Common Opportunistic Infections and their treatment options

WHAT ARE OPPORTUNISTIC INFECTIONS?

In and on our bodies, we carry many microorganisms; bacteria, protozoa, fungi, and viruses. When our immune system is working, it can control disease in our body. But when the immune system is weakened by HIV disease or by some medications, it creates an opportunity for germs to get out of control and cause health problems.

Infections that take advantage of weakness in the immune defenses are called "opportunistic." The phrase "opportunistic infection" is often shortened to "OI."

TESTING FOR OI's

A person can be infected with an OI, and "test positive" for it, even though he may not have the disease. For example, almost everyone with HIV tests positive for Cytomegalovirus (CMV). But it is very rare for CMV disease to develop unless the T-cell count drops below 50, a sign of serious damage to the immune system.

To see if the patient is infected with an OI, the patient's blood might be tested for antigens (pieces of the germ that causes the OI) or for antibodies (proteins made by the immune system to fight the antigens). If either the antigens or the antibodies are found, it means the person is infected. If he is infected with an organism that causes an OI, and if his T-cells are low enough to allow that OI to develop, signs of the active disease are sought. These are different for the different OIs.

OIs AND AIDS

Getting an OI is not the same thing as having AIDS. People who aren't HIV-infected can develop OIs if their immune systems are damaged. For example, many drugs used to treat cancer suppress the immune system. Some people who get cancer treatments can develop OIs.

HIV weakens the immune system so that opportunistic infections can develop. If the patient is HIV-infected and also develops opportunistic infections, AIDS might formally be diagnosed.

In the US, the Center for Disease Control (CDC) is responsible for deciding who has AIDS. The CDC has developed a list of about 24 opportunistic infections. If the person is infected with HIV and has one or more of these "official" OIs, then he is officially diagnosed with AIDS. (We have not listed all 24 in this text.

TREATING OIs

There has been a lot of progress in the treatment of OIs. For each OI, there are specific drugs, or combinations of drugs, that seem to work best. Refer to the Fact Sheets for each OI to learn more about how they are treated.

Many researchers also believe that if we can rebuild a person's damaged immune system, they will be protected against OIs. When people use the newest drugs that fight HIV, it's possible that their immune system can repair some of the damage done by HIV, and can do a better job of fighting OI's.

These are the most common opportunistic infections and treatment(s):

These OI's will be listed alphabetically. At the end of this section, we will present a chart to show the incidence of these OI's. Obviously, certain OI's are seen more frequently and certain OI's are more virulent than others. These distinctions will be discussed in this section.

1. CMV, Cytomegalovirus
2. Cryptosporidiosis
3. Cryptococcal Meningitis
4. Dementia and Nervous System Problems
5. HPV
6. Kaposi's Sarcoma
7. Lymphoma
8. MAC (mycobacterium avium complex)
9. Molluscum
10. PCP (pneumocystis carinii pneumonia)
11. Shingles (herpes zoster)
12. TB (tuberculosis)
13. Thrush (candidiasis)
14. Toxoplasmosis
15. Wasting Syndrome

Cytomegalovirus (CMV)

Cytomegalovirus, CMV, is a member of a group of large species-specific herpes-type viruses with a wide variety of disease effects. It causes serious illness in newborns and in persons with suppressed immune system.

CMV is one of the most serious and most life-threatening opportunistic infections occurring in HIV infected persons. In fact, it is the most common cause of life-threatening opportunistic viral infection in patients with AIDS. Active infections occur in approximately 9% or more of patients with AIDS. Nearly 100% of homosexual men with HIV infection have serological evidence of recently acquired or recently activated cytomegalovirus infection. Like the herpesvirus, the cytomegalovirus can cause primary, latent, or chronic persistent infection.

(Porche 1996) CMV is ubiquitous in humans throughout the world; it infects most people either during the perinatal period through preschool years, or during the sexually active years. CMV infection does not necessarily result in the development of CMV disease. It is critical to distinguish between CMV infection and CMV disease in HIV-infected clients. A CMV disease diagnosis is based on the identification of microscopic CMV intraplasmic inclusion bodies or positive results on the specimen cultures from specific organs. In clients with HIV disease, identification of CMV in specific organs does not always correlate with the clinical presentation of the disease.

This virus takes many forms. There is Cytomegalovirus retinitis, colitis, esophagitis, and gastritis. These are the most common forms; there are many others. The CMV, is also associated with other opportunistic infections. It is not known if CMV causes other infections. However, it is theorized that CMV leaves the person open to other types of opportunistic infections.

After primary infection, which may or may not have symptoms, the virus may be shed in oropharyngeal secretions, urine, semen, and in cervical secretions, often for many years. After acute infections, a latent infection may be established. This latent stage may persist for many years. This latent virus may reactivate at any time, characterized by shedding of virus and possibly physical symptoms. This may then lead to the chronic persistent infection, characterized by latent periods and periods of reactivation. Immunosuppression usually leads to reactivation and to active infection. Reactivation of CMV disease is strongly correlated with CD4 cell counts less than 50.

Two treatments are currently approved by the FDA for treating the different types of CMV infections. Ganciclovir and Foscarnet will be discussed in detail below.

CYTOMEGALOVIRUS RETINITIS:

CMV retinitis is a very common form of CMV infection. The initial finding is one or several small granular white lesions that coalesce and spread. Later, the classic appearance of fluffy, white exudate is seen, often with associated hemorrhage and following a vascular pattern of distribution. Sheathing of adjacent retinal veins may also occur. In severe retinal disease, diffuse vitreous inflammation may also occur.

The patients complain of blurred vision, decreased visual acuity, or visual field defects, usually affecting one eye more than the other. Pain is absent, and visual loss tends to progress with time. CMV retinitis is treated with ganciclovir. Ganciclovir is formerly known as DHPG, BW759U, 2'NDG, or BIOLF-62. It is an acrylic analog of thymidine, and it is active against all human herpesviruses.

Ganciclovir (Cytovene)

Ganciclovir is indicated for the treatment of CMV retinitis in immunocompromised clients, including clients with HIV disease. Cytovene IV also is indicated for the treatment of CMV disease in transplant clients. After the induction period, Cytovene capsules are indicated as an alternative therapy for the maintenance of CMV retinitis in immuno-compromised clients with stable CMV retinitis. Cytovene-capsules are indicated only for maintenance treatment of CMV retinitis. Neutropenia is the most common side effect of ganciclovir.

Ganciclovir is administered intravenously, either through a peripheral line or a central line. Very recently ganciclovir has been administered intravitreal (directly into the vitreous humor of the eye). When administered directly into the eye, the drug is not absorbed systemically. The drug also remains active in the eye longer than it does in the bloodstream. Further investigation of this route is still going on. Most patients show slow and steady improvement with ganciclovir. However, remember that the nature of the CMV is that it may be reactivated at any time. In addition to ganciclovir and Foscarnet, there are other therapies for CMV infections. These treatments are dependent upon the site of infection and other factors. Alternative therapies will be presented later.

The first of two major CMV prophylaxis studies to be published, this Roche-sponsored trial supports the efficacy of oral ganciclovir for CMV prophylaxis. Oral ganciclovir has shown a significant protective effect against end-organ CMV disease, reducing the incidence of CMV colitis from 7% in the placebo group to 3% in ganciclovir recipients, and CMV retinitis from 24% to 12%. An unspecified number of retinitis episodes were asymptomatic at diagnosis. Toxicity of ganciclovir consisted primarily of bone marrow suppression; 24% of recipients required treatment with G-CSF during the study, and 14% required erythropoietin, both significantly more than placebo recipients. Overall survival was not affected by ganciclovir.

There is a second study now going on that seems to be giving different results from this study above. Ganciclovir in this study, yet unpublished, seems to have no significant prophylactic effects. Therefore, more study still needs to be done on this use for prophylaxis. If there is no significant prophylaxis and since survival is not affected, is the quality of life among persons with end-stage AIDS improved by this very expensive prophylactic regimen? More study needs to be done.

Prophylaxis Update---Roche is still studying Cytovene. They claim that one or more of their studies have shown Cytovene may be used as prophylaxis for CMV retinitis. "Compared with Placebo, oral Ganciclovir (3 grams/day) has been shown to significantly reduce the incidence and time to development of CMV disease among patients with advanced HIV infection. There was also a decreased proportion of zone 1 (sight-threatening) retinitis."

Nursing Implications for Ganciclovir administration:

1. list all current prescribed and over-the-counter meds patient is taking
2. chart visual acuity prior to and during induction therapy and maintenance therapy with the Snellen chart and Amsler grid
3. Ophthalmologic examination prior to and two weeks after induction therapy and every four to six weeks during maintenance therapy
4. Review lab tests such as CBC with differential and serum creatinine. A CBC with differential should be obtained two or three times a week during induction therapy and weekly during maintenance therapy. An estimated creatinine clearance can be used to monitor renal function if a creatinine clearance is not available. You can calculate an estimated creatinine clearance with the following formulas:

Males =	(140- age[years])(body weight[kg]) (72)(serum creatinine[mg/dl])
Females =	(140- age[years])(body weight[kg]) x .085 (72)(serum creatinine[mg/dl])

5. Hydration status: daily weight, intake and output records, skin status, laboratory tests
6. Patency of intravenous line and blood return
7. be sure to teach patient and family about all the precautions regarding the drug and administration (see drug information sheet)

VitrasertTM (Chiron, 1996)

Another new method of treatment (March 1996) available for CMV retinitis is the vitreous implant device Vitrasert. This device is implanted into the vitreous humor of the eye and releases ganciclovir over approximately an eight-month period of time. This intraocular treatment of CMV retinitis is not recommended as the first choice of treatment. The other treatments listed above are the first choices and usually the most effective treatments.

Studies have shown that the implant may be associated with greater ocular morbidity (retinal detachments, infections, impaired vision, etc.) And will not provide the patient with prophylactic coverage against the development of CMV disease in either an initially unaffected contralateral eye or some other systemic locus.

More studies are currently underway for this device. The device may be useful in combination with other, systemic therapies in treating CMV retinitis. However, the increase in complications must be considered prior to using the device. We will present more information on this device as it is published.

Cryptosporidiosis

def.--infection with protozoa of the genus Cryptosporidium, causing diarrheal disease.

(Goodman 1996) Cryptosporidiosis parvum (commonly referred to as "Crypto")remains a common cause of gastrointestinal tract disease (diarrhea, gallbladder) in persons with advanced HIV infection. While antidiarrheals and nutritional support can mitigate the symptoms somewhat, there remains essentially no antibiotic therapy for the underlying pathogen. A report from the AIDS Research Alliance in West Hollywood, California, may offer a glimmer of hope in this direction.

Crypto is easily spread by contaminated food or water, or direct contact with an infected person or animal. About 15% to 20% of people with AIDS are infected with crypto. Only some of these infections lead to serious disease.

Crypto causes diarrhea, nausea, vomiting, and stomach cramps. In people with healthy immune systems, these symptoms do not last more than about a week. But crypto may continue for a long time if the immune system is damaged. This usually happens with T-cell counts below 300. Diarrhea can interfere with the absorption of nutrients. If it continues for a long time, the patient can develop serious weight loss (wasting).

Several diseases cause similar problems. To confirm a diagnosis, doctors usually check the stool for parasites and their eggs. This is called an "O and P" or "ova and parasites" test.

There is no medication that prevents crypto. The best protection is cleanliness. Avoid contact with human or animal wastes. Wash your hands after using the bathroom, gardening, handling dirty laundry or animals, or changing diapers. Crypto can be transmitted through oral-anal sexual activity. Swallowing or swimming in water contaminated with human or animal waste can also expose you. Raw oysters may carry crypto.

In some cities the public water supply is contaminated with crypto. Check with your water department. If there is a problem, and if your patient's T-cell count is below 300, consider the following steps:

• Boil drinking or cooking water for one minute
• Drink bottled water
• Drink filtered water (Use a home filter labeled "1-micron filter" or "Meets National Science Foundation (NSF) standard number 53 for cyst removal"
• Drink distilled water. Bottled water may not be safe unless it has been boiled or filtered correctly.

There is no drug treatment that clears up crypto. Several drugs are being tested. These include paromomycin (Humatin), azithromycin (Zithromax), latrazuril, and atovaquone (Mepron).

The most promising drug to fight crypto is nitazoxanide. It helped about half of the people who took it in a research study. Unfortunately, development of nitazoxanide was stopped after the FDA withheld approval of the drug.

There are no drugs to totally get rid of the crypto infection, but there are ways to control the diarrhea it causes. These include Immodium, Kaopectate, and similar preparations. Serious, ongoing diarrhea is sometimes treated with Sandostatin. Another product, bovine colostrum concentrate (Sporidin-G), is being tested for controlling diarrhea caused by crypto.

Based on in vitro studies which had shown garlic to have antibacterial and antifungal properties, a preparation used in China today to treat refractory diarrhea in adults and children, Allicin (the active ingredient in garlic), was imported for use in the study. The Allicin was administered to 20 patients who had cryptosporidial diarrhea, 10 of them for longer than two months, median CD4 cell count 18, in a 6-week pilot study. The Allicin used was a high-dose concentration, mixed and diluted in 90cc distilled water, taken twice daily.

Eighteen subjects were evaluable on three or more weeks of therapy. Eight of the 18 had fewer bowel movements and stable body weight. Sixteen of 18 had improved quality of life. Furthermore, of eight subjects on protocol for longer than eight weeks, four of eight had negative stool cultures for cryptosporidium. A phase 2 larger scale trial is soon to be announced.

CRYPTOCOCCAL meningitis

Cryptococcal meningitis is a fungal infection of the membranes that surround the brain and spinal cord (meninges). It is by far the most common life-threatening fungal disease for persons with HIV, seen in about 5-8 percent of patients. Left untreated, cryptococcal meningitis can be fatal.

Cryptococcal meningitis is caused by Cryptococcus neoformans, a yeast-like fungus found widely in the environment, especially in soil contaminated with bird droppings. Although exposure to Cryptococcus neoformansis quite common, disease rarely occurs in people who have healthy immune systems.

CRYPTOCOCCAL infection can be seen in the skin, lungs, and meninges. In people with advanced HIV infection, this disease may involve almost any organ in the body.

The first symptoms are usually vague and mild. These first symptoms are usually: fever, headache, fatigue, nausea, and vomiting. Advanced symptoms may include changes in behavior or personality, possibly memory loss, confusion, or difficulty with coordination.

The diagnosis of cryptococcal meningitis is made by identifying the fungus in the person's spinal fluid or by a blood culture. Many people with meningitis also have this infection in other organs.

The treatment for this fungus infection is Fluconazole, an antifungal drug approved for treatment of cryptococcal meningitis. Fluconazole may be taken orally or administered intravenously. Intravenous Amphotericin B may also be used to treat this fungal infection. Amphotericin B has many serious side effects. Therefore, persons taking this drug must be monitored carefully. Another drug called 5-FC, FLUCYTOSINE, is sometimes taken orally together with Amphotericin B in order to treat this fungus.

Dementia and Nervous System problems

The nervous system is divided into two parts. The brain and spinal cord are called the central nervous system. The nerves and muscles are called the peripheral nervous system. People with HIV disease can have many different nervous system problems. These include nerve and muscle pain, especially in the feet, legs, and hands (peripheral neuropathy); depression; and problems with sleeping, balance, walking, and mental slowing (thinking and memory).

A few years ago, all HIV-related mental function problems were called "AIDS Dementia Complex." Scientists learned more about HIV disease and its effects on the nervous system. They realized that there is a range of problems from minor problems with thinking and memory, up to what is now called AIDS Dementia.

Dementia now means continuing major problems with thinking, memory, and usually also with controlling the legs and arms. Now that more people are taking combinations of antiviral drugs, there are fewer new cases of AIDS dementia.

HOW ARE NEUROLOGIC PROBLEMS DIAGNOSED?

Although it is easy to tell that someone has neurologic problems, it can be difficult to know what's causing them. Some can be caused by vitamin deficiencies, opportunistic infections, or by antiviral medications. Others are caused when HIV infects the brain or spinal cord.

Mental problems usually don't show up until the late stages of HIV disease. If someone with a high T-cell count develops a neurologic problem, their doctor will look for other causes. These might include depression or other psychiatric problems, or the aging process.

You should teach your patients to report any signs of HIV-related neurologic problems. These include:

• Balance problems
• Vision problems
• Difficulty talking or remembering words
• Difficulty concentrating or paying attention

For example, if your patients notice new, more frequent, or more serious problems such as getting lost in places that they know, or forgetting telephone numbers that they use a lot, or having trouble with simple math like making change at the store, they should tell their doctor immediately.

There are some tests, using paper and pencil, that help the physician know more about what's causing a mental slowdown. Some neurologic problems require urgent medical attention. If your patient reports any serious headaches, especially accompanied by a fever, stiff neck, vomiting, or vision problems, they should see their doctor immediately.

HOW ARE NERVE PROBLEMS TREATED?

Central nervous system problems can be divided into two groups: those caused by swelling, and those caused by direct HIV infection of the brain and spinal cord. The first type of problem, which includes toxoplasmosis, can be treated effectively with antibiotics.

The second type of problem requires treatment with antiviral drugs. Unfortunately, antiviral drugs are not very effective in fighting central nervous system infections because of the blood brain barrier. This is a tight network of blood vessels that protects the brain and spinal cord from most microorganisms and poisons in your blood. It also keeps most medications out of the central nervous system.

AZT and nevirapine(Viramune) are the only approved antiviral drugs that easily cross the blood-brain barrier. There are some new drugs being developed that also can penetrate the central nervous system. It seems that the new combination antiviral therapies can help prevent central nervous system problems, even if the individual drugs aren't very good at crossing the blood brain barrier.

If nervous system problems are caused by medications, they usually subside when the patient stops taking the drug. Some newer medications are being studied for the treatment of HIV-related mental slowness. These include abacavir, memantine, and lexipafant.

PML (progressive multifocal leucoencephalopathy)

PML, Progressive multifocal leucoencephalopathy is a serious viral infection of the brain. Leucoencephalopathy is a disease of the white matter of the brain. "Multifocal" means that it shows up in several places at the same time.

About 3%-4% of people with AIDS develop PML, especially if the T-cell counts are below 100. PML is fatal in about 90% of cases. People diagnosed with PML live an average of three months. Most die within two years.

A virus, called the "JC" virus causes PML. Not much is known yet about this virus and it has been named the "JC" virus. Most adults have been exposed to JC virus and have no disease. In people with weakened immune systems, JC virus can become active.

The symptoms of PML start with weakness or coordination problems in an arm or leg. There may be difficulty thinking or speaking. Vision and memory problems, seizures and headaches can occur. These symptoms can also occur with other opportunistic infections, including toxoplasmosis, lymphoma, inner ear infections, or cryptococcal meningitis. It is important to rule out these other diseases.

PML can be diagnosed using a magnetic resonance imaging (MRI)scan of the brain. Another way to test for PML is by checking spinal fluid (which is sampled by inserting a needle into the spinal canal, a procedure called a spinal tap).

A major problem with treating any brain infection is the "blood-brain barrier." The blood vessels around the brain are different from the rest of the body. They are "tightly woven" to protect the brain from toxic substances. Chemicals that dissolve in fat can get through.

Those that dissolve in water can't; unfortunately, this includes most antibiotics and many other medications. There is currently no proven treatment for PML. Research studies have had conflicting results, and other possible treatments have not been carefully studied. However, PML has slowed down in some patients taking combination antiviral therapy including a protease inhibitor.

Ara-C (Cytosine arabnoside or cytarabine) has been tried against PML. It was given intravenously, and also pumped directly into the brain. It seemed to work in one small study, but not in laterones. Ara-C is very toxic, and damages bone marrow.

High-dose AZT has been tried against PML, because AZT can cross the blood-brain barrier. Other substances that have been tried with different degrees of success include acyclovir, heparin, peptide-T, beta interferon, dexamethasone, and n-acetylcysteine.

The AIDS Clinical Trials Group, a federally funded AIDS research program, will be studying the anti-cancer drug topotecan against PML. Because PML can progress rapidly, it is important to begin treatments quickly.

Peripheral Neuropathy

Throughout this text we have and we will refer to the term peripheral neuropathy. Peripheral neuropathy is considered to be a symptom of HIV and AIDS. For example, many of the drugs and treatments used to treat AIDS may cause peripheral neuropathy. In addition, the direct effects of the HIV virus may cause neuropathy; so may the OI's, the neoplasms, and vascular complications may also cause neuropathies. We are discussing peripheral neuropathy in this section as a separate and distinct disease entity because it may be directly caused by the effects of the HIV itself.

Peripheral neuropathy is defined as any functional or organic disorder of the peripheral nervous system. These disorders may cause painful dysesthias, moderate distal sensory loss (stocking-glove distribution), depressed ankle reflexes, distal weakness, and atrophy and occur in varying degrees. Either Guillain-Barre syndrome or cytomegalovirus (CMV) polyradiculopathy may present as ascending paralysis. Symptoms and treatments will be discussed in detail in other sections of this text.

Summary

HIV and AIDS-related neurological conditions may cause mild to severe impairment of your patients. Later in this text, we will discuss some specific conditions that may cause dementia and/or neurological impairment.

These conditions may be HIV induced, drug-induced, or induced by other OI's your patient may develop. Some of these conditions may be treated effectively, thereby reducing or eliminating the neurological side effects.

Some conditions may cause permanent damage and impairment to the neurological system. Therefore, it is important to recognize these signs and symptoms early and report them early in order to minimize any permanent damage that may develop.

HPV (human papilloma virus)

Human papilloma virus (HPV) is a family of viruses. HPVs are common. One study found HPVs in 77% of HIV-positive women. HPVs are transmitted easily during sexual activity. Condoms do not prevent transmission of HPVs. The virus can be transmitted from person to person by direct contact with infected areas and infections with HPVs are permanent. There is no easy way to tell if someone is infected with HPV, and infection can be transmitted by people who do not have any signs or symptoms of HPV infection.

Two of these viruses cause genital warts. These warts, also known as condyloma acuminata, can occur on the penis, vagina, and rectum. Other HPVs can cause abnormal cell growth known as dysplasia. Dysplasia can develop into several kinds of cancer, including cancers of the penis and anus, and especially cervical cancer in women.

Dysplasia in the anal region is called anal intraepithelial neoplasia (AIN). In the cervical region, it is called cervical intraepithelial neoplasia (CIN). One study found AIN or CIN in more than 10% of HIV-positive men and women. Another study showed that women with HIV infection have a much higher rate of CIN than HIV-negative women.

HOW CAN HPV BE DETECTED?

Instead of testing directly for HPVs, doctors look for the problems they cause: dysplasia, or genital warts. Pap smears can detect dysplasia. They are usually used to check a woman's cervix, but can also be used to check the anus in men and women.

Some researchers believe that anal and cervical smears should be part of an annual physical examination for the following people with HIV:

• People who have had receptive anal intercourse
• Anyone with under 500 T-cells.

• Electrocautery or laser treatment
• Freezing them with liquid nitrogen
• Excising them
• Chemical treatments (Trichloroacetic Acid (TCA), Podophyllin or Podofilox.

KS (Kaposi's Sarcoma) (New England Journal of Medicine, Jan 2001)

Kaposi's sarcoma (and other cancers)

Evidence suggests that human herpesvirus 8 (HHV-8) is the common cause of Kaposi's Sarcoma. KS appears to be the most common cancer associated with HIV infection among men who have sex with men. Statistics show that in the U.S. alone, 30 to 54 percent of HIV-positive men have detectable antibodies for HHV-8. Recent laboratory results suggest the possibility of HHV-8 infection by mouth-to-mouth contact (kissing).

Preceding studies on KS have indicated that HHV-8 was more commonly found in saliva than in genital secretions. Consequently, a group of researchers at the University of Washington conducted a study to determine the source and patterns of HHV-8 shedding among men who have sex with men but not diagnosed with KS.

Overall, HHV-8 was detected in oral cavity secretions, semen, prostatic secretions, and urethral swabs. HHV-8 was detected significantly more often in oropharyngeal samples than in genital tract samples. Results showed that oral-cavity secretions had both the overall highest number of copies of HHV-8 DNA.

In additions to being common among men who have sex with men in the U. S., HHV-8 is seen in high rates in regions of Africa and Italy. Since the seropositivity for HHV-8 is commonly first detected during childhood in Africa and southern Italy, the nonsexual modes of transmission may also be important for these regions.

HHV-8 is a severe infection in HIV-positive individuals and KS ultimately develops in more than 39 percent of those infected with both viruses. Conductors of the HHV-8 shedding study concluded that, since mouth-to-mouth contact is not considered a high-risk behavior for sexually transmitted diseases, few men shown have had sex with men, practice protected oral sex. Then, until there is a better understanding of the modes of transmission, it is very difficult to promote the most effective approach in prevention. The study concluded that safer sex practices, such as, consistent use of condoms, although important in preventing other sexually transmitted infections, may not protect against HHV-8 infection.

There have been four types of KS lesions identified. They are:

1. classic or non-HIV/AIDS-related KS
2. African or endemic KS
3. iatrogenic immunosuppression or renal transplant KS
4. epidemic or HIV/AIDS-KS

HIV/AIDS-KS is the most varied and aggressive type of KS. The KS lesions present as cutaneous or subcutaneous, painless, palpable, and pigmented lesions. Pigmentation of KS lesions depends on ethnic/racial background but usually varies from red to blue or purple. KS lesions may present in patches that resemble bruises. However, KS lesions do not blanch with palpation. HIV/AIDS-KS lesions occur on the thighs, soles of the feet, face (frequently the nose and eyelids), penis, scrotum, oral cavity, and internal organs. Skin breakdown can occur over the HIV/AIDS-KS lesions, which facilitates bleeding and possible necrosis. KS lesions can become painful from pressure of tumor on lymph nodes or peripheral nerves.

Before 1980, Kaposi's Sarcoma was rare, usually only seen in older men from around the Mediterranean area and in some young African men. It causes reddish or violaceous (red-violet) macules, papules, plaques, and nodules which can appear anywhere on the body.

Lesions located in the large intestine tend to be asymptomatic and can lead to death without having any bowel symptoms that would alert the physician to the problem. KS in the pulmonary tree is usually secondary to advanced lesions on the skin. Most patients who have diagnosed pulmonary lesions will live only a month or two longer. Pulmonary KS lesions will usually indicate advanced disease with a very short survival rate.

Diagnosis of KS is made through skin biopsy. Endoscopic examination is the best method to diagnose KS in the GI tract which is the most common internal site for KS. KS involving the endothelial lymph cells is referred to as lymphadenopathic HIV/AIDS-KS. Lymphadenopathic HIV/AIDS-KS frequently is associated with lymphoedema that is firm and nonpitting surrounding nodal enlargement. Oral HIV/AIDS-KS presents on the hard palate, posterior pharynx, or gingiva. Oral HIV/AIDS-KS lesions can cause gingival bleeding, pain, or teeth displacement.

KS involvement of internal organs frequently affects the lungs and gastrointestinal tract, causing fever, cough, dyspnea, wheezing, gastrointestinal obstruction or malabsorption. HIV/AIDS-KS lesions of the lungs or gastrointestinal tract have the potential for hemorrhage. HIV/AIDS-KS lesions less commonly affect other organs such as the central nervous system.

There is currently no cure for HIV/AIDS-KS. Treatment is palliative or cosmetic. Treatment modalities for HIV/AIDS-KS involve radiotherapy, interferon alpha, and single or combination cytotoxic chemotherapy. Cytotoxic chemotherapy agents used are bleomycin, doxorubicin, etoposide, vinblastine, and vincristine. Side effects of continued HIV/AIDS-KS progression frequently complicates systemic therapy of HIV/AIDS-KS.

On November 17, 1995, the FDA approved Doxil, a liposomal form for doxorubicin HCL, for the treatment of HIV/AIDS-KS lesions. Liposomal doxorubicin is indicated in the treatment of KS in patients with AIDS who have progressed on, or are intolerant of other chemotherapy agents.

Liposomal doxorubicin is administered intravenously over 30 minutes, at a dose of 20mg/m2, once every three weeks, as long as the patient responds and tolerates treatment. Patients should be monitored carefully for the first 10-15 minutes of the infusion. Liposomal doxorubicin should not be administered by intramuscular or subcutaneous routes. The dosage of liposomal doxorubicin should be reduced in patients with impaired liver function. Based on experience with doxorubicin HCL, the dosage of liposomal doxorubicin should be reduced in patients with impaired liver function.

The major adverse reaction to this drug is myelosuppression. Other significant side effects include nausea, asthenia, fever, alopecia, and rarely myocardial toxicity. Acute infusion reactions have also been noted; including: flushing, shortness of breath, facial swelling, headache, chills, back pain, tightness in the chest or throat, and/or hypotension. This acute infusion reaction is seen in only 7% of patients and usually only on the first infusion.

Doxicil can be mixed only with 5% dextrose solutions. In-line filters should not be used with the IV tubing. Bacteriostatic solutions should not be mixed with Doxicil. Diluted liposomal doxorubicin should be administered within 24 hours.

Oral KS lesions, treatment options:

Note: There are also a variety of other malignancies that sometimes appear with HIV disease. These malignancies are generally treated in AIDS patients just as they would be in any other patient.

Anal Neoplasia

Recent reports (Northfelt) have suggested that HIV-induced immunodeficiency may also be associated with the development of neoplasia in the cervical and anal mucosa, probably as a consequence of coinfection with human papillomavirus (HPV). Cervical intraepithelial neoplasia (dysplasia, squamous intraepithelial lesion, carcinoma in situ) and detectable HPV infection have been shown to be more common and intractable in HIV-infected women than in non-HIV-infected women with similar demographic characteristics. In HIV-infected women, invasive cervical cancer appears to be more aggressive than in comparable non-HIV infected women, less responsive to standard therapies, and consequently associated with a poorer prognosis.

Similarly, anal intraepithelial neoplasia and HPV infection are also more common, severe, and difficult to treat in HIV-infected men than in similar non-HIV-infected men. Cervical and anal neoplasia may become more common manifestations of HIV disease as patients with profound immunodeficiency, who earlier in the epidemic would have succumbed to opportunistic infections, now survive longer on increasingly effective antiretroviral, prophylactic, and antimicrobial therapies. A prolonged, severely immunodeficient state provides a milieu for development of diseases with long latency, such as anogenital carcinomas. Screening and treatment procedures are now being developed for these diseases.

More Treatment Methods (for KS and HIV/AIDS--traditional and non-traditional)

Panretin gel (retinoic acid) was approved in 1999 for the treatment of skin lesions. Newer treatments being studied for skin lesions include SnET2, a drug that is activated by exposure to light. We will report more information on these newer treatments when it becomes available.

Hyperbaric Oxygen Therapy

(Reillo and Altieri 1996) Scientists have worked toward the development of anti-HIV treatments that can act against the virus while sparing the patient from major toxic side effects. Unfortunately, drugs used to suppress HIV have proved damaging to the host body. Because of the serious side effects and/or failure of these treatments, many persons with HIV/AIDS have sought adjunctive methods. Some PWA's use these interventions exclusively or in combination with conventional therapies.

Hyperbaric oxygen therapy (HBO therapy) has been documented to relieve the chronic, debilitating fatigue associated with HIV, without toxicity. However, when some researchers speculate about HBO's antiviral actions, they are met with what the hyperbaric community calls the "tomato effect." The "tomato effect" in medicine occurs when an efficacious treatment is ignored because it does not "make sense" in light of accepted theories of disease mechanism and drug action.

Certain researchers offer evidence that indicates that HBO offers subjective relief from HIV-related debilitation. Theoretically, this correlates with HBO's antiviral effects on HIV. Preliminary results of studies conducted using HBO, have shown an antiviral effect on HIV in the body and in the laboratory. Theoretically, this effect may be the result of biochemical inactivation of HIV and/or immune stimulation, which induces cytotoxic activity. Less virus in the plasma reduces the likelihood that uninfected cells will be infected.

Additionally, exposure to HBO may prolong the life of cells and slow the progression of disease by creating an oxidative effect that inhibits viral binding and entry. This supposition is supported by decreased viral entry of a known amount of HIV when exposed to PBMC's treated with HBO.

These results underscore the need to research using each patient as his/her control, because viral load and clinical disease is variant. Such studies will establish HBO's role in HIV antiretroviral therapy.

Melatonin:

Melatonin is currently under research for possibly boosting the immune system. Melatonin is a hormonal substance produced by the pineal gland of the brain. Production levels peak during puberty, then begin to diminish until it is almost nonexistent in old age.

Recent popularity is attributed to its use as a natural, nonaddictive sleeping aid, but recent studies are finding other effects. European study findings include the following conclusions:

1. it is a potent antioxidant and penetrates more cells than beta carotene, vitamin E and C
2. a micro-surgery transplant of pineal glands from old to young mice, and vice versa, reversed some effects of aging in the elder mice, while producing "old age" effects in the young mice.
3. melatonin may actually protect the liver from damage due to medications
4. it can reduce / reverse cataracts in mice, another aging reversal activity
5. nightly dosing can boost the performance of the immune system damaged by stress, age, and drugs. This could be related to increased thymus activity
6. the usual dose is 3 mg-5 mg at bedtime for sleep, and up to 10 mg for anti-aging effects, which may be the dosage for optimal antioxidant activity
7. there are special receptors for melatonin on immune system cells, and animal experiments have shown that melatonin use can preserve and even restore their immune system.

From what has been shown in animal and human studies, melatonin could be a rational complimentary therapy. It is so far shown to be nontoxic and fairly reasonably priced.

Xenotransplantation of Baboon Bone Marrow Cells:

Despite great advances and a significant understanding of HIV pathogenesis, no curative treatment modality currently exists. Since baboon bone marrow cells (BBMC) are believed to be resistant to the human immunodeficiency virus, researchers have recently transplanted BBMC into two patients with AIDS, a process known as xenotransplantation. The hope is that the baboon marrow will produce cells that will be resistant to the HIV virus and thereby improve the immune system in the human host.

Ricordi and colleagues in 1994, performed a xenogeneic BBMC transplant in a 56 year-old male with advanced AIDS. This patient died of advanced AIDS after 67 days post transplant. Since engraftment did not occur with this transplant, no improvement in the patient was expected or seen and the patient died as expected from advanced AIDS.

The second protocol occurred in December 1995, under the direction of Dr. Suzanne Ildstad from the University of Pittsburgh. Preliminary reports from this transplant show no engraftment (the transplant did not take). There has been no further reporting of this case in the literature. We will update this as soon as more information is available.

Lymphoma

Lymphoma refers to a dozen cancers that involve B-lymphocytes, a type of WBC. The cells become abnormal, multiply rapidly, and form tumors. These can occur in lymph nodes, bone marrow, intestines, or spinal cord. Lymphoma of the brain or spinal cord is referred to as central nervous system (CNS) lymphoma. Hodgkin's Disease, another type of lymphoma, is rare in people with HIV. So AIDS-related lymphoma is sometimes called Non-Hodgkin's Lymphoma (NHL). In 1985, the Centers for Disease Control added NHL to the list of diseases that define AIDS in people with HIV infection.

The longer you live with a suppressed immune system, the more likely you are to develop NHL. It is serious and fatal, usually within a year. However, the new combinations of antiviral drugs seem to be causing a significant drop in the number of new cases of lymphoma.

The first signs of lymphoma include swollen lymph nodes, fever, night sweats, and weight loss of more than 10%. If the lymphoma is in the central nervous system (brain and spinal cord), the symptoms can include confusion, difficulty speaking, memory loss, seizures, and headache. These symptoms occur with several AIDS-related illnesses, so a diagnosis of lymphoma is usually based on microscopic examination (biopsy) of lymph nodes or other affected tissues.

A case of lymphoma is described in several ways:

• It is graded based on how fast the cancerous cells are growing.
• It is staged (there are stages I through IV) to indicate how much the cancer has spread. Stage I means limited involvement in one place; stage IV means major involvement at multiple sites.
• It is classified based on the cells found in the tumor. Small-cell lymphoma (Burkitt's lymphoma) progresses rapidly. Large-cell "immunoblastic" lymphomas are fast-growing, serious tumors. Large-cell "diffuse" lymphomas are somewhat less dangerous.

WHAT CAUSES LYMPHOMA?

The causes of lymphoma are not clear. Researchers are looking at several factors, including:

• infection with Epstein-Barr virus
• mutations in B-cells
• imbalances in the immune system

A recent study compared people with AIDS who developed lymphoma and those who did not. There were no significant differences in terms of behaviors or drug use. Because so little is known about the causes of lymphoma, there is no known way to prevent the disease.

Most cancers are treated by a combination of drugs (chemotherapy) given in cycles. There are two standard treatments for lymphoma: "CHOP" and "mBACOD." These are initials for the chemotherapy drugs.

For example, CHOP includes:

• Cyclophosphamide,
• Hydroxydaunomycin,
• Oncovin,
• Prednisone

Chemotherapy can clear up lymphoma in almost 50% of patients. But almost 25% of patients whose lymphoma cleared up will get it again within about seven months. Chemotherapy is very toxic, and suppresses the immune system. Common side effects include nausea, vomiting, fatigue, diarrhea, swollen and sensitive gums, mouth sores, hair loss, and peripheral neuropathy (numbness, hot or tingling sensations in feet and/or hands).

Chemotherapy can also damage bone marrow and lead to low counts of red blood cells (anemia) and of white blood cells (neutropenia). Neutropenia can increase the risk of bacterial infections.

Additional drugs are sometimes prescribed to fight these side effects:

• Ondansetron (Zofran) can control nausea and vomiting
• Erythropoietin (EPO, Epogen or Procrit) can stimulate the production of red blood cells
• Granulocyte-colony-stimulating factor (G-CSF, Neupogen) can increase production of neutrophils, an infection-fighting type of WBC.

With central nervous system (CNS) lymphoma, radiation therapy is often used instead of, or in addition to chemotherapy. People who develop lymphoma tend to have very advanced AIDS. They may be fighting several opportunistic infections at the same time.

WHAT ELSE IS BEING STUDIED FOR LYMPHOMA?

New chemotherapy combinations are being tested, including "CDE" and "MGBG." Some researchers are following the suspected link between Epstein-Barr virus (EBV) and lymphoma, and are working on ways to attack EBV.

Summary

• Lymphoma, a cancer involving B-cells, has become more common in people with AIDS. It is a serious and fatal disease. However, the new combinations of antiviral drugs seem to be causing a drop in the number of new cases of lymphoma.
• Lymphoma is treated with chemotherapy drugs. If the disease is in the central nervous system, radiation therapy is also used. Even if lymphoma is cleared up, it tends to return in many people.
• Treatment of lymphoma is difficult because people who get it tend to have very weak immune systems and often have other opportunistic infections at the same time.

MAC (mycobacterium avium complex) also known as MAI, mycobacterium avium intracellulare

MAC and MAI, Mycobacterium avium intracellulare, occurs frequently in persons with HIV disease. MAI is caused by a complex of very common bacteria which are related to tuberculosis. They are found in water, soil, dust, and food. Almost everyone has these bacteria in their body and normally do not cause any problems. However, MAC commonly affects almost 50% of all HIV infected patients with weakened immune systems, especially if their T-cell count is below 50. MAC almost never causes disease in people with more than 100 T-cells.

Typically, MAI does not involve any one site. Instead, MAI can be found in many organs throughout the body. It is found in the lungs, liver, spleen, lymph nodes, bone marrow, blood, and the intestines.

The most common symptoms of MAI include:

• fatigue (extreme tiredness)
• fever and night sweats
• diarrhea
• abdominal pain
• weight loss

Many of these symptoms could result from infections occurring at the same time with other organisms and some patients with MAI may have few symptoms. MAI is usually diagnosed through cultures taken from blood, stool, urine, or bone marrow.

The fevers and night sweats associated with MIA are usually severe and persistent. The patient usually "spikes a temp" of 103 to 105 degrees F. The patient's temperature will be normal, and then suddenly be 103 degrees. There may or may not be chills associated with the high temperatures. The most effective treatments for these fevers are usually Ibuprofen and tepid sponges. Aspirin and/or acetaminophen may be used, but are usually not as effective as ibuprofen. Why this works in unknown, but this combination seems to work for MAI fevers.

There are no proven medical curative therapies or preventive treatments for MAI infections. However, treatment with a four or five-drug regimen has been shown to improve some of the symptoms.

Some of the drugs used singly or in combination are:

• Clofazimine (Lamprene); pain or tingling in hands and feet, nausea, vomiting, can turn skin orange; taken as capsules
• Rifampin (Mycobutin); rashes, nausea, anemia
• Ethambutol (Myambutol); nausea, vomiting, vision problems
• Amikacin (Amkin); kidney and ear problems; taken as an injection
• Clarithromycin (Biaxin); nausea, headaches, vomiting, diarrhea, taken orally or intravenously (max dose 500mg BID)
• Azithromycin (Zithromax); nausea, headaches, vomiting, diarrhea; taken orally or intravenously

The nursing care of patients with MAI includes symptomatic treatment. For example, since it is common for MAI infected patients to spike very high fevers, the patient's temperature should be monitored frequently. The temperature should be taken every 3-4 hours or more frequently. If the drugs do not reduce the fever, the nurse must do everything possible to get the temperature down. Use tepid sponge baths, cool compresses, force fluids, etc. It is not unusual for these patients to have a fever that goes up and down for long periods of time. The nurse should also be vigilant for the long-term effects of high fevers, such as dehydration, hypokalemia, anemia, and others.

Important data on clarithromycin dosing for MAC therapy were presented recently by David Cohen, et al. In a randomized trial using a factorial design, patients with disseminated MAC were randomized to one of two doses of clarithromycin (500 mg twice daily or 1000 mg twice daily) with ethambutol plus either rifabutin or clorfazimine.

An interim review in February 1996 identified increased mortality in the 1000 mg BID clarithromycin recipients which could not be attributed to imbalance in severity of disease among the treatment groups; all patients were switched to 500 mg twice daily. The NIH then issued an alert to clinicians warning against the use of high-dose clarithromycin for therapy. This is particularly important since the use of macrolides as MAC prophylaxis is increasing, and some clinicians might be tempted to treat prophylactic breakthroughs with high doses. This study and data from two previous studies indicate 500 mg BID is the safest therapeutic dose for MAC.

Another alert to clinicians warning against the use of clofazimine in the treatment of MAC. This recommendation was made in light of the Abbott study previously presented by Chaisson et al. comparing a three-drug combination of clarithromycin, ethambutol, and clofazimine. Excess mortality that persisted after control for imbalances in baseline levels of MAC bacteremia was seen in the clofazimine-containing arm. Until new data is available, the combination of clarithromycin (500 mg BID) and ethambutol (with or without rifabutin) should be used as initial therapy for MAC.

Even though there is still no proven prevention, many physicians prescribe azithromycin, clarithromycin, and rifabutin separately or in combination for the prevention of MAC. These drugs are usually prescribed for persons whose T-cell count is less than 75. Once the T-cells have risen above 100 for a period of three to six months, the prevention therapy is usually discontinued.

Molluscum

Molluscum contagiosum is a skin infection. It is caused by a virus. Molluscum causes small bumps (lesions) to appear on the skin. Most of them are less than half an inch in diameter. They have a hard white core. Some lesions have a small dent or dimple in the center. The lesions are the same color as normal skin, but they look waxy. They usually don't hurt or itch.

The molluscum virus is very common, and almost everyone has it in his or her body. A healthy immune system will control molluscum so that if lesions appear, they do not last a long time. People with weakened immune systems can develop molluscum lesions that spread, last a long time, and are very difficult to treat.

Molluscum is not a serious health problem. However, many people find the molluscum lesions to be very unattractive. This can cause serious emotional or psychological problems.

Molluscum can be spread by direct skin contact. It often spreads through sexual activity. Molluscum can infect any part of the skin, but it is especially common on the face or in the groin and pubic areas. Men with HIV often develop molluscum on their face. Shaving with a razor blade can spread it.

Molluscum lesions are treated the same way as warts. Unfortunately, the lesions often return and need to be treated again. They can be frozen with liquid nitrogen. This is the most common method of treatment. They can be burned with an electric needle (electrocautery) or a laser. This treatment can be painful and sometimes leaves scars. They can be treated with chemicals used on warts such as trichloroacetic acid (TCA), podophyllin or podofilox. These chemicals cannot be used on sensitive skin or near the eyes. They can be cut or "scooped" out surgically. This treatment can be painful and can leave scars.

They can be treated with drugs used to treat acne such as tretinoin (Retin-A) or isotretinoin (Accutane). This is a newer approach. These drugs reduce the amount of oil in the skin. The top layer of skin dries out and peels off. These drugs can cause redness and soreness.

Retin-A is a cream that is put onto the lesions. Accutane is taken in pill form. Another new approach is to use the antiviral medications cidofovir or imiquimod. These drugs are applied directly onto the lesions.

Because the virus that causes molluscum is so common, it isn't possible to avoid being exposed to it. However, if you have molluscum you should make sure that the lesions don't touch anyone else. You should also be careful not to spread molluscum to different parts of your body. Be careful not to scratch the lesions or to cut them while shaving. Some doctors think that using an electric shaver helps prevent the spread of molluscum.

The acne drugs tretinoin (Retin-A) and isotretinoin (Accutane) tend to dry out the skin. Dry skin is also a side effect of the protease inhibitor indinavir (Crixivan) and some other antiviral medications. If you take use Retin-A or Accutane to treat molluscum along with antiviral drugs that can cause dry skin, your skin problems could get worse.

PCP (pneumocystis carinii pneumonia)

This particular type of pneumonia was first described in the middle 1950's. It was first described in children with leukemia. The pneumonia was also described in a variety of other patients who had one thing in common; a compromised immune system. This pneumonia is caused by a parasite, called the pneumocystis carinii. Prior to AIDS, this type of parasitic pneumonia was only seen in other immuno-compromised patients and some infants.

Patients with leukemia and with other diseases who were given massive doses of steroids, began to get the pneumonia. Patients with lymphoma developed the disease, because they too, had poor immune systems.

Symptoms:

The very early symptoms or indicators of pneumocystis pneumonia might include: chronic fatigue, weight loss, low-grade fever, malaise, and possibly night sweats. These symptoms may be caused by other opportunistic infections as well as caused by the pneumocystis. However, one or more of these symptoms are usually present before the more severe pulmonary symptoms develop.

There has also been noted a butterfly rash, similar to the one seen with lupus. It is seen on the cheeks and over the nose, again, usually before the pulmonary symptoms occur.

Another possible early symptom of pneumocystis is the "cotton wool spot." This is a disorder of the eye in which there are small infarctions of the nerve layer of the retina. It causes the examiner to visualize small white patches on the retina. These spots usually do not interfere with vision, but might be helpful in diagnosing the pneumonia, since about 25% of pneumocystis patients have these spots.

The acute pulmonary symptoms begin with a dry cough and shortness of breath. These symptoms can advance to very extreme shortness of breath and to respiratory insufficiency, requiring intubation of the patient and mechanical ventilation. Patients who become so severe as to require intubation and ventilation, have only about a 10%-20% chance of survival.

Diagnosis of PCP

Today, there is controversy over how to diagnose this type of pneumonia. Open lung biopsy is the definitive way of diagnosing this pneumonia. Pneumocystis usually produces only a non-productive cough. Therefore, there is usually no sputum to test for the organism. Most experts agree that trans-bronchial biopsy through a bronchoscope is a better choice. Transbronchial lavage has produced large numbers of the organism, and lavage is a much less invasive procedure than even the transbronchial biopsy technique.

The large AIDS center at San Francisco General Hospital now uses an induced sputum specimen with about 80% rate of effectiveness at diagnosing the pneumocystis organism. The physician in charge will weigh the risk of the more invasive procedures and the benefits of early diagnosis of the pneumocystis. It certainly might be worth the risk of 10% pneumothorax complication, in order to diagnose this terrible disease early, so that it could be treated.

There are additional clinical symptoms used to diagnose pneumocystis pneumonia. One additional symptom is a white lesions on the tongue, called Candida Albicans, as mentioned earlier in this text. This along with a normal chest X-ray and some of the early symptoms as mentioned above, are indicative of early pneumocystis disease. Once the disease has progressed so much that there are changes in the chest X-ray, it means that the disease is very severe and life-threatening.

Another early symptom might be a decreased diffusion capacity for carbon monoxide. Another diagnostic tool might be the gallium scan. Those with pneumocystis will have increased WBC uptake of the isotope in the lungs, this is usually due to an increase of inflammation in the lungs and an accumulation of WBC's in the area.

Treatment of PCP:

The treatment of PCP includes (1) prevention of the disease, and (2) treatment of active PCP. PCP is the most common and the most preventable life-threatening opportunistic infection reported in AIDS patients. Mortality rates are 90-100 percent without treatment. Even with treatment, 20-40 percent of patients will die.

Preventing PCP:

Preventing PCP is often linked to the person's CD4 count. The CD4 cell (T4) counts tell how many CD4 cells are in one cubic millimeter of blood. The CD4 cells--important elements of the immune system--relate to the effectiveness of the immune system. The normal CD4 cell count is about 1,000 to 1,500 per cubic ml. Most persons are started on prophylactic therapy when the CD4 cell count drops to about 250. Prophylaxis may also be started even if the CD4 count has not dropped to 250 yet. Prophylaxis may be started if the person has contracted other infections such as thrush, or if he has had PCP in the past. In these cases, prophylaxis is usually indicated even if the CD4 count has not yet fallen to 250.

The most common prophylaxis is drug therapy. The most common prophylactic drug therapy is trimethoprin-sulfamethoxazole combination; also known as TMP-SMX (Septra or Bactrim) taken orally. TMP-SMX costs about $40 a month and is taken orally. However, many users experience adverse reactions, especially fever, rash, nausea, and intense itching.

Dapsone is also effective against PCP. It is often prescribed for people who react badly to TMP-SMX. It costs $15 a month and is taken orally. Side effects are similar to TMP-SMX for some users.

For people who cannot tolerate either of the above drugs, the National Institutes of Health recommends aerosolized pentamidine, (AP). AP is inhaled and treats only the lungs. AP is costly, up to $300 per month. It is also inconvenient, since the drug must be administered at a clinic or doctor's office, or at home using expensive nebulizer equipment.

To this date, there have been conflicting studies as to which treatment is best for preventing PCP. Studies have shown that oral TMP-SMX is more effective than the aerosolized pentamidine. Other studies recommend aerosolized pentamidine. The patient and physician will make a decision as to which therapy is best for that patient and his particular situation.

Treatment of active PCP

The most widely used treatment for a person with an active case of PCP is similar to the prophylactic treatment. In fact, the same drugs that are used for prophylaxis are also used for treatment of active PCP. Oral antibiotics, TMP-SMX and intravenous pentamidine continues to be the standard therapy for PCP.

Until these drugs were developed, pentamidine was almost exclusively used to treat the pneumonia. Pentamidine is a very toxic drug that had been controlled by the government. In fact, it was because of a certain drug investigation that AIDS was discovered in 1981. The Center for Disease Control, CDC, in Atlanta, had 10 cases of pneumocystis reported in 1981. The physicians treating the men requested that this drug pentamidine be used for treating these patients. The ensuing investigation lead to the first reported cases of AIDS and the subsequent discovery of the importance of this disease.

The pneumocystis patients will be given a course of the Septra or Bactrim, usually 14 to 21 days in length. Some patients develop rashes and fever and other side effects from the drug. However, when the drug is withdrawn, the symptoms will usually subside.

Dapsone is also becoming widely used as an alternative for those who do not tolerate the previous therapies. Another treatment is inhaled pentamidine and the combinations of CLINDAMYCIN plus primaquine, and trimethoprim plus dapsone.

As you can see, there are many different combination therapies that may be used. Each patient is evaluated to their response to each therapy. Many factors must be considered when the drug therapies are prescribed. The physician will consider the patient's previous experience with these drugs, their reactions and side effects of the drugs, and many other factors are considered.

Another drug was approved in 1992, Atovaquone (Mepron) for the second-line treatment of PCP. The drug of choice is Septra (above) but for those who cannot tolerate Septra, Mepron would be used. Also, there have been recent reports about a new Septra-resistant form of PCP for which Mepron might be used. (Rodriguez)

Nursing Care:

The nursing care of PCP involves accurate administration of the antibiotics and other medications. The patient with PCP will also require detailed symptomatic respiratory nursing care. Patients with severe PCP may need artificial ventilation. Patients with milder cases may need only rest and supportive care until they are able to be discharged from the hospital.

The patient with pneumocystis, may be on very strict isolation precautions. The staff may be required to wear masks, gloves and/or gowns at all times in order to protect the patient from additional infections and to protect the nursing staff. Always check with the physician's orders when there is a particularly virulent organism present, since other precautions may be necessary. The patients will usually require symptomatic nursing care while they are being treated for the particular organism.

It is also important to consider the emotional well-being of the patient. Be consistent when caring for the patient in the hospital setting. Be sure that the isolation technique used is carried out consistently by all the staff. It is not unusual for some nurses to use gowns, mask, gloves, etc.; and other nurses to use only gloves when caring for the patient.

Some nurses have been known to use full isolation precautions when only gloves have been ordered. This makes the patient feel very "isolated." This demonstrates that some nurses might be afraid of "catching something."

It is generally felt that patients should be on respiratory isolation only if they are confirmed as having active PCP or other contagious lung infection. Otherwise, respiratory isolation is not needed. Of course, if any patient has a frequent and/or productive cough, they will probably be placed on respiratory isolation as a precaution. Remember to be consistent and explain to the patient the reason for the isolation precautions.

Shingles--Multidermal Herpes Zoster

Herpes Zoster is an acute infection caused by the varicela zoster virus, VZV, affecting mainly adults, and characterized by the development of painful vesicular skin eruptions that follow the underlying route of cranial or spinal nerves inflamed by the virus.

The distribution of the pain and vesicular eruptions is usually unilateral, although both sides of the body may be involved. Any sensory nerve may be affected, but the virus in most cases tends to invade the posterior root ganglia associated with thoracic and trigeminal nerves. The pain, which may be constant or intermittent, superficial or deep, usually precedes other effects and may mimic other disorders, as appendicitis or pleurisy. Early symptoms may include GI disturbances, malaise, fever, or headache. The vesicles usually evolve from small red macules along the path of a nerve, and the skin of the area is hypersensitive.

All of the lesions may appear within a period of hours, but they most often develop gradually over a period of several days. The macules will then vesiculate. After about three days, the clear vesicles then become turbid from cellular debris that collects inside the vesicles. After the end of the first week, the vesicles develop crusts. In most cases, the patients' symptoms will also end within this one to two week period. However, symptoms may persist for three to five weeks.

The medical treatment and nursing care for herpes zoster is symptomatic, just like many other types of herpes. The treatment is aimed at reducing the tremendous itch and pain that is usually present with this disorder. Calamine lotion and other similar types of lotions and/or skin soothers are used. Analgesics are used to relieve the pain. Analgesics should be used judiciously.

However, pain control is an important part of the treatment plan, used to help control itching and possible spread of the condition. Topical corticosteroids are used for those with severe disease and for the elderly patients who are at greater risk for the life-threatening complications of herpes that may develop. Surgery would only be used to excise an affected nerve, where severe pain could not be relieved by conventional methods.

Bedrest is usually recommended in the early stages of the zoster infection. In the early stages, the person will usually have a tremendously high fever and other systemic conditions that require bedrest. Also in the early stages, the nurse will use bed cradles and other measures to keep linens off the patient's lesions. The lesions could easily be broken and irritated by linens chafing the skin. The nurse will also use non-adherent dressings, when dressing are necessary. The nurse will also take care in positioning the patient, and with other nursing measures in order to prevent further irritation to the lesions.

The more severe complications of herpes zoster include geniculate zoster, with involvement of the ear, face, and soft palate. Ophthalmic herpes zoster is a severe complication which can lead to corneal damage.

Nursing care of these advanced disease patients is also symptomatic. However, in these cases, there may be specific drug therapies for the nurse to administer.

Most patients recover from attacks of herpes zoster and/or its complications with no permanent effects, except for possibly mild scarring at the sites of some lesions. Also remember that VZV (and most forms of herpes virus) will remain in the body forever. Herpes may then become active sometime in the future.

Studies have shown that VZV remains latent in the body, and a person lacking varicella immunity can acquire chickenpox from a herpes zoster patient (also called shingles). Another form of herpes, called herpes zoster oticus, a herpes infection of the eighth cranial nerve ganglia and geniculate ganglion, may lead to hearing loss.

We know that these viruses may reactivate at any time, especially in HIV infected patients, for the obvious reasons. Any and all treatments for herpes should include the "standard" treatments of all HIV infected patients: good nutrition, no street drugs, lots of rest/sleep, lots of fluids, a once-daily general vitamin supplement, social services and social supports, etc.

There is no known cure and no way to prevent outbreaks of shingles. However, today the disease has been treated with acyclovir, taken five times daily, or given intravenously in severe cases. Two newer drugs, famciclovir and galaciclovir, seem to be more effective against the pain of shingles and need to be taken only three times each day.

In summary; there is no cure for the herpes virus infection in humans. However, there are many different nursing measures that can be carried out, in order to help alleviate the pain and suffering of the disorder. These nursing measures are designed to relieve pain, decrease the severity of the attack, and to help the virus goes into the dormant stage sooner. Some studies have even shown that the virus may be held in the dormant stage for an even longer time due to the newer treatments. Each nurse should remember that the Herpesvirus is yet ANOTHER major disease entity for the HIV infected person to deal with. Remember that these patients will NEED:

• the very latest information;
• your highest level of nursing skill;
• YOU!

The social and psychosocial support systems have proven to be very helpful in maintaining an adequate immune system and in fighting off infections. The nurse should go back to the basics of nursing care when caring for HIV infected/HERPES infected patient. These patients are going to need individual care and attention. It is difficult to give individualized care these days with low budgets and high patient loads. However, the little extra time you spend with your patient is very valuable to your patient!

TB (Tuberculosis)

Most nurses are very aware of TB as a disease process. We mention it here in relation to AIDS, because TB is quite prevalent in HIV infected persons and in persons with AIDS. In persons with a poor immune system, TB can reactivate (if the person was previously infected with the organism) or the person may more easily become infected with the organism.

Tuberculosis (TB) is an infection caused by a special type of bacteria. Tuberculosis usually affects the lungs, but sometimes can affect other organs. TB is a very serious disease worldwide. Almost one-third of the world's population is infected with TB, although a healthy immune system can prevent active disease.

Active TB causes some or all of the following symptoms: coughing for more than three weeks, weight loss, constant fatigue, night sweats, and fevers. These are very much like the symptoms caused by Pneumocystis carinii pneumonia (PCP), but TB can occur at much higher CD4+ levels.

Some of the antibiotics used to treat TB can damage the liver or kidneys. So can some of the drugs used to fight HIV. It can be difficult to take drugs for both TB and HIV at the same time. Also, there is a bad reaction between protease inhibitors and some drugs used to fight TB. Rifampin or rifabutin can drop the levels of protease inhibitors in the blood so that they are less effective. The protease inhibitors can raise the levels of these drugs in the blood so high that the patient can have serious side effects. There are special guidelines for the use of all these drugs if your patient is being treated for HIV and TB at the same time.

Thrush (candidiasis)

Candidiasis is the most common non-life-threatening fungal infection seen with HIV infection. It is caused by a yeast-like fungus, Candida Albicans, affecting the mouth, esophagus, GI tract, lungs, vagina, skin.

Candida is an organism that is normally found in the GI tract in very small quantities. It is one of the many organisms present in the GI tract that normally does not cause a person any problems. However, with a weakened immune system, the candida organism spread to other parts of the body.

The most common form of candidiasis seen in persons with HIV infection is candidiasis of the mouth, Thrush. Thrush is seen in almost all persons with HIV infection and may lead to candidiasis of the esophagus, or lungs. Also, women with HIV infection may develop vaginal candidiasis. Esophageal candidiasis and brohchocandidiasis are more serious forms of the infection which can lead to a diagnosis of advanced HIV disease or AIDS.

Candidiasis infections, although very uncomfortable, are rarely fatal. These infections often interfere with eating and digestion. They may lead to nutritional problems due to the inability to swallow any food or liquids.

Thrush appears as white or grayish patches in the mouth or on the tongue. Esophageal candidiasis causes pain and difficulty swallowing. Vaginal candidiasis causes a discharge and discomfort in the vagina.

Oral thrush is treated with clotrimazole lozenges (Mycelex troches) or a "swish and swallow" preparation known as nystatin. There are several other similar drugs, both oral and IV, used for the same purpose. Esophageal candidiasis is often treated with ketoconazole given by mouth or Fluconazole given by mouth or intravenously.

(PR Newswire 1997) The FDA has cleared a new medication, SPORANOX(r) (itraconazole) Oral solution, for the treatment of thrush. It may also be used to treat candidiasis (below). The oral solution is generally well tolerated. Capsules are also available for treating other fungal infections in other areas of the body.

Candida Albicans; Leukoplakia usually caused by candida, causes white lesions on the tongue. When these lesions are scraped for culturing or for biopsy, they often then begin to grow slender, finger-like projections. This is known as "hairy leukoplakia." The lesions are very difficult to treat.

Toxoplasmosis

Toxoplasmosis is a common infection seen in immunocompromised patients, especially those with HIV infection. Toxoplasmosis is an infection by the Toxoplasma, a genus of protozoa with only one known species, Toxoplasma gondii, an intracellular parasite of cats and other hosts that causes toxoplasmosis in humans.

Toxoplasmosis most often manifests itself by liver and brain involvement with cerebral calcification, convulsions, blindness, microcephaly or hydrocephaly, and mental retardation. The acquired form is characterized by rash, lymphadenopathy, fever, malaise, central nervous system disorders, myocarditis, and pneumonitis. Toxoplasmosis encephalitis is one of the leading causes of morbidity in persons with AIDS. Lifelong treatment is needed to prevent relapses. Azithromycin (AZM) is the drug most often used to treat this condition. It is administered initially in high doses, then a maintenance dose is administered for long time periods.

Cats acquire the organism by eating infected birds and mice. Cysts of the organism are transmitted from cat feces to humans or by human ingestion of inadequately cooked meat containing the cysts. The treatment of this disorder is by the use of the sulfonamide antibiotics along with pyrimethamine. Prevention is accomplished by avoiding cats, litter boxes, and cat feces; good handwashing; and cook meats to at least 140 degrees F.

Wasting Syndrome

AIDS wasting syndrome is the second most common AIDS-related condition, after PCP (pneumocystis carinii pneumonia). The Centers for Disease Control define AIDS wasting as involuntary loss of more than 10% of body weight, along with more than 30 days of either diarrhea, or weakness and fever. Wasting syndrome is linked to disease progression and death. A recent study showed that weight loss of as little as 5% of body weight can have the same negative effects.

Part of the weight lost during wasting is fat, but more important is the loss of "lean body mass," or "body cell mass," which is mostly muscle. Lean body mass is often measured by bioelectrical impedance analysis (BIA), a simple office procedure.

Several factors contribute to AIDS wasting syndrome:

LOW FOOD INTAKE: These include low food intake and low appetite which are common with infections associated with HIV and AIDS. Also, some AIDS drugs have to be taken with an empty stomach, or with a meal, which can make it difficult for some people with AIDS to eat when they're hungry. Drug side effects such as nausea, changes in the sense of taste, or tingling around the mouth, also tend to decrease appetite. Opportunistic infections in the mouth or throat can make it painful to eat, and infections in the gut can cause a feeling of pressure or fullness after eating just a little food. Finally, lack of money or energy may make it difficult to shop for food or prepare meals.

POOR NUTRIENT ABSORPTION: In a healthy person, the small intestines absorb the nutrients from food. In people with HIV disease, several infections (including parasites) interfere with this process. Some research indicates that HIV may directly affect the intestinal lining and reduce nutrient absorption. Also, diarrhea, a frequent side effect of AIDS drugs, causes loss of calories and nutrients.

ALTERED METABOLISM: Food processing and protein building are affected by HIV disease. Even before any symptoms show up, energy output is increased. This might be caused by the increased activity of the immune system. So people with HIV need more calories just to maintain their body weight.

The levels of various hormones, which affect metabolism, seem to change in people with HIV. Finally, cytokines play a role in wasting. Cytokines are proteins that produce inflammation in order to help the body get rid of an infection. People with HIV have very high levels of cytokines, which make the body produce more fats and sugars, but less protein.

Unfortunately, these factors combine in many people to create a "downward spiral." For example, infections may increase the body's energy requirements, and at the same time interfere with nutrient absorption and cause fatigue. This can reduce appetite and make people less able to shop for or cook their meals. They eat less, which accelerates the process. A "standard of care" for AIDS Wasting does not exist yet.

Treatments for wasting syndrome address each of the causes mentioned above:

Low food intake: Reducing nausea and vomiting can increase food intake. Also, appetite stimulants including Megace and Marinol have been used. Megace, unfortunately, is associated with increases in body fat. Marinol, the synthetic form of an active ingredient of marijuana, seems to increase appetite. AIDS activists have long urged the legalization of marijuana, which is reported to be effective both in reducing nausea and in stimulating appetite. In 1997 and 1998, voters in several states legalized the medical use of marijuana. This might help end the government's long-standing opposition to the study of marijuana and lead to the approval of clinical trials.

Poor nutrient absorption: Absorption can be improved by treating diarrhea and the opportunistic infections that cause problems in the gut. Although there has been a lot of progress in this area, two significant parasitic infections - cryptosporidiosis and microsporidiosis - are still extremely difficult to treat. Another approach is nutritional supplements like Ensure and Advera which have been specifically designed to provide easy-to-absorb nutrients, but have not been carefully studied yet.

Altered metabolism: Hormone treatments are being examined. Human growth hormone may be effective in increasing weight and lean body mass, while decreasing fat mass. The product, however, is extremely expensive and could cost more than $40,000 per year to use. Testosterone and anabolic (muscle building) steroids are also under study for their impact on wasting, alone and in combination with exercise. Finally, thalidomide seems to have some value in reversing weight loss due to its ability to reduce levels of cytokines. In previous sections we discussed use of the anabolic steroids to help the patient regain weight. Oxandrin is one of those steroids used for weight gain.

Oxandrin is indicated as adjunctive therapy to promote weight gain after weight loss following extensive surgery, chronic infections, or severe trauma, and in some patients who without definite pathophysiologic reasons fail to gain or to maintain normal weight, to offset the protein catabolism associated with prolonged administration of corticosteroids, and for the relief of the bone pain frequently accompanying osteoporosis.

Remember that all anabolic steroids will have many and potentially serious side effects. These include cardiovascular effects, GI effects, serious liver and kidney effects. Be sure to review all the potential hazards of using anabolic steroids. Be sure the physician is aware of all other medications being used by the patient prior to prescribing the anabolic steroids.

TABLE 1. Percentage* of males with at least one acquired immunodeficiency syndrome-defining OI for whom a given OI occurred first, by disease and human immunodeficiency virus (HIV) exposure mode+ -- Adult/Adolescent Spectrum of HIV Disease project, 1992-1997.

Data for each opportunistic illness are standardized to the sex- or risk-specific proportion of national acquired immunodeficiency syndrome surveillance cases by age, race, year of diagnosis, and country of birth. Data from all cities are weighted equally.

+ Data in this analysis are for the three largest single HIV exposure modes for males observed in the Adult/Adolescent Spectrum of HIV Disease project. Exposure mode-specific data are not presented for 2,457 males with other HIV exposure modes.

& A CDC-sponsored surveillance project that collects data at selected sites in 11 U.S. cities.

@ Differences by HIV exposure mode were significant using the stratified Cochran-Mantel-Haenszel (CMH) statistic (p<0.05).

** In a comparison of data in Tables 1 and 2, the difference by sex for this item was significant using the stratified CMH statistic; the percentage was higher for males (p<0.05).

++ In a comparison of data in Tables 1 and 2, the difference by sex for this item was significant using the stratified CMH statistic; the percentage was higher for females (p<0.05).

TABLE 2. Percentage* of females with at least one acquired immunodeficiency syndrome-defining opportunistic illness (OI) for whom a given OI occurred first, by disease and human immunodeficiency virus (HIV) exposure mode+ --

Adult/Adolescent Spectrum of HIV Disease project,& 1992-1997

* Data for each opportunistic illness is standardized to the sex- or risk-specific proportion of national acquired immunodeficiency syndrome surveillance cases by age, race, year of diagnosis, and country of birth. Data from all cities are weighted equally.

+ Data in this analysis are for the two largest HIV exposure modes for females observed in the Adult/Adolescent Spectrum of HIV Disease project. Exposure mode-specific data are not presented for 627 females with other HIV exposure modes.

& A CDC-sponsored surveillance project that collects data at selected sites in 11 U.S. cities.

@ In a comparison of data in Tables 1 and 2, the difference by sex for this item was significant using the stratified Cochran-Mantel-Haenszel (CMH) statistic; the percentage was higher for females (p<0.05).

** In a comparison of data in Tables 1 and 2, the difference by sex for this item was significant using the stratified CMH statistic; the percentage was higher for males (p<0.05).

++ Differences by HIV exposure mode were significant using the stratified CMH statistic p<0.05).

TABLE 3. Incidence* of acquired immunodeficiency syndrome-defining opportunistic illnesses (OIs) among males, by disease and human immunodeficiency virus (HIV)exposure mode+ -- Adult/Adolescent Spectrum of HIV Disease project,& 1992-1997,

* Per 1,000 person-years standardized to the sex- or risk-specific proportion of national acquired immunodeficiency syndrome surveillance cases by age, race, year of diagnosis, country of birth, and CD4+ T-lymphocyte distribution. Data from all cities are weighted equally.

+ Data in this analysis are for the three largest single HIV exposure modes for males observed in the Adult/Adolescent Spectrum of HIV Disease project. Exposure mode-specific data are not presented for 3,928 males with other HIV exposure modes.

& A CDC-sponsored surveillance project that collects data at selected sites in 11 U.S. cities.

@ Differences by HIV exposure mode were significant using the stratified Cochran-Mantel-Haenszel (CMH) statistic (p<0.05).

** In a comparison of data in Tables 4 and 5, the difference by sex for this item was significant using the stratified CMH statistic; the incidence rate was higher for males (p<0.05).

++ In a comparison of data in Tables 4 and 5, the difference by sex for this item was significant using the stratified CMH statistic; the incidence rate was higher for females (p<0.05).

TABLE 4. Incidence* of acquired immunodeficiency syndrome-defining opportunistic illnesses among females, by disease and human immunodeficiency (HIV) exposure mode+ -- Adult/Adolescent Spectrum of HIV Disease project,& 1992-1997

* Per 1,000 person-years standardized to the sex- or risk-specific proportion of national acquired immunodeficiency syndrome surveillance cases by age, race, year of diagnosis, country of birth, and CD4+ T-lymphocyte distribution. Data from all cities are weighted equally.

+ Data in this analysis are for the two largest HIV exposure modes for females observed in the Adult/Adolescent Spectrum of HIV Disease project. Exposure mode-specific data are not presented for 1,554 females with other HIV exposure modes.

& A CDC-sponsored surveillance project that collects data at selected sites in 11 U.S. cities.

@ Differences by HIV exposure mode were significant using the stratified Cochran-Mantel-Haenszel (CMH) statistic (p<0.05).

** In a comparison of data in Tables 4 and 5, the difference by sex for this item was significant using the stratified CMH statistic; the incidence rate was higher for females (p<0.05).

++ In a comparison of data in Tables 4 and 5, the difference by sex for this item was significant using the stratified CMH statistic; the incidence rate was higher for males (p<0.05).