Browsing by Author "Wilkinson, Eduan"

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    Analysis of viral diversity in relation to the recency of HIV-1C infection in Botswana
    (Public Library of Science, 2016) Moyo, Sikhulile; Vandormael, Alain; Wilkinson, Eduan; Engelbrecht, Susan; Gaseitsiwe, Simani; Kotokwe, Kenanao P.; Musonda, Rosemary; Tanser, Frank; Essex, Max; Novitsk, Vladimir; De Oliveira, Tulio
    Background: Cross-sectional, biomarker methods to determine HIV infection recency present a promising and cost-effective alternative to the repeated testing of uninfected individuals. We evaluate a viral-based assay that uses a measure of pairwise distances (PwD) to identify HIV infection recency, and compare its performance with two serologic incidence assays, BED and LAg. In addition, we assess whether combination BED plus PwD or LAg plus PwD screening can improve predictive accuracy by reducing the likelihood of a false-recent result. Methods: The data comes from 854 time-points and 42 participants enrolled in a primary HIV-1C infection study in Botswana. Time points after treatment initiation or with evidence of multiplicity of infection were excluded from the final analysis. PwD was calculated from quasispecies generated using single genome amplification and sequencing. We evaluated the ability of PwD to correctly classify HIV infection recency within <130, <180 and <360 days post-seroconversion using Receiver Operator Characteristics (ROC) methods. Following a secondary PwD screening, we quantified the reduction in the relative false-recency rate (rFRR) of the BED and LAg assays while maintaining a sensitivity of either 75, 80, 85 or 90%. Results: The final analytic sample consisted of 758 time-points from 40 participants. The PwD assay was more accurate in classifying infection recency for the 130 and 180-day cut-offs when compared with the recommended LAg and BED thresholds. A higher AUC statistic confirmed the superior predictive performance of the PwD assay for the three cut-offs. When used for combination screening, the PwD assay reduced the rFRR of the LAg assay by 52% and the BED assay by 57.8% while maintaining a 90% sensitivity for the 130 and 180-day cut-offs respectively. Conclusion: PwD can accurately determine HIV infection recency. A secondary PwD screening reduces misclassification and increases the accuracy of serologic-based assays.
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    Detection of transmission clusters of HIV-1 subtype C over a 21-year period in Cape Town, South Africa
    (PLoS, 2014-10-30) Wilkinson, Eduan; Engelbrecht, Susan; De Oliveira, Tulio
    Introduction: Despite recent breakthroughs in the fight against the HIV/AIDS epidemic within South Africa, the transmission of the virus continues at alarmingly high rates. It is possible, with the use of phylogenetic methods, to uncover transmission events of HIV amongst local communities in order to identify factors that may contribute to the sustained transmission of the virus. The aim of this study was to uncover transmission events of HIV amongst the infected population of Cape Town. Methods and Results: We analysed gag p24 and RT-pol sequences which were generated from samples spanning over 21-years with advanced phylogenetic techniques. We identified two transmission clusters over a 21-year period amongst randomly sampled patients from Cape Town and the surrounding areas. We also estimated the origin of each of the identified transmission clusters with the oldest cluster dating back, on average, 30 years and the youngest dating back roughly 20 years. Discussion and Conclusion: These transmission clusters represent the first identified transmission events among the heterosexual population in Cape Town. By increasing the number of randomly sampled specimens within a dataset over time, it is possible to start to uncover transmission events of HIV amongst local communities in generalized epidemics. This information can be used to produce targeted interventions to decrease transmission of HIV in Africa.
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    The effect of interventions on the transmission and spread of HIV in South Africa : a phylodynamic analysis
    (Nature Research, 2019-02-25) Wilkinson, Eduan; Junqueira, Dennis Maletich; Lessells, Richard; Engelbrecht, Susan; Van Zyl, Gert; De Oliveira, Tulio; Salemi, Marco
    ENGLISH ABSTRACT: The epidemic in South Africa is characterized by high genetic diversity driven by multiple independent introductions. The bulk of these introductions occurred between 1985–2000 during which time HIV prevalence increased exponentially. Epidemic growth has stabilized in recent years with the implementation of several interventions. Here we identified distinct HIV clades from a large sequence dataset of southern African HIV sequences (n = 15,332). Each clade was characterized using phylodynamic and phylogeographic methods to infer their growth through time and space. The estimated date of origin for the 18 clades that were found, fell between 1979–1992 with strong growth during the 1990’s. Phylogeographic reconstruction revealed wide dispersal of clades throughout the country with the city of Johannesburg as the focal point of viral dispersal. We found clear signs of decreasing growth rate in four of the clades since the advent of interventions, while other clades have continued to growth and expand. Our results demonstrate that interventions do not affect the HIV epidemic universally with major difference between different clades over time and space. Here we demonstrate the utility and flexibility of molecular epidemiological methods and demonstrate how they can potentially be a powerful tool in HIV epidemic monitoring in South Africa.
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    History and origin of the HIV-1 subtype C epidemic in South Africa and the greater southern African region
    (Nature, 2015-11-17) Wilkinson, Eduan; Engelbrecht, Susan; De Oliveira, Tulio
    HIV has spread at an alarming rate in South Africa, making it the country with the highest number of HIV infections. Several studies have investigated the histories of HIV-1 subtype C epidemics but none have done so in the context of social and political transformation in southern Africa. There is a need to understand how these processes affects epidemics, as socio-political transformation is a common and on-going process in Africa. Here, we genotyped strains from the start of the epidemic and applied phylodynamic techniques to determine the history of the southern Africa and South African epidemic from longitudinal sampled data. The southern African epidemic’s estimated dates of origin was placed around 1960 (95% HPD 1956–64), while dynamic reconstruction revealed strong growth during the 1970s and 80s. The South African epidemic has a similar origin, caused by multiple introductions from neighbouring countries, and grew exponentially during the 1980s and 90s, coinciding with socio-political changes in South Africa. These findings provide an indication as to when the epidemic started and how it has grown, while the inclusion of sequence data from the start of the epidemic provided better estimates. The epidemic have stabilized in recent years with the expansion of antiretroviral therapy.
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    HIV-1 Subtypes B and C Unique Recombinant Forms (URFs) and transmitted drug resistance identified in the Western Cape Province, South Africa
    (Public Library of Science, 2014-03) Jacobs, Graeme Brendon; Wilkinson, Eduan; Isaacs, Shahieda; Spies, Georgina; De Oliveira, Tulio; Seedat, Soraya; Engelbrecht, Susan
    South Africa has the largest worldwide HIV/AIDS population with 5.6 million people infected and at least 2 million people on antiretroviral therapy. The majority of these infections are caused by HIV-1 subtype C. Using genotyping methods we characterized HIV-1 subtypes of the gag p24 and pol PR and RT fragments, from a cohort of female participants in the Western Cape Province, South Africa. These participants were recruited as part of a study to assess the combined brain and behavioural effects of HIV and early childhood trauma. The partial HIV-1 gag and pol fragments of 84 participants were amplified by PCR and sequenced. Different online tools and manual phylogenetic analysis were used for HIV-1 subtyping. Online tools included: REGA HIV Subtyping tool version 3; Recombinant Identification Program (RIP); Context-based Modeling for Expeditious Typing (COMET); jumping profile Hidden Markov Models (jpHMM) webserver; and subtype classification using evolutionary algorithms (SCUEAL). HIV-1 subtype C predominates within the cohort with a prevalence of 93.8%. We also show, for the first time, the presence of circulating BC strains in at least 4.6% of our study cohort. In addition, we detected transmitted resistance associated mutations in 4.6% of analysed sequences. With tourism and migration rates to South Africa currently very high, we are detecting more and more HIV-1 URFs within our study populations. It is stil unclear what role these unique strains will play in terms of long term antiretroviral treatment and what challenges they will pose to vaccine development. Nevertheless, it remains vitally important to monitor the HIV-1 diversity in South Africa and worldwide as the face of the epidemic is continually changing.
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    Identifying recent HIV infections : from serological assays to genomics
    (MDPI, 2015-10-23) Moyo, Sikhulile; Wilkinson, Eduan; Novitsky, Vladimir; Vandormael, Alain; Gaseitsiwe, Simani; Essex, Max; Engelbrecht, Susan; De Oliveira, Tulio
    In this paper, we review serological and molecular based methods to identify HIV infection recency. The accurate identification of recent HIV infection continues to be an important research area and has implications for HIV prevention and treatment interventions. Longitudinal cohorts that follow HIV negative individuals over time are the current gold standard approach, but they are logistically challenging, time consuming and an expensive enterprise. Methods that utilize cross-sectional testing and biomarker information have become an affordable alternative to the longitudinal approach. These methods use well-characterized biological makers to differentiate between recent and established HIV infections. However, recent results have identified a number of limitations in serological based assays that are sensitive to the variability in immune responses modulated by HIV subtypes, viral load and antiretroviral therapy. Molecular methods that explore the dynamics between the timing of infection and viral evolution are now emerging as a promising approach. The combination of serological and molecular methods may provide a good solution to identify recent HIV infection in cross-sectional data. As part of this review, we present the advantages and limitations of serological and molecular based methods and their potential complementary role for the identification of HIV infection recency.
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    Molecular characterization of non-subtype C and recombinant HIV-1 viruses from Cape Town, South Africa
    (Stellenbosch : University of Stellenbosch, 2009-03) Wilkinson, Eduan; Engelbrecht, Susan; University of Stellenbosch. Faculty of Health Sciences. Dept. of Pathology.
    ENGLISH ABSTRACT: HIV-1 was first diagnosed within South Africa in 1982. In the 1980’s homosexual transmission dominated the HIV-1 epidemic within the country. In the late 1980’s the second HIV-1 epidemic was recognized amongst heterosexual individuals. Today heterosexual transmission of HIV-1 dominates the epidemic in South Africa. Subtype C HIV-1 is responsible for the overwhelming majority of heterosexual infections. An estimated 95% of all infections in the country are thought to be subtype C related. To date only a few papers have been published on non-subtype C HIV within the country. This study characterized subgenomic and near full-length sequences of non-subtype C HIV-1 viruses from the Cape Town area. The gag p24, pol-integrase, and env gp41 regions of 11 of the 12 samples were characterized by amplification and direct sequencing. Phylogenetic analysis of the sequenced data, with online subtyping tools (REGA and jpHMM) and the drawing of NJ-trees revealed the presence of subtype A1, B, F1 and recombinant viral forms such as AD, AG and AC. One of the isolates was classified as a subtype C and was included for control purposes. Near full-length characterization of four of the samples were attempted, through full genome PCR amplification and sequencing. Analysis of sequenced data with the use of subtyping-, recombination identification, and tree drawing tools revealed a subtype B, and A1 isolate. The other two isolates were identified as possible AC and AD recombinants. The data that was generated will greatly improve our knowledge of non-subtype C isolates circulating within South Africa. Due to the possible impact that the high degree of genetic variation that HIV may have on vaccine design and development and ARV treatment and HIV diagnosis, ongoing research of the epidemiology and spread of HIV within South Africa are needed.
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    Origin and phylodynamics of HIV-1 subtype C in South Africa
    (Stellenbosch : Stellenbosch University, 2013-12) Wilkinson, Eduan; Engelbrecht, Susan; De Oliveira, Tulio; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology, Division of Medical Virology.
    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.