Origin and phylodynamics of HIV-1 subtype C in South Africa

Thesis (PhD)-- Stellenbosch University, 2013.ENGLISH ABSTRACT: The HIV epidemic in the past couple of decades has spread at an alarming rate throughout Southern Africa. Today the region accounts for roughly one third of all HIV infections, while prevalence rates in other areas of sub-Saharan Africa remain low. In the following study, sampled sequences from Cape Town, spanning over a 21-year period were used to investigate the epidemic history of HIV, which was compared to epidemic trends across Southern Africa. Longitudinal sequence data sets were generated from stored patient samples from Cape Town through standard molecular techniques. Firstly, these sequences were used to estimate the date of origin of the HIV epidemic in Cape Town and to reconstruct a demographic history of the epidemic with advanced Bayesian inference methods. These analyses placed the estimated date of origin of the Cape Town epidemic around the mid 1960‟s with periods of strong epidemic growth observed during the mid 1980‟s and 1990‟s. Secondly, reference strains of HIV from Southern African countries were used to estimate the date of origin of the epidemic in the Southern African region. These analyses placed the date of origin of the epidemic in the Southern African region around the mid 1950‟s roughly ten years before the start of the epidemic in Cape Town/South Africa. These sequences were also used for the reconstruction of the demographic history of the epidemic in the region. A two phased growth in the HIV epidemic in the Southern African region was observed with exponential growth occurring in the mid 1980‟s and 1990‟s. Such findings are also supported by HIV prevalence estimates made by some of the leading HIV research centres and government health departments. Thirdly, a large number of homologous reference strains were used to establish the evolutionary relationship of HIV isolates from Cape Town with those from around the world. A close genetic relationship between Cape Town isolates with other South African and other Southern African isolates was observed in these analyses. Finally, large monophyletic clusters of Cape Town isolates, which was observed during the evolutionary inference, were further investigated. After detailed analyses it appears that these transmission clusters of HIV-1 have been in circulation amongst the infected population of Cape Town for several years or decades.AFRIKAANSE OPSOMMING: Die MIV-epidemie het in die afgelope paar dekades teen ´n snelspoed deur Suider-Afrika versprei. Een derde van die globale MIV-infeksies kom hiér voor terwyl ander dele van Afrika aansienlik minder infeksies aantoon. Verskeie studies skryf dit toe aan onder andere: manlike besnydenis, seksuele losbandigheid, migrasie en verskeie politike faktore. Die MIV-epidemie in Suider-Afrika word deur ´n enkele subtipe van die virus oorheers (nl. MIV Subtipe C) terwyl ander subtipes sirkuleer deur die res van sub Sahara-Afrika. In die opeenvolgende studie word DNS-monsters uit Kaapstad (wat oor ´n 20 jaar tydperk strek) gebruik om die oorsprong en verloop van die epidemie te bestudeer. Die data van die Kaapstad epidemie word met die geskiedkundige verloop van die epidemie in Suider-Afrika vergelyk. Deur gestoorde bloedmonsters van Kaapstad te gebruik, was DNS-datastelle gegenereer deur middel van standaard molekulêre tegnieke. Die DNS-monsters was eerstens gebruik om die evolusionêre oorsprong en verloop van die epidemie in Kaapstad te bepaal deur Bayesiaanse Markov-ketting Monte Carlo steekproefneming. Volgense die resultate het die epidemie sy oorsprong in die 1960‟s. Klein periodes van epidemiese groei kon waargeneem word gedurende die 1980's en -90's. Die bevindings is toe vergelyk met die geskiedkundige verloop van die epidemie in Suider-Afrika. Die Suider-Afrika epidemie se oorsprong en verloop was afgelei van DNS monsters wat verkry is van publieke databasisse en die gebruik van soortgelyke Bayesiaanse metodes. Die resultate van die ondersoek het bevind dat die epidemie in Suider-Afrika in die 1950‟s ontstaan het. In vergelyking toon dit 'n stadiger liniêre groei met kort periodes van eksponensiële groei. Verder is ´n standard filogenetiese analise onderneem om die evolusionêre verwantskap van die Kaapstad-monsters te bepaal met ander MIV subtipe C isolate. Die filogenetiese steekproef toon dat die Kaapstad-monster baie nou verwant is aan ander isolate van Kaapstad, Suid-Afrika en Suider Afrika. Buiten hierdie bevindings was transmissie-bondels van MIV in Kaapstad ontdek. Na ´n deeglike verdere filogenetiese ondersoek blyk dit of die transmissie bondels al vir ´n paar dekades deur die geïnfekteerde populasie van Kaapstad sirkuleer.Poliomyelitis Research Foundation (PRF)Faculty of Medicine and Health of the University of StellenboschNational Research Foundation (NRF) of South Africa