BUSINESS WIRE; Monday, February 2, 1998
To Coincide With Completion of Presentation at 5th Conference on Retroviruses and Opportunistic Infections
UCSF researchers are reporting a dramatic decline in several common opportunistic infections in HIV-infected patients at San Francisco General Hospital.
Further studies must be done to tease out the explanation, the researchers say, but the critical factor may be the use of new potent antiretroviral drug combinations, of which HIV protease inhibitors are a critical component.
SFGH continues to see a steady increase in patients with HIV, but the UCSF study shows a decline in several opportunistic infections during the last four years -- particularly in the last year and a half, when protease inhibitor use has accelerated at the hospital.
"The decrease in opportunistic infections is remarkable in this study," says Christopher Holtzer, PharmD, lead author of the study, an assistant clinical professor of pharmacy at UCSF and a clinical pharmacist with the UCSF AIDS program at SFGH. "And the rise in protease inhibitor use correlates with this decline."
Wider use of more effective prophylactic medications may explain some of the pre-1996 reductions, the scientists say, but the declines seen from 1996 through the first half of 1997 -- when the drop was substantial -- may reflect the increased use of the antiviral medications.
The decreases seen between 1994-1997 were: 71.4 percent in pneumocystis carinii pneumonia (PCP); 93.8 percent in cytomegalovirus (CMV) retinitis; 83.6 percent in culture positive mycobacterium avium complex (MAC) infections, and 63 percent in culture positive cryptococcus neoformans meningitis. During the same period, the use of protease inhibitors in the UCSF AIDS program outpatient clinic at SFGH rose 70 percent.
Protease inhibitors act by blocking HIV infection of the immune system's CD4 T-cells. Unhindered, the fighter T cells are able to proliferate, boosting the immune system and allowing it to fight infection better. Given this phenomenon, it is reasonable to assume, says Holtzer, that there would be fewer opportunistic infections in HIV patients.
The UCSF researchers presented their study in a poster session here at the 5th Conference on Retroviruses and Opportunistic Infections on Monday, February 2.
While the UCSF scientists say their data is encouraging, they say more research must be done to clarify the findings. They drew their data on opportunistic infection incidences and protease inhibitor use from different sources, preventing them from making a direct statistical comparison within a patient population.
Moreover, while there have been other reports of decreases in severe opportunistic infections following the widespread use of antiretrovirals, and the researchers themselves also report a 20 percent decrease in HIV-related hospital admissions at SFGH, both data are at odds with another recent study.
In September, Steven Deeks, MD, a UCSF assistant professor of medicine in the UCSF AIDS Program at SFGH, reported that 53 percent of 136 HIV-infected patients who took protease inhibitors developed evidence of drug failure on the treatment.
"The question now, is, `what does all of this mean?'" says Holtzer. "The numbers just don't jibe. We have these large reductions in infections; however, we have reports of virologic failure in the other study. Does the fact that we can detect virus in these people mean that the drugs are no longer worth anything to these patients? We need to clarify the true impact of these new antiretroviral regimens."
Prior to the widespread use of potent antiretroviral regimens, care of HIV-infected patients focused on the prevention and treatment of opportunistic infections and other HIV-related conditions.
The opportunistic infections looked at in the study are serious and can be life-threatening. Pneumocystis carinii pneumonia (PCP) is an infection of the lungs. Retinitis is a viral infection of the retina that causes progressive destruction of the tissue, often eventually leading to blindness even with treatment.
MAC infections are blood borne infections that can manifest themselves anywhere in the body. Cryptococcus neoforms meningitis is an infection of membranes in the brain.
In the UCSF study, the incidence of pneumocystis carinii pneumonia (PCP) dropped from 224 in 1994 to 163 in 1995, to 132 in 1996, to 64 in 1997; in cytomegalovirus (CMV) retinitis, cases dropped from 48 in 1994 to 46 in 1995 to 30 in 1996 and to 3 in 1997; MAC cases dropped from 165 in 1994, to 142 in 1995 to 76 in 1996, and to 27 to date in 1997. In CN meningitis, cases numbered 27 in 1994, 33 in 1995, 23 in 1996 and 10 to date in 1997.
The use of protease inhibitors in the SFGH outpatient AIDS clinic rose from 1.7 percent of patients followed in late 1995, to 43 percent in late 1996 and to 73.3 percent in 1997.
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