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Recipients of chimeric antigen receptor-modified T (CAR-T) cell therapies for B-cell malignancies are immunocompromised and at risk for serious infections. Vaccine immunogenicity is unknown in this population. We conducted a prospective observational study of the humoral immunogenicity of 2019-2020 inactivated influenza vaccines (IIV) in children and adults immediately prior to (n=7) or 13-57 months after (n=15) CD19-, CD20-, or BCMA-targeted CAR-T-cell therapy, as well as controls (n=8). Individuals post-CAR-T-cell therapy were in remission. We tested for antibodies to 4 vaccine strains at baseline and ≥1 time point after IIV using neutralization and hemagglutination inhibition assays. An antibody response was defined as a ≥4-fold titer increase from baseline at the first post-vaccine time point. Baseline A(H1N1) titers in the CAR-T cohorts were significantly lower compared to controls. Antibody responses to ≥1 vaccine strain occurred in 2 (29%) individuals before CAR-T-cell therapy; one individual maintained a response for >3 months post-CAR-T-cell therapy. Antibody responses to ≥1 vaccine strain occurred in 6 (40%) individuals vaccinated after CAR-T-cell therapy. An additional 2 (29%) and 6 (40%) individuals had ≥2-fold increases (at any time) in the pre- and post-CAR-T cohorts, respectively. There were no identified clinical or immunologic predictors of antibody responses. Neither severe hypogammaglobulinemia nor B-cell aplasia precluded antibody responses. These data support consideration for vaccination before and after CAR-T-cell therapy for influenza and other relevant pathogens such as SARS-CoV-2, irrespective of hypogammaglobulinemia or B-cell aplasia. Larger studies are needed to determine correlates of vaccine immunogenicity and durability in CAR-T-cell therapy recipients.Key PointsInfluenza vaccination was immunogenic pre- and post-CAR-T-cell therapy, despite hypogammaglobulinemia and B-cell aplasia.Vaccination with inactivated vaccines can be considered before CAR-T-cell therapy and in individuals with remission after therapy.

We introduce a method for volumetric photoacoustic imaging from a single laser shot using compressive sensing. We demonstrate the accuracy and efficiency of a 3D pressure distribution reconstruction.

The COVID-19 global pandemic has had considerable health impact, including sub-Saharan Africa. In Malawi, a resource-limited setting in Africa, gaining access to data to inform the COVID-19 response is challenging. Information on adherence to physical distancing guidelines and reducing contacts are nonexistent, but critical to understanding and communicating risk, as well as allocating scarce resources. We present a case study which leverages aggregated call detail records into a daily data pipeline which summarize population density and mobility in an easy-to-use dashboard for public health officials and emergency operations. From March to April 2021, we have aggregated 6-billion calls and text messages and continue to process 12 million more daily. These data are summarized into reports which describe, quantify, and locate mass gatherings and travel between subdistricts. These reports are accessible via web dashboards for policymakers within the Ministry of Health and Emergency Operations Center to inform COVID-19 response efforts and resource allocation.

Introduction Heterogeneity of sociodemographics and risk behaviours across the HIV treatment cascade could influence the public health impact of universal ART in sub‐Saharan Africa if those not virologically suppressed are more likely to be part of a risk group contributing to onward infections. Sociodemographic and risk heterogeneity across the treatment cascade has not yet been comprehensively described or quantified and we seek to systematically review and synthesize research on this topic among adults in Africa. Methods We conducted a systematic review of peer‐reviewed literature in Embase and MEDLINE databases as well as grey literature sources published in English between 2014 and 2018. We included studies that included people living with HIV (PLHIV) aged ≥15 years, and reported a 90‐90‐90 outcome: awareness of HIV‐positive status, ART use among those diagnosed or viral suppression among those on ART. We summarized measures of association between sociodemographics, within each outcome, and as a composite measure of population‐wide viral suppression. Results and discussion From 3533 screened titles, we extracted data from 92 studies (50 peer‐reviewed, 42 grey sources). Of included studies, 32 reported on awareness, 53 on ART use, 32 on viral suppression and 23 on population‐wide viral suppression. The majority of studies were conducted in South Africa, Uganda, and Malawi and reported data for age and gender. When stratified, PLHIV ages 15 to 24 years had lower median achievement of the treatment cascade (60‐49‐81), as compared to PLHIV ≥25 years (70‐63‐91). Men also had lower median achievement of the treatment cascade (66‐72‐85), compared to women (79‐76‐89). For population‐wide viral suppression, women aged ≥45 years had achieved the 73% target, while the lowest medians were among 15‐ to 24‐year‐old men (37%) and women (49%). Conclusions Considerable heterogeneity exists by age and gender for achieving the HIV 90‐90‐90 treatment goals. These results may inform delivery of HIV testing and treatment in sub‐Saharan Africa, as targeting youth and men could be a strategic way to maximize the population‐level impact of ART.

Introduction The COVID-19 pandemic has caused widespread disruptions including to health services. In the early response to the pandemic many countries restricted population movements and some health services were suspended or limited. In late 2020 and early 2021 some countries re-imposed restrictions. Health authorities need to balance the potential harms of additional SARS-CoV-2 transmission due to contacts associated with health services against the benefits of those services, including fewer new HIV infections and deaths. This paper examines these trade-offs for select HIV services. Methods We used four HIV simulation models (Goals, HIV Synthesis, Optima HIV and EMOD) to estimate the benefits of continuing HIV services in terms of fewer new HIV infections and deaths. We used three COVID-19 transmission models (Covasim, Cooper/Smith and a simple contact model) to estimate the additional deaths due to SARS-CoV-2 transmission among health workers and clients. We examined four HIV services: voluntary medical male circumcision, HIV diagnostic testing, viral load testing and programs to prevent mother-to-child transmission. We compared COVID-19 deaths in 2020 and 2021 with HIV deaths occurring now and over the next 50 years discounted to present value. The models were applied to countries with a range of HIV and COVID-19 epidemics. Results Maintaining these HIV services could lead to additional COVID-19 deaths of 0.002 to 0.15 per 10,000 clients. HIV-related deaths averted are estimated to be much larger, 19–146 discounted deaths per 10,000 clients. Discussion While there is some additional short-term risk of SARS-CoV-2 transmission associated with providing HIV services, the risk of additional COVID-19 deaths is at least 100 times less than the HIV deaths averted by those services. Ministries of Health need to take into account many factors in deciding when and how to offer essential health services during the COVID-19 pandemic. This work shows that the benefits of continuing key HIV services are far larger than the risks of additional SARS-CoV-2 transmission.

Background Despite policies for universal HIV testing and treatment (UTT) regardless of CD4 count, there are still 1.8 million new HIV infections and 1 million AIDS-related deaths annually. The UNAIDS 90-90-90 goals target suppression of HIV viral load in 73% of all HIV-infected people worldwide by 2030. However, achieving these targets may not lead to expected reductions in HIV incidence if the remaining 27% (persons with unsuppressed viral load) are the drivers of HIV transmission through high-risk behaviors. We aim to conduct a systematic review and meta-analysis to understand the demographics, mobility, geographic distribution, and risk profile of adults who are not virologically suppressed in sub-Saharan Africa in the era of UTT. Methods We will review the published and grey literature for study sources that contain data on demographic and behavioral strata of virologically suppressed and unsuppressed populations since 2014. We will search PubMed and Embase using four sets of search terms tailored to identify characteristics associated with virological suppression (or lack thereof) and each of the individual 90-90-90 goals. Record screening and data abstraction will be done independently and in duplicate. We will use random effects meta-regression analyses to estimate the distribution of demographic and risk features among groups not virologically suppressed and for each individual 90-90-90 goal. Discussion The results of our review will help elucidate factors associated with failure to achieve virological suppression in sub-Saharan Africa, as well as factors associated with failure to achieve each of the 90-90-90 goals. These data will help quantify the population-level effects of current HIV treatment interventions to improve strategies for maximizing virological suppression and ending the HIV epidemic. Systematic review registration PROSPERO CRD42018089505. Electronic supplementary material The online version of this article (10.1186/s13643-019-1024-6) contains supplementary material, which is available to authorized users.

Introduction In 2014, the Government of Thailand recommended pre‐exposure prophylaxis (PrEP) as an additional HIV prevention programme within Thailand's National Guidelines on HIV/AIDS Treatment Prevention. However, to date implementation and uptake of PrEP programmes have been limited, and evidence on the costs and the epidemiological and economic impact is not available. Methods We estimated the costs associated with PrEP provision among men having sex with men (MSM) participating in a facility‐based, prospective observational cohort study: the Test, Treat and Prevent HIV Programme in Thailand. We created a suite of scenarios to estimate the cost‐effectiveness of PrEP and sensitivity of the results to the model input parameters, including PrEP programme effectiveness, PrEP uptake among high‐risk and low‐risk MSM, baseline and future antiretroviral therapy (ART) coverage, condom use, unit cost of delivering PrEP, and the discount rate. Results Drug costs accounted for 82.5% of the total cost of providing PrEP, followed by lab testing (8.2%) and personnel costs (7.8%). The estimated costs of providing the PrEP package in accordance with the national recommendation ranges from US$223 to US$311 per person per year. Based on our modelling results, we estimate that PrEP would be cost‐effective when provided to either high‐risk or all MSM. However, we found that the programme would be approximately 32% more cost‐effective if offered to high‐risk MSM than it would be if offered to all MSM, with an incremental cost‐effectiveness ratio of US$4,836 per disability‐adjusted life years (DALY) averted and US$7,089 per DALY averted respectively. Cost‐effectiveness acceptability curves demonstrate that 80% of scenarios would be cost‐effective when PrEP is provided solely to higher‐risk MSM. Conclusion We provide the first estimates on cost and cost‐effectiveness of PrEP in the Asia‐Pacific region, and offer insights on how to deliver PrEP in combination with ART. While the high drug cost poses a budgeting challenge, incorporating PrEP delivery into an existing ART programme could be a cost‐effective strategy to prevent HIV infections among MSM in Thailand.