AEGiS-GMHC: Toxoplasmosis Prophylaxis

Important note: Information in this article was accurate in 1990. The state of the art may have changed since the publication date.

Toxoplasmosis Prophylaxis

GMHC Treatment Issues; Volume 4 no. 1 January 29, 1990
Victoria Nott

For people who have never been exposed to the parasite that causes toxoplasmosis (T. gondii), prevention of primary exposure is an important strategy. To minimize exposure, people who are HIV-positive should not eat raw or undercooked meat, especially lamb and pork. Hands should be washed after handling raw meat or vegetables and gloves worn while working in the garden. People who have cats should change the litter daily, and wear gloves and masks while doing so (or have someone else handle the litter). Usually, however, toxoplasmosis in AIDS patients is due to reactivation of a previous infection as the waning immune system fails to suppress the parasite. The organism then reproduces, chiefly in the brain, causing central nervous system malfunction and leading to neurological deficits, seizures, changes in mental status and finally coma and death if not treated. For a more detailed description of toxoplasmosis and treatments see Treatment Issues Vol. 3, No. 1.

A large proportion of the U.S. population harbors the parasite T. gondii -- estimates range from 15% to 68%, depending on the region. Infection can be determined by testing for anti-bodies to T. gondii. It is believed that about one-third of AIDS patients who are infected with T. gondii will develop toxoasmosis. It would make sense to conduct trials of prophylactic medication in HIV-infected patients seropositive for T. gondii to see if the incidence of toxoplasmosis can be reduced. Trials have been proposed, but none is yet underway in this country. Some early data are coming in from European studies, where the incidence of toxoplasmosis is higher.

Standard treatment for toxoplasmosis is still the anti- malarial drug pyrimethamine (Daraprim, Burroughs-Wellcome) plus sulfadiazine or another sulfa drug. Maintenance treatment with lower doses of both drugs should be continued for life, since 50% of patients will relapse. Evidence is mounting that clindamycin can be safely and effectively substituted for a sulfa drug for acute therapy and prophylaxis; there has been some success with clindamycin alone (8). Also, the optimal dose of pyrimethamine for suppressing T. gondii is not known, and the amount of drug reaching the brain seems to vary greatly. Drug interactions and combined bone marrow toxicity with AZT also need investigation.

Prophylactic Experience to Date

In Montreal, French researchers reported on 42 HIV- positive patients (17 asymptomatic, 10 ARC, 15 AIDS) given three tablets of Fansidar (pyrimethamine plus sulfadoxine) every 15 days to prevent both PCP and toxoplasmosis. No cases of either disease were seen, and only a few minor side effects were reported. Patients were followed for a mean of 304 days (9).

A West German group reviewed 16 cases and concluded that 2 tablets of Fansidar a week might be of limited value in preventing toxoplasmosis as maintenance therapy. They noted that 4 patients developed toxoplasmosis while on long- term Fansidar for PCP prophylaxis (10).

Serious and even fatal skin reactions to Fansidar have been reported (11). Optimal dosage and possible drug interactions with AZT are uncertain, and the New York clinicians we talked to agreed that there are no good data on whether Fansidar prophylaxis is worth the risk or what the best dose would be.

Dr. Warren Chamberlain, who shares a practice that includes 700 HIV-positive patients in Washington, D.C., has had notable success in preventing toxoplasmosis with Fansidar (12). Dr. Chamberlain was impressed that doctors at Walter Reed Hospital, who were using Fansidar to prevent PCP, were not seeing toxoplasmosis at a time when other clinicians were seeing a growing incidence of the infection. Since then, he has prescribed Fansidar (one tablet a week) for all of his patients whose T4 levels drop below 200, in addition to aerosolized pentamidine for PCP prophylaxis. Patients are not screened for T. gondii antibodies, so not everyone on prophylaxis is at risk. Dr. Chamberlain stressed that he carefully counsels his patients about adverse reactions to the drug. He has rarely seen adverse reactions; but, at the first sign of toxicity, he takes the patient off Fansidar. In three years, his partner, Dr. Samuel Dotson, and he have not seen a single case of toxoplasmosis.

Another German group found 2 tablets of Fansidar per week effective in preventing relapse. Three of 32 patients relapsed as opposed to all six who omitted treatment. These investigators used clindamycin, or clindamycin plus spiramycin, with pyrimethamine as primary treatment for acute toxoplasmosis and found both regimens effective (13).

Planned Trials

Leading U.S. investigators have submitted protocols for primary and secondary toxoplamosis prophylaxis, to be conducted both through AIDS Clinical Trials Group medical centers and community-based groups. Dr. Donald Abrams of San Francisco General Hospital has submitted a trial protocol for primary prophylaxis comparing pyrimethamine versus clindamycin versus placebo. Dr. Benjamin Luft of Stony Brook University in New York favors combining a study with a French trial using pyrimethamine because pooled data would speed results. Final details are being negotiated. A protocol for different doses of pyrimethamine, to be conducted by the CRI in New York City and at two other locations, has been submitted to Burroughs Wellcome (Dr. Donald Armstrong, principal investigator) and is awaiting funding.

Currently, only secondary prophylaxis for toxoplasmosis is recommended to those who have recovered from an acute case. Limited data suggest that primary prophylaxis for those with latent toxoplasma and positive antibody to T. gondii may be beneficial yet risks some toxicity and adverse effects.

900129
GM040103

Copyright © 1990 - Treatment Issues. Reproduced with permission. Treatment Issues is published twelve times yearly by GMHC, Inc. All rights reserved. Noncommercial reproduction is encouraged. Subscription lists are kept confidential. GMHC Treatment Issues, The Tisch Building, 119 West 24th Street, New York, NY 10011 fredg@gmhc.org http://www.gmhc.org

AEGiS is made possible through unrestricted grants from Boehringer Ingelheim, Elton John AIDS Foundation, iMetrikus, Inc., John M. Lloyd Foundation, the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2003. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2003. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .