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Do the common medications for HIV-infected patients in Africa show the desired response much more seldom than previously assumed? At least this is what the outcome of a current study of scientists from Würzburg, Tanzania and South Africa suggests. The impact of this finding would be enormous.
For the region around Lake Victoria in Tanzania, the figures are unambiguous: Around 19 per cent of the adults over 25 who are HIV infected carry viruses in their bodies that are resistant against the medications commonly used in Africa. This is what researchers of the University of Würzburg and of the Medical Mission Hospital, together with their colleagues from Tanzania and South Africa, have found out. For this purpose, the scientists have examined patients of the Bugando Medical Center in Mwanza, Würzburg’s twin city in Tanzania.
What makes the figure so critical: The World Health Organization WHO which is responsible for the guidelines of HIV treatment on the African continent has been assuming a clearly lower value. Based on its surveys, resistances are to be expected in less than five percent of the cases. The reason for the varying figures could be simple: The current WHO guidelines exclude a large part of the population from the random tests.
HIV therapy in Tanzania
There has been a nation-wide therapy programme for HIV-infected patients in Tanzania since 2004. The patients obtain their medications in roundabout 200 therapy centres. By the end of 2007, more than 165,000 patients were included in the programme. Pregnant women who are HIV-positive additionally get the offer of a special treatment in order to prevent the disease from being transmitted to the newborn.
Unlike in the industrialized countries where the pharmacies have a battery of medications available for tailor-made therapies for HIV-infected patients, the physicians in Africa have to make do with only a few pharmaceuticals that are financed from various aid programmes.
This bears the risk that under the therapy, resistant viruses easily develop which then spread among the population. Anyone catching such viruses has much poorer prospects of getting a successful treatment later himself. Thus, the share of patients catching resistant viruses will be the yardstick for therapeutic success in the coming years. In order to control these chances of success, the WHO has called for parts of the African population to be tested for resistances on a regular basis.
Which patients are subject to testing?
However: “The WHO in its guidelines recommends that only patients under 25 years of age are admitted in these studies”, says Carsten Scheller. Scheller is university lecturer and head of department at the Institute for Virology and Immunobiology and has considerably contributed to the Würzburg study. The reason for this restriction in choice sounds plausible: Since it has only been a few years that a therapy against the HI viruses has been available in Tanzania at all, the transmission of resistant viruses is to be observed only in those patients who have only recently contracted HIV. And these fresh infections – according to the WHO reasoning – are most likely found in the younger age group. “Our results, however, suggest that with this choice, the actual dissemination of therapy-resistant viruses in the population is dramatically underestimated”, Scheller says.
The first suspicion that the WHO figures might be too optimistic was expressed by clinicians from Africa. “They found out that in some regions nearly every third patient no longer responds to the medications”, the virologist says. This was the reason for the Würzburg scientists to conduct a study in which also patients older than 25 years were included.
Würzburg: close contacts with Africa
Würzburg seems to be a predestined location for such a study: Here is where, in October 2008, the first German-African graduate college started to work under the leadership of Professor Axel Rethwilm, Head of the Institute for Virology in Würzburg. The research there focuses on HIV, Aids and the associated infectious diseases. Within the college, several Würzburg study groups collaborate with various research teams at the University of Stellenbosch in South Africa. Furthermore, the Tropical Institute of the Medical Mission Hospital in Würzburg under the leadership of the university lecturer, Dr. August Stich, has cooperated with the Burgando University College of Health Sciences and the associated Bugando Medical Center in Mwanza for several years.
The scientists examined 88 patients so far untreated, 68 of whom were older than 25 years. While not a single resistance against the medicines used in Tanzania was found in the under-25-year-olds, a shocking 19 per cent of the older patients were infected with resistant viruses. In total, this corresponds to a frequency of around 15 per cent for the whole random test. “What is particularly bad is that nearly 90 percent of the patients infected with resistant viruses already carry resistances against the backup therapy as well.
Once this is no longer effective, there will be nothing left for the doctors to offer their patients”, says Scheller.
The cause for this high rate of resistance is still a big mystery to date. In addition to the transmission of viruses already resistant at the time of infection, other mechanisms might also play a role. For example, the researchers found residues of HIV medication in two of the samples, although the study participants had stated never to have been treated against HIV. “That suggests that at least some of the patients obtain medications on their own”, Scheller says. However, the researchers suspect that the dark figure could even be significantly higher. After all, the procedure used in this study only verified the medication taken within the preceding two weeks. “Some people might shy away from going to the therapy centre for fear of stigmatization, and prefer buying medications underhandedly”, Scheller assumes.
„We were also surprised at the spread of resistances over the age groups”, he says. This might reflect the fact that older people usually also had older partners who were possibly under therapy already. “And if the partner is treated and the therapy fails, the risk of an infection with resistant viruses is especially high”, Scheller says. The researchers could, indeed, prove the transmission of resistant viruses in two cases, where the resistance had been transmitted from one partner with a therapy to the other.
It is as yet unclear whether the figures from Mwanza can be extrapolated for all of Africa. To gain more clarity, the researchers intend to take up additional regions in a further study within the scope of the programme. One thing is clear, however: “If our figures have a comprehensive validity, we will be faced with a massive problem in the future", Scheller states. Then, the current therapy concept for Africa would have to be reconsidered and increased by essential elements. But according to the researchers, it would be reasonable at this stage already to expand the WHO guidelines to include an all-age control of the dissemination of resistant viruses.
In Europe, HIV patients are under constant medical supervision. The treating physicians quickly see whether or not a medication is effective, and can adjust the therapy accordingly. In Africa, this is different: “There, a patient receives the standard medications over a long period of time. In most therapy centres, monitoring of the viral load in the blood is prevented by cost reasons alone”, Scheller says. This could mean that the patient receives an ineffective therapy for months, with the additional fatal consequence that resistant viruses can easily proliferate.
“What we need in principle is more money for a better therapy in Africa”, Scheller says. The patients could then be tested for potential resistances prior to the treatment, and appropriate medicines could be used for the subsequent therapy. This, however, was a “pious hope”. What seemed to be in the offing at the moment was that the aid programmes will rather be cut than extended.
The researchers hope, however, that their results will resonate with political decision-makers to intensify the efforts for an improved HIV therapy in Africa. After all: The WHO has become aware of the Würzburg study and is presently considering, together with the researchers, to use the results as a basis for new recommendations for resistance tests.
Supported by DAHW
The study was financed with funds of the German Leprosy and Tuberculosis Relief Association DAHW and supported by the graduate college 1522 “HIV/AIDS and associated infectious diseases in Southern Africa”. The scientists have published their results in the journal Plos One:
HIV Drug Resistance (HIVDR) in Antiretroviral Therapy-Naïve Patients in Tanzania Not Eligible for WHO Threshold HIVDR Survey Is Dramatically High. Christa Kasang, Samuel Kalluvya, Charles Majinge, August Stich, Jochen Bodem, Gilbert Kongola, Graeme B. Jacobs, Mathias Mlewa, Miriam Mildner, Irina Hensel, Anne Horn, Wolfgang Preiser, Gert van Zyl, Hartwig Klinker, Eleni Koutsilieri, Axel Rethwilm, Carsten Scheller, Benedikt Weissbrich. Plos One doi/10.1371/journal.pone.0023091
PD Dr. Carsten Scheller, phone: +49 (0)931 201-49928, e-mail: firstname.lastname@example.org
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