Читать книгу Viruses: More Friends Than Foes (Revised Edition) - Karin Moelling - Страница 40

Anti-HIV drugs which failed as oral therapies have recently been developed into drugs for local application in the vagina as protection against sexual transmission of HIV. Worldwide, women want to be responsible for their protection and do not wish to leave that to their male partners. It turned out that the vagina, as a target of microbicides to inactivate microbes and HIV, was surprisingly poorly characterized. Two microbicide trials by the Bill and Melinda Gates Foundation failed at late stages of development and had to be terminated prematurely, as the microbicides were found to enhance, instead of preventing, infections with HIV. In spite of its competence and reputation, the Gates Foundation failed — which must indicate that our state of knowledge is inadequate.

Together with a dozen European scientists I once organized a Global-Exchange EMBO course on HIV/AIDS in Stellenbosch, South Africa, in 2010 with support from the European Molecular Biology Organization (EMBO) and my grant. EMBO started this as one of the first steps to go global outside of Europe. South Africa is the country with the highest HIV prevalence worldwide. 60 young Africans participated, some of them hesitated to apply and did not dare to inform others about it — HIV was a stigmatized topic. The former President of South Africa, Thabo Mbeki, proclaimed for many years that HIV infections could be avoided by taking a shower. This must have killed people.

The students liked the congress bags with the EMBO logo and almost fought for them. We did not have enough, because half the bags disappeared at the customs and never showed up again. The course took place in a safe location at Stellenbosch in a building sponsored by the Swedish Wallenberg Foundation. The students barely dared to travel back and forth to and from Cape Town, and never after sunset. They were afraid to pass by the local townships.

In a township close to Cape Town a million people lived in primitive shelters built of cartons, car tires or corrugated iron. We estimated that for these many people there were about 50 dry toilets, blue cabins aligned next to each other almost outside the village. Instead of visiting the Dutch vineyards we attended a church service in a township. It was all about AIDS — the sermons, the prayers, the decorations and the discussions afterwards, people approaching us foreigners: “We need help” — men think they can get rid of HIV by having contact with a virgin — what a fatal error! On the whole, sadly, I saw little output for my investment of time and effort into the course. Bigger organizations are now increasingly successful.

All microbicide studies have so far failed. Even the results of the most promising one from South Africa, the CAPRISA-trial, which was presented during the EMBO-meeting and at an international AIDS Congress in Rome, where it caused a big splash — turned out to be not directly reproducible. Another microbicide study, PrEP-VOICE, comprising 10,000 women was no success. More than 30% did not take the drug as prescribed — lack of compliance was the explanation — which is often lack of education and perhaps their living standard, with poor housing. A dozen microbicides have failed by now. To prevent unreliable intake of pills by the volunteers, a systemic long-lasting injected medicine is an option, which is under investigation with an integrase inhibitor. Ashley Haase from the University of Minnesota, Minneapolis showed that HIV does not infect the cells lining the vagina, but that the virus bypasses them through cellular junctions. A short-cut taken by the virus — so that cellular compounds are ineffective, as the virus stays outside the cells. Our compound would fit.

Thus the trials were not designed properly because of lack of knowledge. Researchers have to get their “homework” done, was the conclusion. The virus has to be killed before entering the cells. Two clinical trials with microbicides are ongoing in 2016 ((CONRAD 128 and MTN-030/IPM 041) and a vaginal ring was tested with dual functions, against pregnancy and HIV infection with moderate results.