SATuRN's Featured Partner: Division of Medical Virology, Stellenbosh University
Authors: Wolfgang Preiser, Gert van Zyl & Susan Engelbrecht
The Division of Medical Virology at Tygerberg comprises a diagnostic section which, as part of the South African National Health Laboratory Service (NHLS), provides a state-of-the-art, SANAS-accredited virological diagnostic service for the population of the Western Cape province. Its diagnostic staff perform an average of 14,000 tests per month of which almost one half are HIV-related, mostly HIV viral load, infant PCR and combined antibody-antigen tests.
In addition, its academic staff pursue a number of well established research interests. These include the genomic diversity and molecular epidemiology of HIV; immunological aspects of HIV infection relevant to the development of vaccines and novel immunotherapeutic approaches; the diagnosis and monitoring of opportunistic infections, especially hepatitis B virus (HBV); and diagnostic and epidemiological aspects of emerging viral diseases.
When South Africa finally embarked on its antiretroviral roll-out programme in 2004, this turned into a major success. However, from the experience of developed countries where universal antiretroviral coverage became a reality in the mid-1990s, it had to be expected that with the programme coming of age, novel challenges would emerge. One of these is antiretroviral drug resistance .
Based on Prof. Susan Engelbrecht's longstanding interest in HIV diversity, Prof. Wolfgang Preiser's experience with diagnosing and managing drug resistance in the U.K. and in Germany (where resistance testing is part of routine patient management), and Dr. Gert van Zyl's first-hand clinical involvement and interest in epidemiology, the Division developed HIV drug resistance as a new research theme.
This theme comprises a number of different aspects. Because genotypic resistance testing through sequencing is technically demanding and commercially available assays are expensive and may not perform well in our setting, an in house method which is better yet cheaper than comparable commercial tests was developed as part of a Master's project and is now being used routinely.
Tygerberg Virology is currently one of only two NHLS laboratories performing routine diagnostic HIV drug resistance testing. It performs approximately 80 tests per month, no mean feat for a very demanding test which, in addition to the laboratory side, requires the complex task of interpreting results in the context of the individual patient's treatment history. The number of requests for this highly specialised service is expected to increase further once guidelines on resistance testing are released by the SA HIV Clinicians Society.
The Division is conducting systematic surveillance in different groups of patients. Given that the "public health approach" means that patients receive standardised antiretroviral treatment regimens, the aim is to generate reliable data to inform future changes to the treatment protocol.
It was found that of mothers who received a dual regimen for the prevention of mother-to-child transmission of HIV, combining short-course zidovudine with single-dose nevirapine, only half as many (17.1%) developed resistance to the latter compared to mothers not receiving the zidovudine component. This is another significant advantage of the combined regimen, in addition to reducing the risk of neonatal infection.
A high rate of resistance mutations was found in pre-treatment Tanzanian patients not fulfilling the WHO criteria for transmitted resistance threshold surveys. This suggests that baseline resistance may be more common than would be expected from such surveys alone. WHO is currently considering a revision of surveillance recommendations for transmitted HIV drug resistance, to take into account these findings.
Overall however the results obtained so far are encouraging, demonstrating that antiretroviral drug resistance is not yet a major problem for most South African HIV patients. However, as the South African public sector treatment programme grows and the treated cohort "matures", more patients will develop resistance. In parallel, a larger proportion of new infections will then be acquired from those failing therapy and harbouring resistant virus.
A new publication on deep sequencing shed light on low levels of PI resistance in patients with poor adherence is also featured at the SATuRN 2012 report.
Division of Medical Virology , Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University and National Health Laboratory Service (NHLS) Tygerberg
PO Box 19063, Tygerberg 7505, SOUTH AFRICA
Tel: +27 21 938 9353, Fax: +27 21 938 9361
contact: Mrs Sal van Zyl, E-mail: email@example.com
By Wolfgang Preiser (Professor and Head),
Gert van Zyl (Senior Specialist) & Susan Engelbrecht (Professor and Senior Scientist