BETHESDA, Md--In theory, highly active antiretroviral therapies, or HAART, should reduce the incidence of AIDS-related Kaposis sarcoma (KS) and non-Hodgkins lymphomas (NHL) by improving the immune functioning of HIV-infected individuals. Theory appears to be working out, at least with regard to lowering the risk of KS, according to several papers presented at the NCIs 2nd National AIDS Malignancy Conference.
The 1987 introduction of zidovudine (AZT, Retrovir) as an antiviral therapy to counter AIDS was followed by other single agents, their uses in combinations, and finally triple combination therapies that include protease inhibitors, which reached clinical application in 1995.
The double and triple combinations have been shown to reduce the risk of death in AIDS patients. Last year the CDC reported for the first time a decrease in AIDS-related deaths in 1996 and a fall in AIDS incidence between 1995 and 1996.
"These changes in the AIDS epidemic are largely attributable to the effects of combination antiviral therapy," the CDCs Jeffrey L. Jones, MD, told the conference. Yet the question has remained whether HAART and less aggressive therapy have affected the cancer risks associated with AIDS. Dr. Jones offered an encouraging answer. "Further analyses, including the data Im presenting, have shown a protective effect of antiviral therapy on Kaposis sarcoma," he said.
Dr. Jones reported new cancer-trend findings using data from more than 100 hospitals and clinics in 10 US cities and Puerto Rico participating in the Adult/Adolescent Spectrum of HIV Disease (ASD) project. He and his colleagues analyzed medical record abstracts of 19,684 AIDS patients, representing 26,638 person-years, who were seen during the period January 1994 through June 1997.
Participants were 79% male, 60% white, 49% men who had sex with other men, and 25% persons who used injectable drugs. Median age was 35, and median CD4 count when follow-up began was 280 cells/mm3--with a 25th percentile of 50 cells/mm3 and a 75th percentile of 403 cells/mm3.
The researchers looked at trends in seven cancers often associated with AIDS: KS, invasive cervical cancer, immuno-blastic lymphoma, primary brain lymphoma, Burkitts lymphoma, other non-Hodgkins lymphomas, and Hodg-kins disease. "For 14,299 person-years of follow-up time, antiretroviral therapy was prescribed, and for 12,339 person-years, no antiretroviral therapy was prescribed," Dr. Jones said.
The team found statistically significant decreases in KS and primary brain lymphoma but "only during the time of therapy," Dr. Jones said. "This suggests that antiretroviral therapy may be effective in cancer by slowing the progression of HIV disease." However, the other five cancers tracked showed no significant change in incidence with antiretroviral therapy.
Lisa P. Jacobson, ScD, of Johns Hopkins University School of Public Health, reported equally encouraging findings on KS in a study of the effects of HAART on KS and non-Hodgkins lymphoma, the two most common AIDS-associated cancers. She reported data on 1,813 HIV-positive men enrolled in 1984 and 1985 in the longitudinal Multicenter AIDS Cohort (MAC) Study in Baltimore, Chicago, Los Angeles, and Pittsburgh.
For many years, the incidence rate rose for both cancers, but that changed 3 years ago. "From 1989 through early 1995, we see that the average incidence of Kaposis is 25.6 per 1,000 person-years in the MAC, falling down in the last 2 years to 7.5 per 1,000, for a change of one-third of the relative incidence, which was statistically significant," Dr. Jacobson said. "Non-Hodgkins lymphoma has not shown that decrease in incidence."
The researchers matched the 14 MAC patients in their study who were diagnosed with KS in 1996 and 1997 with 273 controls. "None of the cases of Kaposis that occurred in the last 2 years reported any use of HAART," Dr. Jacobson said.
In the lymphoma group, the investigators identified eight cases that occurred in the last 2 years. "We had sufficient information for matching them to controls," she said, "and 1 (12.5%) reported using HAART. This percentage, although showing that the cases are not necessarily occurring among HAART users, is not statistically different from the 34.2% of controls who reported HAART use during the same time. But I want to point out that by July 1997, about 74% of the controls reported using HAART."
Dr. Jacobson said that HAART use has significantly decreased the incidence of KS, but not non-Hodgkins lymphoma. "There may be a slight deflection, but it has not significantly downwardly changed the incidence. The malignancy cases have very low use of HAART," she said.
Study in Military Personnel
A study in progress by Phillip O. Renzullo, MD, of the Walter Reed Army Institute of Research, Rockville, Md, has established the occurrence of malignancy and the use of HAART among military personnel with AIDS. The researchers have not yet, however, determined how this therapy, or lack of it, might affect a patients risk of cancer.
Using data from a three-service study, the HIV Natural History Cohort of Military Beneficiaries, the researchers looked at cancer incidence since 1990. Of the 313 cancers, about 64% were KS; 22%, non-Hodgkins lymphomas; 6.4%, carcinomas; and 2.9%, Hodgkins disease. The percentage of KS diagnoses has declined since 1994, and in 1997 was about 2.5%.