroScan > 7 kPa, meaning 22% had cirrhosis or significant fibrosis) and 25% were prescribed antivirals. Only 6·7% of untreated individuals were treatment eligible under current guidelines. Using the 2024 World Health Organisation guidelines, this increased to 50% due mostly to fibrosis and population prevalence of diabetes. Conclusions Despite advanced liver disease in people living with CHB in the NT, rates of antigen loss in sub-genotype C4 hepatitis B infection are similar to other genotypes. Further work is needed to understand drivers of cirrhosis and significant fibrosis in this population.