COVID-19 vaccine design and vaccination rollout need to take into account a detailed understanding of antibody durability and cross-neutralizing potential against SARS-CoV-2 and emerging variants of concern (VOCs). Analyses of convalescent sera provide unique insights into antibody longevity and cross-neutralizing activity induced by variant spike proteins, which are putative vaccine candidates. Using sera from 38 individuals infected in wave 1, we show that cross-neutralizing activity can be detected up to 305 days pos onset of symptoms, although sera were less potent against B.1.1.7 (Alpha) and B1.351 (Beta). Over time, despite a reduction in overall neutralization activity, differences in sera neutralization potency against SARS-CoV-2 and the Alpha and Beta variants decreased, which suggests that continued antibody maturation improves tolerance to spike mutations. We also compared the cross-neutralizing activity of wave 1 sera with sera from individuals infected with the Alpha, the Beta or the B.1.617.2 (Delta) variants up to 79 days post onset of symptoms. While these sera neutralize the infecting VOC and parental virus to similar levels, cross-neutralization of different SARS-CoV-2 VOC lineages is reduced. These findings will inform the optimization of vaccines to protect against SARS-CoV-2 variants.

Mobile and tablet apps, ubiquitous and pervasive computing, wearable computing and domotics for health.

Background: Despite improvements in treatment and oral pre-exposure prophylaxis (PrEP) access, 1.3 million people acquired HIV in 2022. Six-monthly lenacapavir PrEP could benefit tens of millions of people at high risk of infection. However, prices are currently up to $44 819 per person per year (pppy). Objectives: We projected minimum lenacapavir pricing based on generic mass production and a Cost-Plus (Cost+) model. Methods: Current active pharmaceutical ingredient (API) and key starting materials (KSMs) costs were obtained from export databases. The routes of synthesis (ROS) were analysed to project a cost of goods (COGs). Formulation, vials and profit margin costs were included using standardized algorithms and Cost+ pricing. We estimated prices with scale-up to supply 1 million then 10 million treatment-years, comparing this with national list prices. Results: The lenacapavir API is currently exported from India for $64 480/kg on 1 kg scale. Based on the ROS and KSMs, API COGs of $25 000/kg and $10 000/kg are achievable for a committed demand of 1 million (2 million tonnes/annum of API) and 10 million treatment-years, respectively. Including formulation steps, injectable lenacapavir could be mass produced for approximately $94 pppy for 1 million and $41 for 10 million treatment-years, if voluntary licences are in place and competition between generic suppliers substantially improves. Greater scale-up with improvements in manufacturers’ ROS could reduce prices further. Currently lenacapavir costs $25 395–44 819 pppy. Conclusions: Lenacapavir could be mass produced for <$100 pppy at launch. Voluntary licensing and multiple suppliers are required to achieve these low prices. This mechanism is already in place for other antiretrovirals. To date, Gilead has not agreed lenacapavir voluntary licences with the Medicines Patent Pool.

In 2023, there were 39.9 million people living with HIV (PLWH) worldwide and 630 000 deaths related to HIV. New strategies are needed, and long-acting antiretrovirals (LAAs) are now widely considered to have great potential to help end the HIV epidemic. This systematic review and meta-analysis compare the safety and efficacy of LAA versus standard oral treatment (SOT) for HIV. PubMed and Embase databases, supplemented by ClinicalTrials.gov and grey literature, were searched. Randomized controlled trials (RCTs) reporting efficacy and/or safety of LAA versus SOT for PLWH until June 2024 were included. Efficacy (HIV RNA < 50 copies/mL) and HIV RNA ≥ 50 copies/mL, adverse events (AEs), treatment discontinuation, CD4 count, metabolic parameters and drug resistance were assessed. Prespecified subgroup analyses were conducted. The risk of bias was assessed with Cochrane RoB 2.0. Certainty of evidence was assessed using GRADE. Six RCTs were eligible for inclusion, involving 2829 participants. LAA was non-inferior to SOT in suppressing HIV RNA < 50 copies/mL [Risk Difference (RD), −0.00; 95% CI, −0.03–0.02; P = 0.83; I² = 51%; high quality of evidence (QoE)]. LAA was associated with higher drug resistance (percentage pooled estimate, 57%; 95% CI, 33%–78% versus 9%; 95% CI, 2%–30%; moderate QoE) and risk of grade 1–4 AEs than SOT [Risk Ratio (RR), 1.22; 95% CI, 1.12–1.33; P < 0.001; I² = 62%; moderate QoE]. LAA has non-inferior efficacy compared to SOT. However, participants receiving LAA were at a higher risk of developing drug resistance, cross-resistance and AEs.

Antiretroviral therapy shortages caused by sudden and severe cuts in USAID and PEPFAR have focused attention on strategies to extend antiretroviral supplies and mitigate this crisis. Efficacy data are now available from seven randomized controlled intermittent triple antiretroviral therapy trials. For countries with urgent drug shortages, this evidence supports intermittent dosing 4–5 days-per-week to extend antiretroviral supplies, with clinical benefits for people living with HIV and continued population benefits of minimizing HIV transmission.

In total, 1.3 million people acquired human immunodeficiency virus (HIV) in 2023, well behind the UNAIDS goal of <370 000 infections by 2025. Novel 6-monthly injectable pre-exposure prophylaxis (PrEP) medication lenacapavir is highly efficacious and could be epidemic-changing. However, without equitable access infection rates will continue. Gilead Sciences, the originator, currently charges over $40 000 per person-year for lenacapavir as HIV treatment, far exceeding PrEP cost-effectiveness thresholds, even in the richest countries. Yet the projected cost of production at scale is <$100 per person-year. Gilead's new voluntary license for lenacapavir prevention and treatment undermines access. Middle-income countries with fast-growing HIV epidemics have been excluded; 23% of new HIV infections occur in these countries. A coordinated response from governments, donors, civil society, and the private sector including Gilead is urgently required to ensure lenacapavir access is wide enough to eliminate HIV transmission worldwide. Unless crucial changes to the current license are made, compulsory licences may be required.