Modeling the impact of early HIV treatment on the HIV epidemic in South Africa

Abstract

ENGLISH SUMMARY: Amajor international randomized clinical trial fromStrategic Timing of AntiRetroviral Treatment (START) has found that HIV-infected individuals have a considerably lower risk of developing AIDS if they start taking antiretroviral drugs sooner. According to the guidelines pre-released in September 2015, the World Health Organization (WHO) recommends that ART should be initiated in all adults living with HIV at any CD4 cell count. Following previous WHO recommendations, many governments have steadily changed antiretroviral therapy (ART) guidelines over the last decade. South Africa has revised ART guidelines to increase access to treatment to 500 CD4 cell counts/mm3 or lesswith effect fromthe 1st January 2015. In ART programs, some individuals who initiate ART either fail treatment and switch regimen or dropout from ART, which might undermine the outcomes of ART programs. Thus, in the thesis, we formulated and analyzed new mathematicalmodels that assess the impact of treatment failure and dropout on ART outcomes and associated costs. The models we considered consist of partial differential equations that are structured by time since infection and time since ART roll out. Our results confirmthat early initiation of ART contributes to a steep decline in the number of new HIV infections and HIV deaths, but also show that the benefit of ART might be limited due to the impact of dropout and treatment failure. Despite the uncertainties associatedwith some of themodels’ parameters,such as ART induced sexual behavioral change and ART access rate, with the current trend of ART access rate our simulations show that HIV elimination is not possibly achievable within a decade. To achieve HIV elimination soon, ART access ratemust substantially increase, and the dropout and treatment failure rates must substantially reduce. If individuals keep dropping out of HIV treatment at current rates and they engage in risky sexual contact, HIV incidence will increase unless other intervention measures are taken. Consequently, the burden on the annual cost of providing ART will continue to increase.

AFRIKAANS OPSOMMING: Die ewekansige kliniese proefneming genaamd ‘Strategic Timing of AntiRetroviral Treatment (START)’ het bevind dat MIV-besmette persone ´n aansienlike laer risiko vir die ontwikkeling van VIGS het indien hulle vroeg anti-retroviralemiddels begin neem. Volgens die riglyne vrygestel in September 2015, beveel die Wêreld Gesondheid Organisasie (WGO) aan dat anti-retrovirale terapie (ART) beskikbaar gestelword aan alleMIV-besmette persone, ongeag hulle CD4 telling. Na aanleiding vanWGO aanbevelings in die verlede, het die regerings van verskeie lande stelselmatig hul aanbevelings oor ART die afgelope dekade verander. Suid- Afrika het sy ART riglyne aangepas om sedert 1 Januarie 2015 ART beskikbaar te stel aan individue met ´n CD4 telling van 500 selle/mm3 of laer. Sommige individue staak behandeling of hulle behandeling misluk en verander gevolglik kursus van behandeling. Dit kan die uitkomste van nasionale ART programme nadelig beinvloed. In hierdie proefskrif word nuwe wiskundigemodelle geformuleer en ge-analiseer wat beoog omdie impak van staking of mislukking van behandeling op ART uitkomste en verwante kostes te bepaal. Die modelle wat ons beskou bestaan uit parsiële differensiaalvergelykings wat gestruktureer word volgens die tydverloop sedert MIV infeksie en die aanvang van die ART program. Ons resultate bevestig dat vroeë aanvang van ART bydra tot `n skerp daling in die aantal nuwe MIV-infeksies enMIV sterftes,maar wys ook dat die voordeel van ART beperk kan word deur die impak van staking ofmislukking van behandeling. Daar is onsekerhedewat verband hou met `n paar parameters van die modelle, soos die verandering in seksuele gedrag veroorsaak deur ART en die beskikbaarheid van ART. Ten spyte hiervan toon ons simulasies dat, met die huidige tendens in die koers van toegang tot ART, uitskakeling vanMIV nie haalbaar is binne die volgende tien jaar nie. Om MIV so gou as moontlik uit te skakel, moet beskikbaarheid van ART aansienlik toeneem en die staking van behandeling aansienlik afneem. Indien individue MIV behandeling staak teen huidige koerse en hulle meer geneig is om riskante seksuele besluite te neem, sal MIV insidensie toeneem, tensy ander voorkomende maatreëls getref word. As ´n gevolg, sal die las op die jaarlikse koste van verskaffing van ART bly toeneem.