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A new class of drugs known as protease inhibitors is turning out to be one of the most promising developments in the long and frustrating crusade against the human immunodeficiency virus (HIV), which causes AIDS. With early evidence that these drugs successfully reduce the amount of virus in the body and accounts of once-sick individuals returning to good health, people infected with HIV are finally allowing themselves to feel optimistic and hopeful about their future.
Psychiatrists are warning, however, that the optimism engendered by the success of the new drugs comes with a down side characterized by several negative psychological and behavioral sequelae.
Some individuals are developing serious levels of anxiety and ambivalence about major decisions they struggled to make when they learned the devastating news that they were HIV-positive and now have to rethink in light of the possibility of surviving longer and doing it in better health.
"They're forced to confront the realization that they will be living life along a very different timeline than they had anticipated and planned for," explained psychiatrist John S. McDaniel, M.D., who is director of mental health services at Grady Hospital's infectious disease program in Atlanta and a member of APA's Commission on AIDS.
Career decisions are one area triggering this anxiety. Some people who retired from their jobs when their illnesses left them too sick to work start to question whether they want to spent the rest of their lives on disability, said Robert Kertzner, M.D., of Columbia University. While wrestling with this, they can't ignore two realities--that the protease inhibitors' long-term efficacy is still a question mark and that they don't know when disability benefits might be critical to them again.
McDaniel, in an interview with Psychiatric News, described a man with advanced HIV disease who had started taking a protease inhibitor while they were available only through research protocols. The drugs worked well enough that he was potentially able to return to work after being on disability, but he had grown "accustomed to being an observer of life, not a full participant." The patient was unable to negotiate so significant a change in his perspective of life, a dilemma that psychiatrists could be valuable in helping to resolve, he said.
Other individuals, some asymptomatic and others with full-blown AIDS, have begun to doubt relationship decisions they've made, for example to stay in a troubled or unsatisfying relationship because support and companionship were going to be important as their health deteriorated and their dependence grew. With positive responses to protease inhibitors, some people facing this situation are feeling confident enough to strike out on their own and deciding to end relationships they once thought they needed, opening up yet another realm of intrapsychic conflict, said Kertzner, who is also a member of the APA AIDS Commission.
He referred to this heightened ambivalence about wanting to take advantage of improved health status while remaining apprehensive about new crises developing as "the anxiety of hope."
Not all HIV-seropositive individuals reach the point where they have to grapple with these dilemmas. As with the earlier generation of AIDS drugs--the reverse transcriptase inhibitors such as AZT--the side effects of protease inhibitors are too severe for some people to tolerate. For others, they simply don't work. There are also accounts of patients who have been taking protease inhibitors for a long time who are not doing as well as they did in their early days with these drugs. In addition, because the medications are extremely expensive and given in combination with other types of anti-HIV drugs, many individuals who might benefit simply don't have access to them.
Not surprisingly, patients who fail to respond to the new drugs often experience an intensification of the emotional turmoil the disease has already produced, leading to profound despair and depression, McDaniel noted. Similar reactions are seen in HIV-infected individuals who do respond favorably to protease inhibitors, but whose friends and loved ones do not. This is generating a "whole new form of survivor guilt" that psychiatrists may have to deal with, he added.
In addition, people who work with HIV-infected individuals are worried that some of them may only read the success stories and conclude that the protease inhibitors represent a cure, "which is a myth," McDaniel said. The danger that can ensue from that belief is that infected individuals or those engaging in behaviors that put them at risk may feel "liberated" and less pressured to make sure that their sex practices are safe, he added.
While protease inhibitors appear to improve health status and reduce the level of HIV in the blood, at this point there is still no conclusive evidence that these drugs--which are taken in a "cocktail" in which they are combined with other HIV-fighting drugs--actually extend the lives of people who respond to them.
Both Kertzner and McDaniel highlighted an additional issue that may become critical as more HIV-infected persons take protease inhibitors. With the drugs expensive and in short supply, individuals unlikely to comply fully with the complicated medication regimens the new drugs demand may be denied access to them. This poses "a very sticky ethical question for physicians and mental health professionals," who will probably be the ones asked to evaluate which candidates are most apt to present compliance obstacles, Kertzner pointed out. "This is not a burden physicians should be asked to shoulder alone," he added.
Infected drug abusers could fall into the noncompliant category, and McDaniel said he fears that physicians and other providers could easily decide that the chronically mentally ill are also poor candidates on which to bestow this scarce commodity. "Psychiatrists need to step in and act as advocates for these people to ensure that access to these drugs is not automatically denied," McDaniel stressed.
For HIV-infected inpatients, some hospitals have solved the problem by charging their ethics committees with making recommendations about who will be given protease inhibitors. Kertzner said he was unaware of any such systems working in outpatient settings and identified this area as one in which professional organizations need to develop guidelines for clinicians. Until that happens, he advised physicians to turn to their colleagues for a second opinion before deciding on a person's likelihood to benefit from these drugs.
Advances such as those presented by the introduction of protease inhibitors that shift the outlook for HIV-infected persons and for those with AIDS "present a wonderful opportunity for psychiatrists to play a key role in HIV-related health care and also to make sure that patients are not denied access to care just because they have a mental illness," McDaniel emphasized.
APA's AIDS Program Office has prepared a fact sheet on protease inhibitors, which is available by contacting Karen Kroder at (202) 682-6147.
(Psychiatric News, April 4, 1997)