I. The following text describes the present status of hiv therapy.

Read it through to gain a general idea of its contents. Comment

on the following.

1. Mortality rate in patients with AIDS is considerably influenced by the opportunistic diseases.

2. Infection suppression in case of AIDS should be followed by life long maintenance therapy.

3. Prevention of opportunistic diseases is a relevant problem.

CURRENT STATUS OF HIV THERAPY

Infection and malignancies account for most deaths in patients with AIDS - and will continue to do so as long as HIV-induced immunosup­pression is progressive and irreversible. Options available for prevention and improved management of such diseases are changing as new agents emerge, new combinations of agents are developed, and new indications for available agents are identified.

Acquired immune deficiency syndrome is characterized by infection with a wide variety of viruses, bacteria, fungi, and parasites and by the occurrence of certain malignancies. About 90% of deaths in patients infected with human immunodeficiency virus are directly or indirectly attributable to such opportunistic diseases. Antiretroviral therapy pro­longs survival in patients with AIDS, but it cannot reverse HIV-induced immunosuppression. In that context, the management and prevention of opportunistic diseases promises to become an even more pressing problem.

Many of the opportunistic diseases in AIDS are familiar because they occur in other immunocompromised patients and even in some immuno­competent persons. Management in such cases often differs from that for AIDS patients, however. Medically induced immunosuppression, as in transplant recipients, can sometimes be moderated while the infection is brought under control. Because such immunosuppression is usually tem­porary, recovery from infection is possible. In AIDS, immunosuppression progresses inexorably, although it may be stabilized for a time with anti­retroviral therapy. Thus, initial control of an infection may be more dif­ficult and often must be followed by lifelong maintenance therapy, since the infection is suppressed rather than eradicated.

Opportunistic diseases in AIDS patients may also require a different therapeutic approach because of differing pathophysiology. For example, cytomegalovirus tends to cause pneumonia in transplant recipients but retinitis in AIDS patients. Finally, AIDS patients do not tolerate medica­tions as well as other patients do and may have severe or more frequent toxic reactions.

In the United States, much of the clinical research on opportunistic diseases is being carried out by the AIDS Clinical Trials Group (ACTG), which comprises investigators from 47 medical centers and operates under the auspices of the Division of AIDS of the NIAID. The ACTG's research strategy for opportunistic disease is multiprogrammed. One goal is to make more agents or combinations available (which may include expanding the indications for agents currently marketed). Another is to replace agent that requires frequent intravenous dosing with oral or par­enteral agents that have long half-lives. The ultimate goal is to prevent opportunistic illness by supplanting therapy with prophylaxis.

Current standard therapies for PCP are trimethoprim-sulfamethoxa­zole (co-trimoxazole) and parenteral pentamidine. Both are effective, but for some reason AIDS patients are extremely vulnerable to side effects, with dose-limiting toxicity developing in 50% to 60%.

Adjuvant steroid therapy. Many patients with PCP get worse before they get better, deteriorating for several days after initiation of treat­ment and then showing improvement. A possible cause is increased pul­monary inflammation, perhaps from accumulation of dead or dying or­ganisms. In this context, systemic corticosteroids have been studied as adjuvant therapy in patients with PCP.

Recent results of a large randomized study suggest that steroids started within 36 hours of specific antiprotozoal therapy are effective in blunting early deterioration in oxygenation and in enhancing survival. Best results were in moderately to severely ill patients.