Biology subjects

Bershteyn, A.

Publications and source records attributed to Bershteyn, A..

3 recordsLinked to original sources

bioRxiv2019

The future of a partially effective HIV vaccine: assessing limitations at the population level

ObjectivesMathematical models have unanimously predicted that a first-generation HIV vaccine would be useful and cost-effective to roll out, but that its overall impact would be insufficient to reverse the epidemic. Here, we explore what factors contribute most to limiting the impact of such a vaccine.\n\nMethodsRanging from a theoretical ideal to a more realistic regimen, mirroring the one used in the currently ongoing trial in South Africa (HVTN 702), we model a nested hierarchy of vaccine attributes such as speed of roll-out, efficacy, and retention of booster doses.\n\nResultsThe predominant reasons leading to a substantial loss of vaccine impact on the HIV epidemic are the time required to scale up mass vaccination, limited durability and waning of efficacy.\n\nConclusionsA partially effective HIV vaccine will be a critical milestone for the development of a highly effective, durable, and scalable next-generation vaccine. Accelerated development, expedited vaccine availability, and improved immunogenicity are the main attributes of a vaccine that could dramatically reverse the course of the epidemic in highly endemic countries.

epidemiology↗

bioRxiv2018

Targeting and Vaccine Durability Are Key for Population-level Impact and Cost-Effectiveness of a Pox-Protein HIV Vaccine Regimen in South Africa

BackgroundRV144 is to date the only HIV vaccine trial to demonstrate efficacy, albeit rapidly waning over time. The HVTN 702 trial is currently evaluating in South Africa a similar vaccine formulation to that of RV144 for subtype C HIV with additional boosters (pox-protein regimen). Using a detailed stochastic individual-based network model of disease transmission calibrated to the HIV epidemic, we investigate population-level impact and maximum cost of an HIV vaccine to remain cost-effective.\n\nMethodsConsistent with the original pox-protein regimen, we model a primary series of five vaccinations meeting the goal of 50% cumulative efficacy 24 months after the first dose and include two-yearly boosters that maintain durable efficacy over 10 years. We simulate vaccination programs in South Africa starting in 2027 under various vaccine targeting and HIV treatment and prevention assumptions.\n\nResultsOur analysis shows that this partially effective vaccine could prevent, at catch-up vaccination with 60% coverage, up to 941,000 (15.6%) new infections between 2027 and 2047 assuming current trends of antiretroviral treatment. An impact of up to 697,000 (11.5%) infections prevented could be achieved by targeting age cohorts of highest incidence. Economic evaluation indicates that, if treatment scale-up was achieved, vaccination could be cost-effective at a total cost of less than $385 and $62 per 10-year series (cost-effectiveness thresholds of $5,691 and $750).\n\nConclusionsWhile a partially effective, rapidly waning vaccine could help to prevent HIV infections, it will not eliminate HIV as a public health priority in sub-Saharan Africa. Vaccination is expected to be most effective under targeted delivery to age groups of highest HIV incidence. Awaiting results of trial, the introduction of vaccination should go in parallel with continued innovation in HIV prevention, including studies to determine the costs of delivery and feasibility and further research into products with greater efficacy and durability.

epidemiology↗

bioRxiv2018

Predicting HIV Incidence in the SEARCH Trial: A Mathematical Modelling Study

IntroductionSEARCH is one of four randomized-controlled trials (RCTs) investigating the strategy of community-based treatment-as-prevention (TasP) for the reduction of HIV incidence in sub-Saharan Africa. SEARCH takes place among 32 pair-matched rural communities in three regions of East Africa and exceeded the UNAIDS 90-90-90 targets for HIV testing, linkage to care, and viral suppression in the intervention arm. We used mathematical modeling to estimate expected 3-year cumulative HIV incidence in both arms of the trial, using different assumptions about two main sources of uncertainty: scale-up of antiretroviral therapy (ART) in the control arm, and the degree of mixing between SEARCH residents and non-residents.\n\nMethodsWe used the HIV modelling software EMOD-HIV to configure and calibrate a new model of the SEARCH communities. The 32 trial communities were clustered into six nodes (three for the control arm and three for the intervention arm) using k-means clustering based on community HIV prevalence, male circumcision rates, mobility, and geographic region. The model was parameterized using data on demographics, HIV prevalence, male circumcision rates, and viral suppression data collected at trial baseline in 2013, and calibrated to nodespecific and age-specific HIV prevalence, ART coverage, and population size. Using data on ART scale-up in subsequent follow-up years in the trial, we varied linkage to ART in the control arm and the degree of external mixing between SEARCH residents and non-residents.\n\nResultsIf no external mixing and no additional control arm ART linkage occurred, we estimate the trial would report a relative risk (RR) of 0.60 (95% CI 0.54-0.67, p<0.001), with all simulations showing a significant result. However, if SEARCH residents mixed equivalently with non-residents and ART linkage in the control arm also increased such that the control arm also exceeded the 73% viral suppression target, the RR is estimated to be 0.96 (95% CI 0.87-1.06, p=0.458) and 72% of simulations are non-significant. Given our \"best guess\" assumptions about external mixing and year 3 data on ART linkage in the control arm, the RR is estimated to be 0.90 (95% CI 0.81-1.00, p=0.05), with 49% non-significant simulations.\n\nConclusionThe SEARCH trial is predicted to show a 4-40% reduction in cumulative 3-year incidence, but between 18-72% of simulations were non-significant if either or both ART linkage in the control arm and external mixing are substantial. Despite achieving the 90-90-90 targets, our \"best guess\" is that the SEARCH trial has an equal probability of reporting a non-significant reduction in HIV incidence as it does a significant reduction.

epidemiology↗