new approaches for the prophylaxis and treatment
of opportunistic infections
by Lawrence M. Prescott, Ph.D.
More than 12,000 physicians, infectious disease specialists, research scientists, and other healthcare professionals gathered from around the world at the 35th Interscience on Antimicrobial Agents and Chemotherapy to hear the latest findings in the prevention and treatment of infectious diseases. Special emphasis was paid to HIV/AIDS and AIDS-related opportunistic infections. Listed below are a few of the highlights of particular interest to people living with HIV/AIDS.
valaciclovir for CMV prophylaxis
Administration of the new antiviral agent valaciclovir (Valtrex®, Glaxo Wellcome) to people with advanced HIV disease produces a definite preventive effect against cytomegalovirus (CMV) disease, according to Dr. Judith Feinberg from John Hopkins University School of Medicine in Baltimore, Maryland.
When high doses of valaciclovir (2 gm four times daily) are given to HIV positive people with very low CD4+ cell counts (median~32), CMV disease occurs much less frequently and when it does occur, the time to development of confirmed CMV disease is significantly longer. Furthermore, valaciclovir treatment seems to confer some level of survival benefit, with a trend toward lower mortality rates in valaciclovir-treated individuals compared to persons given the more standard prophylactic approach of acyclovir.
ganciclovir implant for CMV treatment
A novel ganciclovir (Cytovene®, Roche) intraocular device is proving to be a clinically important improvement over intravenous (IV) ganciclovir in the delay of progression of CMV retinitis, reported Dr. Baruch Kupperman, University of California, Irvine, School of Medicine, Irvine, California.
In a large-scale, multicenter, clinical trial, when people with newly diagnosed, untreated CMV retinitis were randomly assigned to either IV ganciclovir or a sustained-release intraocular device implanted surgically continuing one of two different doses of ganciclovir, time to disease progression was much longer with the intraocular implant than with IV ganciclovir, being 194 days versus 72 days respectively. Overall survival was the same in both treatment groups, at 140 days in the implanted patients and 150 days for those on IV ganciclovir.
clarithromycin for MAC prophylaxis
Last year it was pointed out that clarithromycin (Biaxin®, Abbott) is very effective in the prevention of disseminated Mycobacterium avium complex (MAC) infection in people with advanced AIDS. In the latest clinical trial, clarithromycin prophylaxis of MAC infection has been shown to have a decidedly positive effect on survival in those severely immunocompromised persons with AIDS, stated Dr. Mark Pierce from the Vanderbilt University School of Medicine in Nashville, Tennessee. This positive benefit on survival is due primarily to clarithromycin,s ability to prevent MAC infections, since having a MAC infection increases the chances of death significantly in people with advanced AIDS.
When people were given clarithromycin, their average survival period was over 700 days compared to only 537 days for persons who received placebo. In addition, death from any cause was reduced by 28% when people were given clarithromycin prophylaxis.
triple combo for treatment of MAC bacteremia
A three-drug combination of clarithromycin, rifabutin (Mycobutin®, Pharmacia Adria), and ethambutol (Myambutol®, Wyeth-Ayerst) is far superior to a four-drug combination of ciprofloxacin (Cipro®, Miles), ethambutol, rifampin (Rifadin®, Marion Merrell Dow), and clofazimine (Lamprene®, Geigy), according to Dr. S. D. Shafran from the University of Alberta School of Medicine in Edmonton, Alberta, Canada, and a spokesperson for the Canadian MAC Study Group.
In people with MAC infections in the blood, administration of the three-drug combo resulted in eradication of the bacteria from the bloodstream in 69% of treated individuals versus clearing of the blood in 30% of persons who received the four-drug combo. Furthermore, people given the three-drug combination lived longer than those on the four-drug therapy.
fluconazole for cryptococcal meningitis
Fluconazole (Diflucan®, Roerig) at 200 mg daily is preferred to itraconazole (Sproanox®, Janssen) at 200 mg daily as maintenance therapy of AIDS-associated cryptococcal meningitis, said Dr. Michael S. Saag from the University of Alabama at Birmingham.
In a randomized, double-blind, multicenter, clinical trial, among 107 eligible people with AIDS-related cryptococcal meningitis, only two of 52 (3.8%) who received fluconazole experienced documented, cerebrospinal fluid-culture-positive relapses compared to 13 of 55 persons (23.6%) assigned to itraconazole. While 19 people died during the study, none of the deaths in either treatment group was caused by cryptococcal disease.
itraconazole for oropharyngeal candidiasis
Itraconazole oral solution for seven to fourteen days is well tolerated and at least as effective as standard therapy with fluconazole for the treatment of oropharyngeal candidiasis in HIV-positive people, and may be more effective at 14 days, noted Dr. John R. Graybill from the University of Texas Health Science Center in San Antonio, Texas. This provides the person with a useful alternative treatment to fluconazole therapy.
Success, measured as all candidiasis lesions clearing, was seen in 83% of people on itraconazole for seven days, 87% of those on fluconazole for 14 days, and 97% of persons receiving itraconazole for 14 days. Relapse was reported in 59% of the people on itraconazole for seven days, 50% of individuals on fluconazole for 14 days, and 44% of persons taking itraconazole for 14 days.
effects of influenza vaccination
This note is added because of its major significance to all HIV positive people, especially with flu season coming on.
Annual influenza vaccination may be harmful for HIV positive individuals, asserted Dr. Sybil Tasker, Naval Medical Center, San Diego, California.
A recent study pointed out that mean plasma HIV increased from 23,892 copies/ml at the start of the study up to 135,873 copies/ml in the persons vaccinated against influenza while during the same period, individuals who were given a placebo actually had a decrease in viral burden. Since influenza does not cause excess morbidity or mortality in HIV positive people, the use of influenza vaccination might be held in abeyance until further evaluation is made of this practice.
Lawrence M. Prescott, Ph.D. is a freelance medical health and science writer with over 2,000 articles published in the U.S. and abroad. He specializes in infectious diseases, AIDS, oncology, cardiology, gastroenterology, and international public health. Prior to his writing career, Dr. Prescott worked in the fields of infectious diseases, clinical pathology, and public health administration for the World Health Organization in India, Indonesia, Thailand, Malaysia and the Philippines.
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