Combining sexual behavioural survey data, phylodynamics and agent-based models towards a unified framework for HIV prevention research
| dc.contributor.advisor | Nyasulu, Peter Suwirakwenda | en_ZA |
| dc.contributor.advisor | Delva, Wim | en_ZA |
| dc.contributor.author | Niyukuri, David | en_ZA |
| dc.contributor.other | Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics. | en_ZA |
| dc.date.accessioned | 2021-08-04T14:06:04Z | |
| dc.date.accessioned | 2022-02-22T10:16:42Z | |
| dc.date.available | 2022-02-23T03:00:13Z | |
| dc.date.issued | 2021-12 | |
| dc.description | Thesis (PhD)--Stellenbosch University, 2021. | |
| dc.description.abstract | ENGLISH SUMMARY: Background: Sub-Saharan African countries carry a disproportionate burden of the Human Immunodeficiency Virus (HIV) infection. Thus, beyond estimation tools which are used to produce HIV epidemic estimates, there is a need for simulation tools to understand the structure and the dynamics of sexual networks, and HIV transmission underlying factors. This can help to design and implement effective interventions. These simulation tools should be able to take advantage of existing multi-source data. Furthermore, with such multi-data generation tools, we can be able to assess new methodologies and the accuracy of different inferences made from available real-world data. Methods: We developed a unified simulation framework which combines in one model world the simulation of sexual dynamic network, HIV transmission, and between-host viral evolution for infected individuals. We used that simulation framework to run a benchmark study to infer age-mixing patterns in HIV transmission in different sequence missingness scenarios. We used transmission clusters from phylogenetic trees and compute proportions of pairings between men and women who were phylogenetically linked across different age groups. We assessed the usability of our simulation framework through a calibration study. We focused on fitting the simulation framework to summary features from multiple data sources to increase the accuracy of estimates. The case study was the estimation of determinants of HIV transmission network, namely age-mixing patterns in sexual partnerships, distribution of onward transmission, and temporal trend of HIV incidence. We also used simulated polymerase and protease viral data on same transmission network with Simpact Cyan to check in the phylogenetic results, mainly root-to-tip regression, and transmission clusters. Results: The proof of concept of the appropriateness of the modelling framework was determined by the ability to capture HIV transmission dynamics, and the temporal trends of branching times of a phylogenetic tree built from simulated viral sequence data. For age-mixing patterns in HIV transmission, the results of the simulation suggested that proportions of men/women linked to women/men across different age groups, together with the mean and standard deviation of age difference can unveil age-mixing patterns in HIV transmission networks. For the calibration study, the results showed that the relative errors between true benchmark values and post calibration values of the determinants of HIV transmission network were relatively close in the three calibration scenarios. In post-calibration simulation age-mixing patterns and the distribution of onward HIV transmission had relatively small error values, but the age-gender strata temporal trend of incidence was poorly captured. The root-to-tip regression of phylogenetic trees from protease and polymerase data simulated on the same HIV transmission network showed that the dispersion of the genetic distance with branching and sampling times was explained at 95% and 49% for polymerase and protease data, respectively. For transmission clusters, we could still get at least 90% of individuals within big the size clusters if we use polymerase or protease viral sequence data. This showed that even with the short sequences we could still get useful epidemiological data. Conclusion: The unified framework could be used as a data generation method for benchmark studies. This is so despite the simplistic assumption for HIV viral evolutionary dynamic through consideration of host evolution only. These methods could also help to investigate the effect of sexual dynamic network on HIV transmission and estimate age related individual-level features affecting the HIV transmission dynamic. Furthermore, this simulation framework could i) contribute to the advancement of phylogenetic-based inference methodology; and ii) advance epidemiological methods focusing on combining epidemiological data, sexual behaviour data, viral phylodynamics, and agent-based simulation models. | en_ZA |
| dc.description.abstract | AFRIKAANSE OPSOMMING: Agtergrond Afrika-lande suid van die Sahara dra ’n buitensporige las van menslike immuniteitsgebreksvirus (MIV). Benewens assesseringsinstrumente wat gebruik word om ramings van die MIV-epidemie te maak, is simulasie-instrumente ook nodig om die struktuur en dinamika van seksuele netwerke en die onderliggende faktore van MIV-oordrag te verstaan. Dit kan help om effektiewe intervensies te ontwerp en te implementeer. Hierdie simulasie-instrumente moet bestaande multisource-data kan gebruik. Daarbenewens stel sulke instrumente vir die generering van multi-data ons in staat om nuwe metodologiee en die akkuraatheid van verskillende afleidings van beskikbare werklike data te evalueer. Metodes: Ons het ’n verenigde simulasieraamwerk ontwikkel wat die simulasie van seksuele dinamiese netwerk, MIV-oordrag en midde-gasheer virale evolusie vir besmette individue in een modelwereld kombineer. Ons het die simulasie-raamwerk gebruik om ’n maatstafstudie uit te voer om die vermengingspatrone van ouderdomme in MIV-oordrag te beoordeel in verskillende ontbrekende scenario’s. Ons het oordragklusters van filogenetiese bome gebruik en die verhoudings van parings tussen mans en vroue bereken wat filogeneties aan verskillende ouderdomsgroepe gekoppel is. Ons het die nut van ons simulasieraamwerk deur middel van ’n kalibrasie-studie geevalueer. Ons het gefokus op die simulasie-raamwerk om die kenmerke van verskillende databronne op te som om die akkuraatheid van die ramings te verhoog. Die gevallestudie was die beoordeling van determinante van die MIV-oordragnetwerk, naamlik ouderdomsmengingspatrone in seksuele vennootskappe, die verspreiding van verdere oordrag en die tydelike neiging tot MIV-voorkoms. Ons het ook gesimuleerde virale data van polimerase en protease gebruik op dieselfde transmissienetwerk met Simpact Cyan om filogenetiese resultate te monitor, hoofsaaklik regressie van die oorsprong van die wortel en transmissiegroeperings. Resultate: Die bewys of konsep van die geskiktheid van die modelraamwerk is bepaal deur die vermoe om die MIV-oordragdinamika vas te le, en die tydelike neigings van die vertaktye van ’n filogenetiese boom wat opgebou is uit gesimuleerde virale sekwensdata. Vir ouderdomsmengingspatrone in MIV-oordrag, het die resultate van die simulasie voorgestel dat verhoudings tussen mans / vroue en vroue / mans in verskillende ouderdomsgroepe, tesame met die gemiddelde en standaardafwyking van die ouderdomsverskil, ouderdomsmengingspatrone in MIV-oordrag kan openbaar netwerke. Vir die kalibrasiestudie het die resultate getoon dat die relatiewe foute tussen die ware maatstafwaardes en die na-kalibrasiewaardes van die determinante van die MIV-transmissienetwerk relatief naby aan mekaar was in die drie kalibrasiescenario’s. In die na-kalibrasiesimulasie het die ouderdomsmengingspatrone en die verspreiding van verdere MIV-oordrag relatief klein foutwaardes gehad, maar die tydelike neiging van die voorkoms in die ouderdomsgeslagstrata was sleg voorgestel. Die wortel-tot-bopunt regressie van die filogenetiese boom van protease and polimerase data, gesimuleer op dieselfde HIV transmissie netwerk, het daarop gewys dat die dispersie van die genetiese afstand met vertakking en steekproeftyd verduidelik kon word op 95% and 49% vir polymerase en protease data, respektiewelik. Vir transmissiegroeperings kan ons steeds minstens 90% van die individue binne groot groepe kry as ons data van polimeerase of proteasevirale gebruik. Dit toon dat ons steeds nuttige epidemiologiese inligting kan bekom, selfs met kort rye. Afsluiting: Ten spyte van die eenvoudige aanname van die dinamika van die MIV-virusse deur slegs die evolusie tussen die gashere in ag te neem, kan die eenvormige raamwerk gebruik word as ’n instrument vir die generering van data vir standaardstudies. Dit kan ook help om die effek van ’n seksueel dinamiese netwerk op MIV-oordrag te ondersoek en om ouderdomsspesifieke eienskappe op individuele vlak wat die dinamika van MIVoordrag beinvloed, te bepaal. Boonop kan hierdie simulasie-raamwerk bydra tot die bevordering van filogeneties-gebaseerde afleidingsmetodologie. Dit kan ook epidemi-ologiese metodologie bevorder wat fokus op die kombinasie van epidemiologiese data, seksuele gedrag, virale filodinamika en middelgebaseerde simulasiemodelle. | af_ZA |
| dc.description.version | Doctorate | |
| dc.embargo.terms | 2022-02-04 | |
| dc.format.extent | xxiii, 198 pages : illustrations, includes annexures | |
| dc.identifier.uri | http://hdl.handle.net/10019.1/124209 | |
| dc.language.iso | en_ZA | en_ZA |
| dc.publisher | Stellenbosch : Stellenbosch University | |
| dc.rights.holder | Stellenbosch University | |
| dc.subject | HIV infections -- Transmission | en_ZA |
| dc.subject | Sexual behavior surveys | en_ZA |
| dc.subject | Persons -- Sexual behavior | en_ZA |
| dc.subject | UCTD | |
| dc.title | Combining sexual behavioural survey data, phylodynamics and agent-based models towards a unified framework for HIV prevention research | en_ZA |
| dc.type | Thesis | en_ZA |