Author: Siva Danaviah - 2014-10-14

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In a gripping, informative seminar, Dr van Zyl took the audience on a journey through a Tale of 4 Cities (Berlin, Mississipi, Cape Town, Pittsburg) in outlining researcher's strive towards a cure for HIV.

He began the journey in Berlin with the Berlin-patient who was apparently cured following a bone marrow transplant from an individual with the CCR5 Delta 32 mutation that appears to confer protection against HIV infection. This patient's incredible recovery was hailed internationally but replicating this outcome on a larger scale is impractical given the unique nature of this patient's concomitant condition (leukemia) and the prohibitive cost of his treatment. Scepticism abounded among researchers but the hope of a cure based on the Delta 32 mutation persisted. Several years of follow-up indicated that this patient remained suppressed showing no sign of viral rebound.

His next stop was Mississippi, USA and the infant who was initiated on treatment within days of birth in 2010, tested negative and remained suppressed for 27 months, a record in terms of period an individual has remained suppressed without antiretroviral treatment. Again, hope was rekindled and thoughts of an AIDS free generation sprouted. Eliminating HIV in the young ensures that mother-to-child transmission of HIV will no longer be a concern, that infants born infected with the disease no longer had to be exposed to life-long antiretroviral drugs and the associated toxicities and that we, the research community, were that much closer to eliminating this scourge to human health. Alas, it was not to be for on the next leg of this journey, Melbourne, Australia and the International AIDS conference July 2014. The conference followed on the heels of the staggering announcement that the Mississippi baby was found to have detectable viral load and was, in fact, not cured but had rebounded. While extremely disappointing, this child represented the hope that a cure is not inconceivable and a wealth of lessons learnt that would certainly inform future research in the field.

Finally, Dr van Zyl stopped off in his hometown of Cape Town and outlined his own research where he undertook highly sensitive qPCR assays to detect HIV RNA and DNA at single copy levels. This work was conducted in Pittsburgh, USA and was supported by a Fogarty Award that Dr van Zyl received. His preliminary findings revealed distinct viral kinetics in infants infected in-utero or during labour, diagnosed early (within 2 months of birth) and initiated immediately on ART. One of the primary challenges he outlined in cure research is accurately detecting low-level viremia. Current viral detection and quantification methods are not sensitive and reliable enough to detect virus at single-copy levels, they require specialised techniques or large volumes of blood making them challenging and prohibitive on a larger scale. As in the past with the Berlin patient and the Mississippi baby, declaring a patient 'cured' may be premature without the ability to access latently infected cells that may be sequestered within remote or impenetrable anatomical sites. The same is true for antiretroviral treatment that may not permeate to every anatomical and cellular site of HIV infection.

While Dr van Zyl highlighted these challenges inherent to research towards a cure for HIV he was hopeful that such a panacea would be forthcoming. All is not bleak, he emphasised but we do have a ways to go before we can declare that we do indeed have a cure for HIV.

As part of the Africa Centre MRC Flagship seminar series held monthly in the KRITH Building, NRMSM, UKZN, Dr Gert van Zyl presented a talk titled 'Antiretroviral therapy initiated before 2-months-of-age reduces transcriptionally active HIV-1 DNA persistence' on the 19th September 2014.

Gert van Zyl (MBChB, FCPath(SA) Virology, PhD) is a South African trained medical doctor, who specialized in Virological Pathology. He is working for the South African National Health Laboratory Service at Tygerberg Academic Hospital, Cape Town, and is affiliated with Stellenbosch University, Division Medical Virology, where his roles include a diagnostic consultation service, laboratory quality assurance, research, undergraduate teaching and postgraduate supervision. His research interest lies in failure monitoring, antiretroviral resistance testing, factors associated with antiretroviral failure and resistance in adults and children from resource limited settings. Recently he has become involved in the study of HIV-1 persistence in children on long-term antiretroviral therapy collaborating with Prof Mark Cotton, Stellenbosch University, Dr John Mellors, University of Pittsburgh and Dr Mary Kearney, National Cancer Institute, USA.

The Wellcome Trust Africa Centre Genomics Programme and the UKZN MRC Flagship Project present a monthly seminar at the Nelson R Mandela School of Medicine, please visit our seminar webpage to see our current programme.

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