Background:  It has been hypothesized that therapeutic vaccination of HAART-treated primary HIV infection subjects could induce long-term suppression of plasma HIV-1 RNA (pVL) following HAART discontinuation. This randomized, double-blind, placebo-controlled trial was conducted to assess the effect of therapeutic HIV vaccination on pVL following analytical treatment interruption in primary HIV infection.

Method:  We randomized 79 adult subjects from 25 centers (Europe, Australia, and Canada) on long-term (1.5 to 5 years) suppressive HAART (pVL<50 copies(c)/mL) since primary HIV infection, to receive over 24 weeks either  placebo (P),  ALVAC-HIV (vCP1452), or ALVAC-HIV (vCP1452) + Remune, followed by discontinuation of HAART.  The primary efficacy end-point (ITT restart treatment or missing = failure) was the difference (P versus pooled vaccines arms) in proportions of subjects with pVL <=1000 copies/mL at 24 weeks following HAART discontinuation (PT24).

Results:  Pre-vaccination demographic characteristics were similar between treatment arms (median CD4 count: 750 cells/mm³, median HAART duration: 576 days). All subjects completed the vaccination schedule and initiated the analytical treatment interruption, although 7 subjects restarted HAART before the PT24 primary endpoint and were considered failures.  Overall, 15/79 (19%) of subjects had viral load ul<1000 c/mL at PT24, (22% placebo vs 17% pooled vaccines), showing no statistically significant difference between the placebo and pooled vaccine groups (treatment difference: -5.3%, 95CI:  -24.3% - 13.8%).  The treatment difference was broadly similar for the other PT24 pVL cut-offs of ul< 5,000 (37% placebo vs 37% pooled vaccines), <=10,000 (48% placebo vs 44% pooled vaccines), ul< 50,000 (70% plavebo vs 71%  pooled vaccines), and ul< 100,000 copies/mL (74% placebo vs 75% pooled vaccines).  Median CD4⁺ cell change from randomisation was -98 cells/mm³ and was similar across the 3 treatment groups.  No subjects exhibited disease progression.  Adverse events were similar among the groups with no reported serious treatment-related adverse events and no subjects discontinued the vaccination phase because of adverse events.

Conclusions:  This first randomized, double-blind study of therapeutic HIV vaccination in HAART-treated primary HIV infection subjects did not demonstrate a significant benefit of vaccination over placebo in terms of pVL control after HAART discontinuation.  Further analyses will determine if the vaccine regimens resulted in significant HIV-1 specific cellular immune responses.  High compliance (100%) and low rate of adverse events suggest that these vaccine regimens were well tolerated.

Keywords: Therapeutic vaccination; Primary HIV infection; Analytical treatment interruption