Background: The goal was to determine whether 4 cycles of STI can restore HIV-1-specific T-cell responses (CD4+ and CTL) and control HIV-1 replication in patients who started HAART within 90 days after onset of PHI symptoms.

Methods: 12 consecutive patients with sustained viral suppression (<20 copies/mL) and a CD4+/CD8+ ratio >1 after  d4T, 3TC, and indinavir for at least 1 year since PHI were included in an STI program (4 cycles of 2 months off therapy and 2-4 months on therapy; HAART was stopped after each reintroduction when plasma RNA HIV viral load (PVL) was <50 copies/mL). CD4+ LPR to HIV-1 proteins and HIV-1-specific CTL responses, measured by ELISPOT using a panel of HLA class-I-restricted peptides from gag, pol, env and nef proteins were assessed.

Results: 8 patients were homosexual men. Median age was 34 years. Median (range) PVL at PHI was 134,500 copies/mL (3215->1,000,000). After a median (range) of 23 months (12-45) of HAART, all but 1 patient had plasma and tonsil tissue VL <5 copies/mL or <40 copies/mg, respectively. Median (range) CD4+T-cell count was 927 (613-1648) cells/mm³. Median (range) TREC CD4+/10⁶ T cells was 978 (249-2880). None of 12 patients had HIV-1-specific CD4+ (LPR) T-cell responses before first stop. The number of patients who completed the first, second, and third cycles were 12, 12, and 7 cases, respectively. During the first, second, and third period off therapy, mean (SD) PVL rebound was 4.89 (0.7), 3.89 (1), and 3.73 (1.8) and PVL rebound remained <3000 copies/mL in 0/12, 4/12, and 2/7 cases, respectively. The median loss of CD4+ cells was 140, 40, and 19 cells/mm³ during the first, second, and third period off therapy, respectively. There was no correlation between the level of TRECs and the type of virological response. HIV-1 specific CD4+ LPR responses were detected in 5/12, 6/12, and 5/7 cases during each period off therapy, respectively. A weak CTL response was detected at baseline in 6 of 12 patients. The magnitude of the CTL response increased after each cycle off therapy. No genotypic resistance to antiretrovirals was found.

Conclusions: HIV-1 specific T-cell responses can be restored using STI in patients receiving HAART within 90 days after PHI.  However, these responses were associated with a spontaneous control of viremia (<3000 copies/mL) in only one third of cases.