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HIV testing rates are suboptimal among at-risk men. Crowdsourcing may be a useful tool for designing innovative, community-based HIV testing strategies to increase HIV testing. The purpose of this study was to use a stepped wedge cluster randomized controlled trial (RCT) to evaluate the effect of a crowdsourced HIV intervention on HIV testing uptake among men who have sex with men (MSM) in eight Chinese cities. An HIV testing intervention was developed through a national image contest, a regional strategy designathon, and local message contests. The final intervention included a multimedia HIV testing campaign, an online HIV testing service, and local testing promotion campaigns tailored for MSM. This intervention was evaluated using a closed cohort stepped wedge cluster RCT in eight Chinese cities (Guangzhou, Shenzhen, Zhuhai, and Jiangmen in Guangdong province; Jinan, Qingdao, Yantai, and Jining in Shandong province) from August 2016 to August 2017. MSM were recruited through Blued, a social networking mobile application for MSM, from July 29 to August 21 of 2016. The primary outcome was self-reported HIV testing in the past 3 months. Secondary outcomes included HIV self-testing, facility-based HIV testing, condom use, and syphilis testing. Generalized linear mixed models (GLMMs) were used to analyze primary and secondary outcomes. We enrolled a total of 1,381 MSM. Most were ≤30 years old (82%), unmarried (86%), and had a college degree or higher (65%). The proportion of individuals receiving an HIV test during the intervention periods within a city was 8.9% (95% confidence interval [CI] 2.2-15.5) greater than during the control periods. In addition, the intention-to-treat analysis showed a higher probability of receiving an HIV test during the intervention periods as compared to the control periods (estimated risk ratio [RR] = 1.43, 95% CI 1.19-1.73). The intervention also increased HIV self-testing (RR = 1.89, 95% CI 1.50-2.38). There was no effect on facility-based HIV testing (RR = 1.00, 95% CI 0.79-1.26), condom use (RR = 1.00, 95% CI 0.86-1.17), or syphilis testing (RR = 0.92, 95% CI 0.70-1.21). A total of 48.6% (593/1,219) of participants reported that they received HIV self-testing. Among men who received two HIV tests, 32 individuals seroconverted during the 1-year study period. Study limitations include the use of self-reported HIV testing data among a subset of men and non-completion of the final survey by 23% of participants. Our study population was a young online group in urban China and the relevance of our findings to other populations will require further investigation. In this setting, crowdsourcing was effective for developing and strengthening community-based HIV testing services for MSM. Crowdsourced interventions may be an important tool for the scale-up of HIV testing services among MSM in low- and middle-income countries (LMIC). ClinicalTrials.gov NCT02796963.

Background Including structural determinants (e.g. criminalisation, stigma, inequitable gender norms) in dynamic HIV transmission models is important to help quantify their population-level impacts and guide implementation of effective interventions that reduce the burden of HIV and inequalities thereof. However, evidence-based modelling of structural determinants is challenging partly due to a limited understanding of their causal pathways and few empirical estimates of their effects on HIV acquisition and transmission. Methods We conducted a scoping review of dynamic HIV transmission modelling studies that evaluated the impacts of structural determinants, published up to August 28, 2023, using Ovid Embase and Medline online databases. We appraised studies on how models represented exposure to structural determinants and causal pathways. Building on this, we developed a new methodological framework and recommendations to support the incorporation of structural determinants in transmission dynamics models and their analyses. We discuss the data and analyses that could strengthen the evidence used to inform these models. Results We identified 17 HIV modelling studies that represented structural determinants and/or interventions, including incarceration of people who inject drugs (number of studies [ n ] = 5), violence against women ( n  = 3), HIV stigma ( n  = 1), and housing instability ( n  = 1), among others ( n  = 7). Most studies ( n  = 10) modelled exposures dynamically. Almost half (8/17 studies) represented multiple exposure histories (e.g. current, recent, non-recent exposure). Structural determinants were often assumed to influence HIV indirectly by influencing mediators such as contact patterns, condom use, and antiretroviral therapy use. However, causal pathways’ assumptions were sometimes simple, with few mediators explicitly represented in the model, and largely based on cross-sectional associations. Although most studies calibrated models using HIV epidemiological data, less than half (7/17) also fitted or cross-validated to data on the prevalence, frequency, or effects of exposure to structural determinants. Conclusions Mathematical models can play a crucial role in elucidating the population-level impacts of structural determinants and interventions on HIV. We recommend the next generation of models reflect exposure to structural determinants dynamically and mechanistically, and reproduce the key causal pathways, based on longitudinal evidence of links between structural determinants, mediators, and HIV. This would improve the validity and usefulness of predictions of the impacts of structural determinants and interventions.

Introduction Long‐acting injectable cabotegravir (CAB‐LA) demonstrated superiority to daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV pre‐exposure prophylaxis (PrEP) in the HPTN 083/084 trials. We compared the potential impact of expanding PrEP coverage by offering CAB‐LA to men who have sex with men (MSM) in Atlanta (US), Montreal (Canada) and the Netherlands, settings with different HIV epidemics. Methods Three risk‐stratified HIV transmission models were independently parameterized and calibrated to local data. In Atlanta, Montreal and the Netherlands, the models, respectively, estimated mean TDF/FTC coverage starting at 29%, 7% and 4% in 2022, and projected HIV incidence per 100 person‐years (PY), respectively, decreasing from 2.06 to 1.62, 0.08 to 0.03 and 0.07 to 0.001 by 2042. Expansion of PrEP coverage was simulated by recruiting new CAB‐LA users and by switching different proportions of TDF/FTC users to CAB‐LA. Population effectiveness and efficiency of PrEP expansions were evaluated over 20 years in comparison to baseline scenarios with TDF/FTC only. Results Increasing PrEP coverage by 11 percentage points (pp) from 29% to 40% by 2032 was expected to avert a median 36% of new HIV acquisitions in Atlanta. Substantially larger increases (by 33 or 26 pp) in PrEP coverage (to 40% or 30%) were needed to achieve comparable reductions in Montreal and the Netherlands, respectively. A median 17 additional PYs on PrEP were needed to prevent one acquisition in Atlanta with 40% PrEP coverage, compared to 1000+ in Montreal and 4000+ in the Netherlands. Reaching 50% PrEP coverage by 2032 by recruiting CAB‐LA users among PrEP‐eligible MSM could avert >45% of new HIV acquisitions in all settings. Achieving targeted coverage 5 years earlier increased the impact by 5–10 pp. In the Atlanta model, PrEP expansions achieving 40% and 50% coverage reduced differences in PrEP access between PrEP‐indicated White and Black MSM from 23 to 9 pp and 4 pp, respectively. Conclusions Achieving high PrEP coverage by offering CAB‐LA can impact the HIV epidemic substantially if rolled out without delays. These PrEP expansions may be efficient in settings with high HIV incidence (like Atlanta) but not in settings with low HIV incidence (like Montreal and the Netherlands).

Many mathematical models have investigated the population-level impact of expanding antiretroviral therapy (ART), using different assumptions about HIV disease progression on ART and among ART dropouts. We evaluated the influence of these assumptions on model projections of the number of infections and deaths prevented by expanded ART. A new dynamic model of HIV transmission among men who have sex with men (MSM) was developed, which incorporated each of four alternative assumptions about disease progression used in previous models: (A) ART slows disease progression; (B) ART halts disease progression; (C) ART reverses disease progression by increasing CD4 count; (D) ART reverses disease progression, but disease progresses rapidly once treatment is stopped. The model was independently calibrated to HIV prevalence and ART coverage data from the United States under each progression assumption in turn. New HIV infections and HIV-related deaths averted over 10 years were compared for fixed ART coverage increases. Little absolute difference (<7 percentage points (pp)) in HIV infections averted over 10 years was seen between progression assumptions for the same increases in ART coverage (varied between 33% and 90%) if ART dropouts reinitiated ART at the same rate as ART-naïve MSM. Larger differences in the predicted fraction of HIV-related deaths averted were observed (up to 15pp). However, if ART dropouts could only reinitiate ART at CD4<200 cells/μl, assumption C predicted substantially larger fractions of HIV infections and deaths averted than other assumptions (up to 20pp and 37pp larger, respectively). Different disease progression assumptions on and post-ART interruption did not affect the fraction of HIV infections averted with expanded ART, unless ART dropouts only re-initiated ART at low CD4 counts. Different disease progression assumptions had a larger influence on the fraction of HIV-related deaths averted with expanded ART.

Background With the evolving growth of the COVID-19 epidemic, travel restriction policies would need to be adjusted accordingly. Prohibition of mass event may be relaxed for social and economic benefits when virus transmission stops but could bear the risk of epidemic rebound. Against the background of the varied SARS-CoV-2 prevalence internationally, we modelled the potential impacts of pre-event interventions on epidemic risk of holding a mass event when COVID-19 is under control. Methods We developed a mathematical model of SARS-CoV-2 transmission in Guangdong Province, China, where local virus transmission ceased to occur. A large-scale international trade fair was assumed to be held, with influx of people from overseas and rest of China over a short period of time, who participated for 2-week. Scenarios of pre-event intervention (none, quarantine arrangement and polymerase chain reaction (PCR) testing for participants) were compared. The influence of contact pattern, SARS-CoV-2 prevalence outside the province and China, and testing coverage were examined in sensitivity analyses. Results In basecase scenario (no event), the epidemic has been under control since March 2020. The event would lead to the detection of 1% more confirmed cases by 31 July when community contact rate increases to pre-epidemic level. In event scenario without additional interventions, there would be 599 (93%) more new infections comparing with basecase scenario. To avert new infections, quarantining all participants before the event would be the most effective strategy, followed by quarantining all overseas participants and testing all other participants, and testing all participants before the event and on day 7. However, testing strategy is likely to be affected by the SARS-CoV-2 prevalence outside the event province. Conclusions Pre-event interventions are effective for reducing the risk of epidemic rebound caused by an international large-scale event. Universal testing for participants is likely to be an effective and feasible intervention.

Introduction Long‐acting injectable cabotegravir (CAB‐LA) is superior to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV pre‐exposure prophylaxis (PrEP) and could expand PrEP usage. Given price differentials between CAB‐LA and TDF/FTC, evaluating the cost‐effectiveness of potential PrEP coverage scenarios is warranted. Methods We simulated PrEP coverage expansion among men who have sex with men (MSM) via introducing CAB‐LA using two age‐ and risk‐stratified HIV transmission models separately calibrated to local data from a high‐incidence (Atlanta, USA) and a low‐incidence (Montréal, Canada) North American setting. PrEP coverage of HIV‐negative MSM was simulated to increase from 6% to 15%, 30%, 40% or 50% (Montréal) or from 29% to 40% or 50% (Atlanta), within 5 or 10 years, with 0%, 15%, 30%, 50% or 100% of current TDF/FTC users switching to CAB‐LA. Costing took a healthcare payer perspective and included PrEP pharmaceuticals, PrEP programmatic costs and HIV‐related care. Atlanta scenarios considered oral PrEP acquired at average recent market prices (primary analysis), and both settings modelled universal acquisition at the lowest available generic price (LAGP). Simulations were compared to baseline projections without CAB‐LA‐based expansions over 20 years, with costs and disability‐adjusted life years (DALYs) discounted 3% annually. Incremental cost‐effectiveness ratios (ICERs) of expansions were assessed against a$100,000 per DALY averted threshold. Results In Atlanta, scenario median ICERs at recent prices ranged from $ 141,600 (90% CI$60,100−$ 256,000) to$203,800 ($ 99,300− $359,200) per DALY averted. All uncertainty intervals covered $ 100,000. Under universal LAGP TDF‐FTC, median ICERs ranged from$255,800 ($ 112,900− $452,30) to $ 370,700 ( $172,200−$ 669,100). The strongest expansion scenarios were expected to remain cost‐effective until approximately$2800/dose, or approximately $ 1350 with universal LAGP TDF/FTC. In Montréal, scenarios had median ICERs from$920,000 to $ 2,540,000, excluding dominated runs. Conclusions In a high‐incidence Atlanta MSM population, CAB‐LA‐based PrEP expansions are not projected to be cost‐effective, though a minority of simulations achieved cost‐effectiveness. However, lower prices could achieve cost‐effectiveness. In a low‐incidence Montréal MSM population, broad expansions are not expected to be cost‐effective at modelled prices. Prioritizing CAB‐LA to Montréal MSM facing access, adherence or persistence barriers to oral PrEP warrants a cost‐effectiveness assessment.

In animal experimental models, parasitic helminth infections can protect the host from auto-immune diseases. We conducted a population-scale human study investigating the relationship between helminth parasitism and auto-reactive antibodies and the subsequent effect of anti-helminthic treatment on this relationship. Levels of antinuclear antibodies (ANA) and plasma IL-10 were measured by enzyme linked immunosorbent assay in 613 Zimbabweans (aged 2-86 years) naturally exposed to the blood fluke Schistosoma haematobium. ANA levels were related to schistosome infection intensity and systemic IL-10 levels. All participants were offered treatment with the anti-helminthic drug praziquantel and 102 treated schoolchildren (5-16 years) were followed up 6 months post-antihelminthic treatment. ANA levels were inversely associated with current infection intensity but were independent of host age, sex and HIV status. Furthermore, after allowing for the confounding effects of schistosome infection intensity, ANA levels were inversely associated with systemic levels of IL-10. ANA levels increased significantly 6 months after anti-helminthic treatment. Our study shows that ANA levels are attenuated in helminth-infected humans and that anti-helminthic treatment of helminth-infected people can significantly increase ANA levels. The implications of these findings are relevant for understanding both the aetiology of immune disorders mediated by auto-reactive antibodies and in predicting the long-term consequences of large-scale schistosomiasis control programs.

Protective immunity against human schistosome infection develops slowly, for reasons that are not yet fully understood. For many decades, researchers have attempted to infer properties of the immune response from epidemiological studies, with mathematical models frequently being used to bridge the gap between immunological theory and population-level data on schistosome infection and immune responses. Here, building upon earlier model findings, stochastic individual-based models were used to identify model structures consistent with observed field patterns of Schistosoma haematobium infection and antibody responses, including their distributions in cross-sectional surveys, and the observed treatment-induced antibody switch. We found that the observed patterns of infection and antibody were most consistent with models in which a long-lived protective antibody response is stimulated by the death of adult S. haematobium worms and reduces worm fecundity. These findings are discussed with regard to current understanding of human immune responses to schistosome infection.

Pathogens do not normally drive their hosts to extinction; however, Batrachochytrium dendrobatidis, which causes amphibian chytridiomycosis, has been able to do so. Theory predicts that extinction can be caused by long-lived or saprobic free-living stages. The hypothesis that such a stage occurs in B. dendrobatidis is supported by the recent discovery of an apparently encysted form of the pathogen. To investigate the effect of a free-living stage of B. dendrobatidis on host population dynamics, a mathematical model was developed to describe the introduction of chytridiomycosis into a breeding population of Bufo bufo, parametrized from laboratory infection and transmission experiments. The model predicted that the longer that B. dendrobatidis was able to persist in water, either due to an increased zoospore lifespan or saprobic reproduction, the more likely it was that it could cause local B. bufo extinction (defined as decrease below a threshold level). Establishment of endemic B. dendrobatidis infection in B. bufo, with severe host population depression, was also possible, in agreement with field observations. Although this model is able to predict clear trends, more precise predictions will only be possible when the life history of B. dendrobatidis, including free-living stages of the life cycle, is better understood.

Previous studies suggest that protective immunity against Schistosoma haematobium is primarily stimulated by antigens from dying worms. Praziquantel treatment kills adult worms, boosting antigen exposure and protective antibody levels. Current schistosomiasis control efforts use repeated mass drug administration (MDA) of praziquantel to reduce morbidity, and may also reduce transmission. The long-term impact of MDA upon protective immunity, and subsequent effects on infection dynamics, are not known. A stochastic individual-based model describing levels of S. haematobium worm burden, egg output and protective parasite-specific antibody, which has previously been fitted to cross-sectional and short-term post-treatment egg count and antibody patterns, was used to predict dynamics of measured egg output and antibody during and after a 5-year MDA campaign. Different treatment schedules based on current World Health Organisation recommendations as well as different assumptions about reductions in transmission were investigated. We found that antibody levels were initially boosted by MDA, but declined below pre-intervention levels during or after MDA if protective immunity was short-lived. Following cessation of MDA, our models predicted that measured egg counts could sometimes overshoot pre-intervention levels, even if MDA had had no effect on transmission. With no reduction in transmission, this overshoot occurred if protective immunity was short-lived. This implies that disease burden may temporarily increase following discontinuation of treatment, even in the absence of any reduction in the overall transmission rate. If MDA was additionally assumed to reduce transmission, a larger overshoot was seen across a wide range of parameter combinations, including those with longer-lived protective immunity. MDA may reduce population levels of immunity to urogenital schistosomiasis in the long-term (3-10 years), particularly if transmission is reduced. If MDA is stopped while S. haematobium is still being transmitted, large rebounds (up to a doubling) in egg counts could occur.