Subject: Treatment Issues Vol. 5 No. 2 Date: Feb 25 1991 (1026 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& TREATMENT ISSUES -- The GMHC Newsletter of Experimental AIDS Therapies &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& Treatment Issues 52 Volume 5 Number 2 -- Feb 25, 1991 Contents: [items are separated by "*****" for this display] ddC, ddI, AZT Update An Ounce of Prevention: Fungal Infections Pet Guidelines Veterans Administration AZT Study In Brief ***** Antiviral Options: AZT, ddI or ddC Gabriel Torres, M. D. Since ddI and ddC (two drugs similar to AZT) have become available on expanded access programs, it is increasingly difficult for patients and physicians to choose which drug to take. This article summarizes the most recent data on ddC, since updates on ddI and AZT have appeared recently in Treatment Issues, and discusses some of the issues patients and health care professionals need to consider when faced with choosing among these three drugs. ddC: Current Knowledge Dideoxycytidine (ddC) has proven to be a potent inhibitor of HIV both in the test tube and in humans. In Phase I/II studies, conducted by the AIDS Clinical Trials Group (ACTG) to determine dosage and efficacy, ddC was administered to over 300 patients with AIDS or ARC. The trials showed that ddC effectively reduced viral reproduction as measured by p24 antigen levels (l). ddC also proved temporarily to increase T4 cell counts during the first eight to twelve weeks of therapy with gradual declines back to original T4 levels (2). The most frequent toxicity of ddC has been peripheral neuropathy, or nerve damage, primarily in the feet, which seems to occur more frequently at higher doses of drug (greater than 0.03 mg/kg). Symptoms of neuropathy include a sensation of pins and needles, numbness, and pain in the lower legs and feet. Symptoms seem to worsen temporarily after the drug is stopped (a phenomenon referred to as "coasting effect"). In severe cases, neuropathy has taken as long as six months to resolve (3). At lower doses of ddC (greater than 0.01 mg/kg) the neuropathy symptoms are less frequent and more readily reversible. Early identification of the symptoms and discontinuation of drug is the best way to prevent the neuropathy from progressing. Other less common side effects of ddC include skin rashes, mouth ulcers, elevated liver enzymes, and low platelet counts. Rare side effects, which have occurred in isolated cases include hearing loss, kidney failure, and abdominal pain. ddC Availability Under an "expanded access" program initiated in late September 1990, ddC became available for persons with AIDS and advanced ARC, who are unable to stay on AZT. Patients allowed to enter the program cannot tolerate AZT, show signs of progressive disease while on AZT, or are taking drugs incompatible with AZT. To be classified as an "AZT-failure," a patient must have one of the following conditions after taking at least 500 mg/day of AZT for more than six months: three opportunistic infections (OIs) or cancers within six months of treatment; a decline in T4 cell counts by 50, compared to counts when AZT was initiated, or a T4 cell count of SO or less on two occasions one month apart; involuntary weight loss of 2-2.5 lbs. per week for at least four weeks; a measurable increase of virus as reflected in p24 antigen levels; or neurological deterioration or disability requiring special care and hospitalization. To be classified as "AZT-intolerant," a person must have had one of the following reactions to AZT: anemia (decrease in hemoglobin of 2 gm/month); a depletion of white blood cells (total neutrophil count under 750); nausea or vomiting; severe headaches; psychosis; severe agitation or declining muscle strength (i.e., inability to climb stairs) from muscle damage (myopathy) caused by AZT. "AZT ineligible" patients include those who require drugs that are incompatible with AZT, for example ganciclovir therapy for cytomegalovirus (CMV). Also considered "AZT ineligible" are patients who have never taken AZT, but have low white blood cell counts or severe anemia. Additionally, patients who are ineligible for, or intolerant to ddI qualify for the ddC expanded access program. Although these patients are not required to demonstrate ddI intolerance, many who have had side effects from ddI may be candidates for ddC. These patients include those who have developed pancreatitis, hepatitis, elevated uric acid levels or severe diarrhea from ddI. Hoffman-La Roche reports that more than 1,100 patients have been enrolled in expanded access programs for ddC. Of that number, only four patients have developed pancreatitis or elevated pancreatic enzymes, referred to as the amylase level. Of those four patients, two had a previous history of ddI-related pancreatitis. If abdominal pain, nausea or vomiting develop for a patient on ddC therapy, the drug should be discontinued immediately and a medical evaluation for pancreatitis should be performed. If amylase levels are five times higher than normal, ddC should be discontinued even if the patient has no symptoms of pancreatitis. In two patients on ddC, according to Hoffman-La Roche, diabetes and elevated blood sugar levels were reported, possibly suggesting that ddC affects the pancreas. For patients with less advanced disease, and T4 cell counts under 300 (or under 200 in asymptomatic patients) ddC is only available through clinical trials. ddC or ddI Most of the patients receiving ddC or ddI under expanded access programs are patients with advanced disease who have had more than one year of AZT therapy and who have most likely developed AZT resistance. Most of these patients have low T4 cell counts. Expanded access programs for ddI are detailed in Treatment Issues, vol. 4, no. 7. The choice between ddC and ddI requires a careful assessment of the potential toxicities of each drug according to individual patient characteristics. Both drugs are tolerated well, yet require frequent monitoring (physical and neurologic examinations and laboratory assessments) in order to avoid adverse effects. The long-term effects of both drugs are still relatively unknown. Muscle wasting similar to the kind associated with long-term AZT use, has also been reported in several patients using ddI or ddC. Patients who are at risk for pancreatitis due to predisposed conditions are probably better off choosing ddC over ddI. Some of the predisposing conditions include: previous history of alcohol abuse; pancreatitis in the past; elevated triglycerides, uric acid levels, or intravenous pentamidine. All of the above conditions may increase the risk of pancreatitis. For those intolerant of or failing AZT and ineligible for expanded access, the Community Program for Clinical Research on AIDS (CPCRA), a federally-funded program conducting clinical trials at 18 community sites throughout the U. S., is sponsoring a trial comparing ddI versus ddC in patients with T4 cell counts less than 300. In New York, the trial is being conducted by the Harlem AIDS Treatment Group (contact Michelle Harding at 212-694- 4344). In Newark, New Jersey, the Community Research Initiative will conduct the trial (contact William Orr at 201-648-0350). ddC and AZT Ongoing clinical trials combining ddC and AZT are investigating whether this combination offers an advantage over therapy with a single drug. Some trials compare ddC to AZT, others compare combinations of ddC and AZT, and still others evaluate the usefulness of switching back and forth between ddC and AZT 'every week or month. In San Francisco, at the Sixth International Conference on AIDS, preliminary results of a complex trial comparing many different regimens were reported. The arms of this trial consisted of: low dose AZT (150 or 300 mg) combined with ddC (0.005 mg/kg); high dose AZT (600 mg) combined with ddC (0.01 mg/kg); or very low dose AZT alone (150 mg/day) (4,5). In June 1990, 43 of 55 patients Conclusion enrolled in this trial, were still on therapy. Two patients had to discontinue therapy because of neuropathy. Three patients had neuropathy that resolved and four developed low blood counts. All patients showed an early rise in T4 cell counts, which peaked between four and 12 weeks, followed by a gradual fall to original counts. In November 1990, Dr. Douglas Richman gave an update of this trial at a meeting in Washington (6). So far, patients in each arm of the trial showed weight gain and rises in T4 cell counts. The high doses of ddC and AZT seemed to be more effective in suppressing viral reproduction, as measured by p24 antigen levels than the low-dose combinations of ddC and AZT. The least effective regimen seemed to be AZT at 150 mg/day alone. Combination AZT and ddC may have the dual benefits of preventing resistance and minimizing the toxicity of each drug. For example, if AZT and ddC are alternated every other week or month, the time off AZT will allow for bone marrow recovery and the time off ddC will allow for nerve tissue recovery. dditionally, none of the actual antiretroviral ~b~eonwefnits of the drugs will be lost. One trial has shown that neuropathy was more common in patients with pre-existing neurologic abnormalities, patients on high-dose ddC, patients on weekly (as opposed to monthly) alternating and intermittent schedules (7). In the test tube, HIV strains from patients on alternating ddC/AZT remain sensitive to AZT, whereas strains from patients on AZT alone are uniformly resistant to AZT (8). Intermittent schedules where patients are taken off both drugs for any length of time run the risk of resurgent HIV replication and disease progression while not taking drug. Conclusion Though neither alternating, intermittent or combination regimens of AZT and ddC are recommended for general usage, it is imperative that the final results of these clinical trials be made available as soon as possible, since approval of ddC is expected in the near future. Community physicians and their patients need to be educated on the most appropriate dosages, schedules and combinations in order to maximize the benefits and minimize the toxicities of AZT, ddC and ddI. A consensus conference to examine all existing data on ddC, including the data emerging from the expanded access protocol, must occur in the near future to formulate a recommendation on regimens to be used once ddC is approved. ***** An Ounce of Prevention: Antifungal Prophylaxis Victoria Nott Perhaps one of the greatest advances in the management of HIV illness has been the development of preventive treatments for pneumocystis carinii pneumonia (PCP) such as Bactrim, Dapsone and aerosolized pentamidine. In 1987, PCP made up 66% of the AIDSdefining opportunistic infections (OIs) reported to the Centers for Disease Control (CDC) (9). In 1990, reports of PCP had declined to approximately 49% (10). Presumably, PCP prophylaxis has had an effect on the declining incidence of this pneumonia. However, it is clear that not enough people, who require preventive treatment for PCP, are receiving it. And there are many other OIs for which prophylactic strategies are desperately needed. Fungi, one-celled yeast-like organisms also cause infections with great frequency in people with AIDS. Fungal diseases are usually chronic, sometimes severe conditions, which often recur after initial treatment. The most common diseases caused by fungi found in people with AIDS are cryptococcal meningitis, candidiasis (thrush), and histoplasmosis. Other fungal diseases have been seen in people with AIDS, but this article will focus on the prevention of these three diseases. Background There have been important treatment advances for fungal infections in the last few years with the development of a new class of drugs called "azoles." Azole drugs come in many forms. Topical azoles are drugs that are applied directly to the infected area. Miconazole (Monistat), clotrimazole (Mycelex) and ketoconazole (Nizoral) are topical drugs which are currently available on the market. Nystatin (Mycostatin) is another topical drug, prepared either as a lozenge called a troche for oral fungal disease, or as a vaginal insert for vulvovaginal yeast infection. Oral antifungal drugs, including ketoconazole, fluconazole (Diflucan) and flucytosine (Ancobon), are commonly administered for disseminated (body-wide) fungal infection. Flucytosine, however, seems to cause the rapid growth of resistant strains of fungi, and so is sometimes given in combination with other antifungal drugs (11). Patients taking oral azoles need to be monitored for possible liver toxicity. Standard therapy for serious fungal disease has been with amphotericin B (Fugizone), the first antifungal drug approved. Amphotericin B is available only intravenously and is sometimes supplemented with oral flucytosine, although there is no consensus about the benefits of adding flucytosine. Amphotericin B is highly toxic. For long-term use, it is usually administered through a catheter (a tube surgically implanted to allow direct administration of drug into the blood stream). The approval of fluconazole for treatment of cryptococcal meningitis and serious candidiasis is a tremendous step forward because of the drug's low toxicity and availability in pill form. When taken orally, fluconazole can cross the "blood-brain barrier," unlike amphotericin, and has proven to be at least as effective as amphotericin (12). Antifungals as Prophylaxis People with HIV infection who develop serious fungal disease must generally stay on lifelong maintenance therapy at a reduced dose. Currently, there is interest in the possibility of preventing fungal disease from occurring in the first place. While there is no consensus about the ability of azoles to prevent a first outbreak of fungal disease, Dr. William Powderly of Washington University, St. Louis, Principal Investigator of antifungals for the National Institute of Allergy and Infectious Diseases (NIAID), says, "Most of us probably feel this is the way to go, but prophylaxis has not yet been proved safe or effective." With the incidence of life-threatening fungal disease occurring in about 5% of people with AIDS, as opposed to about 50% for PCP, it is much harder to pinpoint who should receive prophylaxis, said Powderly. For instance, it may not be worth the possible toxicity and cost to prescribe prophylaxis for cryptococcal meningitis for everyone under a certain T4 cell count. Since serious side effects are relatively rare with azoles, the more important question may be the exorbitant price charged for certain antifungal drugs, like fluconazole, which is made by Pfizer. The Resistance Debate It is possible that long-term use of antifungal drugs might result in resistance to the drug. Resistance has been a problem with AZT, ganciclovir (therapy for cytomegalovirus, or CMV) and acyclovir (therapy for herpes infections). However, Dr. Powderly believes that resistance to azole drugs is more theoretical than practical. Other doctors are more conservative and express some caution about the use of fluconazole, for instance, as prophylaxis. Dr. Abigail Zuger of Montefiore Hospital in the Bronx, New York, believes that resistance could become a problem when using antifungals as prophylaxis. She expressed concern over a recent report of cryptococcus that became resistant not only to fluconazole but also to amphotericin B after fluconazole was administered. The history of antibiotics includes many instances of organisms developing resistance in response to prolonged use of one drug. Some researchers fear that premature prophylactic use of antifungal drugs may diminish the usefulness of such hopeful new drugs as fluconazole. Cryptococcal Meningitis Cryptococcus neoformans is a one-celled yeastlike organism which can cause a body-wide infection in people with immunosuppression. This infection is thought to be acquired by inhaling fungus into the lungs. Avoidance of this kind of fungus may be difficult, since many people are unaware of exposure. Cryptococcal organisms have been found in many natural sites, including weathered pigeon droppings. Once inhaled, the fungus grows in colonies, infecting the lungs and possibly spreading to the brain. Infection of the brain can cause cryptococcal meningitis, a serious disease that occurs in approximately 10% of all AIDS patients and is fatal in nearly 60% of those infected (13,14,15). The two antifungal drugs used for treatment of cryptococcal meningitis are amphotericin B and fluconazole. One clinical trial provides some evidence that amphotericin B may be superior to fluconazole for initial treatment of cryptococcal meningitis (16). However, the same study shows that fluconazole may be better at controlling relapses (17). It is commonly agreed that any immunosuppressed person who has had cryptococcal meningitis should take maintenance therapy indefinitely to avoid relapses of disease. Often the choice for maintenance therapy is fluconazole. A few skin rashes and two cases of thrombocytopenia (low platelet count) have been reported with prolonged use of fluconazole. In the trial using fluconazole as a prophylaxis for cryptococcal meningitis, Dr. Powderly has observed no severe side effects. Nearly 15% of patients in the trial had nausea, which either improved with time or was controlled by administering smaller doses of drug twice a day, rather than the whole amount at once. Presently, there is only one federally funded trial for prophylaxis of cryptococcus (18). Nearly 360 subjects will take either 200 mg of fluconazole daily to protect the whole body from infection, or they will receive clotrimazole lozenges to protect against oral symptoms. Some participants have been enrolled for as long as a year already, and reports from study coordinators indicate that the trial is "going well." It will be another year before there is any information about the efficacy of these drugs in preventing fungal diseases. Candidiasis (Thrush) Candida albicans is a fungus that causes candidiasis, which is common and can occur in a variety of places in and on the body. The most frequent breeding ground for candida is in the mouth, where it is commonly referred to as thrush. Thrush is a very frequent condition in HIV infection, which has been seen in up to 60% of AIDS patients (19). Thrush can appear as creamy white or yellowish patches in the mouth, which sometimes can be scraped off, or as red splotches in the mouth. The infection may also entail cracks at the corners of the mouth and a sore throat. Oral thrush may progress and cause further infection in the throat, esophagus, and intestinal tract. For women, vaginal thrush, an odorous white, creamy infection of the vulva and/or vagina, may precede oral thrush. Oral thrush responds well to local treatment with clotrimazole troches. Miconazole or clotrimazole are used as intravaginal creams or suppositories for vaginal yeast. For more widespread cases, systemic treatment is with oral ketoconazole or fluconazole (20). Some medical professionals recommend antifungal maintenance therapy indefinitely for severe thrush or vaginal candidiasis. Although some resistance to fluconazole has been observed in people with thrush, it does not seem to be a common occurrence. Dr. Zuger of Montefiore Hospital finds topical Mycelex to be an adequate treatment for most cases of thrush and vaginal candidiasis. Not much work has been done to prevent thrush. One approach currently being tested for oral infection is treatment with a rinse, called Peridex. The active ingredient in Peridex, which is used by dentists for gum disease, is chlorhexidine, a disinfectant that kills candidal organisms in the test tube. Procter & Gamble, the maker of Peridex, is conducting placebo- controlled trials at five sites in order to determine if washing with the prescription mouthwash two to three times daily will delay or prevent oral thrush in HIVpositive people with a history of this condition. The study, which was announced last June, is scheduled to last six months. Dr. Deborah Greenspan, DDS, investigator at the University of California, San Francisco, reported that about 20 patients are already enrolled at the site. Since the study is blinded, no data is yet available. Additionally, at the dental clinic of St. Clare's Hospital, New York City, Peridex is being tried in an unblinded pilot study of 20 patients. The aim of this study is to determine if Peridex, which is much less expensive than topical medications such as Mycelex and Nystatin, is effective as a maintenance therapy. Dr. Stephen Able of St. Clare's reports that Peridex seems to help some patients but not others. For information about enrolling in this Peridex trial, contact Dr. Able at (212) 459-8327. Histoplasmosis Histoplasma capsulatum is a yeast that causes histoplasmosis, a disease which may be asymptomatic, mild or severe. Histoplasmosis can be an elusive infection, affecting many parts of the body, including lungs, lymph nodes and bone marrow. It usually causes a cough, fever, and general malaise. In the U. S. infection seems to be more common in the southeastern, midatlantic and midwestern states. In regions where histoplasmosis is common, infection occurs in 5-10% of patients with AIDS (21). One trial reported that oral ketoconazole was effective in suppressing histoplasmosis for up to two years after initial treatment with amphotericin B (22). Two of ten patients relapsed during the ketoconazole trial (one at six months, and one at 21 months) and were retreated with amphotericin B. Another trial reported successful treatment of histoplasmosis with itraconazole (Sporanex), which is not approved yet in the U. S. (23). Lastly, there was one report of successful maintenance therapy with fluconazole, after initial treatment with amphotericin (24). Currently there are two federally-funded trials to study the effects of itraconazole, which is similar to fluconazole, but does not cross the "blood-brain barrier," which limits itraconazole's potential as a treatment for cryptococcal meningitis. Both of the federally-funded trials, one complete and the other still recruiting patients, are for HIV-infected persons with a history of histoplasmosis to determine whether itraconazole is effective in preventing relapses of disease. Because histoplasmosis is fairly rare in the northeast, New York area and New Jersey hospitals, participating in the trial, report small numbers of patients enrolling. Dr. Kathleen Squires of Cornell Medical Center did report that one trial, which is now closed, had eight patients enrolled at the site (25). None of them had any relapses of histoplasmosis while taking itraconazole. Dr. Joseph Wheat, a principal investigator of the itraconazole trials, reports that the drug shows promise for both acute treatment and maintenance therapy of histoplasmosis. There were no relapses in any of the 33 patients who could be evaluated from the trials. And nearly 25 patients treated with itraconazole for first episodes of histoplasmosis yielded "encouraging" results. The U. S. manufacturer of itraconazole, Janssen Pharmaceuticals, is reportedly seeking approval from the Food and Drug Administration (FDA) to market the drug, and a data review is expected soon. A new trial, currently recruiting patients for a one year study of itraconazole as a treatment for histoplasmosis, will try to determine if itraconazole can prevent disease from returning (26). Patients will take itraconazole daily for 12 weeks and those who do well on it will continue for another year. To enroll or get more information in the New York City area, contact the following people: Patrice Edwards, Albert Einstein College of Medicine at (212) 430-3659; Robert Winters, Cornell Medical Center at (212) 584-9000, ext. 1169; Mercedes Rios, Montefiore Hospital at (212) 920-6563; Brenda Kolatch, St. Luke's/Roosevelt Hospital at (212) 523-6722; or Grace Ouma, Robert Wood Johnson Medical School in New Brunswick, New Jersey at (201) 937-8571. Itraconazole is available by prescription outside the U. S. The People With AIDS Health Group, an underground buyers' club in New York, reports that a healthy supply of itraconazole is available by calling (212) 532-0280. According to a representative of the buyers' club, it is a "popular drug" with clients. Antifungals on the Horizon Schering Corporation is developing another new antifungal drug of the "triazole" class for treatment and maintenance therapy of cryptococcal meningitis and thrush. Two hundred patients worldwide have been treated with this drug, which is called "SCH 39304." The drug is considered to be quite similar to fluconazole, and many fear that those fungal strains resistant to fluconazole may also be resistant to SCH 39304. One recent report from a small open-label trial claims a 43% response rate in patients with cryptococcal meningitis approximately the same rate seen for amphotericin B and fluconazole. Dr. Belle Lee, at San Francisco General Hospital, one site where SCH 39304 is being tested, reports that the drug works at least as well as ketoconazole for thrush. The drug reportedly stays in the body somewhat longer than fluconazole does, and so will require less frequent dosing, said Dr. Lee. The side effects are minor. Data for SCH 39304 are being assembled and will be presented in June at the International Conference on AIDS. Approval and availability of this new drug may help to lower the price of fluconazole. An efficacy trial for oral SCH 39304 in people with cryptococcal meningitis is currently recruiting patients (27). Participants will take drug for 12 weeks, and, for those who respond to treatment, random assignments will be made for drug once a week or once a day for up to a year. For more information call 1-800-TRIALS-A. Additionally, a less toxic form of amphotericin B which incorporates a lipid coating is being tested for efficacy in people with cryptococcal meningitis. A double-blind, dose comparison study funded by The American Foundation for AIDS Research (AmFAR) will compare amphotericin B with this less toxic formation called, amphotericin B lipid complex. All participants will receive fluconazole for 12 weeks after finishing six weeks of drug. For further information about this trial, which is currently recruiting patients, contact Wendie Lubin at (212) 420- 4041 at Beth Israel Medical Center in New York, or Nancy Pietroski at (215) 925-8010, Pennsylvania Hospital, Philadelphia. Conclusion There are, of course, many unanswered questions about the efficacy and safety of antifungal drugs as prophylaxis. Secondary prophylaxis with maintenance therapy is definitely recommended after initial treatment of systemic fungal infection for people who are HIV-infected. There is a need for primary prophylaxis for common fungal infections, but none of the candidate drugs has been proven safe and effective as a standard preventive measure. There is some feeling among community physicians that fluconazole prophylaxis is advisable for persons with T4 cell counts under 100, as a strategy to prevent multiple fungal infections. It is hoped that more solid data will be presented at the Seventh International Conference on AIDS in Florence this June. ***** Pet Care: Special Concerns for People with HlV Infection Arthur Lubell There is no doubt that owning a pet can result in much enjoyment and emotional support. But many HIV-infected people have worried over the risks of contracting disease from their animals. Of course, there is no known evidence that HIV can be acquired or transmitted by cats, dogs or any other non-primates. But some zoonotic diseases (diseases transmitted from animals to people) are of special concern to people who are immunosuppressed. Simple and sensible precautions are advisable to minimize risk (28). This article was written with common domesticated animals in mind. People with more exotic pets may have special concerns and should consult with a veterinarian. If you are adopting a new pet, avoid the following highrisk animals: stray or sick animals, especially animals with diarrhea; and exotic or wild animals such as monkeys. Some veterinarians feel that cats, rather than kittens, are safer pets for immunocompromised people. But the most -important advice is to have new pets examined by a veterinarian before bringing them home. Pet Hygiene Keep your animal clean and well-groomed and make sure it is regularly vaccinated. Control fleas and ticks for your pet's health and your own. It is helpful to control roaches and flies because insects can sometimes carry zoonotic diseases. Also, minimize contact with your pet's saliva, urine, feces and vomit. Be especially careful to avoid your pet's licks, if you have sores on your face or hands. Clean up bodily fluids with disinfectant (use a solution of one ounce of bleach to a quart of water). When possible have someone who is not immunocompromised help with cleaning up after your pet. Remember to wash your hands after handling your pet, especially before eating or smoking. It is helpful to keep your pets indoors. By doing so, you may be better able to protect them and yourself from contagious diseases carried by outdoor animals or found in infected soil. Pet Food Feed your animal commercial pet foods only. Do not feed it raw or undercooked meat, eggs or unpasteurized milk. Also, do not let your pet drink from the toilet. If possible keep pets inside, or on a leash when outside, to stop them from eating infected rodents or birds, infected feces or soil, and garbage, where there may be raw meat. It is also important to control rodents indoors, as much as possible. Birds Parrots and parakeets can acquire a rare but serious zoonotic disease called psittacosis. Transmission of this infection from birds to humans has been traced to contact with pigeons, ducks, turkeys, and chickens. The psittacosis organism is inhaled by humans and can cause high fever, chills and shaking, a dry cough and chest pains. Headache seems always to be the most prominent and severe symptom. Tetracyclines (drugs which are similar to penicillin) are effective in the treatment of psittacosis infection. On the whole, psittacosis is a fairly rare infection. Cryptococcus is a fungal organism which has been found in old pigeon droppings. It is possible for people to become infected by breathing the fungus into their lungs. Cryptococcal infection is known to have a particularly rapid progression in people with AIDS and can infect the brain. Prevention is difficult, since most people with cryptococcal infection are unaware of exposure to pigeon droppings or other sites in nature where the fungus grows. Cat-Specific Concerns Research so far has identified cats as the major source of pet- transmitted infections to the immunocompromised. This section focuses on diseases associated with cats and how their owners can minimize risk of infection. Litter Box It is preferable to keep the litter box away from kitchen and eating areas. If at all possible, have someone else change the litter box daily. Use disposable plastic liners and change them with each new litter. Never dump used litter directly into the trash. Instead seal the plastic liner with a twist tie and place in a plastic garbage bag for disposal. Wearing a face mask will offer extra protection. Disinfect the litter box regularly, as recommended by most veterinarians. Use boiling water and let stand for five minutes. This is the only disinfectant procedure which kills toxoplasma eggs. Always wash your hands after cleaning the litter box. Use plastic or rubber gloves for extra protection. Toxoplasmosis Cats may be carriers of the protozoan Toxoplasma gondii, which is a parasite that invades healthy cells. Raw or undercooked meat may also contain the parasite in cysts, or pockets, containing thousands of organisms. When ingested the cysts are broken down by digestive fluids, and release invaders, called tachyzoites, which enter the bloodstream. These organisms have a special affinity for the heart and skeletal muscle and are known to infect the brain. Toxoplasma gondii may also take on another form, called oocysts or fertilized eggs, which are produced during the sexual cycle of toxoplasma organisms. Members of the cat family can carry and excrete these parasite eggs at a rate of 10 to 20 million per day for 10 to 15 days after ingesting the organism. Cats first come in contact with the parasite through other outdoor animals, infected soil or prey, such as birds and rodents, or from their mother during pregnancy. The oocysts themselves become infectious 24 hours after excretion. They are spread to humans by contact with infected cat feces, or warm, moist soil where they can live for months. Additionally, direct contact with any material contaminated by the infected cat feces can result in human infection. Controlling your cat's diet is the best way to prevent a pet from developing disease. It is worth noting that after a primary infection, most healthy cats will not shed oocysts again. Even if reinfection occurs, the volume of oocysts shed is so reduced that it may be insufficient to transmit disease. You may be able to determine if your cat has already been infected by consulting a veterinarian. Another important prevention strategy is to cook all meats well-done -- especially lamb and pork. Toxoplasmosis in HIV Historically, toxoplasmosis has been feared mainly for its damage to the human fetus. In the general adult population, it is a relatively harmless infection for people with normally functioning immune systems. Upon infection, most healthy adults come down with generalized flu-like symptoms: chills, fever, headache, muscle pain, and inflammation of the lymph nodes. It is estimated that between a third and a half of the American population have been exposed to toxoplasma. Most people have developed antibodies to toxoplasma which keep them safely asymptomatic. Toxoplasmosis in people with HIV is usually a reactivation of a past infection. When the immune system of a person who has been previously exposed to toxoplasma becomes weakened by AIDS, a reactivation of toxoplasma may result in serious illness, especially encephalitis (inflammation of the brain). Toxoplasmic encephalitis, formerly considered a rare disease even in immunocompromised adults, is now the most commonly recognized opportunistic infection of the central nervous system in patients with AIDS. Approximately 30% of people with AIDS who have been previously infected with toxoplasma will develop toxoplasmic encephalitis (29). Detailed articles on toxoplasmosis appeared in Treatment Issues vol. 3, no. 1 and vol. 4, no. l. Feline Leukemia Virus (FeLV) and Feline Immunodeficiency Virus (FIV) FeLV and FIV are different from their human counterparts, and neither is known to be transmittable to humans. Signs or symptoms for both diseases may be somewhat similar. The following are symptoms in cats to look out for: weight loss; decreased appetite; diarrhea or constipation; blood in feces; enlarged lymph nodes; difficulty with breathing; excessive drinking or urination; evidence of pain while eating; poor coat condition; skin rashes or sores; and infected or swollen gums which may result in tooth loss (30). Diagnosis of FIV disease is based on the cat's history, clinical signs, and results from an FIV-antibody test. Blood tests may indicate FeLV, but a negative test result does not necessarily imply immunity to the virus. An FeLV-positive cat may live for months or years without signs or symptoms of the disease. While there is no cure for either FIV or FeLV, some drugs and steroids for infected cats may temporarily control virus-related conditions, or allow for short periods of remission. There is a vaccine for FeLV, but it is recommended for healthy, FeLV- negative cats only. Recently, some controversy has arisen concerning the vaccine's efficacy, and newly developed FeLV vaccines should be available at vet clinics and offices in the future. FIV and FeLV weaken a cat's immune system, making it more susceptible to zoonotic diseases, which can be spread to humans. Treatments and supportive care can be complicated and expensive, as well as painful and prolonging for the pet. Some professionals recommend that people with immunosuppression give up cats that are infected with either FeLV or FIV, but the decision is personal and should be discussed with both a physician and a veterinarian. Cat Scratch Disease It is estimated that there are 8,000 cases of catscratch disease (CSD) annually in the United States. Infection occurs primarily among children and adolescents, and now a growing number among people with AIDS. In people with normal immune function, a pimple develops at the site of a cat bite or scratch within three to ten days. Swelling at the bite or scratch, and sometimes swelling throughout the body may persist for months, accompanied by fever, fatigue, headache, weight loss, and other symptoms. Throughout these symptoms, the cat may remain healthy and have negative skin tests. Even in the most severe cases, CSD is a benign illness for healthy adults and the prognosis is uniformly good, with no fatalities reported. In immunosuppressed patients, however, the illness may be more dangerous. In one case reported in the medical journal AIDS, a patient developed large painful lesions under the skin of his arms and legs, as well as red nodules on the larynx. After one week of treatment with 500 mg of erythromycin every six hours, the condition improved (31). CSD is sometimes misdiagnosed as Kaposi's sarcoma because the lesions resemble each other. The following clinical features may help to differentiate between the KS lesions and CSD lesions: CSD lesions bleed more easily and have a red base; CSD lesions are usually tender or painful and are associated with an underlying bone lesion. Most importantly, CSD lesions respond to antibiotic therapy, including erythromycin, doxycycline and drugs used to treat tuberculosis, but do not respond to penicillin, cephradine, nafcillin or dicloxacillin (32). While CSD seems to be a relatively rare complication of AIDS, it may be worth taking special skin tests for the bacteria causing CSD and to have a biopsy of suspicious skin lesions. If appropriate, antibiotic therapy can be initiated to resolve the lesions. To avoid scratches, HIV-positive people should keep their cats' nails trimmed short and may wish to discuss the pros and cons of declawing with a veterinarian. The disease, which is rare, seems to be more often transmitted by kittens than adult cats. Conclusion Recent studies indicate that pets enhance the quality of life for the aging and ill. The psychological and physical benefits of pet ownership are especially important to people with AIDS. However, planning ahead is important, and there is nothing wrong with finding a new home for your pet should you decide you can no longer take care of it. For more information on pet care call Pets Are Wonderful Support (PAWS): (415) 824-4040 or Pet Owners with AIDS/ARC Resource Services, Inc. (POWARS) (212)744-0842. Special thanks to Jill Nord, M. D. who researched and wrote the section on Cat Scratch Disease. ***** New AZT Study Questions Early Use Kevin Armington A recently completed study on the benefits of early-use AZT has been extensively, and often inaccurately, covered in the lay media. This study, conducted at several Veteran's Administration hospitals (VAs) throughout the country, evaluated 338 participants -- half started AZT when their T4 counts fell below 500, and the other half waited until their counts reached 200 before beginning treatment. The authors claim that there was no difference in overall survival for people starting AZT early vs. late. They did conclude that AZT slowed progression of HIV disease, but that this benefit was not experienced by people of color. Many factors throw the conclusions of the VA study into question. For instance, trial participants received an enormous dose of AZT: 1500 mg/day. AZT was originally licensed at 1200 mg/day for people with AIDS, ARC or T4 counts below 200. Studies since then have demonstrated that 600 mg/day is possibly more effective. When the licensing for AZT was expanded to include people with T4 counts under 500, the dose indicated was 500 mg/day. In addition, a recent study has hinted that 300 ma/day might be just as effective as 600 mg/day. Test tube studies have shown that people on higher doses develop resistance to AZT faster than those on lower doses perhaps a factor effecting the outcome of the VA study. It is interesting to note that six cases of dementia occurred in this trial, all in the delayed treatment group. This finding would seem to support early use of AZT, from a neurological standpoint. Many of the news reports in the lay press on this study reported that people of color did not gain benefit from AZT in this study. What these reports failed to note is that most of the participants who are people of color had lower red and white blood cell counts on average at the beginning of the study. Considering the toxicity of the excessive dose used, it is not surprising that people with lower blood cell counts progressed more rapidly. This study was not designed to measure whether different racial groups derive more or less benefit from AZT, so this phenomenon cannot be considered an accurate analysis of any potential difference. Three other major AZT studies have shown no difference in racial groups receiving AZT. But it is remarkable that reliable studies have not been done yet to specifically answer this question. Finally, this study is much smaller than two other studies that have shown a clear difference in progression to AIDS for people receiving no treatment vs. AZT. Trial 016 conducted by the AIDS Clinical Trials Group evaluated 711 patients and trial 019 evaluated 1338 patients. These placebo-controlled studies stand in sharp contrast to the VA study, in which everyone received AZT, but at different stages. The larger trials show that participants receiving A ZT have delayed disease progression. Many of the original trial participants are still being followed, but no data showing a difference in survival have been reported yet. If these data are available, they must be made public as soon as possible. ***** In Brief Low-Dose Bactrim: A paper on the use of Bactrim to prevent PCP was published in the British medical journal Lancet this month. The authors found that Bactrim taken three times a week prevented PCP in 116 patients for up to 42 weeks. No cases of PCP occurred in these patients and only 10% had to stop taking the drug due to allergic reactions. Many patients who take Bactrim to prevent PCP take it daily, but a much higher percentage develop toxicity at that dose (around 50%). It is not news in the community that Bactrim prevents PCP, but less frequent dosing should make this drug, which is much cheaper and easier to take than aerosolized pentamidine, a treatment option for more people. Treatment Issues Survey: Last spring, we asked our readers to give us some feedback about themselves and their assessment of Treatment Issues by filling out a survey. The responses have been carefully read and we will be making many of the changes you suggested in a newly redesigned Treatment Issues that will appear soon. Many thanks to the 1500 (11% of the mailing list at that time) readers who took the time to fill out and return the survey. Here are a few facts about those who responded: Male 1218 82.7 Female 246 16.7 HIV+ 407 27.6 HIV- 406 27.6 ARC/AIDS 530 36 Unsure 93 6.3 63% of those who responded read Treatment Issues for personal reasons, 21% for professional reasons, and 16% for both personal and professional reasons. 30% of readers in the New York City metropolitan area have called abouX clinical trials listed in Treatment Issues. Overall, readers reported that Treatment Issues meets their needs well. None of the planned changes will be major, but some common suggestions will be incorporated in a "new and improved" newsletter; for example, a glossary will be added. Many suggestions about topics that have not been covered in Treatment Issues have been slated for future issues. We encourage our readers to offer further topic suggestions. Footnotes: 1 Yarchoan R et al. Phase I studies of ddC in HIV infection as a single agent and alternating with sidovudine. Lancet i:76- 81, 1988. 2 Merigan TC et al. Circulating p24 antigen levels and responses to ddC in HIV infections. Ann Intern Ned. 110: 189-194,1989. 3 Dubinsky RM et al. Follow-up of neuropathy from ddC. Lancet i: 832,1988. 4 Powderly W et al. Toxicity associated with ddC. Lancet i: 1106,1990. 5 VIth Int Conf on AIDS, abstracts ThB. 23, SB. 426, San Francisco, June, 1990. 6 AIDS Clinical Trial Group Meeting, Nov. 11-14, 1990, Washington, D. C. 7 VIth Int Conf on AIDS, abstract SB. 425, San Francisco, June, 1990. 8 VIth Int Conf on AIDS, abstract ThA. 263, San Francisco, June, 1990. 9 CDC, AIDS weekly surveillance Report-U. S., P. S, 0ctober S, 1987. 10 CDC, HIV/AIDS Surveillance, Year-End Edition, p. 16, January 1991. 11 Braunwald E et al. Harrison's Principles of Internal Medicine. 11th Edition, p. 737,1987. 12 Sugar A et al. 0verview: Treatment of Cryptococcal Meningitis. Rev Inf Dis 12:5338-5348, March-April, 1990. 13 Kovacs JA et al. Cryptococcosis in the acquired immunodeficiency syndrome. Ann Intern Med. 103: 533-538, 1985. 14 Eng RH et al. Crytococcal infections in patients with AIDS. AM J Med. 81:19-23,1986. 15 Zuger A et al. Cryptococcal disease in patients with AIDS. Ann Intern Med. 104:234-40, 1986. 16 Larsen RA et al. Fluconazole compared with amphotericin B plus flucytosine for cryptococcal meningitis in AIDS, Ann Intern Med 113:183-87, 1990. 17 ibid, pp 177-179. 18 ACTC Trial #981 is a separate arm of FCP prophylaxis trial 081. 19 Kaplan MH et al. Dermatolofflc findings and manifestations in AIDS. J Am Acad Derrnatol 16:486-506, 1987. 20 Meunier F et al. Therapy for oropharyngeal candidiasis in the immunocompromised host: a randomzed doubleblind study of fluconasole vs. ketoconasole. Rev Inf Dis 12, Supp 3:5364- 368,1990. 21 Larsen R. Asoles and AIDS. J Inf Dis 163: 727-730, 1990. 22 Vth Internat Conf on AIDS, abstract MBP. 80, Montreal, June, 1989. 23 ibid, MBP. 81 24 ibid, MBP. 79 25 ACTG trial # 084. 26 ACTC trial # 120. 27 ACTG trial # 125, and AmFAR trial # SCH00oo1 28 These guidelines were adapted from Safe Pet Guidelines a publication of Pets are Wonderful Support (PAWS), P. O. Box 460489, San Francisco, CA 94146; (415) 826-8058. 29 McCabe et al. Toxoplasmosis The Time Has Come. NEJM 318:5;313-315. 30 Cornell Feline Health Center. The Feline Leukemia virvs and the Feline Immunodeficiency Virus. Cornell University, College of Veterinary Medicine. Ithaca, NY 14853-6401. 31 Van der Wouw PA et al. Disseminated cat-scratch disease in a patient with AIDS. AIDS 3:751,1989. 32 Koehler JE et al. Cutaneous vascular lesions and disseminated cat-scratch disease in patients with AIDS and AIDS-related complex. Ann Int Med 109 (6):449, 1988. ___________________ Other Resources The AIDS Treatment Registry provides up-to-date information on clinical trials of antivirals, immunomodulators, and drugs for HIV-related infections and cancers in New York and New Jersey. Their easily readable guide can be obtained by calling (212) 268-4196. The AIDS Drug Assistance Program provides many free medications used by people with HIV infection to those whose income is under $44,000 for a single person. For more information, call 1-800-542-2437. American Foundation for AIDS Research (AmFAR)also publishes a catalog of trials involving experimental drugs. To order the "AIDS/HIV Experimental Treatment Directory", write to AmFAR at 1515 Broadway, Suite 3601, New York, N.Y. 10036, or call (212) 719-0033. "AIDS Treatment News" is a biweekly report which chronicles current developments in experimental and alternative treatments and deals with public policy issues. Contact John S. James at P.O. Box 411256, San Francisco,CA 94141 or call (415) 255-0588. Project Inform publishes a newsletter called "PI Perspective" on experimental treatments with in-depth political analysis. Another excellent resource is their drug hotline: 1-800-822-7422. Body Positive is a organization for people who are HIV-positive. They publish a monthly newsletter called "The Body Positive." Write to: 208 West 13th St., New York, NY 10011 or call 212-633-1782. Also providing services to seropositives is an organization called "Positive Action". For more information, call (212) 727-7768. Treatment Issues is GMHC's newsletter devoted to providing reliable information on experimental AIDS therapies. Describing an experimental therapy should not be construed as recommending it. All new treatments should be done under a physician's care. Treatment Issues is published ten times yearly. Copyright 1990 Gay Men's Health Crisis, Inc. All rights reserved. Non-commercial reproduction is encouraged. Subscription lists are kept confidential. Editor: Kevin Armington Medical Consultant: Gabriel Torres, M.D. Technical Assistance: Wayne Kawadler Writers: Mike Barr Darren Britten Dave Roche Gabriel Torres, M.D. GMHC, Department of Medical Information, 129 West 20th Street, New York, NY 10011. &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display