On the virology and immunology front lines, McGill researchers are working to help turn the HIV tide.
By Andrew Fazekas
The numbers are indisputably grim—the UNAIDS AIDS Epidemic Update 2007 reported that AIDS annually claims more than two million lives—yet, in the past 25 years AIDS has moved from a guaranteed death sentence to a serious chronic illness. Three McGill virology and immunology investigators, all longtime AIDS researchers, are working to understand how HIV is transmitted, how it evolves to foil drug treatment and how to best disseminate crucial knowledge—and increase hope in a once hopeless situation.
The Botswanan Subtype
As an advocate for HIV/AIDS policy reform, Mark Wainberg isn’t afraid to make noise. Whether debating Kenyan president Daniel Arap Moi on the subject of condom promotion, or waving a placard proclaiming “Put the Sex and Drugs Back in HIV Prevention” at the 2006 International AIDS Conference, his is a very public battle. But there’s another side to this firebrand scientist. In the McGill University AIDS Centre’s new $5-million high-security biocontainment lab at the Jewish General Hospital, Wainberg and his colleagues have been waging a quieter war—on the microscopic scale.
Wainberg is the director of research at the hospital and director of the AIDS Centre—and recognized as a world expert who has made multiple contributions to the field of HIV-fighting drugs. His late-eighties identification of the anti-viral properties of the 3TC drug, for one, was a revelation; today 3TC is a vital part of a drug cocktail that delays the onset of many of AIDS’ worst symptoms. But, because today’s drug may prove useless against tomorrow’s virus, HIV is a moving target. To zero in on the growing problem of drug resistance, Wainberg is working jointly with the Harvard AIDS Institute to establish study sites in Botswana. “It’s an extremely important subject because HIV mutates all the time and is capable of becoming resistant to every single drug that we’ve developed,” says Wainberg. “HIV changes even faster than the influenza virus, making it a huge problem for researchers.” But time is not on their side. Worries are that we may be on the verge of a dramatic surge in cases of drug resistances among those currently taking the antiretroviral therapies throughout Africa.
That’s why Wainberg and his team’s discovery of a unique genetic variability in the HIV virus in Botswana is all the more timely. By sampling the blood of thousands of infected volunteers, they sequenced the DNA of the virus and revealed that the specific subtype of the virus (known as subtype C) circulating in Botswana is different from that which dominates Europe and North America. The mutation process and the effect of drugs on that process, researchers are learning, appear to vary from one subtype to another. The virus found in Botswana may be one of the most genetically variable of all the subtypes, but the nature of those specific drug-resistant mutations remains a mystery.
Wainberg speculates that the implications of this ground-breaking project (primarily funded by the Canadian Institutes of Health Research, with additional funding from the International Partnership on Microbicides—which includes researchers from Kenya, Mozambique, Namibia, Nigeria, South Africa, Tanzania, Uganda, Zimbabwe—and the Fonds de la recherche en santé du Québec), may be far reaching. “These findings could potentially have important ramifications on how we can bring treatments not only to the entire African arena, but beyond.” He next hopes to expand the study northward to Cameroon and the Ivory Coast.
Zimbabwe’s Information Goldmine
Working on HIV/AIDS tests patience and perseverance. For Dr. Brian Ward, the potential for making huge positive impacts—both on patients and the overall health care community—keeps him coming back. A world authority in infectious diseases and immunology, Ward is the past chief of the McGill University Health Centre’s Division of Infectious Diseases and is also associate director of the McGill Centre for Tropical Diseases.
Starting in 1996, Ward and his colleagues at Johns Hopkins and at the University of Zimbabwe began tracking mothers and babies in and around Harare, Zimbabwe. The two-year study, one of the largest of its kind, explored the protective effects of administering vitamin A to newborns and their mothers. While the results unfortunately did not show the expected protective effect, a veritable goldmine of data was collected in the form of breast milk, blood and DNA samples from more than 14,000 women and their babies; these precious samples filled 15 freezers. Ward believes these samples may hold the key to understanding the mechanisms that underlie mother-child HIV transmission.
The country’s political and economic turmoil over the last decade, however, has spilled over to directly affect Ward’s planned follow-up research projects. The increasing tensions within Zimbabwe have made it difficult even to maintain the safety and integrity of the sample archive, let alone use it to full scientific advantage. Any attempt to transport the archive out of Zimbabwe would likely be met with serious resistance; like many others in the developing world, the government of Zimbabwe has decreed that Zimbabwean samples should not leave the country. This factor, compounded by political uncertainty, makes it difficult to impossible to work with the archived samples both inside and outside the country.
While the archive awaits more detailed genetic and immunologic analyses, Ward and his principal collaborator, Jean Humphrey from the Johns Hopkins Bloomberg School of Public Health, have forged on. The researchers have developed a community-focused program that integrates mother-to-child HIV transmission prevention into established maternal and child health units at a steadily growing number of Zimbabwean mission hospitals. This program, funded by the Canadian International Development Agency and the United Kingdom Department for International Development, is based on their observation that early mixed feeding (adding anything to a child’s diet other than breast milk) can markedly increase HIV transmission. They are currently exploring ways to support women to breastfeed exclusively for the first six months and then wean abruptly to alternate foods, a “simple” intervention made very difficult by rapidly rising inflation rates. Their program also incorporates the administration of anti-retrovirals around the time of birth, nutritional supplementation and efforts to bring the entire community together to slow the spread of HIV. These investigators are currently helping more than 20 hospitals reduce vertical transmission of HIV.
If Dr. Christos Tsoukas gets his way, soon HIV patients in remote regions will have access to the world’s best health care, thanks to the broad reach of telemedicine. Using electronic communications technology, consultative, diagnostic and treatment services can be transmitted across great distances, bridging once-prohibitive geographic gaps. “Teaching—educating both patients and their local doctors—is all part and parcel with telemedicine,” says Tsoukas, professor of medicine and experimental medicine, associate director of the McGill AIDS Centre and head of the Division of Allergy and Clinical Immunology. “It’s all about conveying information to keep people alive in a timely and concise fashion.”
The internationally renowned AIDS researcher has just wrapped up a three-year, CIHR-funded feasibility study to develop artificial intelligence tools to determine the best course of treatment for HIV patients. The project involved nine research centres located on five continents, making it readily apparent that innovative ways of capturing data and communicating with his colleagues was required. The solution: link the McGill University Health Centre, the Benghazi HIV Children’s Centre (Libya), the Postgraduate Institute of Medical Education and Research (Chandigarh, India), a public hospital in Athens, Greece, and a clinic in Brazzaville in the Republic of the Congo in real time using the Internet.
The idea to use telemedicine came to Tsoukas three years before, when he had a rare opportunity to examine an HIV outbreak among 427 Libyan children. Because of diplomatic sanctions and a trade embargo, very few outside physicians were allowed to visit the North African country and medical supplies from the West were limited. Tsoukas noticed that the Libyan staff, although professional, lacked the knowledge of how to manage patients and use available treatments. These deficiencies had the potential to hinder the children’s well-being. “They had to treat patients from scratch because the centre didn’t have an ongoing program of education,” he recalls. “The staff had no means of attending international conferences, limited access to the important medical journals and no knowledge of new therapies that were in current use in the West.”
By integrating technological elements of broadband Internet communications and information technology, Tsoukas’s multidisciplinary McGill team hopes to provide patient care, training and coaching of medical workers so that those infected can be managed efficiently over the long term.
“This can be a chronic disease and people are going to have it for the rest of their lives, thus we want to make sure that they’re controlling the virus for years, not days,” says Tsoukas. “But laboratory tests, monitoring and graphical representation of data are required to allow doctors to easily identify any developing trends and thus improve long-term management.”
Tsoukas first encountered the deadly virus back in 1982 when he was one of the first scientists to show that hemophiliacs who were receiving blood products were at high risk of developing AIDS—and, therefore, that the general population was also in danger of contracting HIV through transfusions of donated blood. Before anti-HIV treatments were available, he remembers seeing a patient die every three days. “It was depressing during those bleak early years of the epidemic,” he recalls. “We had little to offer our patients. Today, many people with HIV are living normal lives because of the availability of new anti-HIV drugs. Despite this progress, I find it necessary to continue my work on HIV vaccine development and to focus on teaching young doctors, both at McGill and abroad. I want to make sure that one day soon no one in my care will die from the disease.”
Next: Children of HIV