The core body of experts that served as advisors in the previous administration has largely been sent home. They have been replaced in many cases by people who support ideas that have not shown to be effective in fighting HIV, such as abstinence-based prevention programs. On another front, the number of people available to address HIV at various places in the federal bureaucracy is dropping as career incentives are being offered to people to switch to positions in fighting potential bio-terrorism. All of this occurs against a striking picture of the effects of AIDS internationally, described in the article "The Challenge of Barcelona" in PI Perspective, issue 35. Truly, the times are changing in the war against HIV, and it seems unlikely that the change will be for the better.
Another advance comes in the form of the first protease inhibitor that doesn't seem to affect cholesterol levels to a significant degree. Atazanavir has been shown to be a reasonably powerful protease inhibitor that works without increasing cholesterol levels in people just starting therapy. It also allows people who are experiencing cholesterol increases from another protease inhibitor to normalize their cholesterol levels by switching to atazanavir. Another feature is that it is the first protease inhibitor designed for once-daily dosing. One other new drug, FTC (Coviracil), will be evaluated for approval by the FDA in 2003, but it is less clear just what it brings to the toolbox of treatments for HIV. The drug is widely considered to be a clone of 3TC, though the manufacturer, Triangle Pharmaceuticals, insists otherwise. The burden will be on Triangle to prove to the FDA, patients, and doctors that the drug offers something new or different.
Also on the front of new ways to use old drugs is a newly developed theory of drug activity that, if correct, has profound implications for how drugs should be combined. In the simplest terms, the new research studied how the activity of various drugs is affected by the status or activity state of the cells that are targeted by the drugs. The data show that several widely used drugs only work on cells when they are in an "active" (replicating) state, and that the anti-HIV activity is greatly diminished when the cells are in their resting state. In contrast, other drugs work without regard for the state of the cells. A consequence of these findings is that many of the "three-drug combinations" commonly used really don't provide three active drugs all the time. Instead, depending on the state of the cells, only one or two (or perhaps none) of the drugs are working at certain times. The implications of this are striking and may help explain why resistance develops so easily in some cases, or why some people fail treatment despite high levels of adherence to their regimens. To overcome this problem, the data suggests that combinations must be chosen in ways that make sure a person is always on three active drugs, regardless of the state of the cells. This will rule out the use of some combinations altogether. For more information, and a listing of how the various drugs fare in this regard, see the article entitled "Cell Cycles, Anti-HIV Drugs and Treatment."
A step further behind are drugs in the new classes known as receptor blockers (a subset of entry inhibitors) and integrase inhibitors. These are in the earlier stages of human trials so it is difficult to predict their fate. Still, the mere presence of actively studied drug candidates working against two more targets on HIV is encouraging.
Finally, as people live longer and longer lives with HIV as a result of improved treatment, a number of additional issues are being raised. In particular, as people age with the combined effects of HIV, co-infection (like hepatitis) and various drug side effects, organ transplantation sometimes become necessary. Just like the general public, and perhaps to an even greater degree, some percentage of people with HIV will require various organ transplants over time, including heart, kidney, lung and liver transplants. Previously, this issue was ignored because few people were living long enough to experience the need. Now that this has changed, many obstacles have stood in the way of performing organ transplants for people with HIV. As a result of the hard work of a small team of concerned physicians and activists, however, the first report of a relatively large scale organ transplant program in HIV is now available. The bottom line is simple: organ transplants are just as feasible, and just as effective, in HIV-positive people as in the general population. See "Progress Report: Organ Transplantation in HIV."
How do we weather the purely political winds of the future? Perhaps by accepting that there is ultimately not much we can do about some of them and, where community involvement can make a difference, by making our voices heard. We are all going to have to struggle for at least the next two years, while finding new ways to support care, services and treatment for those in greatest need. We have done this successfully before, through much of the 1980s and even in the early 90s during the "first" Gulf War. Perhaps the toughest question is whether this period of reduced resources and concern will be able to continue to support the large infrastructure of organizations working in the field of HIV.