TreatmentUpdate60; Volume 7, No. 6 - June 1995
Sean Hosein

In this study, researchers recruited 21 male HIV-infected subjects, at least half of whom had a CD4+ cell count of 39 cells. Subjects did not have symptoms of CMV infection but were all producing CMV, detected in their urine samples. Moreover, blood samples from 15 subjects also had CMV. As with our earlier report, subjects received a range of doses and schedules of cidofovir(HPMPC; Vistide(tm)). To reduce kidney damage, doctors gave some subjects 1 litre of saline before they started to receive cidofovir. All subjects receiving cidofovir 5 mg/kg/week or more took 2 g probenecid 3 hours before receiving the cidofovir and 1 g at two and eight hours after they received cidofovir.

* RESULTS-TOXICITY

The most common side effect of HPMPC was kidney damage. Technicians first detected increased protein and sugar in the urine samples of subjects; indicating that kidney damage had occurred. Seventeen subjects had protein detected in their urine samples at some point during the study. In most subjects, the kidney damage was temporary. One subject, who also received the anti-HIV drug d4T (stavudine), developed some heart damage during the study. When he stopped taking both drugs, he recovered after several months.

* SERIOUS SIDE EFFECTS

Two subjects developed skin rashes when given probenecid. Doctors gave these subjects Tylenol and the antihistamine Benadryl(R). Despite these measures, one subject had a severe reaction and went into shock. He later recovered and never again received probenecid. Another subject had severe nausea when given probenecid and cidofovir and left the study.

* ANTI-CMV EFFECTS

In this study, as the dose of cidofovir increased, production of CMV fell. Three subjects who received 5 mg/kg twice weekly "did not have detectable CMV after 3 weeks". Production of CMV did not immediately resume when these subjects stopped taking HPMPC. In other subjects, CMV could once more be detected in the urine "up to 2 months after the last dose of cidofovir."

* CMV IN THE BLOOD

At the start of the study, 15 subjects had blood from which CMV could be 'grown' or cultured. Despite receiving cidofovir, CMV could still be cultured from their blood samples. Indeed, 6 subjects who had 'negative' blood cultures developed 'positive' blood cultures. One subject who continued to produce CMV in his blood developed an intestinal infection from that virus 5 weeks after he stopped receiving cidofovir. Doctors treated him with intravenous ganciclovir, and 2 weeks later technicians could not culture CMV from his blood or urine samples. In another subject, CMV could be cultured from his blood samples despite receiving 7.5 mg/kg of cidofovir every three weeks. As in the previous case, after a 2-week course of ganciclovir, technicians could not culture CMV from his blood or urine.

* WHAT NEXT?

Results from this study suggest that cidofovir 5 mg/kg twice weekly is too toxic, while the same dose once weekly or 7.5 mg/kg every 3 weeks has potential benefit without some of the more severe risks. Probenecid can reduce the toxicity of cidofovir. Larger and longer studies of cidofovir need to be done in subjects with symptoms of CMV disease so that researchers can show possible benefits.

REFERENCES:

1. Polis MA, Spooner KM, Baird BF, et al. Anticytomegalovirus activity and safety of cidofovir in patients with Human Immunodeficiency Virus infection and cytomegalovirus viuria. Antimicrobial Agents and Chemotherapy 1995;39(4):882-886.

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Copyright © 1995 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284  http://www.catie.ca