NEW YORK (Reuters Health) May 13 - HIV-infected patients respond better to Remune, a therapeutic vaccine, when they have high CD4 cell counts, low viral loads, and low immune activation prior to treatment, investigators report. According to Dr. Ronald B. Moss, it appears that immunization will afford optimal control of HIV replication in patients being treated with effective antiretroviral agents or those who begin immunization early in the course of their illness.

Dr. Moss, of The Immune Response Corporation in Carlsbad, California, and associates enrolled 38 HIV-infected individuals in a 36-week study, which is described in the May issue of Clinical and Experimental Immunology. Subjects were given intramuscular injections of the vaccine at 12-week intervals.

Immunization should boost the proliferative response of lymphocytes, Dr. Moss told Reuters Health, so that cells recognize the virus and proliferate. In the study, they defined a successful patient response to immunization as a stimulation index >5, calculated as the number of proliferative cells in the presence of antigen divided by those proliferating in the absence of antigen.

Positive results were observed in 29 patients, who responded to HIV-1 antigen, and in 27 patients, who responded to native p24 antigen. Baseline CD4 cell counts were the best independent predictor of lymphoproliferative response (p = 0.008). Proliferative response was negatively associated with baseline plasma HIV RNA and IgG levels.

"Thus, a pool of T-helper cells prior to vaccination may be required in order to allow memory CD4 cells to respond to HIV antigen,"

the authors postulate.

"If we want to see a true benefit to therapeutic vaccination, we may need to focus on [patients] with low virus levels and high CD4 cell counts," Dr. Moss said. He added that failure to concentrate on a similar patient population may be why no overall effect was observed in a trial of Remune previously reported (see Reuters Health report, October 31, 2000). Patients in that study exhibited a "very wide spectrum of HIV disease," and many in the group were not using antiretroviral therapy.

Dr. Moss and his associates plan to study patient cohorts that are optimally suppressed by active drug therapy, as well as those in early stages of infection whose viral load is still low.

Ultimately, he hopes that clinicians "could use therapeutic immunization for people with HIV in the same way as we currently use cancer immunotherapy, where cancer patients are treated only intermittently with chemotherapy."

"Another goal of this approach would be for patients to be able to stop their antiretroviral therapy altogether, but it is premature to say that such a strategy would be successful," he said.

Clin Exp Immunol 2002;128:359-364.