INITIAL STUDIES ON ACTIVE IMMUNIZATION OF HIV-INFECTED SUBJECTS USINGA GP120-DEPLETED HIV-1 IMMUNOGEN - LONG-TERM FOLLOW-UP

In 1987, exploratory clinical studies were initiated to determine whet her the development of AIDS in HIV-infected individuals might be delay ed or prevented by immunization with an inactivated HIV preparation. P reclinical studies had shown the preparation to be safe and immunogeni c. Twenty-three patients with biopsy-confirmed persistent generalized lymphadenopathy (CDC III) and two with asymptomatic HIV infection and CD4 lymphocyte counts between 135 and 769/mm(3) were studied, of whom eight (32%) had additional HIV-related symptoms. Over a 3-year period, they received a median of eight open-label inoculations of 100 mu g o f inactivated gp 120-depleted HIV-I Immunogen in incomplete Freund's a djuvant (IFA), Clinical, general laboratory, immunologic, and virologi c parameters were followed for up to 6 years. No serious treatment-rel ated adverse experiences were reported, nor was accelerated HIV diseas e progression seen. Twelve patients developed a delayed-type hypersens itivity response (HIV-DTH) to the immunogen and nine showed fourfold o r greater increases in anti-p24 antibody titers. In the follow-up peri od, 10 of the 25 patients developed AIDS and one with Kaposi's sarcoma (KS) at baseline progressed. Of the 12 patients who became HIV-DTH-re sponsive, one developed an opportunistic infection (OI), occurring app roximately 5 years from study onset, and subsequently died. One additi onal HIV-DTH responder developed KS. Of the 13 patients who remained H IV-DTH-nonresponsive, nine (69%) progressed to AIDS and seven of these have died. Differences were also observed in terms of HIV-DNA copy nu mber, CD4 percentages, and anti-p24 antibody patterns between the HIV- DTH-responsive and -nonresponsive groups, suggesting a more favorable clinical course in the former. HIV-1 Immunogen in IFA appears to be sa fe and immunogenic. Further studies are indicated to determine clinica l efficacy of the HIV Immunogen as well as the significance of the app arent correlation between HIV-DTH responsivity and a more favorable cl inical course.