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

Methods:  Patients were given a 34-week continuous HAART with hydroxyurea. Those with plasma viral load < 50 copies/mL entered the structured treatment interruption phase consisting of 3 periods of 2, 4, and 8 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 HIV-specific CD8⁺ T-cell response was evaluated by ex vivo IFN-g ELISpot after stimulation of PBMC with pools of 15-mer peptides derived from Env, Gag, Pol, and Nef. Specific CD4⁺ T-cell responses were measured using both IFN-g ELISpot and proliferation assays after stimulation with HIV gag p24 protein. Responses were analyzed in the 22 subjects who underwent all 3 structured treatment interruptions.

Results:  At week 0, the CD8⁺ T-cell response, measured by total spot forming cells (SFC), was 1903±2980 SFC/10⁶ PBMC (median 903). This response decreased to 543±756 (median 256) at week 34. The changes in SFC numbers then paralleled those of plasma viral load along the HAART/structured treatment interruption phases, reaching a maximum after the third structured treatment interruption (2659±3456). At week 84, the intensity of this response remained high, 2270±2601 (median 1260). The frequency of the CD4⁺ T-cell responses regularly increased, from 27% and 18% at week 0 to 73% and 59% at W84, in ELISpot and proliferation assays, respectively. However, the intensity of responses remained low throughout the period, with a median of 78 SFC/10⁶ PBMC and a median stimulation index of 4.1 at week 84. Overall, the CD4⁺ T-cell response did not appear to be influenced by plasma viral load changes during the structured treatment interruptions. Patients were categorized as high or low/no responders according to the median value of their response at week 84, and their plasma viral load at week 108 were compared. High CD8 responders had a higher plasma viral load than low responders (4.4 vs 3.9 log₁₀ copies/mL, p = 0.04). In contrast, no significant difference was observed in plasma viral load according to the CD4 T-cell responses.

Conclusions:  This structured treatment interruption strategy allows the maintenance of a high specific CD8⁺ T-cell response, despite a low plasma viral load at week 84, in contrast to what is observed in patients continuously treated since acute primary HIV infection. This strategy also allowed the development of a specific CD4⁺ T-cell response, similar to that observed in continuously treated patients. However, this trial failed to demonstrate any effect of HIV-specific immune response on the control of plasma viral load.

Keywords: CD8 and CD4 T Cell Responses; Primary Infection; Structured Therapeutic Interruptions