NEW YORK (Reuters Health) – HIV-infected patients have greater viral rebound and reduced time to resumption of antiretroviral therapy after therapeutic immunization with the ALVAC-HIV vaccine, according to a report in the July 11th AIDS.
“We cannot forget HIV is attacking the heart of the immune system, i.e., the CD4 T lymphocytes that are also essential for vaccines to induce specific immunity,” Dr. Brigitte Autran from Hopital Pitie Salpetriere in Paris told Reuters Health. “Therefore, the road will be long before we solve the issue of how to generate an efficient vaccine against HIV without activating the target cells for HIV.”
Dr. Autran and colleagues in the ORVACS Study Group evaluated the immunogenicity and efficacy of two different immunization strategies with the ALPAC-HIV vaccine in 65 chronically HIV-infected patients receiving combination antiretroviral therapy.
With a 4-injection strategy (but not with a 3-injection strategy), there was a significant net gain in HIV-specific peripheral blood mononuclear cells (PBMCs), the authors report, but no booster effect was seen after the last vaccine administration in either group.
At week 24, 54 patients (19 four-injection, 20 three-injection, and 15 placebo) entered a treatment interruption phase. By one month after treatment interruption, HIV-RNA became detectable in all patients except one in the placebo arm, the researchers note, and at week 36, median HIV-RNA was significantly higher in the immunization groups than in the placebo group.
By week 48, 14 of 19 patients in the 4-injection group and 10 of 20 patients in the 3-injection group reached virologic or immunologic criteria to resume antiretroviral therapy, the investigators say, compared with only 3 of 15 patients in the placebo group.
The authors conclude that although the ALVAC-HIV vaccine “induced significant T-cell immunogenicity,” this immunity “was associated with less control of viral replication.”
“Research on vaccines has to continue even on therapeutic vaccines,” Dr. Autran maintains. She urges, however, that clinical researchers “be cautious at selecting very carefully the vaccine to be tested by performing solid Phase I and Phase II studies without HAART interruption (in the case of therapeutic vaccine studies) prior to exposing patients to further treatment interruptions and risk of virus relapses.”