Nonhuman primate experimentation is an ethically charged issue, one where reasonable people can have very different opinions. In Madison, the issue has attracted considerable media interest. Here I will share some facts about HIV and my lab’s work with nonhuman primates. First, a few statistics: last year, an estimated 2,700,000 people became infected with HIV; 2,000,000 people died of an AIDS-related illness; and 33,000,000 people are living with HIV globally. Treatment programs are expanding and are saving lives. I saw the power of the drugs first hand in Uganda. Patients who would have died a few short years ago are living longer, healthier lives thanks to drugs provided by the President’s Emergency Plan for AIDS Relief, among other programs. Nevertheless, antiretroviral treatment of HIV is not a cure. Treatment requires strict adherence and a lifelong commitment to difficult and often painful medications. The drugs themselves are expensive and it is estimated that there are two new infections for every person who is newly enrolled in treatment.
It is with this in mind that my laboratory searches for clues to inform the development of a preventative HIV vaccine by studying nonhuman primates infected with simian immunodeficiency virus, SIV (in addition to our work with HIV+ human volunteers). While it is true that HIV does not cause AIDS in macaque monkeys, several well characterized strains of SIV do. By infecting macaque monkeys with these viruses, we can study the immune response in ways that are impossible in humans. To cite just one example, it is now thought that many of the most important events in HIV disease happen in the first weeks immediately following infection (reviewed by world-class HIV researcher and MD Ashley Haase in this review, available in most academic libraries). The virus replicates to higher levels than at any other time during the disease; often more than 1,000x higher than in later infection. The consequences to the immune system are devastating. There is a massive loss of immune cells, particularly in the intestines. Learning how to combat the virus during this time could lessen the severity of HIV and prolong the lives of infected people.
More urgently, figuring out how to coax the immune response to fight the virus earlier and with greater vigor might offer the promise of limiting the infection. Defining what sort of immune response is capable of most effectively containing the virus is a central focus of my laboratory and, indeed, the laboratories of other researchers at UW and around the world. We think that the clues to the right type of response are seeded in the hours, days, and weeks after infection. Unfortunately, people do not know when they are infected with HIV. Despite the war waged between the virus and the immune system, newly infected people generally feel fine. Some develop a generalized ‘flu’ that is otherwise unremarkable. Conventional HIV tests that look for HIV antibodies aren’t useful; the antibodies typically take a month or more to develop. So how do you study these early events? You infect macaques with known strains of SIV and carefully monitor them at defined intervals throughout the first few weeks. By learning more about the genetics of the macaques and how the immune system works, we can begin to get hints about a successful immune response. Recently our lab has developed tests that allow us to study the immune genes of macaques with unprecedented resolution; these tests and ones like them enabled us to learn that a broadly directed immune response appears pivotal in the control of SIV. Ongoing work is exploring this hypothesis in greater detail, but it might indicate that future HIV vaccine candidates should endeavor to elicit broad immunity, an approach whose feasibility was recently tested by another group studying macaque monkeys.
It would be premature and self-aggrandizing to say that our work alone will contribute meaningfully to the development of an AIDS vaccine. But as part of a coordinated global effort, that is our goal. And towards this goal, I’m proud to say that some of my SIV macaque research (e.g., selection of viral variants by cellular immune responses) has improved our understanding of HIV immunity and pathogenesis. Now, more than ever before, the peer-reviewed literature describing these studies is available to the general public. Most research manuscripts published in the last three years have been deposited in PubMed Central. Links to my articles can be found here.
Some might argue that the knowledge we have gained and continue to pursue does not justify the means, that the similarity between humans and nonhuman primates is such that our research is unethical. On this, I simply disagree. We do not take our ethical considerations lightly, but I believe that human health and alleviation of human suffering is paramount. In the five years that I have run my research laboratory, we have infected 33 macaques with SIV. To put that in perspective, 5 people are infected with HIV every minute of every day. In the last seven minutes, or in approximately the time it took you to read this, more than 33 people will have become infected with HIV. Even if you are reading this and don’t agree with our work, I’d ask you to think about those 33 people. Think about their families and loved ones, their hopes and dreams, and what having HIV will do to their lives. And try to understand, even if you don’t agree, why I believe our work towards preventing those infections – even when it requires infecting macaques with SIV – is worthwhile and absolutely ethical.
21 March 2010