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Estimating effectiveness in HIV prevention trials with a Bayesian hierarchical compound Poisson frailty model.

ABSTRACT: Inconsistent results in recent HIV prevention trials of pre-exposure prophylactic interventions may be due to heterogeneity in risk among study participants. Intervention effectiveness is most commonly estimated with the Cox model, which compares event times between populations. When heterogeneity is present, this population-level measure underestimates intervention effectiveness for individuals who are at risk. We propose a likelihood-based Bayesian hierarchical model that estimates the individual-level effectiveness of candidate interventions by accounting for heterogeneity in risk with a compound Poisson-distributed frailty term. This model reflects the mechanisms of HIV risk and allows that some participants are not exposed to HIV and, therefore, have no risk of seroconversion during the study. We assess model performance via simulation and apply the model to data from an HIV prevention trial. Copyright © 2016 John Wiley & Sons, Ltd.

SUBMITTER: Coley RY

PROVIDER: S-EPMC5039019 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Estimating effectiveness in HIV prevention trials with a Bayesian hierarchical compound Poisson frailty model.

Coley Rebecca Yates RY Brown Elizabeth R ER

Statistics in medicine 20160211 15

Inconsistent results in recent HIV prevention trials of pre-exposure prophylactic interventions may be due to heterogeneity in risk among study participants. Intervention effectiveness is most commonly estimated with the Cox model, which compares event times between populations. When heterogeneity is present, this population-level measure underestimates intervention effectiveness for individuals who are at risk. We propose a likelihood-based Bayesian hierarchical model that estimates the individ ...[more]

PMID: 26869051

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Project description:BackgroundGlobally, child mortality and morbidity remain a serious health challenge and infectious diseases are the leading causes. The use of count models together with spatial analysis of the number of doses of childhood vaccines taken is limited in the literature. We used a Bayesian zero-inflated Poisson regression model with spatio-temporal components to assess the number of doses of childhood vaccines taken among children aged 12-23 months and their associated factors.MethodsData of 19,564 children from 2003, 2008, 2013 and 2018 population-based cross-sectional Nigeria Demographic and Health Survey were used. The childhood vaccines include one dose of Bacillus-Calmette-Guérin; three doses of Diphtheria-Pertussis-Tetanus; three doses of Polio and one dose of Measles. Uptake of all nine vaccines was regarded as full vaccination. We examined the multilevel factors associated with the number of doses of childhood vaccines taken using descriptive, bivariable and multivariable Bayesian models. Analysis was conducted in Stata version 16 and R statistical packages, and visualization in ArcGIS.ResultsThe prevalence of full vaccination was 6.5% in 2003, 14.8% in 2008, 21.8% in 2013 and 23.3% in 2018. Full vaccination coverage ranged from 1.7% in Sokoto to 51.9% in Anambra. Factors associated with the number of doses of childhood vaccines taken include maternal age (adjusted Incidence "risk" Ratio (aIRR) = 1.05; 95% Credible Interval (CrI) = 1.03-1.07) for 25-34 years and (aIRR = 1.07; 95% CrI = 1.05-1.10) for 35-49 years and education: (aIRR = 1.11, 95% CrI = 1.09-1.14) for primary and (aIRR = 1.16; 95% CrI = 1.13-1.19) for secondary/tertiary education. Other significant factors are wealth status, antenatal care attendance, working status, use of skilled birth attendants, religion, mother's desire for the child, community poverty rate, community illiteracy, and community unemployment.ConclusionAlthough full vaccination has remained low, there have been improvements over the years with wide disparities across the states. Improving the uptake of vaccines by educating women on the benefits of hospital delivery and vaccines through radio jingles and posters should be embraced, and state-specific efforts should be made to address inequality in access to routine vaccination in Nigeria.

Project description:The occurrence of a genetic bottleneck in HIV sexual or mother-to-infant transmission has been well documented. This results in a majority of new infections being homogeneous, i.e., initiated by a single genetic strain. Early after infection, prior to the onset of the host immune response, the viral population grows exponentially. In this simple setting, an approach for estimating evolutionary and demographic parameters based on comparison of diversity measures is a feasible alternative to the existing Bayesian methods (e.g., BEAST), which are instead based on the simulation of genealogies.We have devised a web tool that analyzes genetic diversity in acutely infected HIV-1 patients by comparing it to a model of neutral growth. More specifically, we consider a homogeneous infection (i.e., initiated by a unique genetic strain) prior to the onset of host-induced selection, where we can assume a random accumulation of mutations. Previously, we have shown that such a model successfully describes about 80% of sexual HIV-1 transmissions provided the samples are drawn early enough in the infection. Violation of the model is an indicator of either heterogeneous infections or the initiation of selection.When the underlying assumptions of our model (homogeneous infection prior to selection and fast exponential growth) are met, we are under a very particular scenario for which we can use a forward approach (instead of backwards in time as provided by coalescent methods). This allows for more computationally efficient methods to derive the time since the most recent common ancestor. Furthermore, the tool performs statistical tests on the Hamming distance frequency distribution, and outputs summary statistics (mean of the best fitting Poisson distribution, goodness of fit p-value, etc). The tool runs within minutes and can readily accommodate the tens of thousands of sequences generated through new ultradeep pyrosequencing technologies. The tool is available on the LANL website.

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Estimating effectiveness in HIV prevention trials with a Bayesian hierarchical compound Poisson frailty model.

Publications

Estimating effectiveness in HIV prevention trials with a Bayesian hierarchical compound Poisson frailty model.

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