The existence of the Human Immunodeficiency Virus (HIV) and the disease it causes, Acquired Immunodeficiency Syndrome (AIDS), is a good demonstration of the capability of evolution to find exceedingly successful designs. As a retrovirus, HIV becomes a permanent feature of the infected person’s genome. It infects and kills slowly immune system cells, the helper T cells, macrophages, and dendritic cells, that are critical for cell-mediated immunity, thus disabling a person’s primary defense (Wikipedia article). Its lethality is secondary to infection (death is due to other opportunistic pathogenic organisms or cancer) and slow, allowing lots of time for the virus to be transmitted to other hosts. Its main mode of transmission, sexual intercourse, is the result of a basic human psychological drive. HIV could only be worse for humankind if it were more easily transmitted (like through exhaled air) or if it infected germ cells (sperm and eggs). For those with an anthropomorphic bend, HIV is a good demonstration that God is either highly moral (punishing people for having sex), immoral (giving people sexual desire and then punishing them), or amoral (and a damn good designer).
Last week though, there was news deserving of thanksgiving. Bionor Pharma, a small, public company in Oslo, Norway, announced progress in its effort to development a therapeutic vaccine for treating AIDS. The intent of the vaccine is not to prevent infection but complement drug therapy (Antiretroviral Therapy or ART) by helping the immune system fight the infection and recover to the point where it can resist the opportunistic infections. Such a vaccine may also allow for decreased doses (less expensive, less likely to induce drug-resistant HIV variants, fewer and/or less severe side effects) or interrupted dosing (ART involves multiple drugs and twice daily dosing). On November 18, Bionor announced that a secondary analysis of Phase IIB trial data found that the vaccine, called Vacc-4x, caused an “unexpected statistically significant reduction in viral load (amount of HIV virus)” (Bionor Nov PR). The finding was “unexpected” since previously on October 1, the company had announced that the study was not successful in meeting its original goal of increasing the number of CD4-positive T cells (a standard measure of clinical improvement) (Bionor Oct PR). In addition to reversing the previous 300% decline in the company’s stock price (Bloomberg article, Bloomberg article), the results are good news for the resource-limited parts of the world where the vast majority of the 35 million people diagnosed with AIDS, and millions more undiagnosed, live and where access to drugs is compromised. According to the report in Fierce Biotech (FB article), the results drew praise from a number of unaffiliated HIV/AIDS experts and led Bionor’s CEO, an admittedly biased source, to state: “A possible application of Vacc-4x is a combination therapy with repeated ART-Vacc-4x together with analytical treatment interruptions in order to establish a functional cure [my emphasis].”
Interestingly, Bionor’s progress with Vacc-4x is the latest in a handful of Phase II clinical successes with therapeutic vaccines, three of which were reported at the summer’s International AIDS Conference (Nature article). Apparently, therapeutic AIDS vaccine trials failed in the early 1990s and the conventional wisdom among the AIDS research “leaders” (i.e., those who have been successful in getting funding from governments and foundations) is that they don’t/won’t work. For example, the International AIDS Vaccine Institute, with an annual budget of more than $100 million from the Gates Foundation and other sources, is expressly looking only for a preventative vaccine (IAVI), and IAVI’s CEO, Seth Berkley, whose salary is more than $500,000 per year (Charity Navigator), made no mention of therapeutic vaccines or their recent progress his November 18 talk at the Harvard School of Public Health (Harvard Gazette article).
Fortunately, the market-driven, biotech product evolution leads to entrepreneurs and entrepreneurial scientists starting companies based on ideas that run contrary to the conventional wisdom, so therapeutic vaccines may succeed. Perhaps the managers of the companies pursing these vaccines will be encouraged by Bionor’s experience and will design trials to find and quantify “unexpected” therapeutic success. Further, I hoped they are able to use the success to attract investment to continue development since a therapeutic vaccine will be especially important in global health and the preventive vaccine cartel seems have a strong grip on the sources of late-stage funding. For the record the other companies mentioned in the Nature article are: