Research Group: HIV Drug Resistance and Immunopathology Group

Group head  
Name:  Theresa Rossouw
E-mail:  [email protected]
Telephone:  012 319 2626

 

A brief description of research activities: 

Our group works in three main, interrelated and complementary research areas: the clinical and basic science aspects of Human Immunodeficiency Virus-1 (HIV) infection; HIV-associated comorbidities; and the socio-ethical aspects of biomedical research, especially HIV-related research. Our main focus has been on understanding the drivers of disease progression and treatment failure. We have assessed the nature and frequency of HIV-1-associated drug resistance mutations in adult patients failing treatment using an in-house genotypic drug resistance assay and showed very high levels of drug resistance in patients failing first-line ART. This work also extended to the paediatric population where we evaluated the effect of peripartum ART on the efficacy of subsequent ART in children, specifically with regards to the consequent development of HIV-1-associated drug resistance and treatment failure, in collaboration with the University of Washington, Seattle, USA. Coupled with this work, we have also been involved in assessing public health-level early warning indicators for drug resistance in settings where resistance testing is not readily available. This resistance work has been presented at a number of national and international conferences, including the preeminent international HIV conference, the Conference on Retroviruses and Opportunistic Infections (CROI), and has been published in both the clinical science and public health fields, including a letter in Nature and articles in AIDS, Pediatric Infectious Diseases, Database, BMC Health Services Research, as well as an invited editorial in Clinical Infectious Diseases, one of the leading journals in the field of infectious disease.

The problem of HIV-associated chronic, systemic immune activation as a driver of both the development of HIV treatment failure and drug resistance as well as non-AIDS-defining chronic conditions have become the focus of our HIV research in the last six years. We have identified a set of circulating biomarkers of immune activation which may be predictive of responses to ART. We have explored the clinical implications of such immune activation in both adult and paediatric populations and four articles have been in high-quality journals, such as Mediators of Inflammation. This work has also served as the impetus for a large study in collaboration with the international PharmaAccess Studies to Evaluate Resistance (PASER) network, where we assessed associations between chronic immune activation and different ART regimens, geographic regions and HIV subtypes. We found significant differences and these findings have been presented at CROI and a number of articles have been submitted for publication. We recently turned to explore whether systemic immune activation may also lie at the heart of the immunological and metabolic aberrations found in HIV-exposed-but-uninfected children and I am currently heading the laboratory work for a large international study aimed at understanding the clinical, immunological and metabolic consequences of ART exposure in-utero. Worrisomely, these children have also been shown to have delayed neurodevelopment and the pilot study demonstrated associations between macrophage activation profiles and smaller head circumference and have been presented at a number of international and national conferences.

The group’s basic science and clinical research efforts have been reinforced by a social science dimension. I am specifically interested in the quality of informed consent obtained in medical research in general and in HIV research in particular. I have been involved in collaborative research on the future use of biological samples (that is especially important in the emerging era of biobanking) and the implications this holds for the kind of information included in informed consent documents. This work has been published in an international biomedical journal. Based on this work, I have been invited to become part of an international working group looking at the ethical and social implications of HIV cure research. This collaboration brings together researchers from South Africa, the United States of America and China and is viewed as pioneering work in the field since it represents one of the few instances where the ethics is preceding the science. We explored diverse issues such as the implications of the use of the word "cure" when only remission will most likely be achieved (published in the preeminent journal, AIDS). We have also conducted interviews with a diverse group of patients, researchers, clinicians, activists and policymakers to explore which informed consent processes need to be in place for such research to be ethically accountable. Our findings have been published in major ethics journals and more articles are being completed.

 

Current group members (incl. group head):

Name Position Qualification(s) e-mail address
Theresa Rossouw Associate Professor, Immunology MBChB, MPhil, MPH, DPhil, PhD [email protected]
Helen Steel Senior scientist BSc, MSc, PhD [email protected]
PG Students      
Gisela van Dyk PhD student BSc, MSc [email protected]
Temitope Sokoya PhD student BSc, MSc [email protected]
Louise du Toit PhD student BSc, MSc [email protected]
Andrea Prinsloo PhD student BSc, MSc [email protected]
Morris Madzime PhD student BSc, MSc [email protected]
Sanele Ngcobo PhD student BMCP, MPH [email protected]
Karmishtha Hutheram PhD student BSc, MSc [email protected]
Bong-Akee Shey PhD student BSc, MSc [email protected]
Mieke van der Mescht MSc student BSc Honours [email protected]
Difuro Masemola MFamMed student MBChB [email protected]
Gbenga Ogundana MFamMed student MBChB [email protected]

 

Post-graduate students graduated in the past 5 years:

Name of student Degree Date of qualification
G Makubele MSc Immunology 2014
Dr JM Mabena MMed Fam Med 2016
Dr N Akerele MMed Fam Med 2016
Dr B Maphosa MPH 2017
Dr B Ndhlovu MPH 2018
Ms TO Sokoya PhD Medical Immunology 2018
Collaborator
Mr G Malherbe PhD Medical Immunology 2015
Mr P Mahasha PhD Medical Immunology 2015

 

National and international collaborations:

National:

  1. Human Sciences Research Council. Drs C van Zyl and C Prinsloo. Project: Research Integrity. 2014 – present.
  2. Pharmacovigilance Centre, Sefako Makgatho University. Prof R Summers. HIV Pharmacovigilance. 2010 - present
  3. Department of Microbiology, University of Pretoria. Prof M Kock. Research project: Prospective Study Of Myconostica’s Fxgtm: Resp (Asp +) Test For The Detection Of Pneumocystis Jirovecii (Carinii). 2006 – present.
  4. South African Centre for Epidemiological Modeling and Analysis (SACEMA). Prof M Nieuwoudt. 2012 – present.
  5. Centre for Medical Ethics & Law, Department of Medicine at Stellenbosch University. Prof K Moodley. Project: An exploration of the ethical complexities inherent in the collection, use, storage and export of biological samples in research: perspectives of potential and current clinical research participants in South Africa. 2008 – present.
  6. Department of Internal Medicine, University of the Witwatersrand. Proff C Feldman and F Venter. Research project: Investigating the relationship between cigarette smoking, markers of immune activation and HIV-1 treatment failure. 2012 – present.

International:

  1. University of Washington, Seattle, USA. Department of Laboratory Medicine. Prof L Frenkel. Research project: Principal Investigator: Evaluate the Effect of Peripartum ART on the Efficacy of Subsequent ART in Children. 2008 - present
  2. Southern African Treatment and Resistance Network (SATuRN), a network of laboratories and clinical sites in South Africa and Botswana contributing to a common database of genetic sequences. It was established in conjunction with researchers at Stanford University, USA (Prof Robert Shafer, Prof David Katzenstein) and the Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium (Prof Anne-Mieke Vandamme, Pieter Liebin). 2008 - present
  3. University of Washington, Seattle, USA. Department of Interdisciplinary Arts & Sciences. Prof J Crane. Research project: The Social Context of Curing HIV Among Infants: From Mississippi to South Africa and Back. 2013 – present
  4. Carleton University, Ottawa, Canada. Department of Health Science. Studies to improve understanding of the interactions between HIV infection, innate immune responses, chronic immune activation and inflammation and cellular metabolic processes. 2015 – present.
  5. International Social and Ethical Working Group on HIV Cure, which involves researchers from the United States of America, China and South Africa and strives to explore the intended and unintended consequences of biomedical research into an HIV cure. 2014 – present.

Media articles/interviews/etc.:

  1. Television appearance (eNCA) 2014: Interview: HIV and sex workers.
  2. HIV Cure video in collaboration with the University of Stellenbosch.

 

Awards/distinctions of the past 5 years:

  1. Invited plenary address at the Southern African HIV Clinician Society Conference held in Johannesburg, 2016.
  1. Nominated for 2015/2016 National Science and Technology Forum award for Communication for outreach and creating awareness (for an outstanding contribution to Science and Technology and innovation by a team or individual)
  1. Second runner-up publication in the Clinical Sciences at the Faculty of Health Sciences of the University of Pretoria in 2014.
  1. Mediators of Inflammation article has been recognized by the South African Medical Research Council as one of the top articles for the second quarter of 2014.

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