SAN FRANCISCO -- Despite the effectiveness of antiretroviral drugs, HIV patients are still very vulnerable to opportunistic infections, according to new research by AIDS specialists at the University of California, San Francisco.
This vulnerability has important implications for developing optimum treatment strategies, the UCSF researchers emphasize.
In presentations at the Interscience Conference on Anti-Microbial Agents and Chemotherapy here today (September 27), the researchers reported study findings on two different infections common in HIV patients and how they relate to highly active antiretroviral therapy, known as HAART.
There is only limited information on the impact of HAART on AIDS-related opportunistic infections because it is still a recent treatment approach. Initiated three years ago, HAART uses a combination of powerful drugs, including protease inhibitors and reverse transcriptase inhibitors, to subdue HIV infection and give the body the chance to increase its supply of infection-fighting CD4+ T-cells that are destroyed by HIV.
One of the new research reports focused on the incidence of cytomegalovirus (CMV) retinitis, a serious eye disease that can lead to blindness. The second looked at development of drug resistance in the respiratory tract of HIV patients who underwent prophylaxis therapy to prevent a bacterial infection caused by Mycobacterium avium complex (MAC), which causes serious illness that ultimately leads to wasting and death if untreated.
Findings from the CMV research were both good and bad, said Mark Jacobson, MD, lead investigator and a UCSF associate professor of medicine who treats patients at San Francisco General Hospital Medical Center.
An objective of the study was to look at the natural history and outcome of new AIDS-related CMV retinitis cases, both before and during HAART. The study included HIV patients with newly diagnosed retinitis between 1994-1999.
"On the positive side, the incidence of CMV retinitis in the HIV population is now 25 percent of what it was in the pre-HAART era, and we've seen no increase in this rate since HAART became available. The disturbing finding, however, is that among new retinitis cases, about 50 percent are occurring in patients who have failed to respond to HAART. Thus, we need to continue investigating the factors that lead to CMV retinitis," he said.
In addition, data showed a relationship between the effectiveness of anti-CMV therapy and HAART. The eye disease healed and did not reactivate in patients who underwent retinitis therapy and then had a good response to follow-up HAART. However, the retinitis did reactivate in patients who, despite anti-CMV therapy, had no follow-up HAART or a poor response to HAART.
The study findings are important for initial decision-making about anti-CMV treatment, Jacobson said. "Knowing that the clinical outcome of new CMV retinitis cases can be predicted based on likely future response to HAART, we can make the optimum choice among the available anti-CMV treatments for the patient from the earliest time of diagnosis."
In the second study on MAC prophylaxis, researchers looked at the development of resistance to two antibiotics, clarithromycin and azithromycin, that belong to a class of drugs called macrolides.
In addition to being used to prevent MAC infection, both drugs commonly are used to treat respiratory infections unrelated to MAC in all types of patients, not just the HIV population.
Study results showed that the bacteria normally present in the respiratory tract of HIV patients developed high-level resistance to the antibiotics within six weeks of starting prophylaxis.
According to lead investigator Judith Aberg, MD, the study results have key implications for determining optimum HIV treatment during the current HAART era. Respiratory infections are the leading cause of death among AIDS patients, and macrolides are frequently given as first line therapy. They may not be effective, however, in patients who have previously had treatment with this class of drugs. Patients who are responding to HAART may be doing well enough that they don't need prophylaxis, she said.
"The risks versus benefits must be carefully evaluated. We want to protect patients from MAC, but we also want to prevent them from developing resistance to antibiotics," said Aberg, who is a UCSF assistant professor of medicine and also treats patients at San Francisco General.
In the pre-HAART era, macrolides were standard treatment as prevention therapy against MAC infection in AIDS patients whose CD4+ counts were below 75, according to Aberg. Now with HAART, many patients may have CD4+ counts that are higher.
The main conclusion from study findings, she said, is that careful consideration should be given to continuing use of macrolides for MAC prophylaxis when CD4+ counts have increased and to using macrolides for infection treatment if a patient has been on a macrolide previously.
Both research studies were supported by grants from the NIH UCSF Center for AIDS Research and the UC Universitywide AIDS Research Program,
In addition, the CMV retinitis study received a grant from Research to Prevent Blindness, Inc., and the macrolide bacterial resistance study received support from Abbott Laboratories.