Declining National Rates Of HIV-Related Deaths And Illnesses Due To Combination Antiretroviral Therapy With Protease Inhibitors

An article published in the March 26 issue of the New England Journal of Medicine shows that aggressive combination antiretroviral therapy -- specifically including protease inhibitors -- dramatically reduces death rates and opportunistic infections in HIV-infected patients.

The nationwide study described in the article found that the number HIV-related deaths decreased from almost 30 per 100 person-years in 1994 to about 9 per 100 person-years by mid-1997. At around the same time, prescription rates of combination antiretroviral therapy increased from 25 percent of patients seen in 1994 to 94 percent by June 1997, with dramatic increases noted in prescription of combination regimens including protease inhibitors from 2 percent in mid-1995 to 82 percent by June 1997.

Similarly, incidence of three major opportunistic infections, Pneumocystis carinii pneumonia, Mycobacterium avium complex and cytomegalovirus retinitis, declined from 22 cases per 100 person-years overall in 1994 to 3.7 cases for 100 person years by mid-1997.

"Changing patterns of antiretroviral treatment have reduced the morbidity and mortality of HIV-infected patients," said infectious disease specialist Frank J. Palella, M.D., of Northwestern University Medical School.

"Specifically, combination antiretroviral therapy accounted for the largest proportion of such reductions," he said.

Reductions in death and disease were clearly linked to the increasing use of combination antiretroviral therapy, with the most dramatic decline coinciding with growing use of protease inhibitors, Palella said.

"Our data suggest that intensive combination therapy including protease inhibitors should be considered the standard of care for patients with advanced HIV infection," he said.

Palella was lead author on the study, conducted in collaboration with researchers from the HIV Outpatient Study, a nationwide consortium of nine HIV clinics and research centers.

Another of the study's striking findings was that patients with private insurance were more often prescribed protease inhibitors and had lower mortality rates than those on Medicare/Medicaid. However, Palella noted that use of protease inhibitors in the period from 1994 to mid-1997 had increased markedly for both those with private and publicly funded health care.

Protease inhibitor use did not differ significantly when patients were grouped by gender, race or age, although injection drug users were slightly less likely to receive protease inhibitors. Further, the large declines in mortality rates were seen regardless of gender, race, age or HIV transmission risk category.

The researchers analyzed data over a 42-month period from each of approximately 1,250 HIV-infected patients in each of four levels of increasing intensity of prescribed antiretroviral therapy: no antiretroviral therapy; single therapy; combination antiretroviral therapy not including a protease inhibitor; and combination therapy with a protease inhibitor. Death rates and incidence of opportunistic infection were compared by antiretroviral level, drugs prescribed to prevent opportunisitic infection, patient demographics (i.e., gender, age, ethnicity and mode of HIV acquisition), and CD4 cell count (a measure of drugs' efficacy) at first study visit, as well as method of payment (i.e., private insurance, Medicare/Medicaid, self-pay and Ryan White Care Act prescription programs). Death rates and protease inhibitor prescription rates were then analyzed by source of payment.

Palella's co-researchers on this study were Kathleen M. Delancy and Diane J. Aschman, Health Research Network of Apache Medical Systems, Inc., Chicago; Scott Holmberg, M.D., Anne C. Moorman and Glen A. Satten, Centers for Disease Control and Prevention, Atlanta, Ga.; Mark O. Loveless, M.D., Oregon Health Sciences University, Portland, Ore.; Jack Fuhrer, M.D., State University of New York, Stony Brook, N.Y.; and other HIV Outpatient Study (HOPS) Investigators.