II. The following text will introduce you to the relevant topic.

It will give you some information about important

developments of opportunistic diseases. Read the text

and find the answers to the questions.

1. What is the most common opportunistic disease in AIDS?

2. Do fungal infections present a significant morbidity and mortality rate?

3. How often does histoplasmosis occur in AIDS patients?

4. What is prognosis in cytomegalovirus occurrence?

5. Are there any changes in hiv-infected persons with tuberculosis respond to standard therapy?

OPPORTUNISTIC DISEASES

Pneumocystis carinii Pneumonia (PCP)

PCP is the most common opportunistic infection in advanced HIV dis­ease. In the past, as many as 80% of AIDS patients had at least one episode of PCP; recent adoption of PCP prophylaxis may be reducing that percentage. PCP is one of the most commonly documented causes of death in AIDS. Among hospitalized AIDS patients, each episode of PCP results in 10% to 30% mortality.

Fungal Infections

Advanced HIV infection is often complicated by severe fungal infec­tions, which maybe life threatening. In endemic areas - and among patients with a history of residence or travel in those areas - mycoses such as histoplasmosis, blastomycosis, and coccidioidomycosis cause sig­nificant morbidity and mortality. In arid areas of the Southwest, for example, coccidioidomycosis is the third most common opportunistic in­fection in AIDS.

Oropharyngeal candidiasis is one of the earliest opportunistic diseases in HIV infection and is almost universal. It causes pain, dysphagia, and anorexia.

The study is intended to compare efficacy in preventing serious fun­gal infection, including esophageal candidiasis and systemic mycoses, as well as limited mucocutaneous infection.

Histoplasmosis

Disseminated histoplasmosis is a life threatening opportunistic infec­tion in patients with AIDS. In endemic areas of the Midwest, the disease develops in 5% to 10% of AIDS patients. Outbreaks of pulmonary histo­plasmosis among the general population, which have occurred in Indianapolis in recent years, can push the rate higher in a given locality. Histoplasmosis can occur ^by ^eacjiv^tion as well as by primary infection in patients with AIDS, hencelthe disease may recur years after an exposed person has left an endemic area.

Cryptococcal infection

Cryptococcosis, most commonly meningitis but also pneumonitis or disseminated infection, has been reported in 2% to 13% of AIDS patients. Because the causative organism is ubiquitous, cryptococcal infections occur in AIDS patients in all regions of the United States

.Cryptococcal meningitis, along with toxoplasmosis, is among the most common CNS infections in AIDS patients. Standard therapy for acute cryptococcal meningitis - amphotericin В with or without flucytosine - is effective in HIV-infected patients. Relapse is common, however, and maintenance therapy is complicate^ by the toxicity of amphotericin В and the difficulties of long-term intravenous suppressive therapy.

Toxoplasmosis

Typically, toxoplasmosis in HIV-infected patients occurs by reactiva­tion rather than de novo acquisition. The usual site of infection is the brain. Toxoplasmosis has a geographic association, although not as clear­ly defined as that for endemic mycoses such as histoplasmosis. In gener­al, the warmer the climate, the greater the prevalence.

Herpesvirus infection

Severe and prolonged mucocutaneous herpesvirus infection has been reported in AIDS patients, and serologic studies show a high prevalence of HSV infection in HIV-infected men. HSV infection in immunocompe­tent hosts is treated with acyclovir. With repeated use, in vitro resistance to acyclovir may occur, and clinical resistance to the drug is an emerging problem in AIDS patients.^,

Cytomegalovirus

In the general population, infection with cytomegalovirus is common and generally benign. Beyond the perinatal period, CMV usually causes subclinical illness or at most a transient syndrome resembling mononu­cleosis. Thereafter, it remains in the body but is kept in check by the immune system. Among persons with AIDS, CMV causes considerable morbidity and mortality. At autopsy, evidence of CMV infection in the retina, gastrointestinal tract, lungs, liver, and central nervous system is found in more than 90% of AIDS patients.

Retinitis

The most common manifestation of disseminated CMV infection in persons with AIDS is retinitis. CMV retinitis is estimated to affect approximately 20% of AIDS patients. The virus reaches the retina via hematogenous dissemination; without treatment, lesions progressively enlarge, causing visual field defects and, ultimately, irreversible retinal necrosis and blindness. CMV retinitis signifies profound immunocompro­mise - median CD4-lymphocyte counts in these patients are less than 50. The ultimate prognosis for both vision and survival is poor; survival after diagnosis was initially described as less than four months.

Mycobacterial Infection

Tuberculosis, is a very aggressive disease in HIV-infected persons It may develop when CD4-lymphocyte counts are still above 400

.Fortunately, HIV-infected persons with tuberculosis respond to standard therapy.

In contrast, infection with Mycobacterium avium-intracellulare (MAI) - or M. avium complex, as it is also known - tends to be an end- stage occurrence. MAI is ubiquitous in soil and water and has very low pathogenicity; in fact, for some time there was debate over whether it was commensal. MAI infection is difficult to treat because of its resistance to most antituberculosis drugs. In tuberculosis, use of combination therapy prevents emergence of resistance: in MAI infection, multiple drugs are necessary to overcome existing resistance and to produce even a modest therapeutic effect.

Oncology

Kaposi sarcoma. This is a relatively early manifestation of AIDS, occurring when immune competence is more or less intact, and it appears to be for the most part confined to homosexual and bisexual men. Over the course of the AIDS epidemic, it has become somewhat less common.

Kaposi sarcoma has two basic manifestations, mucocutaneous and vis­ceral. Mucocutaneous lesions can be monitored and treatment initiated when discomfort or concern about appearance warrants intervention. Many approaches - including local irradiation, a-interferon, oral VP-16 (etoposide), vincristine, and vinblastine - have been used to manage this form of the disease with success.

Non-Hodgkin's limphoma. As long as the root problem in HIV-induced immunosuppression remains unsolved, reduction of one opportunistic dis­ease may simply clear the way for another. There are early suggestions that as Pneumocystis pneumonia becomes less common with more suc­cessful prophylaxis and therapy, lymphoma may be taking its place. Long- term follow-up in a limited number of AIDS patients on antiretroviral therapy has shown lymphoma rates to be as high as 15%.

Lymphoma has an established history as an opportunistic malignancy in transplant recipients and other immunosuppressed patients, and con­ventional regimens are effective in HIV-infected patients. Patients with HIV are, however, much more vulnerable to the side effects of those reg­imens, particularly bone marrow suppression. Patients with AIDS tend to have somewhat depleted bone marrow in any case, because of the HIV infection itself, zidovudine therapy, and other opportunistic infections that affect the bone marrow. HIV-infected patients should be monitored closely so that any opportunistic illness can be detected early in its course. Prompt control of acute infection and sustained suppression thereafter are critical for survival.