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

As doctors in North America have gained experience treating and preventing some of the infections seen in AIDS, patients are living longer than when the epidemic first appeared. As patients survive longer with "very low CD4+ cell counts", they can develop infections that were not commonly seen at the start of the epidermic. The sight-threatening infection CMV retinitis is increasingly being diagnosed in North American patients with AIDS. That virus can also cause ulcers in the throat and intestines, as well as infecting nerve cells inside and outside the brain. In a few patients CMV can cause pneumonia. Standard treatment for CMV is intravenous ganciclovir or foscarnet. These drugs have side effects and CMV can become resistant to them. Details about standard therapy for CMV infection appear in TreatmentUpdate 56. We now report on new options for managing CMV infection.

* ORAL GANCICLOVIR

Researchers in the USA treated subjects who had CMV retinitis with a 2 or 3 week course of intravenous ganciclovir. As maintenance, some subjects received oral ganciclovir 1 g three times daily. On average, subjects given oral ganciclovir had worsening retinitis "5 to 12 days earlier than [subjects] who received [intravenous] ganciclovir." (In this trial doctors made decisions about the effectiveness of the therapy by looking at photographs of the part of the eye damaged by CMV: the retina. Researchers consider decisions made by judging photographs to be more 'objective' than finding out what patients can or cannot see on eye charts). The difference between the 2 groups in the amount of time for retinitis to develop was not statistically significant. 50% of patients were protected from worsening retinitis for between "32 and 45 days" when treated with intravenous ganciclovir or foscarnet. In the USA, the FDA has approved the use of 1 g oral ganciclovir 3 times daily as "maintenance treatment" for CMV retinitis once patients have first received treatment with intravenous ganciclovir or foscarnet. In a future issue of TreatmentUpdate we will present data from a study of oral ganciclovir in the EU.

* ORAL GANCICLOVIR-PREVENTION FOR SOME

In other experiments, researchers in the USA found that some subjects with less than 100 CD4+ cells given oral ganciclovir were less likely to develop CMV disease than others given placebo (an inactive therapy). The following subjects developed CMV disease:

- 31% on placebo - 17% on oral ganciclovir

Thus despite receiving oral ganciclovir, a large proportion of subjects (nearly 60%) developed CMV disease (mostly retinitis) anyway. Researchers think that the high rate of breakthrough may be due to:

- poor absorption of oral ganciclovir - virus became resistant to the drug - subjects may not have taken their drug as directed.

Side effects seen in subjects receiving oral ganciclovir included bone marrow damage and low blood levels of certain white blood cells and platelets. In the USA, the use of oral ganciclovir to prevent symptoms of CMV infection will cost at least $39/day US. At this time we do not have data on quality of life and survival from subjects in this study.

* EYE IMPLANTS-RISKS AND BENEFITS

In TreatmentUpdate 56 we report results from a study of slow release pellets of ganciclovir placed inside a device (commonly called implants) in the eyes of subjects. The advantages of the implant over standard therapy can include:

- high concentrations of drugs in the eye - no bone marrow or kidney damage - less risk of bacterial infections - less frequent blood work - possible improved quality of life

Against these advantages there are potential disadvantages:

- $5,000 per implant every 6 months - complications from surgery

Indeed one researcher warns that "[eye surgeons] with less surgical skill or experience may have higher complication rates, and it must be recognized that these complications can have a disastrous impact on vision".

* EYE IMPLANTS AND SURVIVAL

As one researcher notes, "there are no data directly comparing survival of subjects receiving the [eye implant] with others receiving intravenous therapy for CMV retinitis". In the study on the eye implant, 50% of subjects survived for about 10 months. In another study where subjects received "intravenous maintenance ganciclovir", half of them survived for about 9 months. In another study, 50% of subjects receiving intravenous foscarnet survived for between 13 and 14 months.

* CIDOFOVIR-INTRAVENOUS

Preliminary results from trials of intravenous cidofovir (HPMPC; Vistide(tm)) suggest that "5 mg/kg given weekly for 2 weeks, then once every 2 weeks" appears to stop further damage to the eye.

* CIDOFOVIR-LIPOSOMES

Researchers in the USA have made tiny spheres of fat (called liposomes) containing high concentrations of HPMPC (1 mg). Injected into the eyes of rabbits infected with a herpes virus, the liposomes provided prolonged protection from eye damage, lasting between 5 and 8 months. The doctors who made the liposomes were not working for Gilead Sciences which has a monopoly on the use of HPMPC for treating CMV infections in humans. See this issue of Treatment Update for an article on eye injections of HPMPC.

* ANTIBODIES AGAINST CMV

Giving subjects who receive transplanted organs (who also receive immunosuppressive drugs) high doses of intravenous anti-CMV antibodies seems to reduce the incidence of CMV disease. In subjects with AIDS these antibodies have not yet provided benefit.

* OTHER THERAPIES

Research continues with other drugs such as "anti-sense" compounds, specially designed anti-CMV antibodies, and eye injections of ganciclovir, foscarnet or cidofovir (see pages 11-13 of this issue for details on cidofovir).

REFERENCES:

1. Polis MA and Masur H. Promising new treatments for cytomegalovirus retinitis. Journal of the American Medical Association 1995 ;273(18):1457-1459.

2. Besen G, Flores-Aguilar M, Assil KK, et al. Long term therapy for herpes retinitis in an animal model with high-concentrated liposome-encapsulated HPMPC. Archives of Ophthalmology 1995;1 13:661-668.

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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