amfAR Fellows Tackle AIDS Drugs, Vaccines
By Jeffrey Laurence, M.D.
May 16, 2007—amfAR-supported fellows took the lead this month in two key areas of AIDS research—vaccine development and new HIV therapeutics.
At the Scripps Research Institute in California, amfAR fellows Drs. Rosa Cardoso and Florence Brunel tackled the problem of vaccine potency. Their work is described in two articles in the April issue of the Journal of Virology. Dr. Hendrik Huthoff, at King’s College London School of Medicine, investigated the HIV accessory protein Vif, a promising target for new drug development, again publishing his work in April’s Journal of Virology. Finally, Dr. Jacqueline Reeves, formerly an amfAR fellow at the University of Pennsylvania and now at Monogram Biosciences in San Francisco, writing in Virology, investigated targets for the newest class of anti-HIV drugs, the co-receptor antagonists.
Dr. Reeves’s work is particularly critical to an understanding of how viral resistance to a class of HIV drug in the final stages of development, the CCR5 co-receptor inhibitor, might develop and become manifest. In April of this year, an FDA advisory panel met to consider approval of the first drug in this class; maraviroc, also known as Celsentri. In multiple clinical trials over the past three years, maraviroc has shown great effectiveness in reducing viral loads and increasing CD4 counts, even in individuals resistant to multiple kinds of existing AIDS drugs. We are particularly heartened by these developments, as amfAR-funded scientists were among the first to discover the critical role played by the HIV co-receptors, a fact acknowledged in a keynote presentation announcing results of the maraviroc trials at the national AIDS conference known as CROI, held this February in San Francisco.
Dr. Reeves utilized a monkey AIDS virus, SIV. Like the most common types of HIV, SIV requires the CCR5 protein for infection. She made mutant SIVs that were strongly limited in their ability to attach to CCR5, anticipating that such virus strains would be markedly limited in their disease-causing potential. This seemed to be the case at first glance: the level of virus in the blood of monkeys infected with the mutant SIV was reduced by 99 percent compared to normal SIV. However, the infected monkeys’ T cells continued to die, most notably in areas surrounding the intestines. And AIDS was not prevented.
Dr. Reeves’s work highlights the need to monitor development of viral resistance, looking not simply at levels of T cells and virus in the blood but also in the gut, in order to accurately assess the effectiveness of new anti-HIV drugs.
Dr. Laurence is amfAR’s Senior Scientific Consultant.