A French trial combining a therapeutic HIV vaccine with interleukin-2 (IL-2) shots and treatment interruptions has shown that after nearly two years, individuals who received the vaccine and IL-2 saw their viral load stabilise during treatment interruption at levels tenfold lower than unvaccinated participants. The regimen also halved the amount of time they spent on HAART.
The ANRS 093 trial randomised placebo-controlled study started with subjects receiving a schedule of four shots of a combined vaccine, or a placebo, spaced four weeks apart. The vaccine consisted of two components, the ALVAC 1433 vaccine which encloses HIV env and gag proteins inside a canarypox vector, and HIV lipopeptide, which consists of HIV gag protein fragments attached to lipid ‘tails’.
The subjects were then given, again at four-weekly intervals, three cycles of interleukin-2 or placebo injections (two injections a day for five days).
Eight weeks after the last IL-2 cycle – 40 weeks into the study - subjects were taken off HAART and their viral load measured every four weeks. They were not put back on treatment unless their viral load was over 50,000 at one measurement or over 10,000 at two consecutive measurements.
The final results of two years of follow-up were presented at the 12th Retrovirus Conference. Interim results were published in 2003.
By the end of the 100-week study, which was competed by all but one of 37 subjects, vaccinated subjects spent 42.8 per cent of the time in treatment interruptions compared with 26.5 per cent for control subjects. Their full-time HAART was reduced by 45 per cent compared with 23 per cent for the controls.
During subsequent treatment breaks the ‘set point’ viral load reached in vaccinated subjects (defined as the viral load four weeks into a break) declined in vaccinated subjects but not in controls, with the difference reaching statistical significance in the second and subsequent breaks. By the third treatment interruption the set-point vial load in vaccinated subject was nearly a log lower than controls (3.66 compared with 4.53 logs, or 4,500 versus 35,000).
All subjects experienced CD4 declines over the study but the fall in vaccinated subjects was only a third of that in control subjects (57 versus 179). AIDS-related illnesses were experienced by no vaccinated subjects but five control subjects (two thrombcytopenia (low platelet count), two shingles and one Kaposi’s sarcoma).
Levy Y et al. Sustained control of viremia following therapeutic immunisation in chronically HIV-1-infected individuals: long-term follow-up of the ANRS 093 trial. Twelfth Conference on Retroviruses and Opportunistic Infections, Boston. abstract 133LB, 2005.