By Inez Rossouw, 26 Nov 2013, Bloemfontein - Dolutegravir, a drug aimed against the human immunodeficiency virus (HIV), might not elicit any resistance to it. This was revealed at the Southern African HIV/TB drug resistance and monitoring workshop hosted by the Southern African Treatment and Resistance Network (SATuRN) at the Medical School of the University of the Free State.
Prof Mark Wainberg from the McGill University AIDS Centre in Montreal, Canada, unravelled data gained from three studies (called SPRING, SINGLE and FLAMINGO) indicating that no mutations developed against dolutegravir over a period of 2 years of treatment. Furthermore, the virus did not develop resistance against any other drugs used in combination with dolutegravir to make up the highly active trio needed to effectively treat HIV infection. This was only seen in patients started on dolutegravir as part of first line treatment and not when used as second or third line treatment as mutations already induced by other drugs negated this effect. A success rate of 88 to 90 % in suppressing viral replication when dolutegravir was used as first line therapy was diminished to about 63% when it was introduced after the failure of other drugs.
Prof Tulio de Oliviera from the Africa Centre for Health and Population Studies, University of KwaZulu-Natal and director of SATuRN responded: 'It is very exciting that a drug of this potential is currently being investigated, but similar expectations were held for another group of HIV drugs, the protease inhibitors. Not all of those were met. We should be cautious and await more evidence.'
For two days the hallways of the medical school sizzled with heated discussions in foreign languages. Delegates from around the globe were attracted to the 8th workshop of this kind. HIV resistance cases, new treatment regimens, approaches to the problem of non-adherence among patients, were passionately debated and thought through. A new feature of this workshop was its association with the largest African network on HIV drug resistance monitoring: PASER (Pan-African Studies to Evaluate Resistance), led by Prof Tobias Rinke de Wit from the Amsterdam Institute for Global Health and Development at the Academic Medical Center, University of Amsterdam. Highly esteemed academics like Prof Mark Wainberg, Prof David Katzenstein from Stanford University in the USA, Prof Deenan Pillay from the University College London and the new head of the Africa Centre, Dr Catherine Orrell from the Desmond Tutu HIV Foundation in Cape Town, Dr Ava Avalos from Botswana, Prof Sulaiman Akanmu from Nigeria and Prof John Frater from the Oxford University in England were among the delegates and speakers. Uganda, Kenya, Belgium, Brazil, the Netherlands, Switzerland, Zambia, Lesotho, Swaziland and Zimbabwe added further colour to the kaleidoscope of participating countries. Thorough discussion of patient cases from these regions allowed the more than 200 delegates to learn from one another's experiences, translating HIV resistance testing outcomes into better clinical care for current and future patients.
The lead representative from the World Health Organisation in the area of HIV drug resistance, Dr Silvia Bertagnolio, gave an overview of the WHO strategies in this area. South Africa has recently adopted even more ambitious guidelines in this respect, with routine drug resistance testing for all South Africans who fail 2nd line treatment.
Resistance testing is an essential tool in the management of some HIV patients, but it is recognised that its added value rests upon the so called 'viral load tests'. These tests, already widely used in Southern Africa, give essential information regarding the ability of the drugs to prevent the virus from replicating. Low viral load means few viruses detected in the blood stream. This implies the drugs are working and the virus is not resistant to them (yet). Of the utmost importance is that a high viral load must be recognised as a possible emergency. The action required upon this high viral load is an intensive effort of several months to motivate the patient to take the HIV drugs each and every day. A subsequent follow up viral load is then done and if still high it means the drugs have stopped working; the virus might be resistant and replicating freely. A decision must then be taken to either change the patient to a new regimen or send the patient for a drug resistant test to help decide which regimen to prescribe next.
The workshop was preceded by a joint meeting of the PASER and SATURN networks, which are working towards increased collaboration. New projects and progress reports on existing ones were scrutinized and technical information related to HIV drug resistance testing was shared. The clinical implications of laboratory work were teased from the data and applied to resistance programs in the Southern African region.
Sponsors invested in this excellent workshop which will positively impact on the clinical ability and knowledge of all participants and ultimately on the care of HIV patients. The sponsors include the CDC (Centers for Diseases Control and Prevention, USA), the Embassy of the Kingdom of the Netherlands in Pretoria, the Wellcome Trust, the European Union, PASER, the Africa Centre and the University of the Free State.
SATuRN includes 24 research partners in southern Africa. They have collated more than 7000 resistance genotypes linked to treatment and clinical information and host two of the best HIV drug resistance databases in the world. They have been working with a network of academic laboratories to develop and implement a cheaper resistance genotype test. They have also delivered training in drug resistance testing and management to over 2500 physicians and nurses in southern Africa and recently published a case book, which has already achieved best-seller status with approximately 10 000 copies printed and distributed.
PASER is a project supported by the Amsterdam Institute for Global Health and Development, which aims to provide sustainable solutions to major health problems across the planet, by forging synergies between disciplines, health care delivery, research and education.
PASER has as objective to monitor and survey HIV drug resistance in adults and children in sub-Saharan Africa, build capacity, expand access to affordable diagnostics, put HIV drug resistance on the international agenda and inform African policy makers to make best-possible decisions with respect to national HIV treatment programs.