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Oral pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) provision via online pharmacies (henceforth online PrEP and PEP) offers promise in increasing biomedical HIV prevention coverage. In this study, we aimed to estimate the cost-effectiveness of online PrEP and PEP scale-up in western Kenya. We adapted a network-based model, EMOD-HIV, to simulate online PrEP and PEP implementation from 2026 to 2036; costs and use of online PrEP and PEP and client characteristics were informed by the ePrEP Kenya pilot study, which evaluated online PrEP and PEP provision in Nairobi and Mombasa, Kenya. Other parameters were obtained from surveillance data and published literature. Eligible clients were aged 15-49 years reporting condomless sex with non-marital partners. We assumed online PrEP and PEP provision was implemented through public-private partnership, with the Kenya Ministry of Health providing PrEP and PEP drugs and service delivery costs paid by the online pharmacy (and charged to clients). We estimated HIV infections, HIV-related deaths, and disability-adjusted life-years (DALYs) averted compared with the baseline scenario of background oral PrEP only. We calculated incremental cost-effectiveness ratios (ICERs) assessing only costs incurred by the Kenya Ministry of Health over 35 years and used a supply-side threshold of US$500 per DALY averted. We calculated 95% uncertainty intervals (UIs) across 100 parameter sets. Online PrEP and PEP was projected to reach population coverage of 0·7% (95% UI 0·7-0·8) for PEP and 0·3% (0·2-0·3) for PrEP and avert 13·9% (10·1-17·1) of HIV infections over 10 years. HIV-related deaths were reduced by 4·3% (95% UI 2·0-6·9) over the 35-year time horizon. The intervention was cost-effective from the Kenya Ministry of Health perspective (ICER $212 [95% UI 15-1409] per DALY averted). In a scenario assuming only online PEP availability (to isolate the effect of PEP), 11·6% (95% UI 8·6-15·2) of HIV infections were averted (ICER $210 [95% UI 41-3798] per DALY averted). The intervention remained cost-effective when varying PrEP and PEP effectiveness and assuming HIV testing and treatment disruptions. Online PrEP and PEP can avert substantial HIV infections, even with low population coverage. PEP was responsible for most intervention health benefits, likely due to high observed demand for PEP compared with PrEP in the pilot study. Leveraging private retailers can be efficient for scaling up HIV prevention in an era of shrinking donor funding. Gates Foundation.

Critiques of economic growth are receiving increased scientific and public attention. The post-growth literature discusses how wellbeing can be achieved for all within planetary boundaries. However, current welfare states, which play a crucial role in supporting health and wellbeing, are often seen as growth dependent. The drivers of welfare state growth dependencies and related policy responses remain poorly understood. In this Review, we address this gap and provide an overview of drivers and policy responses, by performing a semi-systematic literature review. The Review identified key drivers that the literature suggests, such as the growth dependence of employment and related welfare funds, rent extraction and for-profit provisioning, increasing inequality, ageing societies, political power of vested interests, and environmental impacts. Policies proposed as responses to these drivers include maintaining employment without growth, using less growth dependent revenues, restricting rent seeking and political power of vested interests, implementing predistributive and redistributive policies, implementing preventive health-care approaches, and mitigating climate change. We argue that a more holistic assessment of policies should consider the interaction between the supply of welfare funding and demand for welfare spending. Finally, we summarise views in the literature on whether welfare state growth independence can be achieved within a capitalist system.

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Kaposi sarcoma (KS)-associated herpesvirus (KSHV), otherwise known as HHV-8, causes KS and several lymphoproliferative disorders including KSHV-associated multicentric Castleman disease, KSHV-associated inflammatory cytokine syndrome, primary effusion lymphoma, and KSHV-positive diffuse large B-cell lymphoma not otherwise specified. KS represents a substantial burden of disease in sub-Saharan Africa and in people with HIV worldwide. Diagnosis relies on pathology, but quantitative KSHV DNA measurements can help identify multicentric Castleman disease and KSHV-associated inflammatory cytokine syndrome and monitor treatment response. Alongside antiretroviral therapy, a stage-stratified approach to KS treatment indicates systemic therapy for advanced disease or to mitigate the risk of the related immune reconstitution inflammatory syndrome. The latter condition constitutes a therapeutic challenge, as do multicentric Castleman disease and KSHV-associated inflammatory cytokine syndrome, which are likely to be underdiagnosed. Research on novel treatment approaches, such as immunomodulatory regimens, as well as diagnostic and monitoring strategies, is underway.

Family Planning (FP) is central to reproductive autonomy; however, structural barriers and restrictive gender norms limit equitable access to modern contraceptive methods in South Asia. We aimed to synthesize the current evidence on determinants of modern contraceptive use among married women of reproductive age in South Asia. We searched Medline, Scopus, Embase, and CINAHL from 1st January, 2015 to 23rd April, 2026. Observational studies from South Asian countries using multivariate analyses to examine determinants of modern contraceptive use among married women of reproductive age (15-49 years) were included. Risk of bias was assessed using the Joanna Briggs Institute (JBI) tool. Generic inverse variance method was used to estimate pooled odds ratios and 95% confidence intervals in RevMan. The review was registered with PROSPERO(CRD42024542764). There were 78 studies with 2,212,823 study participants that met the inclusion criteria and 70 studies were included in the meta-analysis. Women's formal education and employment (OR: 1.35, 95% CI: 1.08-1.70, I2 = 74; OR: 1.20, 95% CI: 1.01-1.42, I2 = 0%), spousal involvement in decision-making (OR: 2.79, 95% CI: 1.17-6.65, I2 = 66%), access to health facility with FP services (OR: 2.13, 95% CI: 1.12-4.05, I2 = 0%), media exposure (OR: 1.26, 95% CI: 1.10-1.45, I2 = 0%), and counselling from healthcare workers (OR: 1.57, 95% CI: 1.05-2.35, I2 = 0%) were associated with higher modern contraceptive use, but some estimates were based on limited studies hence should be interpreted with caution. Strengthening women's empowerment, increasing male engagement, and improving access of FP services are essential for equitable access of modern contraceptive methods across South Asia. This study was not funded by any individual or agency.

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Non-sputum-based tuberculosis tests are a global priority because sputum-dependent diagnostics systematically miss populations at highest risk of disease, including people living with HIV. We evaluated the diagnostic accuracy of a next-generation urine lipoarabinomannan assay. In this two-centre diagnostic accuracy study, we enrolled adults aged 18 years or older, regardless of their HIV status, with presumptive pulmonary tuberculosis, attending outpatient clinics in South Africa and Uganda. Participants who had received tuberculosis treatment within the previous 2 months or had an unknown treatment history were excluded. Demographic and clinical data, including HIV status and CD4 cell count, were collected alongside urine, blood, and sputum. We compared the diagnostic accuracy of the Biopromic lipoarabinomannan assay (BP-LAM; Biopromic TB LAM, Biopromic, Solna, Sweden) and WHO-recommended Determine TB LAM Ag assay (LF-LAM; Abbott, Santa Clara, CA, USA) against an extended microbiological reference standard (eMRS; sputum Xpert MTB/RIF Ultra [Ultra; Cepheid, Sunnyvale, CA, USA], culture, or both). Sputum induction was available in South Africa. Secondary outcomes were diagnostic yield and accuracy stratified by subgroups (HIV, CD4 cell count stratum, country, and sputum scarcity status), including design-locked and prototype assays. We tested urine from 629 participants (282 from South Africa and 347 from Uganda) collected between Oct 5, 2018, and March 11, 2022. 315 individuals with tuberculosis and a random selection of 314 without tuberculosis underwent urine testing. 250 (40%) of 626 participants were female and 376 (60%) were male; the median age was 34 years (IQR 19-60). BP-LAM had higher sensitivity than LF-LAM (63% [95% CI 58-69] vs 22% [18-27]; p<0&#xb7;0001) and similar specificity (93% [90-96] vs 89% [85-92]; p=0&#xb7;067). BP-LAM sensitivity was similar regardless of HIV status (67% [58-76] for people with HIV vs 62% [55-69] for people who were HIV-negative; p=0&#xb7;39) but was higher in people with HIV and CD4 counts less than or equal to 200 cells per &#x3bc;L (79% [63-90] vs 58% [44-72] for people with HIV and CD4 count >200 cells per &#x3bc;L; p=0&#xb7;041). Specificity of BP-LAM was significantly lower in people with HIV than in individuals who were HIV-negative (90% [83-94] vs 96% [92-99]; p=0&#xb7;016). The design-locked BP-LAM had better specificity than the prototype (93% [90-96] vs 85% [80-88]; p<0&#xb7;0001). Diagnostic yield was significantly higher for Ultra (82% [78-86]), followed by culture (72% [68-77]) in comparison with BP-LAM (61% [56-66]; p<0&#xb7;0001), and LF-LAM yield was significantly lower (29% [24-33]; p<0&#xb7;0001), with similar patterns across HIV status. BP-LAM yield was similar to that of Ultra when sputum induction was unavailable (67% [55-79] vs 64% [49-78]; p=0&#xb7;82). BP-LAM showed higher sensitivity than LF-LAM, including in HIV-negative people, and identified a similar number of cases as sputum Ultra when sputum induction was unavailable. Further validation and implementation studies are warranted. Global Health Technology Fund (GHIT) programme and EDCTP2 programmes supported by the EU.

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Orphan drug policy in the European Union faces a double price-and-innovation gap: a small fraction of rare diseases receive important resources while the overwhelming majority are under- or un-researched, leaving most rare disease patients facing high unmet medical needs. The European Commission's reform proposals, notably the Pharma Package and the European Biotech Act, seek to rebalance incentives by adjusting market exclusivity. We argue that, while these reforms move in the right direction, they are insufficient to foster meaningful innovation while safeguarding affordability, and that a broader, more structural approach is needed. We show how proposals from the Draghi Report could complement the reforms through an EU-level HTA Coordination Office, a US-style EU ARPA-H, and expanded regulatory sandboxing. We then propose two additional instruments: public-private Special Purpose Vehicles to de-risk high-need innovation, and EU-level joint procurement to strengthen affordability and create predictable demand. Ultimately, only a coherent, well-calibrated framework can align industrial policy with the EU's ambition of leaving no rare-disease patient behind.

The GLP-1 receptor agonist semaglutide reduces clinically important kidney outcomes in people with type 2 diabetes and chronic kidney disease (CKD). We aimed to assess the pooled effects of semaglutide on kidney outcomes in prespecified analyses of participant-level data from the diverse populations of the SELECT, FLOW, and SOUL randomised placebo-controlled trials. Participants with CKD (FLOW) or atherosclerotic cardiovascular disease (SELECT and SOUL) were randomly assigned semaglutide (once-weekly subcutaneous 1&#xb7;0 mg [FLOW], once-weekly subcutaneous 2&#xb7;4 mg [SELECT], or once-daily oral 14 mg [SOUL]) or matching placebo, added to standard of care. The primary outcome in this pooled analysis was time to first occurrence of a kidney composite, defined as onset of persistent 50% or greater reduction in estimated glomerular filtration rate (eGFR), kidney failure (persistent eGFR <15 mL/min per 1&#xb7;73 m2, or initiation of kidney replacement therapy), kidney-related death, or cardiovascular-related death. Safety was also assessed. The pooled participants from the trials (N=30&#x2008;787) had a mean follow-up of 39&#xb7;5-47&#xb7;5 months. Among participants assigned to semaglutide, 973 first events of the primary kidney composite occurred compared with 1134 first events for placebo (hazard ratio [HR] 0&#xb7;84 [95% CI 0&#xb7;77-0&#xb7;91]). First events of a narrower secondary kidney composite (excluding cardiovascular-related death from the primary outcome) were also reduced with semaglutide versus placebo (347 and 416, respectively; 0&#xb7;80 [0&#xb7;69-0&#xb7;92]). Safety outcomes were overall similar between groups, and in line with other GLP-1 receptor agonist trials. Serious adverse events were numberically lower with semaglutide than with placebo. Data pooled from three large phase 3 trials suggest that semaglutide reduces the risk of major kidney outcomes in a broad population with cardio-kidney-metabolic disease while having a favourable risk-benefit profile. In people with cardio-kidney-metabolic disease, with and without diabetes, semaglutide (oral or injected) prevents kidney-related and cardiovascular complications and induces adverse events in line with GLP-1 receptor agonist studies, regardless of baseline characteristics within the cardio-kidney-metabolic spectrum. This was a participant-level analysis conducted in a large database of three randomised controlled trials of similar design and examining the same treatment, but there were some differences in participants' baseline characteristics, and in the dose and route of administration of treatment. This pooled analysis adds evidence for the benefit of GLP-1 receptor agonists in general, and semaglutide in particular, in a broad population of people with cardio-kidney-metabolic disease, suggesting that the benefit of semaglutide might not be explained only by its glycaemic effects, weight-management effects, or both. Novo Nordisk.

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Artemisinin partial resistance (ART-R) has been confirmed in four sub-Saharan African countries since 2020, but evidence from Ethiopia is limited to molecular surveys without phenotypic confirmation. We aimed to determine whether ART-R met WHO criteria in Ethiopian Plasmodium falciparum populations during 2024-25, integrating day-3 parasite positivity after artemether-lumefantrine treatment, Pfkelch13 genotyping, and the ring-stage survival assay (RSA)0-3 h on culture-adapted field isolates. We conducted a prospective, multisite, surveillance study at five sentinel health facilities in Ethiopia (Rama, Werkamba, Mehoni, Bako, and Metehara). Patients aged 6 months or older with uncomplicated P falciparum malaria confirmed by microscopy received artemether-lumefantrine according to bodyweight (six doses during 3 days). Pfkelch13 was genotyped by Nanopore sequencing and Pfhrp2/Pfhrp3 deletions were assessed by quantitative PCR. The RSA0-3 h was performed on culture-adapted field isolates. Follow-up occurred on days 0 and 3. The main outcome was day-3 parasite positivity rate (defined as microscopically detectable asexual P falciparum parasitaemia on day 3 after initiation of artemether-lumefantrine). This study is registered with ClinicalTrials.gov, NCT07527182 (completed). Patients were enrolled from June 6 to Dec 8, 2024, during the 2024 P falciparum transmission season at all five sentinel sites and from July 1 to Nov 8, 2025, during the 2025 transmission season at Werkamba. 3207 febrile patients were assessed for malaria, of whom 2771 were excluded and 436 (14%) were P falciparum-positive on microscopy. 277 (64%) patients were enrolled, of whom 153 (55%) returned for the day-3 parasitological assessment and 124 (45%) were lost to follow-up. 172 (62%) of 277 patients were male and 105 (38%) were female. The median age was 20&#xb7;0 years (IQR 10&#xb7;0-30&#xb7;0). 243 (88%) had P falciparum monoinfection by PCR and 34 (12%) had P falciparum and Plasmodium vivax co-infections undetected by microscopy at enrolment. The day-3 parasite positivity rate was 19&#xb7;6% ([95% CI 14&#xb7;1-26&#xb7;6] in 30 of 153 patients with available data). 26 (9%) of 277 enrolled patients carried a validated Pfkelch13 mutation and were positive on day 3, exceeding the WHO 5% threshold for confirmation of ART-R. A strong age-dependent gradient was observed in a post-hoc analysis, with six (38%) of 16 patients younger than 5 years, 14 (35%) of 40 aged 5-15 years, and ten (10%) of 97 older than 15 years (p=0&#xb7;00035). R622I was detected in 143 (53%) samples of 271 genotyped isolates. Carrying an R622I mutation was associated with day-3 positivity (26 [33%] of 79) in a univariate analysis (crude odds ratio [OR] 7&#xb7;85 [95% CI 2&#xb7;58-23&#xb7;91]; p=0&#xb7;0003). After adjustment, the association remained strong and independent (adjusted OR 9&#xb7;96 [95% CI 3&#xb7;39-36&#xb7;35]; p<0&#xb7;0001). Of 70 P falciparum field isolates on day 0 collected for culture adaptation, only six were successfully maintained. Five R622I isolates carried the Pfkelch13 R622I mutation and exceeded the 1% in vitro threshold for ART-R (mean survival rates of 1&#xb7;41% [SD 0&#xb7;27] for EW04, 2&#xb7;69% [0&#xb7;90] for EW14, 1&#xb7;07% [0&#xb7;52] for EW23, 3&#xb7;76% [0&#xb7;35] for EW38, and 1&#xb7;29% [0&#xb7;04] for EW56). Pooled with the wild-type strains, all five R622I isolates exceeded the 1% threshold compared with three wild-type isolates that did not exceed this threshold (p=0&#xb7;018). Pfhrp3 was the most frequent deletion (39&#xb7;8% [95% CI 32&#xb7;6-47&#xb7;4]; in 66 of 166 patients), followed by double Pfhrp2/Pfhrp3 deletion (23&#xb7;5% [17&#xb7;7-30&#xb7;5]; in 39), wild-type (23&#xb7;5% [17&#xb7;7-30&#xb7;5]; in 39), and Pfhrp2 deletion (13&#xb7;3% [8&#xb7;9-19&#xb7;3]; in 22). R622I prevalence was similar across all four deletion categories (range 42-56%; p=0&#xb7;47). Ethiopia is the fifth sub-Saharan African country now meeting WHO confirmation criteria for ART-R. High R622I prevalence and double deletion rates, consistent with distinct selective pressures, represent a dual threat to treatment and HRP2-based diagnosis of P falciparum malaria in this region. Fondation pour la Recherche M&#xe9;dicale, Institut Universitaire de France, Agence Nationale de la Recherche, Universit&#xe9; de Strasbourg, and the National Natural Science Foundation of China. For the Amharic translation of the abstract see Supplementary Material section.

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