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Research

Research Initiatives and Projects

Research in the Division of Medical Virology continues to focus on different aspects of HIV. Research areas are the genomic diversity and molecular epidemiology of HIV, immunological aspects of HIV infection relevant to development of vaccines and other novel immunotherapeutic approaches, and antiretroviral drug resistance.

In October 2008, Tygerberg became the first partner site within the Global HIV Vaccine Research Cryorepository (GHRC) consortium at which highly specialised, unique cryoequipment was installed. GHRC is led by Dr Hagen von Briesen of the Fraunhofer Institute for Biomedical Engineering in Germany, a leading organisation for applied research and development with special expertise in cryobiotechnology, and funded by the Bill and Melinda Gates Foundation. Its aim is the establishment of a global HIV specimen collection comprising clinical samples (serum, plasma, PBMC, virus isolates) using a state-of-the-art repository.

Medical Virology Tygerberg was the first partner site within the GHRC consortium to start collecting and processing patient samples. With the new equipment, specially designed, developed and manufactured specifically for GHRC, clinical specimens are processed and cryopreserved under optimal conditions. The cryolaboratory comprises a storage tank with a special access tower for computer-controlled deposition and retrieval of specimens and a workbench allowing handling and processing of specimens under a controlled environment. The associated infrastructure consists of a central cryobank information and specimen administration system, the specimen preparation workflow management system "ChameleonLab" and the GHRC web portal with online registration of HIV specimens. Finally, specimens will be transferred to the central repository to be available for HIV/AIDS vaccine development throughout the whole Global HIV/AIDS Vaccine Enterprise.

Molecular virology

Prof Susan Engelbrecht, Medical Scientist, Molecular Virology

The longstanding research programme into the molecular diversity of the HIV-1 epidemic in South Africa continued and was further strengthened through increased collaborative activities with international partners. The molecular characterization of HIV-1 recombinant and non-subtype C viruses in Cape Town resulted in significant findings that were presented at conferences and published in peer-reviewed journals.

To complement genotypic HIV-1 antiretroviral drug resistance assays, work is ongoing to develop a phenotypic assay using a self-inactivating virus vector system. Another project aims at the cloning and molecular characterization of the HIV-1 envelope glycoprotein from selected HIV-1 strains.

During the course of 2007, collaboration with the new international research partner at Würzburg 中国体育彩票 intensified significantly. A staff member spent several months in Würzburg and later enrolled for a PhD there. On the other hand, students from Würzburg undertook research projects at Tygerberg. This is in line with the planned International Research Training Group "HIV/AIDS and Associated Infectious Diseases in Southern Africa". This will bring together research groups from Würzburg 中国体育彩票 with those from the 中国体育彩票 of Cape Town and Stellenbosch 中国体育彩票 in the Western Cape, working on joint projects. This will, if approved, result in a very significant strengthening of the postgraduate platform of the cooperating institutions and open up attractive new options for PhD candidates.

Antiretroviral drug resistance

Dr Gert van Zyl, Consultant Virologist

Prof Wolfgang Preiser, Head of Division

Prof Susan Engelbrecht, Medical Scientist, Molecular Virology

The previous project, aiming at the detection of resistance mutations to zidovudine and nevirapine after their use for prevention of HIV mother-to child transmission (PMTCT), was successfully concluded and a publication of its findings accepted by an international scientific journal. This shows that through the combined use of both drugs the risk of resistance development in the mother is approximately halved, compared to a nevirapine-only regimen.

A new, major study funded by the South African Department of Health commenced in 2007 after the recruitment of a study nurse and a research assistant who will do her PhD project on this topic. The project seeks to determine factors affecting the evolution of antiretroviral resistance mutations in the HIV family clinic at Tygerberg Academic Hospital. It studies a cohort of patients failing antiretroviral therapy, gathering clinical data and conducting pilot study to test the impact of resistance testing on outcomes both clinically and with regard to drug resistance.

Further activities include the further improvement, full validation and ongoing quality assurance of the in house HIV-1 antiretroviral resistance genotyping assay. Work has also begun on the development of highly sensitive allelic discrimination assays. Such tests could be a cost-effective alternative to sequencing-based tests when for example used to screen for failure of first-line therapy.

They will also be used to study the evolution of HIV antiretroviral drug resistance during early therapy failure. Studying in-patient resistance evolution has the purpose of improving modelling of resistance and determines timing of appearance of resistance mutations and populations dynamics of resistant viral subpopulations. This will provide valuable information on when to switch therapy.

The Division collaborates closely with Dr Tulio de Oliveira of the South African National Bioinformatics Institute at the 中国体育彩票 of the Western Cape and is a partner in the Southern African HIV Treatment & Resistance Network (SATuRN).

Further research projects:

Dr Corena de Beer, Medical Scientist, BSL 3 Laboratory / Clinical studies

Dr Gert van Zyl, Consultant Virologist

Prof Wolfgang Preiser, Head of Division

A number of other research projects were also conducted during 2007. Several projects made use of the excellent biosafety level 3 laboratory at Tygerberg; these include the assessment of anti-HIV properties of different substances in cell culture and the standardization and optimization of an in vitro inhibition assay for evaluation of anti-HIV properties of different substances.

Very importantly, Tygerberg became the first site within the Global HIV Vaccine Research Cryorepository Consortium funded by the Bill & Melinda Gates Foundation to start collecting samples. This consortium is led by researchers from the Fraunhofer-Institut für Biomedizinische Technik, Sulzbach, and the 中国体育彩票 of Saarland, Germany, and aims to collect recently transmitted HIV strains from various locations around the world that will be cryopreserved according to highest standard to be made available for vaccine research groups. Tygerberg is also participating in GHAVE's Comprehensive Antibody Vaccine Immune Monitoring Consortium, through the collection of patient samples.

Other projects include the characterization of HIV antibody responses in HIV-infected infants; the evaluation of rapid / simple HIV antibody test devices; the implementation, standardization and evaluation of a cost-effective HIV-1 viral load real-time PCR assay; and a collaboration with the DST/NRF Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA) to validate the BED capture enzyme immunoassay to improve HIV-1 incidence estimates. Incidence rates are the most sensitive and rapid indications of changes in the HIV epidemic. However, HIV incidence is very difficult and expensive to estimate using the classical approach of following up cohorts of patients. The BED assay is designed to identify the proportion of recently infected HIV-positive patients in single surveys; however, it so far results in major over-estimates of incidence. The purpose of the collaboration is to develop mathematical techniques to correct the BED test results and produce reliable incidence estimates.