Background:  PRIMSTOP (ANRS 100), a multicenter, prospective trial, evaluated the ability of structured treatment interruptions to induce anti-HIV immune response and to control HIV replication following HAART discontinuation in patients with primary HIV infection.

Methods:  Patients with early acute symptomatic primary HIV infection were given 34-weeks of continuous therapy combining didanosine, stavudine, nelfinavir, and hydroxyurea. At week 34, patients with plasma viral load <50 copies/mL entered the structured treatment interruption phase that consisted of 3 consecutive periods of 2 (week 34 to 36), 4 (week 48 to 52), and 8 (week 64 to 72) weeks off HAART, each separated by 12 weeks on HAART. HAART was permanently stopped at week 84 and patients were followed up until week 108. The primary and secondary efficacy endpoints were the proportions of subjects with plasma viral load < 50 and < 1000 copies/mL, respectively, at week 108.

Results:  Of the 29 patients enrolled, 3 were lost to follow-up (at week 20, week 34, week 74) and 26 completed the trial and are analyzed hereafter. Baseline characteristics were as follows:  21 male/5 female; median age 32 years; median plasma viral load 5.25 log₁₀ copies/mL; and median CD4 515 cells/mm³. In all, 22 patients underwent all 3 structured treatment interruptions and had no major violations to the protocol. All 26 patients remained off therapy at week 108. No patient died or developed an AIDS-defining event. Hydroxyurea was stopped in 52% of the patients, because of grade 3 neuropathy in 2 of them. At week 108, only 1 patient had plasma viral load < 50 copies/mL, while 7/26 (27%) had plasma viral load < 1000 copies/mL, and median plasma viral load was 4.0 log₁₀ copies/mL (IQR:  2.84; 4.45). Only sex was significantly associated with a plasma viral load < 1000 copies/mL at week 108: 4 of 5 women vs 3 of 21 men (p = 0.01). No other parameter, either at baseline (age, number of positive Western blot bands, CD4/CD8 counts, plasma viral load, cell-associated HIV-DNA, anti-HIV CD4 and CD8 response) or at week 84 (hydroxyurea exposure, cell-associated HIV-DNA, anti-HIV CD4 and CD8 response) predicted virological success (plasma viral load < 1000 copies/mL) at week 108. A major PI resistance mutation (90M) developed in 3 patients.

Conclusions:  This trial failed to confirm that a significant proportion of primary HIV infection patients can maintain suppression of viremia after a sequence of HAART/structured treatment interruptions followed by HAART discontinuation, even while HAART was initiated very early after primary HIV infection and included didanosine and hydroxyurea. In addition, this strategy was associated with the selection of protease gene-resistance mutations in 3/26 patients. Of note however, 6 months after HAART discontinuation, no patient had resumed HAART.

Keywords: Structured therapeutic interruptions; hydroxyurea