French Therapeutic Vaccine Strategy shows promise

Two therapeutic vaccines administered along with highly active antiretroviral therapy (HAART) significantly lengthened the time that chronically infected HIV patients could interrupt their anti-HIV treatment, French researchers say. They presented the 100-week findings of Trial 093 of the French National Agency for AIDS Research (ANRS) at the Twelfth Conference on Retroviruses and Opportunistic Infections in Boston last February (Abstract 133LB, Yves Levy et al.).

Therapeutic HIV vaccines aim to boost the body's own immune response to the virus. Structured intermittent therapy (SIT), the carefully planned and temporary discontinuation of antiretroviral drugs, can give patients a much welcomed hiatus from the expensive and toxic medications. The ANRS trial is designed to see whether supplementing HAART with a duo of test vaccines plus interleukin-2 helps keep the level of virus in the blood suppressed for longer periods of time once individuals with chronic infection stop HAART.

The first phase of the study showed that therapeutic immunization did indeed enhance HIV-specific immune responses and prolong viral suppression among the 70 trial participants ^[1]. During the first 40 weeks of the trial, the 70 participants received either HAART alone or HAART plus an injection of the HIV vaccines ALVAC-HIV and Lipo-6T each month for 4 months, followed by 3 week-long cycles of interleukin-2 at weeks 16, 24 and 32. At week 40, HAART was interrupted and not resumed as long as the viral load remained low. After 12 weeks, eight out of 33 (25%) immunized individuals remained off antiretroviral drugs compared to two out of 37 (5%) non-vaccinated participants.

The trend continued through the second phase, which followed the patients for another 48 weeks. At week 100 of the trial, 38% of vaccinated individuals and 19% of non-vaccinated patients were off HAART. Their median time off treatment was 177 days and 89 days, respectively. On average, immunized individuals remained off HAART 42.8% of the time compared to 26.5% for non-immunized participants. Vaccinated patients also had significantly lower viral loads 4 weeks after the first, second and third treatment interruptions. In addition, five non-immunized individuals but none of the vaccinated patients developed an AIDS-defining illness during treatment interruption.

The patients who received the vaccine preparation cut nearly 45% off the time on antiretrovirals, the trial's director, Yves Levy, said in a written statement. He cautioned that the results are still in the research domain, and indicated that a larger clinical trial will be needed to fully demonstrate whether the therapeutic vaccine reduces the amount of antiretroviral drugs taken and thus their potentially undesirable effects.