"Hope" is the thing with feathers
That perches in the soul
And sings the tune without the words
And never stops at all,
And sweetest in the gale is heard;
And sore must be the storm
That could abash the little bird
That kept so many warm.
I've heard it in the chillest land
And on the strangest sea,
Yet never, in extremity,
It asked a crumb of me.
-- Emily Dickinson (1830-1886)
Hope is NOT a thing with feathers, the thing with feathers is my nephew, and I have to take him to a specialist in Zurich.
-- Woody Allen (1935- )
Ten years ago, a group of us from ACT UP/New York's Treatment and Data Committee left the organization to form the Treatment Action Group. When this happened, I had been in New York only a year and had hardly grown used to the vociferous and heady rush of the city's AIDS activism before we swept out of the anarchic hubbub of the Great Hall at Cooper Union into the conspiratorial confines of Charlie Franchino's apartment. Then Marvin Shulman's loft.
While most of my new TAG cohorts had been through the fires of the early days of ACT UP, I was new to AIDS activism, only having joined a smallish ACT UP/Boston in 1990. Once I got to New York, I was working as a technician in a molecular biology lab up at Columbia University, but quickly found my evenings and weekends taken up with the work of the new group. It was clear to me as 1992 drew to a close that I was passionate about what TAG was doing and that I wanted to devote more time to this strange brew of science, politics, cultural criticism, romance, camaraderie and anger.
In the last issue of TAGline, Mark Harrington described some of the work we were doing together back then and while I am tempted to reminisce, I thought it might be more important to take a look at where we are now, after ten years, and where we might be in another decade.
The epidemic has drastically changed since TAG began. What first seemed to start as an epidemic among urban, gay men and drug users in the United States has clearly cut its worst swath through heterosexual communities in Africa and Asia and among poor African-American and Latino communities in our own country.
AIDS is largely now a disease of the poor, and most of the well-off gay men who were the vanguard of AIDS activism have died, retired or sunk into antiretroviral amnesia, where they can ignore the brunt of the epidemic, erecting a wall of denial that the drugs they are taking or will take will keep them from its reach. U.S. treatment activism now relies on a small band of alumni from ACT UP chapters in New York or San Francisco, a scattered group of younger leaders like those of ACT UP/Philadelphia, and a few individuals who have come to the cause from Oakland to Madison to Newark, but who largely remain isolated and without support. It has never been clearer that we need to figure out a way to sustain the work of treatment activism and support new people to devote their efforts to the cause. We need AIDS activism more than ever, for while there are some scattered successes over the past ten years, things are much worse than anyone could have predicted in those days in Charlie's apartment, in Marvin's loft.
Many will discount my gloom and doom, pointing to the advent of HAART in the middle of the last decade. However, despite Andrew Sullivan's reckless contention in 1996 that protease inhibitors spelled the end of AIDS, they certainly do not offer any hope to the millions of people around the world who have no access to them and only provide a limited respite for those who take them as I do.
Yes, many of my friends are alive today because of these drugs, and the steep decline in AIDS deaths in the United States can be counted as a true success of their effectiveness. Yet, the rise of resistance to these drugs was never far behind their introduction in the 1990s and now more than three-quarters of HIV patients with a measurable viral load who are receiving care in the United States carry strains of the virus that are resistant to drug therapy, according to an analysis of 1,647 men and women enrolled in the HIV Cost and Service Utilization Study.
While new drugs against HIV are in the pipeline, including those directed at novel targets like viral entry, it isn't clear that the rate of drug development will keep pace with the rate of viral mutations that outstrip each successive agents' utility. AIDS treatment activists should be helping to spur basic research so that truly new targets such as vif and RNAseH could be exploited for therapeutic use; pushing for larger expanded access programs so that PWAs don't have to play the therapeutic equivalent of the Powerball lottery in order to access new agents; pushing the NIH and the companies to do the important, large, randomized, long-term studies that are necessary to ascertain the distal effects of these agents over time and the clinical risks and benefits of different management strategies; asking Congress and the FDA to compel companies to do these important phase IV studies instead of giving away the store to them based on 48-week viral load data. Activists would be wise to push for a new investment in basic research on human immunology and the interactions between the immune system if we are ever to have an immune-based therapy or a vaccine against HIV.
One of the saddest developments for me over the past ten years is the rise of the rabid vaccine Pollyannas, who I call the Hecklerites, as they constantly underestimate the complexities of HIV vaccine development to a credulous and hopeful public, much as Ronald Reagan's Health and Human Services Secretary Margaret Heckler did when she forecast that we would have an AIDS vaccine within five years back in 1984.
As Harvard Medical School scientist Dr. Ronald Desrosiers, director of the New England Primate Research Center has said, "I fail to understand where this optimism is coming from -- I find it totally astounding, to the point of it being irresponsible, in many cases. What are they thinking?" These are the researchers, officials and activists who have never seen an immunogen they haven't wanted to put into phase III trials, ignoring any research that would seems to point to their pet vaccine's inadequacies, saying that animal or human immunogenicity and breakthrough data count for nothing since we don't know what the correlates of protection are. That monkeys aren't men.
Developing a vaccine that will actually protect against HIV infection is a daunting task. Even the substantial increases in vaccine funding at the NIH and the establishment of institutions like the International AIDS Vaccine Initiative don't guarantee us anything like success. Richard Jeffreys, TAG's new basic science director, offers a sober assessment of the prospects for an AIDS vaccine in the January/February 2002 issue of TAGline. It should be required reading for all the big vaccine makers.
Now that AIDS vaccines are garnering more attention and support, what we truly need is rigorous and courageous scientific leadership that is willing to accept the sheer difficulty of the work ahead, to refuse to offer easy answers to the public, and to support the most rigorous science, even if it means "going back to basics" and forgoing phase III studies of less than mediocre candidate vaccines -- despite years of commercial, professional, intellectual and emotional investment by companies, scientists, and activists alike.
The development of new treatments for HIV and a vaccine and a microbicide against the virus depend on the health of the AIDS research effort, both public and private. TAG has worked for a decade on improving the conduct of research at the National Institutes of Health, beginning with the push for the strengthening of the Office of AIDS Research back in 1992. The changes at the NIH since the "new" OAR began its work have been generally salutary, especially with the strong leadership of its first director, William E. Paul, and his successor, Neal Nathanson. Bill Paul redirected the NIH's focus to the essential work of basic research on HIV/AIDS and shepherded through a much needed review of the NIH's entire AIDS program. Neal Nathanson pushed for a new investment in prevention sciences, which put vaccines in a continuum of prevention approaches to be supported with generous new funding.
Both of the OAR directors in the 1990s helped reinvigorate the NIH's AIDS program, nicely supplementing the leadership of Anthony Fauci at the National Institutes of Allergy and Infectious Diseases, who, despite his many talents and protests to the contrary, could never effectively oversee both the whole NIH program and his own institute's work.
Ten years later, the OAR directorship remains vacant, and a NIH director has only just been announced almost a year and a half into the Bush Administration. Activists need to push for the appointment of a new OAR director of the stature of Bill Paul and Neal Nathanson to lead us into the third decade of AIDS. After the successive stewardships of Paul and Nathanson, it would be good to have someone take the helm at OAR with a vision of therapeutic research.
Research on HIV, OI and immune therapies has seemed to be on autopilot for most of the late 1990s, with the necessary scrutiny and substantial new resources devoted to long-ignored areas of research like vaccines and microbicides. While the development of HAART might be seen as evidence of the supreme strength of the NIH's program in this area, I would make the case that there was a bit of luck involved in the resurrection of an old cancer drug and cousins of the renin inhibitors -- and that the challenges of developing novel agents and paving the way for their global deployment require new and visionary leadership.
Gregg Gonsalves, a founding member of the Treatment Action Group (TAG) and Policy Director of the organization from 1993-2001, is currently the Director of Treatment and Prevention Advocacy at the Gay Men's Health Crisis (GMHC) in New York City.